ST Emlyns Critical Appraisal 2019

FOREWORD
This book brings together the best of the journal club posts from the St
Emlyn’s blog and podcast. Journal Clubs have been a focus of our work and
research for many years, initially as a face to face entity, but in recent years
more commonly online and through the use of #FOAMed and social media.
The St Emlyn’s team keeps an eye out for any papers that might change our
practice, challenge our research assumptions or which illustrate important
aspects of critical appraisal. This year we bring together a range of papers
that we believe to be relevant to all emergency and critical care clinicians.
We don’t pretend that these papers represent a comprehensive survey of the
literature, merely an interesting and accessible sample of what is out there.
Together with other #FOAMed blogs and podcasts we aim to help readers
be up to date across their practice. In this combined effort we would like to
highlight colleagues who hold similar views and invite you to visit and
subscribe to their blogs. A non-exhaustive list is shown below (with our
apologies if we have left any of our valued friends and partners off the list).
The Skeptic’s guide to Emergency Medicine with Ken Milne, Chris,
Anthony and Kirsty
Don’t forget the Bubbles from the DFTB team
EMCRIT with Scott Weingart, Rory Spiegal & Josh Farkas
Resus.me with Cliff Reid
emlitofnote with Ryan Radecki
FOAMcast with Lauren Westafer and Jeremy Faust
The Bottom Line Duncan Chambler and colleagues on the best of ICU
papers
Life in the Fast Lane as always :-) for weekly links to literature reviews
We really hope you enjoy the summaries. As always, we’d love you to give
us feedback via the blog or via our social media links.
Simon Carley and Liz Crowe

Editors
AUTHORS
Stevan Bruijns
Dr Stevan Bruijns is a South African/ British emergency physician (dual
trained). His interests include quality improvement, emergency care
development and research access in African low-resourced settings. He is
honorary associate professor of emergency medicine with the University of
Cape Town and the chief editor of the African Journal of Emergency
Medicine. Stevan is a person of action and like for things he does to be
useful to others. He has worked in a number of settings, including resource-
rich and resource-poor ones. Stevan currently works at Yeovil District
Hospital in Somerset, UK. He also serves on the Royal College of
Emergency Medicine's Global Emergency Medicine committee.
All Posts Website
Richard Carden
Dr Richard Carden MBChB MSc BSc (Hons) PGCert FHEA MAcadMEd

RAMC(V) Dr Richard Carden MBChB MSc BSc (Hons) PGCert FHEA
MAcadMEd RAMC(V) is an Emergency Medicine Trainee in London. He
is currently a PhD Candidate in Trauma Sciences at the Centre for Trauma
Sciences. He is a Major in the British Army with 335 Medical Evacuation
Regiment. He is a Co-Founder of the National Trauma Research and
Innovation Collaborative and Module Lead for the MSc in Emergency and
Resuscitation Medicine at QMUL. You can find him on twitter as
@richcarden
All Posts Website
Simon Carley
Professor Simon Carley MB ChB, PGDip, DipIMC (RCS Ed), FRCS (Ed)
(1998), FHEA, FAcadMed, FRCEM, MPhil, MD, PhD is Creator,
Webmaster, owner and Editor in Chief of the St Emlyn’s blog and podcast.
He is Professor of Emergency Medicine at Manchester Metropolitan
University and a Consultant in adult and paediatric Emergency Medicine at
Manchester Foundation Trust. He is co-founder of BestBets, St.Emlyns and
the MSc in emergency medicine at Manchester Metropolitan University. He
is an Education Associate with the General Medical Council and is an
Associate Editor for the Emergency Medicine Journal. His research
interests include diagnostics, MedEd, Major incidents & Evidence based
Emergency Medicine. He is verified on twitter as @EMManchester
All Posts Website
Chris Gray
Dr Chris Gray BSc(Hons) MBBS MRCP(UK) MRCEM AICSM is an ST6

in Emergency Medicine and Intensive Care Medicine, training in
Manchester and the North West. He is also an ALS, APLS, and ETC
instructor and keen educator. He is @cgraydoc on twitter
All Posts Website
Dan Horner
Dr Daniel Horner BA MBBS MD PgCert MRCP (UK) FRCEM FFICM is

an editorial board member on the St Emlyn’s blog and podcast. He is
Professor of Emergency Medicine of the Royal College of Emergency
Medicine. He is a consultant in Emergency Medicine and Intensive Care at
Salford Royal NHS Foundation Trust. He is chair of the national exemplar
centre Thrombosis Committee and Regional lead for Injuries and
Emergencies on the NIHR Clinical Research Network. He is a Senior
clinical lecturer at the University of Manchester and collaborator with the
University of Sheffield. You can find him on twitter as @RCEMProf
All Posts
Laura Howard
Laura Howard. MBChB, MRCEM is an Editorial Board Member on the St

Emlyn’s blog and podcast. She is an emergency physician trainee and
clinical and doctoral (PhD) fellow in Emergency Medicine Manchester
Metropolitan University. She co-founded the ED Spa Project
(@edspa_mcr). She was the RCEM Young Investigator of the Year 2016.
Her reseach interests include emergency medicine, wellbeing,
compassionate care, triage. She is regularly invited to speak on the topic of
well-being. Her PhD is on triage (funded by the Manchester Triage Group)
and she is a member of the Wellbeing Committee at the Royal College of
Emergency Medicine. You can find her on twitter as @laurahoward10
All Posts Website
Pete Hulme
Dr Peter Hulme MB ChB, FRCEM, DTM&H, is a consultant in adult and
paediatric emergency medicine in Central Manchester. His interests include
tropical medicine, trauma, quality improvement, audit and medical
education.
All Posts Website
Natalie May
Dr. Natalie May, MBChB, MPHe, MSc, PGCert Medical Education,

FRCEM, FACEM is section lead for paediatrics and medical education. She
is an Editorial Board Member of the St Emlyn’s blog and podcast. She is a
specialist in Emergency Medicine (Australia) and a Specialist in Emergency
Medicine with Paediatric Emergency Medicine (UK). She works as Staff
Specialist in Prehospital and Retrieval Medicine with the Ambulance
Service of New South Wales (aka Sydney HEMS). She also works as aStaff
Specialist, Emergency Medicine, St George Hospital (South Eastern Sydney
Local Health District). Her research interests include medical education,
particularly feedback; gender inequity in healthcare; paediatric emergency
medicine. You can find her on twitter as @_NMay
All Posts
Zaf Qasim
Dr Zaf Qasim is an attending physician in Emergency Medicine and Critical

Care based at the University of Pennsylvania in the United States. He has
particular interests in trauma, prehospital care and advanced resuscitation
and is widely regarded as an expert in practical resuscitation procedures.
You can find him on Twitter as @ResusOne
All Posts
Charlie Reynard
MB. ChB, Academic Clinical Fellow, President's Doctoral Scholar,
Honorary Lecturer, TERN regional representative. Manchester, Greater
Manchester, United Kingdom
All Posts Website
Chapter 1
ROCURONIUM OR
SUXAMETHONIUN FOR RSI
We’re always a little cautious (scared) about entering any sort of emergency
airway debate on social media as opinions are usually strongly held, and
evidence is often of the lighter variety. One of the more controversial
questions is in the use of first choice paralytics for ED RSI. In the past we
used suxamethonium for its rapid action, but it does have rather a lot of side
effects which have led to be being described locally as a ‘dirty’ drug.
Rocuronium on the other hand has fewer side effects, but does not have the
long tradition of use in anaesthesia and takes slightly longer to work.
So what’s best? Does it matter? What do we mean by best anyway? And is
this really an important question anyway considering the debates that fly
back and forth on twitter and in journals? On the BestBets site there are
articles from 2011 that describes little difference (1), there is a more recent
review on the Cochrane site that favours Suxamethonium for intubating
conditions (2). Several studies have used a lower dose of rocuronium which
may not work well in emergency patients (we advocate 1.2mg/Kg as in this
study, but others use as little as 0.6mg/Kg). In fact there are many other
papers out there on this topic, but the debate continues about doses,
outcomes and significance. Right up front I’ll say that I pretty much always
use Rocuronium these days, with the occasional caveat as described below,
although some of my colleagues still routinely use Suxamethonium (and it
still works!).
This week we have a paper in JAMA (3) that hopes to answer the question
of whether they are equivalent in practice. As always please follow the links
to the full paper and read it yourself before making any decisions on your
practice 3 .
What kind of paper is this?
It’s an RCT which is the appropriate design to look for difference in
performance of two interventions as in this study. RCTs are great for this,
but we must remember that they are not good at looking for rare
complications as you generally need vast numbers of patients to do this.
That’s relevant here because some of the proposed differences between the
drugs, such as rates of anaphylaxis and malignant hyperthermia are so rare
that they could not be picked up in a study of this size.
Patients were block randomised in this study to take account of the large
number of recruiting centres.
Tell me about the patients.

This is a nationwide French study in the prehospital environment. Adult
patients requiring prehospital RSI were included. An impressive 1248
patients were included. Inclusion was based on the need for intubation in
the opinion of the prehospital doctor on scene. Cardiac arrest patients were
not included. Typical exclusions were known allergies, muscle disease and
pregnancy. This leaves a fairly heterogeneous group of conditions, ages and
pathologies which pragmatically reflects our work here in Virchester.
Although this was a prehospital study its findings should be relevant to the
resus room.
The most common reason for intubation was coma due to neurological
disease or poisoning. Fewer than 10% of patients were trauma patients.
What did they do.

Patients were randomised to either 1mg/Kg of suxamethonium or 1.2mg/Kg
of rocuronium. Two induction agents were recommended, either etomidate
or ketamine, although additional agents could be used at the physicians
discretion. Clinicians were not blinded to the drug used and since we see
fasciculations in the majority of patients receiving suxamethonium it’s
probably not possible to do so.
Patients were intubated using a Mac 3 or 4 blade with direct laryngoscopy.
If that failed they followed their local failed airway algorithm.
What about the outcomes?

This is an important question in any anaesthesia based trial, as there are
many potentially important outcomes. Laryngoscopy view, intubation
success, time, mortality, complications and more could be considered
important, but arguably in a trial specifically looking at the intubating
conditions their chosen outcome, that of first pass success, seems
reasonable.
Importantly this was a non-inferiority trial (4).It is designed to tell us
whether one of these drugs is notably inferior to the other. This changes the
stats and the sample size calculations, as opposed to a trial where we might
be attempting to find a true difference between the two drugs. The authors
chose a non-inferiority margin of 7%, in NNT terms that’s about 1 in 14
patients. So if the difference was one additional success (on average) for
every 15 patients then the authors would consider that non-inferior. This is
not the same as saying the two drugs are no different, just that they don’t
differ by as much as a pre-set amount (in this case 7%).
Tell me the results.

The main outcome, that of first pass success showed a difference of 4.8%
favouring suxamethonium. However, this did not reach the inferiority
threshold of the trial and therefore the authors conclusion is that the two
drugs have not been shown to be inferior to each other. Confidence intervals
were wide at -9% to infinity.
The primary outcome of first pass success was 74.6% in the rocuronium
group vs. 79.4% in the suxamethonium group.
In terms of the secondary outcomes there was little difference between the
two drugs.
So they are the same then?

Well not quite. The difference of 4.8% is quite large and interestingly if this
was a superiority study (which it is not) then that would be statistically
significant (Chi Squared 3.986, p=0.0459). So the authors are not saying
that they are the same, but rather that they have not demonstrated inferiority
at the preset limit of 7%. I still have concerns that this is quite a large
difference for such an important procedure. However, this is mitigated by
the fact that the overall failure rates were close 1.8% for roc vs. 0.7% for
sux. Supporters of sux may well look to the overall difference and the
failure rates as evidence to maintain their practice.
Similarly the long action of rocuronium is seen as a problem by some,
largely in relation to sedation and awareness. Personally I think that’s a
failure of a sedation plan post intubation rather than a pharmacokinetics
issue. In Virchester we usually use a combination of Propofol and
Remifentanyl post induction. I will admit to still using Thio/sux in some of
my status epilepticus patients in the ED.
The first pass success rate may be on the low side, perhaps because patients
do not seem to have been optimised for intubation. In Virchester we
routinely position, use bougies etc. to obtain as high a first pass rate as
possible, It’s not clear that this was done here.
Most importantly, and eloquently explained on the EMCRIT blog (5) is the
fact that studies like this can never assess rare complications. We know that
rocuronium and suxamethonium are paralytic drugs that work, and so
finding little or no difference between them should be no real surprise. For
me it’s more about the potential risks associated with each drug. We know
that suxamethonium has many adverse features, some of which are
potentially fatal to our patients. Rocuronium simply does not have much in
the way of complications. At one time it was thought to cause more
anaphylaxis, but the recent NAP6 study disputes this (6).
Global health perspective

From a global health perspective there are two key points. The first is quite
straight forward: rocuronium is not included on the WHO essential drug
list. Although it might be available in some settings (such as South Africa
where Tim below practices), it is unlikely to be available in the majority of
low- and middle-income settings.
The second point is that low- and middle-income countries lack critical care
beds. The vast majority of low- and middle-income countries lack any
published data on critical care capacity. The World Bank’s dataset does not
specifically describe critical care bed capacity, and hospital beds per 1000
patient data are between 5 and 15 years out of date.
Additionally, most critical care units in low- and middle-income countries
are located in large city referral hospitals. This essentially means that a
prehospital service is required to connect critically ill patients to critical
care beds. And yet formalised prehospital services are lacking or largely
inadequate in the majority of these settings.
Mould-Millman found that only one in five surveyed African countries had
government-financed prehospital systems; only one in four had a toll-free,
public-access telephone number. Basic emergency medical technicians and
Basic Life Support-equipped ambulances made up 84% of services.
I guess you can see where I’m going with this. Intubating a patient (whether
using rocuronium or suxamethonium) in these settings is but a small part of
an unpredictable patient journey – often resulting in a dead end due to
highly variable resource restrictions.
Sadly as healthcare is not free in many low- and middle-income settings, a
high-stakes-uncertain-benefit decision to intubate is often not perceived as
appropriate practice. Charmaine Cunningham wrote an excellent blog about
this paradox, which is well worth a read (even if you are UK-based).
When considering intubation in low- and middle-income settings, it is
imperative to first have a clear understanding of the scope of the critical
care service that underpins the local system. When appropriate to use,
suxamethonium will remain the unquestionable primary choice in these
settings.
The bottom line

This study fails to find a difference between rocuronium and
suxamethonium. However, the decision as to which to use is complicated by
more than just first pass success rates and there are clearly clinicians out
there who still favour one over the other. On balance, the lower
complication rate of rocuronium places it as first choice in Virchester ED.
Simon Carley @EMManchester
References
1. Herbstritt A. Is rocuronium as effective as succinylcholine at facilitating laryngoscopy during rapid sequence intubation?
BestBets. https://bestbets.org/bets/bet.php?id=2280. Published 2011. Accessed 2019.
2. Tran DT, Newton EK, Mount VA, Lee JS, Wells GA, Perry JJ. Rocuronium versus succinylcholine for rapid sequence
induction intubation. Cochrane Database of Systematic Reviews. October 2015. doi:10.1002/14651858.cd002788.pub3
3. Guihard B, Chollet-Xémard C, Lakhnati P, et al. Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation Success
Rate Among Patients Undergoing Out-of-Hospital Rapid Sequence Intubation. JAMA. December 2019:2303.
doi:10.1001/jama.2019.18254
4. Lesaffre E. Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis. 2008;66(2):150-
154. https://www.ncbi.nlm.nih.gov/pubmed/18537788.
5. Farkas J. Rare and Catastrophic complications. EMCRIT. https://emcrit.org/pulmcrit/rare-catastrophic-complications/.

Published 2019. Accessed 2019.
1. Cook T. NAP 6. National Airway Project. https://www.nationalauditprojects.org.uk/NAP6home. Published 2019. Accessed

2019.
1. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Prehospital Care, Resus & Crit Care
2. TAG: airway, C3AP6, CC3, FOAMed, rapid sequence induction, suxamethonium

Chapter 2
PSEUDO PEA IN THE ED
I don’t know if this has ever happened to you but when I was still a registrar,
often I’d be in the midst of a resuscitation or major trauma case someone much
cleverer than me would suggest a novel treatment that’d I’d never heard of and
I’d be too embarrassed to admit that I had no idea what they were talking about.
‘Good idea’ I’d nod in agreement unconvincingly. ‘Let’s go for it’
One such time was during the resuscitation of a woman in her 60’s who had been
transferred to Virchester with a thoracic dissection for the cardiothoracic
surgeons. Pre-hospital she’d deteriorated and gone into PEA cardiac arrest. We
carried out standard advanced life support, poured in O type blood and during a
pause in CPR I did a quick xiphoid view with the cardiac ultrasound probe. We
could see the ventricles contracting weakly but no pulse could be felt.
‘That’s pseudo-PEA’ my consultant declared. ‘Let’s carry on’.
Sadly the odds were stacked against our patient and although she did get a ROSC
and palpable pulse her dissection was deemed unsurvivable by the surgeons and
active treatment was withdrawn.
This was the first time I’d heard the phrase pseudo-PEA (also known as low flow
PEA, near-PEA or PEA-like status) as it wasn’t something I’d been taught on
Advanced Life Support courses. I’ve since become more familiar with the phrase
and it’s implications but for people less familiar this recent paper is an excellent
review. The abstract is below, but as we always say, please go read the full paper
yourself before drawing any conclusions or changing your practice (1).
Background
What is Pseudo-PEA and how does it differ from ‘true’ PEA?
True PEA is the presence of organized electrical activity on cardiac monitor
without a palpable pulse and no cardiac motion on POCUS.
Pseudo-PEA is organized electrical activity on cardiac monitor without a pulse
but with cardiac motion on point of care ultrasound (POCUS).
This is a narrative review paper that evaluates the diagnosis and management of
patients in pseudo-PEA and discusses the impact on emerging patient outcomes.
A thorough review of the literature was undertaken by the authors looking for
the following search terms: ‘‘pseudo pulseless electrical activity”, ‘‘pseudo
PEA”, ‘‘near PEA”, ‘‘near pulseless electrical activity”, and ‘‘pseudo
electromechanical dissociation”. A total of 9 articles were deemed suitable for
review. Full details of the search strategy are shown in Fig. 1 of the paper.
What were the main results?

Use of Ultrasound in diagnosing pseudo-PEA
POCUS is the main way of diagnosing pseudo-PEA. In a study by Salen et al 2
11 out of 34 (32%) patients studied who were in PEA were found to have cardiac
activity on ultrasound.
Zengin et al 3 compared transthoracic echocardiograph and ultrasound doppler
in cardiac arrests. TTE was found to be faster and more accurate than doppler
ultrasound and manual pulse checks. In 37 cases of PEA TTE identified 7 (19%)
cases of pseudo PEA vs 2 cases with ultrasound doppler of the left femoral
artery.
Whilst transthoracic echocardiography may be quicker and simpler it can’t be
done during active chest compressions. This is where Transoesophageal
echocardiography (TOE) may be of benefit and has been used by Teran et al 4
during cardiac arrests. Although the numbers are small (33 patients) TOE has
shown some promise and can be used to give good quality cardiac images, real
time feedback on the quality of CPR and can differentiate fine VF from asystole
and pseudo-PEA from true PEA.
–Therapeutic approach to Pseudo-PEA

Diagnosing pseudo-PEA is critical as management can differ from true PEA.
Prosen et al 5 used TTE to diagnose pseudo-PEA and then gave an IV bolus of
20 IU of vasopressin to these patients then waited 15 seconds without chest
compressions before feeling for a palpable pulse and then continuing CPR if no
pulse was palpable. 15/16 (94%) of patients achieved ROSC and of these, eight
patients (50%) attained a good neurological outcome (Cerebral Performance
Category 1 – 2). The benefit of vasopressin was thought to be due to
haemodynamic stabilization with peripheral vasoconstriction.
Paradis et al 6 looked at the effects of CPR synchronised to systole or diastole in
pigs induced into pseudo-PEA. Peak aortic pressure in systolic synchronization
was 86.7 vs 69.3 in diastolic synchronization (P < 0.0001), and coronary
perfusion pressure in systolic synchronization was 37.6 vs 30.2 in diastolic
synchronization (P = 0.0001). This suggests that synchronizing external chest
compressions with cardiac systole is beneficial rather than diastolic
synchronization for pseudo-PEA patients. The reason for this benefit is that chest
compressions are not impairing ventricular filling during systole. Only 8 subjects
were included but this potentially could be very useful if similar findings were
replicated in humans.
-Prognosis of patients in pseudo-PEA

We’re all aware of the poor prognosis of patients in cardiac arrest but three
studies have shown increased rates of ROSC in patients with pseudo-PEA
compared to true PEA. Chardoli et al 7 found ROSC in 43% of pseudo-PEA
patients compared 0% (no ROSC) in true PEA 7 .
In another study by Flato et al 8 in ICU patients out of 27 patients with pseudo-
PEA, 6 survived to hospital discharge, whereas out of 5 patients with true PEA,
none of them survived to hospital discharge.
The most comprehensive paper was a systematic review and metanalysis by Wu
et al 9 combining 11 studies and 777 patients in PEA. It found that Pseudo-PEA
patients more likely to obtain ROSC (RR 4.35, p < 0.00001). 15 patients
survived to discharge all of them were in pseudo-PEA.
What’s the bottom line?

It’s really important to differentiate pseudo-PEA from true-PEA because ROSC
and survival rates are higher in pseudo-PEA.
The evidence for the different management options vasopressin and CPR
synchronised to systole are limited but make sense physiologically and would be
important areas for future research. Indeed a further paper looking at
synchronous CPR in pigs has just been published showing further promise.
POCUS should be a core skill for all emergency physicians and will help us
make a diagnosis of pseudo-PEA.
True PEA has a worse prognosis than pseudo-PEA so diagnosing that may aid
decision making in cessation of cardiac arrest.
42-86% of all PEA is pseudo-PEA. As this is more common than people
probably realise more research should be done in this area to try to improve
outcomes for patients. (Salen et al)
Thanks for reading, I’d love to hear your comments and who knows maybe this
will help you be the ‘clever’ doctor the next time you see a patient in PEA (or is
it actually pseudo-PEA?).
Pete Hulme @tropdocpete
References
1. Rabjohns J, Quan T, Boniface K, Pourmand A. Pseudo-pulseless electrical activity in the emergency department, an evidence based
approach. The American Journal of Emergency Medicine. October 2019. doi:10.1016/j.ajem.2019.158503
2. Salen P, Melniker L, Chooljian C, et al. Does the presence or absence of sonographically identified cardiac activity predict resuscitation
outcomes of cardiac arrest patients? The American Journal of Emergency Medicine. July 2005:459-462.
doi:10.1016/j.ajem.2004.11.007
3. Zengin S, Gümüşboğa H, Sabak M, Eren Ş, Altunbas G, Al B. Comparison of manual pulse palpation, cardiac ultrasonography and
Doppler ultrasonography to check the pulse in cardiopulmonary arrest patients. Resuscitation. 2018;133:59-64.
doi:10.1016/j.resuscitation.2018.09.018
4. Teran F, Dean A, Centeno C, et al. Evaluation of out-of-hospital cardiac arrest using transesophageal echocardiography in the
emergency department. Resuscitation. 2019;137:140-147. doi:10.1016/j.resuscitation.2019.02.013
5. Prosen G, Križmarić M, Završnik J, Grmec Š. Impact of Modified Treatment in Echocardiographically Confirmed Pseudo-Pulseless
Electrical Activity in Out-of-Hospital Cardiac Arrest Patients with Constant End-Tidal Carbon Dioxide Pressure during Compression
Pauses. J Int Med Res. August 2010:1458-1467. doi:10.1177/147323001003800428
6. Paradis NA, Halperin HR, Zviman M, Barash D, Quan W, Freeman G. Coronary perfusion pressure during external chest compression
in pseudo-EMD, comparison of systolic versus diastolic synchronization. Resuscitation. October 2012:1287-1291.
7. Chardoli M, Heidari F, Rabiee H, Sharif-Alhoseini M, Shokoohi H, Rahimi-Movaghar V. Echocardiography integrated ACLS protocol
versus conventional cardiopulmonary resuscitation in patients with pulseless electrical activity cardiac arrest. Chin J Traumatol.
2012;15(5):284-287. https://www.ncbi.nlm.nih.gov/pubmed/23069099.
8. Flato U, Paiva E, Carballo M, Buehler A, Marco R, Timerman A. Echocardiography for prognostication during the resuscitation of
intensive care unit patients with non-shockable rhythm cardiac arrest. Resuscitation. 2015;92:1-6.
9. Wu C, Zheng Z, Jiang L, et al. The predictive value of bedside ultrasound to restore spontaneous circulation in patients with pulseless
electrical activity: A systematic review and meta-analysis. Erdoes G, ed. PLoS ONE. January 2018:e0191636.
doi:10.1371/journal.pone.0191636
. CATEGORY: #FOAMed, Cardiology, Emergency Medicine, Journal Club, Resus & Crit Care
2. TAG: cardiac arrest, FOAMed, PEA, ultrasound
Chapter 3
RISK SCORES FOR CARDIAC

CHEST PAIN: THE FIRST HEAD-
TO-HEAD COMPARISON!
Suspected cardiac chest pain: everyone sees it, everyone has a different
clinical pathway, and everyone has a different risk score for it.
This week the Emergency Medicine Journal published our paper
“Comparison of four decision aids for the early diagnosis of acute coronary
syndromes in the emergency department” headed by Rick Body, directly
comparing different risk scores for acute myocardial infarction.
The abstract is below, but also please go and read the full article (1) and
draw your own conclusions before changing your practice.
What did we do?
We examined the diagnostic accuracy of a new high-sensitivity troponin I
(hs-TnI) assay when used with chest pain risk scores.
It’s a nested study within the larger trial, the Bedside Evaluation Sensitive
Troponin study (BEST) (2).
. In short BEST was a multicentre prospective observational study that
examined the diagnostic accuracy of different troponin assays for acute
myocardial infarction.
It included any emergency department patient with suspected cardiac chest
pain, the usual exclusions of STEMI and pain greater than 12 hours in
duration were applied. A bespoke chest pain proforma was filled in by
treating clinicians which collected the data for different risk scores.
The outcome, acute myocardial infarction, was diagnosed by the serial
troponin results run on the local assay and interpreted according to the third
universal definition of acute myocardial infarction.
14 of the 18 centres had plasma samples available to run the Siemens
ADVIA Centaur high-sensitivity troponin I assay and subsequently
contributed to this nested study.
What did we find?

From the larger study of 1,487 patients we included 999 patients. The
prevalence of AMI was 13.2% which is in keeping with previous work.
Unfortunately, we couldn’t calculate all the risk scores for the 999 patients
due to missing data. Most of the missing data was for the cardiac risk
factors or for the subjective variables (e.g. typicality of the symptoms).
Four risk scores and one troponin strategy were compared; a troponin only
strategy (limit of quantification <3ng/L), TMACS (1,3) , HEART (4) , TIMI
(5) , and EDACS (6).
Details of the decision aids TMACS calculates the probability of ACS by
Details of the decision aids. TMACS calculates the probability of ACS by
adding all the above numbers up and then multiplying the total (t) by 1 / exp
– (t). Digital calculators are available.
With the HEART score, patients usually score 1 point if they have a
troponin level above the 99th percentile and 2 points if their troponin is at
least 3 times above that normal range. To improve its sensitivity, we
modified this such that patients with hs-TnI <3ng/L would score 0 points;
and patients with hs-TnI above the sex-specific 99th percentile would score
2 points. Those in between would score 1 point. During her recent
presentation at EUSEM in Prague, this is how Barbra Backus suggested we
might modify the HEART score in the era of high-sensitivity troponin
testing.
The ranking
A high sensitivity is achievable for a troponin only strategy (hs-TnI <3ng/L
on arrival) and TMACS, both at 99.2%. The other scores (TIMI, EDACS
and HEART) all had sensitivities below 99% for AMI.
However, the troponin-only strategy wasn’t as efficient as TMACS. Using
the troponin-only strategy would have allowed 28.8% of patients to be
reassured with one test, whilst TMACS would have ruled out 46.5% of the
total after one test. Impressively EDACS could rule out 48.3% of patients,
but this was at the detriment of sensitivity (96.2%).
Risk scores listed in order of results
Enough waffle: what does this mean?

This paper suggests that if you have this high sensitivity troponin I assay
and you want:
High sensitivity, highest negative predictive value and a high rule out rate
– then TMACS is for you.
Highest sensitivity and simplicity: a troponin-only strategy fits your
mantra
Highest rule-out at the cost of sensitivity; EDACS is your match, though
TMACS was not so far behind
CAVIATS
This is one study (albeit multi-centre)
This is only with one assay (Siemens ADVIA Centaur high sensitivity
troponin I)
I’m an author on the paper and involved in the wider implementation of
TMACS
This was a nested study and there is missing data
Global health perspective

It is worth noting that high-sensitivity troponin I is not widely used
globally. Sadly there appears to be a good market in low- and middle-
income setttings, for the troponin assays that are no longer considered
useful in high-income settings. A small, retrospective study performed in
such a low- and middle-income setting, revealed a large number of patients
with a final diagnosis of unstable angina (almost unheard of within our
setting), despite the use of a troponin test in the work-up. (Kabongo D,
Kalla M, Allgaier R, et al. Describing suspected non ST-elevation acute
coronary syndrome using troponin at a regional, public South African
emergency centre with the Roche cardiac reader. SA Heart.
2018;15(2):102-7)
Then there is the issue of resource availability. A small survey conducted at
the 2016 International Conference on Emergency Medicine in Cape Town
suggests that the management of ACS can be hampered by more than the
absence of troponin testing assays: lack of a pre-hospital service, 12-lead
ECGs, as well as what we would consider basic treatment (aspirin,
anticoagulants and PCI). (Beukes JG, Hendrikse C, Bruijns SR. Lack of
Acute Care Resources to Diagnose and Treat Acute Coronary Syndrome in
Lower-Income Settings. Global heart. 2018;13(1):35)
Given that international guidance on ACS management almost exclusively
refers to practice in high-income settings, it is vital when practicing in low-
and middle-income settings to be clear what the accuracy of the assay in use
is – on second thought, that is probably good advice no matter where you
practice.
Bottom line
For me this study supports strategies using T-MACS, hsTnI <3ng/l strategy
or EDACS. It also reaffirms that troponin-only strategies can be enhanced
by risk scores.
Charlie Reynard @Reynard_EM
References
1. Body R, Morris N, Reynard C, Collinson PO. Comparison of four decision aids for the early diagnosis of acute coronary
syndromes in the emergency department. Emerg Med J. November 2019:emermed-2019-208898. doi:10.1136/emermed-2019-
208898
2. HRA U. BEST STUDY. Health Research Agency. https://www.hra.nhs.uk/planning-and-improving-research/application-
summaries/research-summaries/the-best-study/. Published 2014. Accessed December 2019.
3. Body R, Almashali M, Morris N, et al. Diagnostic accuracy of the T-MACS decision aid with a contemporary point-of-care
troponin assay. Heart. January 2019:768-774. doi:10.1136/heartjnl-2018-313825
4. Backus BE, Six AJ, Kelder JC, et al. Chest Pain in the Emergency Room. Critical Pathways in Cardiology: A Journal of
Evidence-Based Medicine. September 2010:164-169. doi:10.1097/hpc.0b013e3181ec36d8
5. Antman EM, Cohen M, Bernink PJLM, et al. The TIMI Risk Score for Unstable Angina/Non–ST Elevation MI. JAMA. August
2000:835. doi:10.1001/jama.284.7.835
6. Than M, Flaws D, Sanders S, et al. Development and validation of the Emergency Department Assessment of Chest pain Score
and 2 h accelerated diagnostic protocol. Emerg Med Australas. January 2014:34-44. doi:10.1111/1742-6723.12164
1. CATEGORY: #FOAMed, Acute Coronary Syndromes, Acute Medicine, Cardiology, Emergency
Medicine, Journal Club, Troponins
2. TAG: CAP7, CC5, chest pain, Manchester, TMACS, troponin

Chapter 4
LEVEL PEGGING? THE PEGED

STUDY
It’s not often you see a mate as a lead author in the New England Journal of
Medicine (NEJM). When you do, it needs celebrating. Hats off to
Associate Professor Kerstin de Wit (nee Hogg), who with a group of world
leading thrombosis experts, published an impressive piece of work this
week on the use of clinical probability adjusted d-dimer thresholds for
exclusion of PE in the emergency department/outpatient setting (1). Kerstin
is a Virchester alumnus and produced her doctoral thesis in the UK,
publishing the MIOPED study (2) and pioneering the evidence base for
ambulatory management of VTE. She has since emigrated to Canada,
working first at Ottawa with Phil Wells and co, then onto Hamilton where
she now practices as an emergency physician and thrombosis/haemostasis
clinician. She has done loads in the last decade, but this recent project gives
us a clear reason to officially celebrate her contribution to the literature.
Congratulations Kerstin et al.
HOWEVER. This does not mean the PEGeD is exempt from critical
appraisal. I am sure Kerstin would think the same and want to encourage
scientific discourse. No stone is left unturned in Virchester, irrespective of
friendship status. As such, I sat down to have a good look at this article. We
suggest you do the same, and the full text (unfortunately not FOAMed) can
be found here:
What’s it all about then?
The premise behind this paper is that we are still overtesting in our attempt
to exclude PE. The authors suggest only 30% of the patients we evaluate
clinically have both a low pretest probability by Wells score and a negative
d-dimer by normal conventional cutpoint. As such, the implication is that
70% of patients go on to have definitive investigation through chest
imaging. I am not sure this is entirely true in clinical practice (as a number
of patients get better/don’t show up for imaging/are discharged after
consultant review with no scan), but I do agree in general with the concern
on overtesting.
If the patient does get imaged, this can be useful in confirming diagnosis or
identifying alternate pathology, but comes with multiple risks; radiation
exposure, costs, delays in care, contrast reactions and most importantly, the
diagnosis of small PE’s unlikely to progress or recur. If anticoagulation
treatment is started in this latter group, say hello to 3 months of tablet
taking, a 2% major haemorrhage rate (3) and a 9.1% case fatality rate –
even in the best of circumstances. If your patient has clear bleeding risks,
renal failure, poor compliance or other complex medical issues, you have
just made life very difficult for everyone.
Thus, the PEGeD authors propose a hypothesis to reduce imaging rates in
two ways: firstly by adjusting the cutpoint for a ‘positive’ d-dimer test
(which you will remember is a continuous, not a binary variable from our
previous discussions (4) ) in those patients with a low clinical pretest
probability (C-PTP) and secondly by applying a d-dimer test to more than
just ‘low’ C-PTP patients. Both good and interesting ideas.
I was surprised though, to see little mention in the background of other
recent approaches towards this same goal. The concept of age adjusted d-
dimer (5) has been around for a long time, which follows a similar
argument. In addition, other groups have already experimented
with differing risk scores and graded thresholds for d-dimer (6) . We’ll
come back to this in the results, but keep it in mind.
This seems like a very good time to mention that the new NICE VTE 2020
guidelines are out for stakeholder consultation in the UK at present (7) , and
have several specific recommendations supporting the use of age adjusted
d-dimer testing for exclusion of PE.
You have until Christmas Eve to comment. Don’t say we never tell you
anything…
How was this trial designed?

PEGeD was a prospective management study. Patients with symptoms or
signs suggestive of PE were managed according to a set PEGeD protocol; if
you had a low C-PTP (as per the three tier Wells score) and your d-dimer
was <1000ng/ml, you were discharged with no imaging. If you had a
moderate C-PTP and your d-dimer was <500ng/ml, you were discharged
with no imaging. If you were high risk, you got imaging. All participants
were followed up for 90 days to determine relevant outcomes.
Interestingly, patients were approached to participate either during
diagnostic work up or afterwards, and provided verbal or written consent
depending on the ethics committee viewpoint. I say this is interesting, as
verbal consent after discharge is really a type of waiver/ deferred consent,
such as the type you would use for emergency care research in unconscious
patients. This particular group should have been perfectly capable of
considering whether or not they wanted to be involved, and then agreeing at
the time.
However, it is without doubt a simpler version of emergency care research
to include all patients and manage them to a particular protocol within the
ED, when they may be tired/ in pain/ anxious and reluctant to think about
research. It is essentially opt-out consent – you call them after the fact and
ask if it is OK to still use their data. But you have already essentially done
the research intervention.
Of course, this should be fine for all observational research. The reason I
find this particularly interesting, is that the study authors were actually
changing clinical care (assuming that prior to the study, most sites were
using conventional cutpoints).
Who was involved?

Over 3 years, the investigators enrolled participants through ED or
outpatient clinics in Canada (apart from one random inpatient) into PEGeD,
but it is not entirely clear across how many centres. The aim was to exclude
children (<18), pregnancy, palliative cases, those on anticoagulation or who
had received at least 24h therapeutic dose anticoagulation, those patients
who had undergone major surgery (undefined) in the last 21 days or those
who had violated the protocol (recent chest imaging or d-dimer result was
known prior to inclusion). They also excluded those patients geographically
inaccessible for follow up. These last 2 exclusion criteria are always hard to
police within a pragmatic study like this one – how do you stop someone
taking a cheeky look at the d-dimer (taken at triage) before assessment of
C-PTP? Tricky. It’s always really tough to get people to do a C-PTP score
in practice without looking at anything else, especially in the context of a
pragmatic trial like this. If they do see the d-dimer result, this would
undoubtedly creep into their C-PTP score either through conscious or
subconscious bias.
What was the primary outcome?

Although with studies like this it would be nice to know who actually had a
PE and who didn’t, you simply cannot image every patient for ethical
reasons. As such, similar to previous diagnostic accuracy studies, the
primary outcome here was one of symptomatic, objectively confirmed VTE
over the next 90 days, evaluated by a central adjudication committee with
predefined criteria.
This is good, because it addresses the core question at the mind of every
clinician. If I discharge this patient without imaging, using this diagnostic
strategy, what is the chance I have missed a clinically relevant VTE event,
or someone will come back dead?
However, this strategy for outcomes is not without issue. The inclusion of
DVT within the composite means that false positive outcomes are likely – if
I discharge someone using this strategy, who does not have a PE, but then
gets a DVT in 4 weeks time for another reason, is this truly a failure of the
original diagnostic strategy? Likewise, we talk about symptomatic disease,
but remember these patients have been counselled to return in the event of
any symptoms that may be related to PE. They will be better informed, and
more anxious, than your average patient. And you as a clinician will be
more likely to image them if they return with symptoms, having not had
imaging in the first place. Thus we are not being entirely objective, some
would argue.
The choice to use this outcome drives the sample size calculation. If you
want to be sure that discharging patients with a low C-PTP and d-dimer
<1000ng/ml has a low subsequent VTE event rate, then you need to
estimate this rate and further estimate how many patients you require, to
ensure a high level of precision (narrow confidence intervals around this
estimate). The authors propose an event rate of 0.8%, but do not provide a
reference for this. The next sentence is a little confusing, but I think they are
suggesting that in a cohort of patients with a VTE prevalence of 2%, a
sample of 1036 patients would be able to identify a miss rate of 0.8% with
an upper boundary of the 95% confidence interval at 1.5%. This suggests
that in order for their sample to be adequately powered, and for the authors
to deem their diagnostic strategy a success, they could still report a VTE
event rate of around 1 in 66 patients discharged. They double the 1036
(assuming that low/moderate C-PTP makes up only 50% of those
evaluated) and add a further 1.5% potential drop-out rate, ending with a
sample size required of >2000 patients needed, who have a low/moderate
C-PTP and d-dimer below their proposed cutpoint. Make of all that what
you will.
A word on d-dimer testing

It is always worth highlighting that d-dimer assays are not universal and
reported in variable units. The two common assays report in either d-dimer
units (DDU) or in fibrinogen equivalent units (FEU). FEU are essentially
double the quantitative value of DDU. Therefore 250 DDU is equal to 500
FEU. The kicker is that most assays will report both these units in ng/ml.
You therefore often need to ask your lab what they are using, to be clear
how this affects your care.
This is particularly important with any graduation of d-dimer cutpoint. The
authors report 500ng/ml as the routine cutpoint in Canada, which is
assumed to be FEU. They are changing this in the study to 1000ng/ml in the
low C-PTP group. All well and good. In my institution however, our lab
reports in DDU – as such, our routine cutpoint is 250ng/ml. As such, I
would transfer this study design to mean that in my patients with a low C-
PTP, I might be able to discharge patients with a d-dimer below 500 – not
1000ng/ml. Other centres will have a routine cutpoint of 230ng/ml (DDU),
therefore the novel cutpoint would become 460.
Interesting stuff. Speak to your lab, understand what you use, and be clear
how it relates to the established literature figure of 500ng/ml FEU as a
routine cutpoint. The authors pragmatically allowed different institutions to
use their routine assays in the study, which is helpful and makes the
research more generalisable. They report five different assays used and
touch on this issue, including different local outpoints in the legend for table
1. Have a read.
Ok, tell me about the patients recruited?

Centres assessed 3133 patients as meeting the inclusion criteria, although
there is no denominator for this to cover which patients were missed. As
such, and given we don’t know the number of recruiting centres, we can’t
really be entirely clear on whether this was a consecutive or convenience
sample.
941 met one or more exclusion criteria, 136 did not provide consent and 39
were recruited in error, leaving us with 2017 patients for analysis. Only
1325 of these had a low/mod C-PTP and a negative d-dimer by study
cutpoint, but this is indeed overall more than the 2000 they set out to get.
Of interest, only 2.3% of these 2017 patients had a high C-PTP, and only
10.8% had a moderate C-PTP (irrespective of d-dimer result). This, I think,
gives us a good insight into the study population; >85% were low risk.
Remember, the inclusion criteria were allcomers with signs or symptoms of
PE. This worries me a little that recruiting centres made a decision to
consciously or subconsciously include/recruit only those who they deemed
to be at very low risk for PE. This compounds the concerns above, about
convenience versus consecutive recruitment. I’d be interested to know if
these numbers are generalisable to other countries and clinical settings.
In the low C-PTP group (Wells 4 or below) with a positive d-dimer result
(>1000ng/ml), 18.6% had PE on initial clinical imaging. Of the group
discharged after initial imaging was negative (but remember, who had a
positive d-dimer), 1 (0.5%) had a VTE confirmed at 90 day follow up.
In the moderate C-PTP (Wells 4.5 to 6) group with a positive d-dimer result
(>500ng/ml), 24.2% had PE on initial clinical imaging. Of the group
discharged after initial imaging was negative, 0 had a VTE confirmed at 90
day follow up.
In the high C-PTP group (Wells >6), 40.4% had PE on initial clinical
imaging. Of the group discharged after initial imaging was negative, 0 had a
VTE confirmed at 90 day follow up.
Other points of interest in the baseline characteristics? Patients were a mean
age of 52 (18), and median duration of symptoms was 5 days. The authors
also break the Wells score down by individual factors contributing to
documented C-PTP category, which is a fascinating insight into the medical
mind. Tachycardia was the most frequent positive variable in the low risk
group, for example. PE was the most likely diagnosis in 98% of patients
deemed high risk (remember less than half of this group actually had PE on
imaging) and 83% in the moderate risk group (<25% had PE on imaging).
Just goes to show. A total of 13 patients were lost to follow up.
And what are the headline results?

Well, in 1325 patients with a low or moderate C-PTP and a negative d-
dimer (below the clinical probability adjusted threshold), 0 had subsequent
VTE within the next 90 days. This is good news. The knock on from this is
that 315 chest imaging scans were avoided in patients with a low C-PTP
(who had a d-dimer between 500-999) and 40 avoided in the moderate
group (assuming they would routinely be imaged irrespective of d-dimer
result). The authors suggest a relative reduction in the need for imaging of a
third (from 51.9% with a conventional strategy, down to 34.3% with the
PEGeD protocol).
There were no attributable deaths within the cohort. There were 2 cases of
VTE on follow up; 1 in a patient with a low C-PTP, positive d-dimer (1200)
and negative CTPA, who then went on to be diagnosed with a DVT during
follow up, and second in a patient with low C-PTP, positive d-dimer and
positive CTPA who went on to be diagnosed with recurrence despite
treatment. Hardly a failure of the diagnostic strategy in question, I am sure
you’ll agree.
The authors also then went on to assess how their strategy would compare
to other recently published options, such as the use of an age adjusted cut
point in the over 50’s, or the YEARS algorithm (8) . This is where it gets
very interesting. In the study cohort, both the age-adjusted and YEARS
strategies also reduced chest imaging rates compared to a conventional
strategy. In the low C-PTP group, PEGeD was the best by a pretty
comfortable margin. However, the PEGed strategy actually resulted in more
chest imaging compared to the others, in the moderate C-PTP group. Lastly,
Age adjusted d-dimer and PEGeD faired equally in high C-PTP chest
imaging rates, but YEARS avoided imaging in a further 10 patients here.
The difficulty with interpreting this last paragraph, is that we aren’t
presented with any data on specificity – would the YEARS algorthim have
missed some disease in these high C-PTP patients? It’s hard to tell.
All sounds very impressive. Any concerns?

The authors rightly point out early on in the limitations that without
capturing a screening log, there are worries about this cohort being a
convenience sample. The concern here is that investigators would
selectively recruit uncomplicated patients or people at fairly low risk of
VTE, such that they could prove the success of their new strategy. The
authors defend their results with a post-hoc analysis of excluded patients,
showing a low VTE event rate. These patients of course got into the study
(and were later excluded) therefore I am not sure they say much about those
patients who the investigators did not approach/screen. A more convincing
argument follows that the prevalence of PE by C-PTP category in this study,
were similar to those found within other recent North American
publications (9) . This supports the idea that the authors have not misjudged
baseline risk through selective enrollment.
I think it is worth also highlighting that this is not a randomised study. This
raises 2 issues. First, although you may conclude from a piece of work like
this that the PEGeD strategy is safe, you have not compared it
contemporaneously to standard care. As such, you don’t really know
whether patients have got better care or not, and we can’t really be sure that
they have. If the additional chest imaging investigations in a standard care
group picked up a few aortic dissections for example, that would be worth
noting. Outcomes like that are not found in prospective management
research such as this, and all benefits are theoretical compared to what the
authors perceive would have been done, and what would have resulted. It is
also difficult to use studies like this when evaluating the totality of the
evidence; bodies like NICE will often exclude observational management
studies, or downgrade them significantly due to lack of randomisation.
The primary outcome in PEGeD is not mortality. And it is not singular, it is
composite (10) , with does carry some baggage. Is it a patient related
outcome measure? I would say so – patients would presumably be very
clear that what they want from a diagnostic work up is to have a potentially
life threatening pathology excluded, with the minimum fuss and
investigation. Would they really be happy without imaging however, even if
the risk of an event was deemed very low. Not for me to say. And this
endpoint is industry standard and mirrors that of all other trials in this field,
so just a discussion point really, rather than a criticism.
A bigger concern is the lack of patients in the moderate C-PTP with
negative d-dimer group. The PEGeD authors combine 40 patients from this
cohort alongside >1200 in the low risk C-PTP group. I am not certain this is
a representative sample of those patients with moderate clinical risk, and
would want to see more data here. It also leaves things quite confusing for
those of us who use a dichotomised Wells score, such as that recommended
by NICE. Which of these 40 patients had a Wells score of 5 or 6? They are
the patients of interest for me in particular and the numbers I suspect are
unfortunately too low to draw any serious conclusions..
Lastly – some of the numbers don’t quite add up. If you look at the patient
flow diagram in figure 1 for example, you will see that 467 patients in the
low C-PTP group and 179 in the moderate C-PTP group had chest imaging
for investigation of PE. In table 1 where the same data is presented, these
numbers are 465 and 179 respectively. Small differences, but they can make
a big difference in a study like this. I think also, the PEGeD minus Age
adjusted chest imaging sum for low C-PTP patients is wrong in Table 3.
This should be a negative, surely? Little things, but a bit worrying to see in
the NEJM.
Global heath perspective from Stevan Buijns
It is worth noting that clinical probability testing is not as straight forward
in settings with high HIV and tuberculosis prevalence – such as seen in
many low- and middle-income settings. Both diseases are associated with
an increased risk in VTE. What makes this complex, is that these also
substantially increase the differential diagnosis: HIV increases the risk for
opportunistic infections, and tuberculosis causes haemoptysis, is strongly
associated with COPD (which also increases VTE risk) and often results in
a chronically abnormal chest x-ray which is difficult to interpret. Given that
lower respiratory tract infection is the top cause of mortality on the African
continent, dyspnoea is considered a very common acute presentation.
There is very little research on the topic of C-PTP for PE in low- and
middle-income settings. A small, retrospective study reported poor
correlation between the revised Geneva Score and finding PE in such a
population (11). Although C-PTP for PE is often applied in these settings, it
should be used with due caution.
It goes without saying that resource limitations often dictate the diagnostic
work-up – the absence of testing for d-dimer or imaging for PE poses
significant challenges in low- and middle-income settings.
Bottom line – Do you think we should adopt this?

I think the PEGeD supports what most of us already think. That in patients
with a low C-PTP for PE, the current d-dimer cutpoint is probably set too
low. This data provides compelling evidence that in this low risk group, the
bar can probably be raised higher than it can with age adjustment alone, can
be raised higher in younger patients (not just the over 50’s) and can be
raised up to where YEARS will allow. However, due to some minor
concerns around selection/inclusion and the low numbers of patients with a
moderate C-PTP, I am not sure I am willing to use the rule on this group. In
the UK I am also fairly hamstrung by NICE guidelines (12) , which
dichotomise the Wells score into unlikely (4 and below) and likely (>4)
risk; if I went against this by using the suggested d-dimer cutpoint in
someone with a Wells score of 5 (moderate risk by three tier / likely by
dichotomised Wells) and there was any sort of adverse outcome, I would
feel very very vulnerable indeed. Despite my protestations on the evidence
base.
As such – if my patients have a Wells score of 4 or below and I don’t really
think they have PE, I will make sure to PEGeD or age adjust their d-dimer
if over 50 and now consider PEGeDing their d-dimer threshold if under
50. I would hope this may reduce my rate of V/Q and CTPA imaging, but I
will retain my gestalt and clinical skill – if I can’t find any other possible
reason for the symptoms, I’ll pursue whatever imaging I think necessary.
Any last messages?

The low incidence of PE in this ambulatory cohort reinforces how often we
look to exclude this disease, and how we still probably overconsider this
issue. Remember to use other diagnostic strategies when working up these
patients, including the PERC rule (13,14) where appropriate (also featuring
in the new NICE guidelines) and just because someone mentions the letters
P and E, that doesn’t commit you to excluding the pathology. This is all
about risk, gestalt and your clinical decision making. As we have said many
times (15) . Some of this can be shared with the patient of course. Tell them
what you are thinking. Then, they can tell you what they think. That
matters.
Congrats again to Kerstin on a really impressive piece of work and we look
forward to hearing what you all think.
Dan Horner @RCEMProf

References
1. Kearon C, de Wit K, Parpia S, et al. Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability. N Engl
J Med. November 2019:2125-2134. doi:10.1056/nejmoa1909159
2. Hogg K. Outpatient diagnosis of pulmonary embolism: the MIOPED (Manchester Investigation Of Pulmonary Embolism
Diagnosis) study. Emergency Medicine Journal. February 2006:123-127. doi:10.1136/emj.2005.027110
3. Linkins L-A, Choi PT, Douketis JD. Clinical Impact of Bleeding in Patients Taking Oral Anticoagulant Therapy for Venous
Thromboembolism. Ann Intern Med. December 2003:893. doi:10.7326/0003-4819-139-11-200312020-00007
1. Horner D. VTE Masterclass. St Emlyn’s. https://www.stemlynsblog.org/vte-masterclass-with-dan-horner-at-rcem15/. Published
2015. Accessed December 2019.
1. Righini M, Van Es J, Den Exter PL, et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism. JAMA.
March 2014:1117. doi:10.1001/jama.2014.2135
1. Rezzaie S. The Years Study. REBEL EM. https://rebelem.com/the-years-study-simplified-diagnostic-approach-to-pe/.
Published 2019. Accessed December 2019.
1. NICE U. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing (2019).
NICE. https://www.nice.org.uk/guidance/indevelopment/gid-ng10087/consultation/html-content-2. Published 2019. Accessed
December 2019.
2. Pol LM, Dronkers CEA, Hulle T, et al. The YEARS algorithm for suspected pulmonary embolism: shorter visit
time and reduced costs at the emergency department. J Thromb Haemost. March 2018:725-733. doi:10.1111/jth.13972
3. Sharif S, Eventov M, Kearon C, et al. Comparison of the age-adjusted and clinical probability-adjusted D-dimer to exclude
pulmonary embolism in the ED. The American Journal of Emergency Medicine. May 2019:845-850.
doi:10.1016/j.ajem.2018.07.053
4. Cordoba G, Schwartz L, Woloshin S, Bae H, Gotzsche PC. Definition, reporting, and interpretation of composite outcomes in
clinical trials: systematic review. BMJ. August 2010:c3920-c3920. doi:10.1136/bmj.c3920
5. Bulajic B, Welzel T, Vallabh K. Clinical presentation and diagnostic work up of suspected pulmonary embolism in a district
hospital emergency centre serving a high HIV/TB burden population. African Journal of Emergency Medicine. September
2019:134-139. doi:10.1016/j.afjem.2019.05.003
6. NICE U. Pulmonary Embolis,. NICE. https://cks.nice.org.uk/pulmonary-embolism. Published January 2019. Accessed
December 2019.
1. MD C. PERC Rule. MD CALC. https://www.mdcalc.com/perc-rule-pulmonary-embolism. Published 2019. Accessed
December 2019.
1. Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in
emergency department patients with suspected pulmonary embolism. J Thromb Haemost. August 2004:1247-1255.
doi:10.1111/j.1538-7836.2004.00790.x
1. Carley Si. Making good decisions in the ED. St Emlyn’s. https://www.stemlynsblog.org/making-good-decisions-in-the-ed-
rcem15/. Published 2015. Accessed 2019.
1. CATEGORY: #FOAMed, Acute Medicine, Ambulatory Care, Emergency Medicine, Journal

Club, thromboembolism
2. TAG: CAP7, CC5, FOAMed, NEJM, pe, PEGeD, pulmonary embolus

Chapter 5
INTRANASAL FENTANYL VS.

KETAMINE FOR ANALGESIA IN
PED
Last year we reviewed a pilot RCT comparing IN Fentanyl vs IN Ketamine

in kids (1,2) . We concluded that they were probably similar in analgesic effect
but that Ketamine had a higher adverse event rate.
Here in Virchester that previous paper did not change practice as we use IN
Diamorphine, but we are aware that there are plenty of people out there
using Fentanyl in the UK (which we imagine is probably similar to
Diamorphine as it's an opiate), and a few centres using IN Ketamine.
This week JAMA Paediatrics has published a similarly sized RCT
comparing the two drugs for children with extremity trauma (3) . The abstract
is below, but as we always say, please go read the full paper yourself before
drawing any conclusions or changing your practice.
It's an RCT which is exactly what we want to see when comparing two
treatments. More precisely this is an RCT designed to show non-inferiority,
in other words a trial to investigate that the two treatments are so similar
that it does not really matter which one we use. That seem reasonable based
on past data in small trials which indeed suggests that this is the case.
I'm a little confused as to whether this trial was originally designed as a
superiority or a non-inferiority trial. The original description of the trial on
clinicaltrials.gov (4) is unclear in this regard, but arguably looks more like a
superiority trial. I cannot see a stats analysis plan.

Patients were recruited from a single centre paediatric ED in the US (note
that US PEDs take kids up to age 18 as opposed to 16 in the UK). Those
with a painful extremity injury and with a pain score of greater than 35 out
of 100 were eligible for inclusion (with the usual exclusions such as low
GCS etc.).
Interestingly there were only 90 patients in this trial which seems a small
number to me. Non-inferiority trials usually require more patients than
classical RCTs seeking a difference against a null hypothesis. It's also a very
similar number to the previous 'pilot' trial that advocated a much larger
number in any future study. The sample size study is described in the paper,
concluding that only 90 patients are required to show non-inferiority of an
overall (mean) difference of 10mm on a 100mm scale. I think my concern
in small trials like this is that just analysing mean scores may miss
important, but small numbers of patients who have a poor outcome.
What did they do?

Patients received either 1.5mg/Kg ketamine or 2ug/Kg fentanyl IN via an
atomiser device. Participants and practitioners were masked to the
intervention, although anyone who has ever used ketamine will know that
it's often pretty easy to tell who has had it, and so the effectiveness of
masking in these trials is always open to question.
Data was collected both by direct observation and interestingly by video
monitoring which allowed minute by minute monitoring and review.

In terms of analgesia (the main outcome), there was little difference
between the two medications, and both medications were effective in
reducing pain. From the perspective of the principle outcome measure the
data supports the assertion that there is little difference between the two
medications at 15, 30 or 60 mins post administration.
The main secondary outcome in this trials was the incidence of adverse
events, which is important as it's one of the main reasons clinicians decide
between ketamine or opiates depending on which particular side effects the
clinician is most concerned about.
In this study there were more adverse events in the ketamine group (49
patients) vs. fentanyl (14 patients) although these were all minor and
perhaps expected.
Global health perspective (Steven Bruijns)

It is worth noting that fentanyl is not included in the World Health
Organization's essential drug list for children (5) (diamorphine is not included
at all). Ketamine on the other hand is included in IV form. This is in no
way a reflection of whether any, or all of these drugs would be available in
countries around the globe, or even emergency care settings within
countries. It is highly likely that most global health clinicians would stick to
ketamine - and likely use it IM and not intranasal (irrespective whether
atomisers are available or not). We would urge clinicians to familiarise
themselves with the ketamine side-effects reported in this study, and
specifically make provision within a low-resourced setting that these can be
effectively managed if needed prior to using it.
Any other concerns?
We've now seen several small trials in this area specifically looking at
ketamine vs fentanyl (1–4,6) . The future must surely be a much larger and
definitive trial and/or a meta-analysis. We are unlikely to learn much more
from any future small trials of 50-100 patients.
If you follow twitter then no doubt you will have thought at some point that
ketamine is the best drug for anything and everything. Whilst I do think it's
a great drug, this paper is a reminder that it isn't always the best, and that
twitter memes are not CPD.
What's the bottom line?
In this small study there was little difference between the two medications
in terms of analgesia but a higher number of adverse events with ketamine.
For us this means that we would favour fentanyl. In Virchester it means we
will be sticking with Diamorphine as although not tested in the study it's
likely to be closer in action to fentanyl as opposed to ketamine.
References
1. Carley S. Intranasal ketamine vs fentanyl for kids. St Emlyn’s. https://www.stemlynsblog.org/jc-intranasal-ketamine-vs-
fentanyl-for-kids-st-emlyns/. Published 2018. Accessed 2019.
1. Reynolds SL, Bryant KK, Studnek JR, et al. Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to
Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures. Miner JR, ed. Acad Emerg Med. November
2017:1430-1440. doi:10.1111/acem.13313
2. Frey TM, Florin TA, Caruso M, Zhang N, Zhang Y, Mittiga MR. Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction
for Extremity Injuries in Children. JAMA Pediatr. February 2019:140. doi:10.1001/jamapediatrics.2018.4582
1. PRIME I. Pain Reduction With Intranasal Medications for Extremity Injuries (PRIME). clinicaltrials.gov.
https://clinicaltrials.gov/ct2/show/NCT02778880. Published 2016. Accessed 2019.
2. WHO W. Model list of essential medicines. WHO. https://www.who.int/selection_medicines/list/en/. Published June 2017.
Accessed November 2019.
3. Graudins A, Meek R, Egerton-Warburton D, Oakley E, Seith R. The PICHFORK (Pain in Children Fentanyl or Ketamine)
Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine and Fentanyl for the Relief of Moderate to Severe Pain
in Children With Limb Injuries. Annals of Emergency Medicine. March 2015:248-254.e1.
doi:10.1016/j.annemergmed.2014.09.024
. CATEGORY: #FOAMed, Acute Medicine, Ambulatory Care, Emergency Medicine, Journal

Club, thromboembolism
. TAG: CAP7, CC5, FOAMed, NEJM, pe, PEGeD, pulmonary embolus

Chapter 6
HINDSIGHT BIAS
Here at St Emlyn’s we’ve always prided ourselves on being reflective

clinicians. We’ve written blogs on feedback(1), reflection (2), coaching
(3) and much more all of which rest on the principle that we it’s important
to look back at what happened such that we can learn from events. This is
not peculiar to St Emlyn’s of course, the concept of case review (e.g.
mortality and morbidity meetings), is well established in medicine (4–7).
In addition we’ve also argued that it’s quite tricky to be a good judge of
self. My talk at SMACC in Sydney (8) revolved around the idea that we
cannot truly know ourselves and that we need the objectivity of others to
help us understand how we perform in the clinical environment.
But what if that desire to reflect, review and feedback is biased? Wouldn’t
that affect the quality of the learning that came come out of any review
process? This is a problem known as hindsight bias, that process whereby
we judge prior actions based on the outcome rather than the decisions made
at the time. How often have you been told about a poor patient outcome
only to hear the story of how it happened and to declare ‘I would never
have done that’? I’ll admit to thinking this far too often, perhaps it’s a
natural protective response, before checking myself and asking the better
question of ‘why did that appear to be the right decision to that clinician at
the time it was made?’.
The question remains as to how influential hindsight bias is in our opinions,
and in particular when we are reviewing exceptional events (positive or
negative).
This week and old friend of St Emlyn’s, Prof. Tim Coates, highlighted
a paper that examines the influence of hindsight bias in reviewing tough
clinical cases (9).
The abstract is below, but as we alway say please go and read the full
paper yourself.
This is a survey design, but with elements of randomisation. Participants
were delivered an online survey, but the elements of the survey that the
participants saw were randomised as described below. It’s an interesting
design to test participants understanding of how data can be interpreted in
light of clinical outcomes.
So what exactly did they do?

The authors recruited 93 clinicians of various grades. I think this was done
through a single institution and opportunistically. Ideally it would have been
preferable to have a more systematic approach to participant recruitement as
agreement to take part may in itself put bias into the study.
They only recorded participant seniority and so we can’t really know much
about the baseline characteristics of the participants. We do know that they
were all doctors.
Once they had agreed to participate they took a web-based survey that
included three clinical vignettes. From an EM perspective these were all
relevant. Chest pain, swollen lower limbs and headache are all important
presentations to the ED that can result in significant risk to patient and
clinician. Although the vignette description of what happened to the patient
on their first visit was always the same, the participants received a random
outcome of either alive or dead. They were then asked to rate the quality of
care the patient received at the hypothetical first visit from very poor care
through to excellent care.
What did they find?

In two of the three scenarios the participants rated the care as much worse
when the patient died as opposed to when they lived. This difference did not
change when consultants were compared with more junior doctors. The
final case (chest pain) did not show the same level of variability (they did
not randomise the order that participants encountered the cases).
What is also interesting to me is the range of scores for each of the
scenarios. Although there were central tendancies to scoring in all
scenarios, all scenarios received the full range of scores (from excellent
through to very poor).
So should we believe this paper?
There are a number of caveats here. It’s a small, single centre, UK study
where recruitment strategies are unclear and we don’t know much about the
participants.
That said, the findings are consistent with what is known about hindsight
bias as a concept, and this demonstrates a similar effect in clinical medicine,
and in particular in the assessment of adult emergency medicine cases.
So what does this mean?

The authors appear to have demonstrated that hindsight certainly exists
when looking at cases where the outcome has been poor, they have also
shown significant variability in the opinion of what good quality care is.
For me, the lesson here is that when we review cases, particularly those
where the outcomes are less than perfect we need to be mindful of hindsight
bias, we need to ask ourselves to try and imagine alternative outcomes and
to be kind to those involved.
It’s also a reminder that when we are assessing clinical judgement it’s
important that we look at the decision making process and not just what
happened. As we’ve said many times before, the clinical outcome of a
patient is based upon a combination of clinical decisions PLUS
luck/uncertainty. We should never forget this.
Ross Fisher reminded me recently that the term bias itself has a number of
associations with it and perhaps a better phrase is ‘cognitive disposition’, as
they are inherent in all of us and not easily controlled.
Lastly, the UK is embarking on a new process to examine hospital based
deaths. The new Medical Examiner role will review all deaths to look for
opportunities to learn and potentially to determine where harms have
happened (10) . The potential impact of hindsight bias on this new process
is, as yet, undetermined.
References
1. May N. Testing Testing. St Emlyn’s. https://www.stemlynsblog.org/testing-testing/. Published 2013. Accessed 2019.
1. May N. On reflection. St Emlyn’s. https://www.stemlynsblog.org/on-reflection/. Published 2018. Accessed 2019.
1. Carley S. How to Coach and Feedback with your team. St Emlyn’s. https://www.stemlynsblog.org/how-to-coach-feedback-
team-st-emlyns/. Published 2018. Accessed 2019.
2. Rafter N, Hickey A, Condell S, et al. Adverse events in healthcare: learning from mistakes. QJM. July 2014:273-277.
doi:10.1093/qjmed/hcu145
3. David G. [To make good use of medical error]. Bull Acad Natl Med. 2003;187(1):129-136; discussion 136-9.
https://www.ncbi.nlm.nih.gov/pubmed/14556459.
4. Higginson J, Walters R, Fulop N. Mortality and morbidity meetings: an untapped resource for improving the governance of
patient safety? BMJ Qual Saf. May 2012:576-585. doi:10.1136/bmjqs-2011-000603
5. George J. Medical morbidity and mortality conferences: past, present and future. Postgrad Med J. November 2016:148-152.
doi:10.1136/postgradmedj-2016-134103
1. Carley, Simon. The power of peer review. St Emlyn’s. https://www.stemlynsblog.org/smacc2019-the-power-of-peer-review/.
1. Banham-Hall E, Stevens S. Hindsight bias critically impacts on clinicians’ assessment of care quality in retrospective case note
review. Clin Med. January 2019:16-21. doi:10.7861/clinmedicine.19-1-16
2. BMA B. Implementation of the medical examiner system. BMA.
https://www.bma.org.uk/advice/employment/ethics/implementation-of-the-medical-examiner-system. Published
1. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Teamwork, The philosophy of EM, Workforce
2. TAG: CC23, CC25, CC8, FOAMed, hindsight, retrospectoscope
Chapter 7
TRANEXAMIC ACID (TXA) IN

HEAD INJURY. THE CRASH-3
RESULTS.
St Emlyn’s had sight of a pre-publication copy of the CRASH-3 trial from the
trial team. This allowed us to prepare this blog in advance of publication. The
trial authors have not been involved in this review and have allowed us to say
whatever we like without interference or oversight.
Tranexamic acid (TXA) is now well established in the management of
bleeding trauma patients. CRASH-2 (1) and subsequent trials have shown
that it is highly effective and that the benefits are best realised if given early.
This effect is seen in other bleeding conditions, such as post partum
haemorrhage where TXA was shown to decrease bleeding and save lives (2) .
If you need a reminder (in cartoon form) on how TXA works, click the link
below.
By Hywell Roberts for LSHTM https://vimeo.com/user23820206

What about in head injured patients though? They are a slightly different
group to our poly/bleeding trauma patients. The amount of bleeding that they
sustain intracranially is substantially smaller and to a degree is ‘controlled’ in
that you can only bleed so much within the cranium before you die. However,
TXA has been shown to reduce the overall amount of bleeding in most
circumstances where it has been tested, and with a low side effect profile,
including in small studies of TXA in head injury (3) . Could TXA be used to
reduce the amount of bleeding following isolated brain injury and if so would
that have an effect on mortality? This is especially interesting as TXA was not
shown to be of benefit in patients with spontaneous intracranial bleeding (4–
6) and so the outcome is far from certain.
Today we have the results of CRASH-3 (7) to answer this question. CRASH-
3 8 is a placebo controlled, double blind, randomised controlled trial of TXA
in isolated head injury.
The abstract is below, but as always we strongly recommend you read the full
paper yourself and come to your own conclusions. The paper is currently open
access, so there is no excuse not to.
What sort of paper is this?
It’s a placebo controlled RCT which is exactly what we want to see when
researchers test an intervention such as a drug therapy. The research group
have extensive experience in running international RCTs. Patients were
randomised using an envelope system, primitive but reasonable under the
circumstances.

They recruited isolated head injury patients with what sounds like two time
entries into the program.
Patients with GCS <13 on arrival
Any patient with GCS 13-15 and blood on CT scan
Patients had to be recruited within 3 hours of injury, although when the trial
started they recruited up to 8 hours post injury. That changed when subsequent
evidence suggested that TXA was not beneficial after 3 hours (8) . Patients
with a significant extra-cranial injury were excluded.
It’s important to understand what the authors describe as
mild/moderate/severe in this paper. My understanding is that they stratified
according to the following definitions.
Mild GCS 14-15
Moderate GCS 9-13
Severe GCS 3-8
GCS 3 with or without pupillary signs.
Patients were recruited across a 7-year period (2012-2019) in 175 hospitals in
29 countries. They ranged across a whole range of health economies, notably
with North America not participating (more on this later).
What did they do?

Once recruited the patients received 1g TXA as a bolus and then an 8-hour
infusion of 1g of TXA. This is the same regime as in previous trials like
CRASH-2 (1) and WOMAN (2). The infusion is quite interesting as a
concept. At the recent RCEM conference one of the lead investigators alluded
to the origin of the infusion. It was suggested that the decision to use an
infusion in CRASH-2 was because of the need to maintain TXA in the system
of a patient who may be bleeding it out. That’s not really a concern in isolated
head injury and might not then be needed – although we don’t really know.
The outcomes?
At this stage they are reporting the early outcomes. Death at 28 days post
injury and any perceived complications. Death was the primary endpoint of
the study.
So what did they find?

They recruited 12,737 patients to the trial of which 9,202 were recruited
within 3 hours. The headline results are a little complex as it rather depends
on which group you look at. In essence the main results can be summarised as
follows:
1. Overall head injured related deaths if treated within 3 hours: 18.5% TXA vs.
19.8% placebo (855 vs 892 events, relative risk = 0·94, 95% CI 0·86-1·02).
So NOT significant statistically.
1. If we excluded GCS 3 or bilateral unreactive pupils at baseline deaths:
12·5% TXA vs 14·0% placebo (485 vs 525 events, RR=0·89, 95% CI 0·80-
1·00).
2. Mild/Moderate head injury deaths: 5.8% TXA vs 7.5% placebo (166 vs 207
events, RR=0·78 95%CI 0·64-0·95). So this is statistically significant.
3. Deaths in severe head injury: 39.6% TXA vs 40.1% placebo (689 events vs
685 events, RR=0·99, 95%CI 0·91-1·07) not statistically significant.
4. Deaths of both pupils react: 11.5% TXA vs 13.2% placebo. Statistically
significant
5. Deaths if one or more unreactive pupil: 52.3% TXA vs. 50.8%. Not
statistically significant.
So you might say that this was a negative trial, and I ‘m sure that there will be
some people who argue this. The overall headline figure is that there is not a
statistically significant difference if you give TXA to all patients with head
injury (GCS <13 or intracranial blood). The significant findings are in the
sub-groups. At St Emlyn’s we are always deeply sceptical about sub-group
analyses, but on this occasion we think they can be justified.
It’s worth noting that these subgroup analyses were pre-specified. You must
always be cautious about subgroup analyses, but on this occasion, I think they
are reasonable. Pre-specified and based on pathophysiology seems OK to me.
In the secondary outcomes there was no increase in thromboembolic events.
There was no significant difference in disability either, but remember that
there were more people alive to answer that question in the TXA group.
Talk to me about timings.

There is a big push in trauma patients to get TXA in early as there is
relationship between early administration and better outcomes in other trials
(9–11). In CRASH-3 a similar relationship was found with better outcomes if
the drug is given as soon as possible post injury. This relationship makes
pathophysiological sense and is in keeping with a combined analysis of past
large RCTs in trauma and post partum bleeding (12).
Make it really simple to explain.

OK. Not everyone loves stats as much as St Emlyn, so let’s convert the
positive findings into numbers needed to treat.
1. If your patient as a GCS of 9-15 with any blood on CT then you need to
treat 59 patients with TXA to save one head injury related death at 28 days.
2. If your patient has bilaterally reactive pupils you need to treat 58 patients
with TXA to save head injury related death at 28 days
3. If your patient does not have unreactive pupils and is not GCS 3 then you
need to treat 67 patients to save one head injured related death at 28 days.
That’s close or better an NNT than TXA in bleeding trauma 1 and is getting
close to my usual benchmark of aspirin in MI (42 since you are asking).
Even better, have a look at this infographic from Kirsty Challen on the key
messages from the trial (with slightly different groupings to the above).
From Kirsty Challen @kirstychallen
Note that these are the head injury related deaths. and not all cause mortality.
Since the trial did not show an increase in thromboembolic events between
groups then it’s tricky to see how TXA might have raised or lowered non-
head injured related deaths. Similarly TXA could not have an impact no non-
head injured deaths. The overall difference in all cause mortality had a RR of
0.96 (0.89-1.04), which is roughly an NNT of 60 (but not statistically
significant). The rationale for using head injury deaths as opposed to all cause
deaths may be controversial. You can read more about their rationale in the
detailed statistical analysis plan (13).
Also note that NNTs are susceptible to local factors and won’t stay the same
across different populations. We present them here as a way of comparing the
data, but be mindful that these would not translate directly to your practice.
OK, but doesn’t TXA have complications?

It’s a debatable topic. Patients who are critically unwell or injured have higher
rates of thromboembolic events irrespective of whether they are taking TXA
or not, but it’s a legitimate concern as it could be pathophysiologically argued
that TXA might increase thromboembolic rates. The authors have looked for
this and have found no increase in rates between TXA and placebo. There are
reports of increased thromboembolic events in the use of TXA, but those are
mostly observational studies where survivor bias may influence the results
(14) . In many other trials with better methodologies there appears to be no
convincing increase in events (15,16).
So we give it to every trauma patient then?

Well probably. We know that it works in bleeding trauma 1 and we now know
that it works in isolated head injury. However, we don’t really know if it
works in multi-system trauma or in kids. However, it’s probably reasonable to
extrapolate that it is safe to give to polytrauma patients and there is already a
consensus to give TXA to bleeding children patients at a reduced dose. Since
we are unlikely to get a separate trial for either group I think it’s reasonable to
go ahead and use it (personal opinion).
We may still need to think about the way that we give the TXA. As mentioned
earlier the bolus followed by an infusion was (allegedly) chosen on the basis
that the patient who is bleeding out may bleed out their TXA and so need an
infusion to keep levels up in the newly transfused blood. However, infusions
are a pain in practice and I wonder if we might see a trial of a different regime
at some point.
There are of course skeptics many around the use of TXA (17–22),
predominantly in North America and Australia, although both regions have
begun to adopt the therapy in trauma in recent years for bleeding trauma
patients. There are some who still believe that it should only be given once
fibrinolysis is proven on TEG or ROTEM (21) . The idea of such targeted
therapy is intellectually attractive, but is not borne out by the pathophysiology
– think horses, doors and bolted if you want to wait until fibrinolysis is known
before treating it. There will also be others who dismiss the findings here
because it involves patients in low or middle income countries. It’s true that
LMICs have different healths systems, but that did not seem to affect the
results in this paper.
What do others think?

It’s likely that ths study will generate a lot of debate and that’s great. We
would recommend you have a look at some of the other #FOAMed reviews
out there to get a more global perspective
badEM badem.co.za/crash-3/
EMCRIT https://emcrit.org/pulmcrit/CRASH3/
SGEM http://thesgem.com/2019/10/sgem270-crash-3-txa-for-traumatic-
head-bleeds/
The resus room https://theresusroom.co.uk/crash-3/
EMLitofnote https://www.emlitofnote.com/
REBEL EM https://rebelem.com/crash-3-txa-for-ich/
The bottom line.

Until we see/hear otherwise the @stemlyns view is that:
TXA has been shown to reduce bleeding related deaths in a variety of
settings suggesting that it fundamentally improves outcomes for patients
with life threatening bleeding.
TXA should be given to all mild/moderate head injured patients with
evidence of bleeding on CT scan.
TXA should be given to all patients who have bilaterally reactive pupils and
blood on CT scan.
Patients with head injury PLUS extra-cranial injury TXA should be given to
patients within 3 hours.
It’s cheap and easy to give, it’s safe and effective. Maybe it’s not that ‘cool’
does not arrive by helicopter and it doesn’t cost thousands, but that should not
put you off. There is an old saying that the ideal product is quick, cheap and
good. The joke is that you can only have 2 of 3. Well maybe this is one
occasion when you can have all 3.
References
1. Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of
tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol
Assess. March 2013. doi:10.3310/hta17100
2. The Lancet. WOMAN: reducing maternal deaths with tranexamic acid. The Lancet. May 2017:2081. doi:10.1016/s0140-
6736(17)31111-x
3. Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, Thinkamrop B, Phuenpathom N, Lumbiganon P. Tranexamic acid for
patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emerg Med.
2013;13:20. https://www.ncbi.nlm.nih.gov/pubmed/24267513.
4. Rezaie S. Tich – 2. REBEL EM. https://rebelem.com/tich-2-txa-for-spontaneous-ich/. Published July 30, 2018. Accessed October
14, 2019.
5. Sprigg N, Flaherty K, Appleton JP, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an
international randomised, placebo-controlled, phase 3 superiority trial. The Lancet. May 2018:2107-2115. doi:10.1016/s0140-
6736(18)31033-x
1. Horner D. Tich Tich Boom. St Emlyn’s. http://www.stemlynsblog.org/jc-tich-tich-boom-txa-in-ich-st-emlyns/. Published May 22,
2018. Accessed October 14, 2019.
1. Roberts I. CRASH-3. The Lancet. https://www.thelancet.com/. Published October 14, 2019. Accessed October 14, 2019.
2. London School of Hygiene and Tropical Medicine L. CRASH 3. Clinical Trials. https://clinicaltrials.gov/ct2/show/NCT01402882.
Published July 26, 2011. Accessed October 10, 2019.
3. Roberts I, Edwards P, Prieto D, et al. Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms. Trials.
2017;18(1):48. https://www.ncbi.nlm.nih.gov/pubmed/28143564.
4. CRASH-2 collaborators., Roberts I, Shakur H, et al. The importance of early treatment with tranexamic acid in bleeding trauma
patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096-1101,1101.e1-
5. Roberts I. Tranexamic acid in trauma: how should we use it? J Thromb Haemost. 2015;13 Suppl 1:S195-9.
https://www.ncbi.nlm.nih.gov/pubmed/26149023.
6. Gayet-Ageron A, Prieto-Merino D, Ker K, et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in
acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. The Lancet. January
2018:125-132. doi:10.1016/s0140-6736(17)32455-8
1. Roberts I. Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international,
randomised, double-blind, randomised controlled trial. Research
Gate. https://www.researchgate.net/publication/326525129_Tranexamic_acid_for_significant_traumatic_brain_injury_The_CRASH-
3_trial_Statistical_analysis_plan_for_an_international_randomised_double-blind_placebo-controlled_trial. Published July 2018.
Accessed October 14, 2019.
1. Myers S, Kutcher M, Rosengart M, et al. Tranexamic acid administration is associated with an increased risk of posttraumatic
venous thromboembolism. J Trauma Acute Care Surg. 2019;86(1):20-27. https://www.ncbi.nlm.nih.gov/pubmed/30239375.
2. El-Menyar A, Sathian B, Wahlen B, et al. Prehospital administration of tranexamic acid in trauma patients: A 1:1 matched
comparative study from a level 1 trauma center. Am J Emerg Med. April 2019. https://www.ncbi.nlm.nih.gov/pubmed/31060862.
3. Neeki M, Dong F, Toy J, et al. Tranexamic Acid in Civilian Trauma Care in the California Prehospital Antifibrinolytic Therapy
Study. West J Emerg Med. 2018;19(6):977-986. https://www.ncbi.nlm.nih.gov/pubmed/30429930.
4. Binz S, McCollester J, Thomas S, et al. CRASH-2 Study of Tranexamic Acid to Treat Bleeding in Trauma Patients: A Controversy
Fueled by Science and Social Media. Journal of Blood Transfusion. 2015:1-12. doi:10.1155/2015/874920
5. Thomas S, Moore E, Moore H, et al. Tranexamic Acid for Trauma Resuscitation in the United States of America. Semin Thromb
Hemost. December 2016:213-223. doi:10.1055/s-0036-1586226
6. Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma. Journal of Trauma and Acute Care
Surgery. June 2013:1575-1586. doi:10.1097/ta.0b013e318292cc54
7. Khan M, Jehan F, Bulger EM, et al. Severely injured trauma patients with admission hyperfibrinolysis. Journal of Trauma and
Acute Care Surgery. November 2018:851-857. doi:10.1097/ta.0000000000002022
8. Huebner BR, Dorlac WC, Cribari C. Tranexamic Acid Use in Prehospital Uncontrolled Hemorrhage. Wilderness & Environmental
Medicine. June 2017:S50-S60. doi:10.1016/j.wem.2016.12.006
1. Brohi K. Tranexamic Acid in trauma. SMACC. https://smacc.net.au/2015/10/karim-brohi-on-tranexamic-acid-in-trauma/.
. CATEGORY: #FOAMed, Critical Care, Emergency Medicine, Head injury, Journal Club, Prehospital
Care, Resus & Crit Care, Trauma
. TAG: CC3, CC5, CMP3, FOAMed, head injury, HMP3, Major Trauma, tranexamic acid, txa
Chapter 8
THE METABOLIC AND BIOCHEMICAL

CHARACTERISTICS OF PACKED RED
CELL TRANSFUSIONS
In the UK it’s now standard practice in hypovolaemic/bleeding trauma to use packed red
cells as the first line resuscitation fluid. That’s what we keep in the fridge in the emergency
department resus room of most hospitals and trauma centres, and in many if not most cases
the first IV fluids the patient receives will be in the form of O-ve packed red blood cells.
Following this and the activation of a major haemorrhage protocol we hope to catch up to a
1:1:1 ration of RBCs:FFP:Platelets (1) , but initially it’s likely to be packed red cells.
Some services are now stocking FFP in the resus room (or in the prehospital environment)
and there is a movement towards the use of whole blood (2) as we have discussed before on
the St Emlyn’s site, but for the majority of units in the UK, packed RBCs will be in first. In
major trauma it’s likely that several units (4 or more) will be rapidly transfused into the
patient and I suspect that you, like me have probably done this many times.
So stop for a second and ask yourself what’s actually in a bag of packed red blood cells and
in particular what the metabolic implications of the contents are. Can you? I’m not sure I
could either until I followed a recent twitter chat around the use of blood in prehospital care.
Dr Nick Crombie, who leads the RePHILL trial (more of this later) tweeted the following
which made me stop and think.
That was part of a debate about the use of interventions in prehospital care that are yet to be
proven/replicated and I think in specific reference to the PAMPER trial which showed a
benefit to the early use of FFP in major trauma patients (3) (Ed – we’ve covered that on
the blog here (4) ).
Most of us don’t like normal saline in trauma for many reasons that I won’t expand on here
beyond saying that it as supra-normal sodium and chloride levels, and interestingly a pH of
5.5 (gosh). What about blood though? We give enough of it so perhaps we should think about
it’s metabolic profile.
A quick search of PubMed was a little disappointing as I did not find a huge amount of data
out there, but there is this paper from 2001 (5) .
What type of paper is this?
It’s an experimental study. It’s not a patient focused study, rather a descriptive experimental
study of the characteristics of packed red blood cells.
What did they do?

Very simply the authors took blood samples from pre-transfusion bags of packed RBCs and
ran them through a blood gas analyser. They looked in some detail about whether the age of
the blood made a difference to these values.
What are the headline results?

Across all units the results are really interesting. I’ve summarised them below.
These are remarkable values if we are trying to manage the metabolic insult that our patients
suffer as a result of trauma. Packed cell transfusions have the potential to alter the acid-base
balance of our patients and to produce an additional metabolic burden on the patient.
The authors also looked at the effect of age on these values. In their study much of the blood
was pretty fresh (hence the average of about a week). In the UK colleagues suggest an expiry
date of 35 days and so the values in practice could be much worse than those in the table
above (see full paper for details). As an example, at 5 days the potassium estimate was
28mmol/l
Sadly, the concerns don’t end there. transfused cells have depleted levels of 2,3 DPG and
therefore lack the ability to release oxygen to the tissues in the way that fresh, whole blood
does (6) . Not only that but low pH reduces the binding of oxygen to haemaglobin (7) . So
it’s double whammy of red cells taking up less O2 in an acidic environment, and then being
less able to release because of low levels of 2,3,DPG. It also takes a significant amount of
time to replace the 2,3 DPG (8) which means that the red cells that we think we are
transfusing are just not going to perform in the same way that we expect the patient’s own
red cells to do (9) .
via
Wikipedia https://en.wikipedia.org/wiki/Oxygen%E2%80%93hemoglobin_dissociation_curve
We also know that calcium is removed from packed RBC packs and that we need to replace
calcium as part of major haemorrhage protocols (10) . We rarely get on top of the
hypocalcaemia in trauma as rapidly as we think we do, despite knowing that hypocalcaemia
is bad for the heart. Citrate is the anticoagulant used in blood products and it binds calcium
and magnesium. This can result in myocardial depression and/or coagulopathy.
I could go on and on about the problems of managing the replacement of blood loss, but
can’t finish without reminding us of the effects on coagulation. Packed cells do not clot and
although we aim for 1:1:1 resuscitation we rarely achieve it in the early stages of
resuscitation. Stored red cells also adversely affect coagulation pathways independently of
calcium replacement (11,12) .
What does this mean in practice?

It’s important that we understand the characteristics and potential implications of the fluids
that we give to patients. It’s clear that packed red blood cells are not physiologically normal
with respect to normal acid base/electrolyte/lactate values. What is less clear to me (Ed –
please add comments below on this if you’re an expert in these matters) is how these
metabolic abnormalities are adjusted and mitigated physiologically. Clearly this happens else
our patients would rapidly die of hyperkalaemia (and more), but how is less clear to me.
You mentioned RePHILL….

The RePHILL trial is a UK trial looking at the early (prehospital use of blood and plasma in
major trauma patients. It’s recruiting now and should report in the next year or so. That trial
may well lead us to a better understanding of the early use and metabolic impact of early
blood products in trauma. You can read more about the trial here.
The bottom line.

All intravenous fluids have the potential for benefit and for harm. As clinicians we should
understand what they contain and how that might affect our patients. Packed red cells are not
whole blood and they too have the potential for harm. As prescribers we should know what
they contain and how they might influence our patients.
We should also be mindful that when we call some fluids, ones that were previously the
mainstay of treatment in trauma as ‘poisonous’ or ‘dangerous’ for our patients then we must
understand that the current strategy of packed red cells as first resuscitation fluid may not be
the panacea that some think it to be (Ed – I’ve used fluids such as Gelofusine, Saline,
Haemaccel in my career). So the next person who tells you that Saline is rubbish because it’s
acidotic, does not carry oxygen, contains poisonous ions and stuffs up coagulation, do
remember that the bag of packed red cells shares many of the same characteristics.
So what do I do tomorrow with my bleeding trauma patient you might ask? Ideally I would
give fresh whole blood. If you don’t have that and you’re giving packed red cells be aware
and actively manage the coagulation, temperature, calcium, potassium and everything else
that may result from massive transfusion.
Finally, I’m really looking forward to the results of several trials in this area such as
Cryostat, RePHILL and more, pRBCs are probably not going to be the only solution for our
trauma patients.
References
1. Carden R. Getting the Balance Right. St Emlyn’s. http://www.stemlynsblog.org/jc-getting-balance-right-proppr-trial/. Published 2013. Accessed 2019.
1. Qasim Z. Whole Blood in Trauma. St Emlyn’s. Whole Blood in Trauma. Published 2018. Accessed 2019.
2. Sperry JL, Guyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med.
July 2018:315-326. doi:10.1056/nejmoa1802345
3. Carley S. Top 10 trauma patients. St Emlyn’s. http://www.stemlynsblog.org/top-10-trauma-papers-2018-2019-for-traumauk-conference-st-emlyns/.
4. Sümpelmann R, Schürholz T, Thorns E, Hausdörfer J. Acid-base, electrolyte and metabolite concentrations in packed red blood cells for major transfusion in
infants. Paediatr Anaesth. 2001;11(2):169-173. https://www.ncbi.nlm.nih.gov/pubmed/11240874.
5. MacDonald R. Red cell 2,3-diphosphoglycerate and oxygen affinity. Anaesthesia. 1977;32(6):544-553. https://www.ncbi.nlm.nih.gov/pubmed/327846.
6. Wikipedia W. Bohr Effect. Wikipedia. https://en.wikipedia.org/wiki/Bohr_effect. Published 2019. Accessed 2019
7. Stan A, Zsigmond E. The restoration in vivo of 2,3-diphosphoglycerate (2,3-DPG) in stored red cells, after transfusion. The levels of red cells 2,3-
DPG. Rom J Intern Med. 2009;47(2):173-177. https://www.ncbi.nlm.nih.gov/pubmed/20067168.
8. Yaojin Li, Yanlian Xiong, Ruofeng Wang, Fuzhou Tang, Xiang Wang. Blood banking-induced alteration of red blood cell oxygen release ability. Blood
Transfusion. 2015. doi:10.2450/2015.0055-15
9. Lyon RM, de Sausmarez E, et al. Pre-hospital transfusion of packed red blood cells in 147 patients from a UK helicopter emergency medical service. Scand
J Trauma Resusc Emerg Med. February 2017. doi:10.1186/s13049-017-0356-2
10. Aucar JA, Isaak E, Anthony D. The effect of red blood cell age on coagulation. The American Journal of Surgery. December 2009:900-904.
doi:10.1016/j.amjsurg.2009.05.034
11. Aucar JA, Sheth M. The storage lesion of packed red blood cells affects coagulation. Surgery. October 2012:697-703. doi:10.1016/j.surg.2012.07.011
. CATEGORY: #FOAMed, Critical Care, Emergency Medicine, Resus & Crit Care, Trauma
. TAG: Bleeding, blood, CC5, CMP3, FOAMed, transfusion, trauma, Trauma Research
Chapter 9
MACINTOSH VS. MCGRATH

LARYNGOSCOPY IN PRE-
HOSPITAL CARE
There has been an ongoing debate about the use of video laryngoscopy
(VL) in emergency and critical care (1–4) . Proponents speak of the better
visibility and ability to teach using video systems whereas those preferring
a direct laryngoscopic (DL) approach speak to a more rapid, tried and tested
technique. A few studies exist which in general have favoured DL owing to
the increased time, equipment and process steps required for VL, but in
truth we don’t really know. The field is also complicated by the wide range
of different equipment, patients and settings that previous trials have
described.
In my personal practice I use a DL approach using a Macintosh blade, but I

have access to a McGrath videolaryngoscope if I need it. So far (touch
wood) I’ve not needed a VL as a rescue device very much, as DL in our
unit seems to work very well.
This month we have a paper in Critical Care Medicine that looks at VL vs.
DL in a population similar to my ED population and thus it’s a paper that
might help inform the debate (5) . The abstract is below, but as we always
say, please read the full paper before making up your mind on the validity
of the outcomes.
It’s a randomised controlled trial which is an appropriate and high quality
method to compare two interventions, in this case VL vs. DL. This is
described as an equivalence study.
Tell be about the equivalence concept?

The authors talk of this study as an equivalence study with the aim of
detecting a difference of up to 6.5%. That’s an equivalence of achieving
intubation at any point and not at first pass which is arguably a better
concept in these sort of trials. Moreover, that’s quite a big difference and
more than we would accept in clinical practice (Ed – would you consider a
6.5% difference equivalent?). They originally intended to recruit over 900
patients to be sure of this, but following an interim analysis at the half way
point the trial was stopped (Ed – though this is not described why though).
Personally I think that was a mistake based on the original power
calculation accepting a very wide degree of what is equivalence. It also
means that many of the sub group analyses rely on quite small numbers.

This study was conducted in the prehospital setting in Austria. Their HEMS
service randomised patients who required tracheal intubation to a first
attempt with either a McGrath videolaryngoscope (VL) or a standard
Macintosh laryngoscope (DL). If the first attempt failed then the clinician
could choose whether to swap to the other device or continue with the same
method.
The patients were aged >17 and as you would expect in a HEMS service
pretty sick. Half of them were in cardiac arrest, the rest a broad mix of
medical and surgical patients. Notably the number of trauma patients was
roughly a third of those enrolled.
Patients in cardiac arrest were intubated without drugs, all the others got an
RSI package. A variety of drugs were used, but the vast majority included a
paralytic agent (sux or roc).
The groups look fairly even at baseline, but the high proportion of patients
in cardiac arrest probably accounts for the skewed aged distribtion with an
overall average of 65.
What did they find?

They managed to randomise and analyse 514 patients, which makes this a
moderately sized study. Overall the authors state that there is no difference
between the techniques, but I’m not so sure.
For success at first pass the rates were 83% for DL and 79% for VL. To be
precise it was a 3.97% difference with wide confidence intervals. Certainly
wider than the 6.5% stated in their power calculation. It’s also a fairly low
first pass success rate. I ran an analysis of just the first pass success rates
using a Fisher exact test (6) and the result is not significant (p=0.26) so we
cannot draw a conclusion here, apart from the fact that the trial is
underpowered to show quite a significant difference. I also ran the stats for
a power calculation on detecting a 4 percent difference as seen here and
such a trial would require around 1500 patients in each group.
The study describes up to 4 further attempts, and these got the success rates
up to 95.3 (DL) vs 93.8 (VL) at second attempt and then slightly better with
third and fourth until alternative airways were created in the remainder. By
the final attempt there was only a 0.4% difference and so the authors claim
equivalence. However, there was considerable swapping around of
laryngoscopes if the first attempt failed. A subgroup analysis, albeit with
small numbers, suggests that changing laryngoscopes increases the chance
of success.
The authors suggest that the McGrath gives a better view, but that is is more
difficult to use and is more prone to technical difficulties. A whole bunch of
sub analyses have been performed that suggest differences and possible
explanations for this, but they are mostly small numbers of patients
analysed and not corrected for multiple analyses.
So does this answer the question about whether VL is better than DL?
Not really in my opinion. This study tells us that if you have both available
then the chances of success are high. First pass attempts might be better
with DL, but we don’t really know.
It’s also worth noting that this study used the McGrath with a standard
blade such that it can be used as a DL, and so there is an argument here that
the differences are really rather minimal. There is a hyperangulated X blade
available for the McGrath which requires a different technique to achieve
intubation. If you can use the McGrath as a DL, then is this study really that
much of a comparison of difference in technique? Arguably the VL first
approach should lead to a greater first pass success owing to the ability of
the operator to move from a DL to a VL technique seamlessly, but that does
not seem to have been the case here.
What’s the bottom line?

Well done to the authors for conducting a prehospital RCT on a time critical
intervention. The effort and team work to achieve this must have been
remarkable.
In terms of the results, the bottom line appears to be that both techniques
work in the majority of cases. Having access and training on both devices
achieves a very high success rate following up to 4 attempts at
laryngoscopy.
References
1. Carley S. Did video kill the laryngoscope star? St Emlyn’s. http://www.stemlynsblog.org/video-laryngoscopy-an-rct-in-trauma-
st-emlyns/. Published 2013. Accessed 2019.
2. Carley S. If the video laryngoscope was stroke thrombolysis. St Emlyn’s. http://www.stemlynsblog.org/of-course-if-the-video-
laryngoscope-was-stroke-thrombolysis/. Published 2013. Accessed 2019.
3. Lewis SR, Butler AR, Parker J, Cook TM, Smith AF. Videolaryngoscopy versus direct laryngoscopy for adult patients
requiring tracheal intubation. Cochrane Database of Systematic Reviews. November 2016.
doi:10.1002/14651858.cd011136.pub2
4. Janz DR, Semler MW, Lentz RJ, et al. Randomized Trial of Video Laryngoscopy for Endotracheal Intubation of Critically Ill
Adults*. Critical Care Medicine. November 2016:1980-1987. doi:10.1097/ccm.0000000000001841
5. Kreutziger J, Hornung S, Harrer C, et al. Comparing the McGrath Mac Video Laryngoscope and Direct Laryngoscopy for
Prehospital Emergency Intubation in Air Rescue Patients. Critical Care Medicine. August 2019:1.
doi:10.1097/ccm.0000000000003918
6. stat pages. Fisher Exact test. statpages. https://statpages.info/ctab2x2.html. Published 2019. Accessed 2019.
. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Prehospital Care, Resus & Crit Care
. TAG: airway, C3AP6, CMP2, CMP3, FOAMed, HMP3, macintosh, mcgrath

Chapter 10
SUSTAINABILITY AND CLIMATE

CHANGE IN ANAESTHESIA
Healthcare has a huge environmental impact and contributes to climate change (1)
. This appears to be irrefutable (Ed – there will be skeptics), with effects from
transportation, greenhouse gases (notably Nitrous Oxide and other anaesthetic
gases) and the high volume of single use items/packaging and production.
On a personal level it’s interesting to reflect that at home we recycle as much as
we can, and yet at work there is far less impetus or encouragement to sort and
recycle on a daily basis (although @drcjf pointed out that our hospital has won
awards for environmental awareness and change). Vast amounts of plastics and
paper are simply thrown into landfill or incineration. In some cases this will be
unavoidable (contamination for example). The point is that our behaviours within
healthcare are not as overtly focused on recycling and the reduction of
environmental impact.
The NHS has arguably made significant progress already with a carbon reduction
strategy in place since 2009. Back then the carbon impact of the NHS was 21
Million tonnes of CO2 per year, larger than some medium sized countries. Since
then some progress has been made but there is much to do.
in this paper Cliff Shelton and colleagues describe how anaesthesia can impact on
the environment and perhaps change to reduce that impact (2) . It’s well worth a
read and a consideration of how other specialities can reduce their impact too. In
brief the editorial suggests that by changing our practice, by considering
environmental impacts when we adopt new practices, by recycling and reviewing
our equipment and through educating ourselves and our colleagues we may be
able to reduce the impact of anaesthesia on the environment. A good example
would be in reducing the use of Desflurane which is pretty awful as a greenhouse
gas (3,4) .
Not everyone will agree with this of course. Recent twitter debates have
questioned the need for medical students and doctors to receive training on
environment and sustainability. ‘Teach them medicine’ is the retort to suggestions
that climate should be part of the curriculum. This is a false dichotomy in my
opinion. Healthcare outcomes and activity have always been intimately linked to
world that we live in. Any change to our environment will impact the health of
our patients, and ourselves. In the UK this is increasingly accepted. The NHS has
a centre for sustainable healthcare (The sustainable development unit (5) ), and
ambitious targets to reduce the carbon footprint of healthcare (6) . The national
regulator, the GMC, requires that
“newly qualified doctors must be able to apply the principles, methods and
knowledge of population health and the improvement of health and sustainable
healthcare to medical practice. (7) ”
GMC Outcomes for Graduates 2018
This is requiring schools to change their curricula. Other specialities are similarly
looking to reduce the impact of their activities on the environment (8) .
Emergency Medicine and sustainability/environmental impact.

Climate change can certainly impact on the ED workflow. For example, natural
disasters can significantly impact on emergency department use in the short to
medium term, but global trends such as heatwaves also result in increased
cardiorespiratory disease presentations (9) .
There are many, many examples of how what we do influences the environment
and much that we can draw from this editorial. Reducing waste, avoiding high
impact, recycling waste, reducing nitrous oxide use are all strategies that we could
adopt.
Nitrous oxide is a good example as it has a very significant contribution to global
warming. In healthcare it’s used a lot in anaesthesia, obstetrics and in emergency
care. Alternatives exist with a lesser impact and this may be a reason to switch to
other inhalational agents like methoxyflurane for some patients, or to non-
inhalational agents for others. For more on that question and some technical facts
have a look at the twitter trail below. However, this is a good example of where
we need to think about the entire cycle of what we do in healthcare.
Methoxyflurane (Penthrox) may be less impactful as a gas, but as it is produced in
a non-recyclable plastic ‘whistle’ the argument is not as straightforward as it
might seem.
The Royal College of Emergency Medicine recently announced that it is
disinvesting from oil and gas producers in its investment portfolios in common
with other healthcare organisations. It has been suggested that this was
precipitated by concerns raised from a younger generation of clinicians who
(perhaps) are more environmentally aware than the older generations.
#FOAMed and the environment.
There are clearly potential benefits from using #FOAMed resources in teaching
and education to reduce the travel impacts of meetings. Sharing what we have as
widely and as openly as possible can only be a good thing. However, many of us
involved in #FOAMed also travel internationally to speak and take part in
conferences. The impact of this should not be underestimated and as a result
groups such as St Emlyn’s are not carbon neutral. Reducing travel, flying
economy and/or carbon offsetting are options 10 , but we must recognise that
clinical education is not exempt from considering our environmental impact.
Keep an eye on @codachange for more links on the environmental impact of
healthcare and consider following some of the organisations linked in the tweet
below.
Final thoughts.
There is no doubt that there is increasing awareness of sustainability and
environmental impact around the world. Healthcare is no exception and I
understand that this issue will increasingly be an issue for all of us in the next few
years. This paper is a useful and timely reminder that climate change is a
healthcare issue. It’s was open access (Ed – I don’t think it is anymore), so there is
no reason not to read and share widely. Individually and organisationally we
should all look for opportunities to reduce our impact, so on your next shift I
invite you to keep a mental tally of the impact of healthcare, and to look for
opportunities to make a change.
References
1. King’s Fund U. Climate Change. King’s Fund. https://www.kingsfund.org.uk/projects/time-think-differently/trends-broader-
determinants-health-climate-change. Published 2012. Accessed 2019.
2. Shelton CL, McBain SC, Mortimer F, White SM. A new role for anaesthetists in environmentally‐sustainable healthcare. Anaesthesia.
March 2019:1091-1094. doi:10.1111/anae.14647
3. Alexander R, Poznikoff A, Malherbe S. Greenhouse gases: the choice of volatile anesthetic does matter. Can J Anesth/J Can Anesth.
November 2017:221-222. doi:10.1007/s12630-017-1006-x
4. Charlesworth M, Swinton F. Anaesthetic gases, climate change, and sustainable practice. The Lancet Planetary Health. September
2017:e216-e217. doi:10.1016/s2542-5196(17)30040-2
5. SDU N. About us. Sustainable Development Unit. https://www.sduhealth.org.uk/. Published 2019. Accessed 2019.
1. SDU N. Natrual Resource Footprint. Sustainable Development Unit. https://www.sduhealth.org.uk/policy-strategy/reporting/natural-
resource-footprint-2018.aspx. Published 2018. Accessed 2019.
2. GMC U. Outcomes for graduates. GMC. https://www.gmc-uk.org/education/standards-guidance-and-curricula/standards-and-
outcomes/outcomes-for-graduates. Published 2018. Accessed 2019.
1. Tun MS (SanYuMay. Fulfilling a new obligation: Teaching and learning of sustainable healthcare in the medical education
curriculum. Medical Teacher. June 2019:1-10. doi:10.1080/0142159x.2019.1623870
2. Cheng J, Xu Z, Bambrick H, et al. Cardiorespiratory effects of heatwaves: A systematic review and meta-analysis of global
epidemiological evidence. Environmental Research. October 2019:108610. doi:10.1016/j.envres.2019.108610
1. AMSA AMSA. Sustainable Events Guide.
AMSA. https://www.amsa.org.au/sites/amsa.org.au/files/FINAL%20Code%20Green%20Sustainable%20Events%20Guide_Dedication.pdf.
. CATEGORY: #FOAMed, Emergency Medicine, Global Health, Public Health, The philosophy of EM
. TAG: CC16, CC25, climate, environment, FOAMed

Chapter 11
LATEST LOWER GI BLEEDING

GUIDANCE
The management of the patient with apparent lower GI (gastro-intestinal)

bleeding is, in my experience at least, somewhat variable. Unlike upper GI
bleeding where the standards and expectations are reasonably well known
(1,2), the lower GI bleed patient in the ED seems to be managed at the
whim of whomever might be on call that day. This combined with the well
trodden turf wars about who admits (or does not admit) the patient means
that these patients can be complex.
They can also be really, really sick……., or not, as the range of conditions
stretches across a range of pathologies from simple haemorrhoids through
to catastrophic bleeding from diverticular disease, cancer, vascular
malformations and more.
In other words, it’s all a little complex and whilst variation and
individualised care might be a good thing for some patients, I’m mindful
that some guidance and agreed strategies for investigating and managing
these patients is a good idea.
So, thanks to Michael for spotting a new guideline for the management of
these patients in the Journal ‘Gut’ (3) . (Ed – this was also covered by The
Breach blog back in May. If you’ve not checked out ‘The Breach then we’d
recommend it as another EBM blog for EM https://the-breach.com/new-
guidelines-on-lower-gi-bleeding/ (4) ).
The paper (3) is currently open access so as we always say here at St
Emlyn’s, go read the paper yourself and come to your own conclusions.
This is a consensus guideline based on experts from the British Association
of Gastroenterology. In that respect this is not like a systematic review or
meta-analysis where the data is king. Rather it is a collection of experts who
have brought together their experience to interpret the evidence. This is
common to many guideline development strategies, and indeed the authors
have adhered to a guideline development structure (5) , but as a critical
appraisal exercise it is important to recognise that this may create bias in the
conclusions.
The authors have reviewed a range of studies, blended this with their
experience and opinions to deliver a series of consensus statements, and a
resulting flow chart that might guide clinicians in the management of lower
GI bleeds. As the paper covers both diagnostics and initial interventions it is
very relevant to the EM community.
Who wrote the guidelines?

There are 17 authors from surgery, medicine, epidemiology, research and
radiology. It does not looks as though there is any emergency medicine
representation. The lead author has extensive experience and primary
research in this area (6) .
What are the main findings?

These are best described in the full open access paper and you should read
them there. These are my summary points for those especially important to
the emergency medicine community, together with some unanswered
questions as Ed comments
1. Patients presenting with lower gastrointestinal bleeding (LGIB) should be
stratified as unstable or stable (unstable defined as a shock index >1). (Ed
– shock index is a blunt tool to assess shock – I think we can do better
than simply the SBP and HR)
1. Stable bleeds should then be categorised as major or minor, using a risk
assessment tool such as the Oakland score (7) (Ed – the Oakland score is
apparently named after the first author of this study and was validated in
fewer than 300 patients, of whom only 184 were discharged home and of
which 5% had an unsafe discharge such as rebleeding, transfusion, Hct
drop, death, readmission. That seems quite high to me. Other scores are
available)
1. Patients who have stopped bleeding and who have an Oakland score ≤8
points, with no other indications for hospital admission can be discharged
from the ED for urgent outpatient investigation (Ed – again look at the
score (8) . It is possible to get to below 8 with some strange combinations,
but I suspect they would be rare and you can always override the score in
a patient who gives significant concern)
2. Patients with a major bleed should be admitted to hospital for
colonoscopy on the next available list. (Ed – yep, but consider when that
is with current pressures and weekends etc.)
3. If a patient is haemodynamically unstable or has a shock index (heart
rate/systolic BP) of >1 after initial resuscitation (Ed – this is not really
well defined for me, what does after initial resuscitation mean
exactly?) and/or active bleeding is suspected then CT angiography should
be used to localise the site of blood loss before planning endoscopic or
radiological therapy
4. If no bleeding sites is found on CT Angiography or colonoscopy and the
patient has haemodynamic instability then consider that this may be an
upper GI bleed with rapid transit of blood to the lower bowel.
5. Catheter angiography/embolisation should be performed as soon as
possible after a positive CTA to maximise chances of success. In centres
with a 24/7 interventional radiology service, this should be available
within 60 min for haemodynamically unstable patients (Ed – what about
those centres without on site 24/7 – should we transfer at this point?
Could this be an ED-ED transfer process?)
6. Non surgical interventions should be tried first. Laparotomy rarely
needed.
7. Transfusion thresholds will be similar to other critical care conditions.
(Hb trigger 70 g/L and a Hb concentration target of 70–90 g/L after
transfusion) should be used, unless the patient has a history of
cardiovascular disease, in which case a trigger of 80 g/L and a target of
100 g/L (Ed – same as in other conditions really, often tricky to tailor in
the actively bleeding patient)
1. Coagualtion management is vital (Ed – There are a number of specific
recommendations about the management of coagulopathy. These are
familiar to us as they are pretty much the same as management for other
bleeding emergencies whilst on anticoags).
1. All hospitals should have a GI bleeding lead and agreed pathways for the
management of acute LGIB (Ed – presumably this one). Hospitals that
routinely admit patients with LGIB should have access to 7/7 on-site
colonoscopy and the facilities to provide endoscopic therapy (Ed not
stated as 24/7 and they probably don’t mean that)
2. All hospitals that routinely admit patients with LGIB should have access
to 24/7 interventional radiology either on site, or via a formalised referral
pathway to another hospital (Ed – I’d agree but this is really quite
uncommon in the UK unless we centralise these admissions).
Discussion
These seem to be helpful and useful practical and pragmatic
recommendations for the management of LGIB. It is interesting to see how
the authors balance the strength of their opinions with the strength of the
evidence. In many cases there is little correlation between opinion and
evidence, although in their defence the authors are quite open about this. It
does mean that we must understand that the overall level of underlying
evidence from high ranking trials is relatively low, but this may be the best
evidence available at this time. An example is the recommendation for
angiography in the haemodynamically unstable patient, this is described
as Strong recommendation, low quality evidence which is almost the
opposite of what we expect in evidence based medicine. Several of the
other recommendations contain this apparent cognitive dissonance.
The potential to identify a group of low risk patients suitable for out patient
management is attractive under the current pressures we face. However, the
risk stratification tool has a 5% failure rate, has not been validated outside
the UK, and in a relatively small data set. I think it could be used, but with a
good overall clinical review to identify patients in whom other concerns
would make discharge unsafe.
From my perspective the adoption of the strategies in this paper is
problematic. The strength of the evidence underlying many aspects are
moderate/weak and are thus heavily influenced by expert opinion. I would
like to see EM input into any guidelines that might influence our
management as the evidence base for the safe to discharge cohort is
arguably limited. For admitted patients the paper has some great
suggestions which are rather reliant on the availability of in patient and out
patient services to back up the initial assessment and risk stratification. In a
large centre such as Virchester many of these will be possible to achieve
and have the potential to improve the patient experience. However, in
smaller hospitals with less robust access to endoscopy, angiography and
interventional radiology these suggestions will be challenges and perhaps a
network approach will be required
References
1. Gray C. Upper GI Bleeding. St Emlyns. http://www.stemlynsblog.org/upper-gastro-intestinal-bleeding-at-st-emlyns/. Published
2016. Accessed 2019.
1. Beardsell I, Carley S. Induction podcast on GI Bleeding. St Emlyns Podcast. https://www.stemlynspodcast.org/e/induction-
podcast-managing-upper-gi-bleeding-in-the-ed/. Published 2016. Accessed 2019.
1. Oakland K, Chadwick G, East JE, et al. Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from
the British Society of Gastroenterology. Gut. February 2019:776-789. doi:10.1136/gutjnl-2018-317807
2. Stevenson B. Guidelines on lower GI bleeding. The Breach. https://the-breach.com/new-guidelines-on-lower-gi-bleeding/.
Published May 2019. Accessed August 2019.
3. Brouwers MC, Kerkvliet K, Spithoff K. The AGREE Reporting Checklist: a tool to improve reporting of clinical practice
guidelines. BMJ. March 2016:i1152. doi:10.1136/bmj.i1152
1. Linkedin L. Kathryn Oakland. LinkedIn. https://www.linkedin.com/in/dr-kathryn-oakland-md-97ab2076/. Published 2019.
Accessed 2019.
1. Oakland K, Jairath V, Uberoi R, et al. Derivation and validation of a novel risk score for safe discharge after acute lower
gastrointestinal bleeding: a modelling study. The Lancet Gastroenterology & Hepatology. September 2017:635-643.
doi:10.1016/s2468-1253(17)30150-4
1. Calc M. Oakland Score. MDCalc. https://www.mdcalc.com/oakland-score-safe-discharge-lower-gi-bleed. Published 2019.
Accessed 2017
. CATEGORY: #FOAMed, Clinical Guidelines, Critical Care, Emergency Medicine, Gastro, Journal
Club, resuscitation
. TAG: CAP16, CC1, CC2, CC21, CC5, FOAMed, Gastrointestinal

bleeding, guidelines, HMP4, journal club, LGIB
Chapter 12
THE RESUSCITATIVE CARE

UNIT
Ordinarily when we bring a Journal Club post, it’s because we want to

present some form of data that can make a difference to your clinical
practice. This week it’s slightly different as we’ve picked up more of a
concept paper on the use of resuscitative care units or RCUs.
I think this is on my mind as I’ve recently had shifts in the ED that have
been extremely busy with critical care cases. In my typical 8-hour shift
there will inevitably be an RSI, often more than one, arterial lines, central
lines and other procedures in the resus room that blur the boundaries
between the tribes and geographies of emergency and critical care. It’s
made me reflect on how we deliver critical care in the ED and how in
Virchester I believe we have an excellent relationship between the various
teams. In large part this is because five of my consultant colleagues are dual
trained in emergency medicine (EM) and intensive care medicine (ICM).
Most of my ED consultant colleagues and senior trainees are comfortable in
airway management and critical care interventions (but clearly know when
to get help and are not scared or embarrassed to do so). It’s a team effort all
and certainly not an area of practice for egos IMHO (remember that the
airway belongs to the patient and not to any particular tribe or speciality).
We are not unique in this across the UK and there’s another good example
of interspeciality working in Edinburgh as described in this blog
on teaching and maintaining RSI skills (1,2).
Anyway, back to the paper. It’s an opinion piece published in the EMJ on
the anatomy of RCUs. These are departments or in many cases ‘areas’ that
sit outside of the main ICU and which are designed to provide short term
critical care interventions to either avoid a full ICU admission and/or to
specifically focus on the first few hours of critical care which are focused
on resuscitation agility and diagnostics. The paper is open access on the
EMJ (3) site so follow the link and read it for yourself. You might notice a
few familiar authors from the #FOAMed and #SMACC world.
Our department has a reputation for lots of patients requiring critical care
and that often means that our resus room feels like an extension of the
ICU/CCU. That leads to crowding and significant pressures on patient flow
and staff workload which will be familiar to many readers. Whilst we
believe that we offer great care there are very real concerns that critical care
patients who have extended stays in the ED may have worse outcomes (4–
6).
The RCUs described in the paper vary in size, scope and staffing but there
are some common themes.
ED led (usually with crit care fellowship training)
Geographically separate from main ICU
Close/adjacent to ED
Admission from host ED and for transfer in from other EDs
High level procedures e.g. ECMO, REBOA, VAD management
The authors suggest that by focusing the care of the critically ill patients on
a smaller area and staffing model the outcomes may improve. No data is
given to support this, but at face value there is some sense in this.
Is this a model for the UK?

The paper is largely US based and we must remember that this changes how
we view the opinions. Staffing, training and finances are very different in
the US and these do not easily translate to the UK. Most of the units
described are staffed by critical care enthusiasts who have either undergone
an addition critical care fellowship or are in the process of doing one.
Nurses too often have additional critical care qualifications. This is not the
case in the UK, where the engagement with critical care and resuscitation
activity varies between departments and individuals. I suspect that in any
UK model there would likely be a closer link with anaesthetics and critical
care and that might be a concern to many emergency physicians who would
be somewhat upset if those tribes came and took away the critically ill and
injured aspects of our workload. My personal opinions on this are
reasonably well known, in that I do think that the consultant emergency
physician of the future should be competent in the resus room and my
understanding is that the new college curriculum will emphasise this
(though it’s not finalised yet so I don’t really know). It will also be
interesting to see how the current cohort of EM trainees going through
PHEM training will impact on the ability for EM consultants to maintain
and develop their critical care skills. A lot of PHEM training involves the
development and appraisal of critical care interventions and I cant see that
skill set being constrained by where that individual happens to be working
that day.
There is perhaps a paradox in this paper in that the authors quote Peter Safar
(7,8), one of the founding fathers of critical care who described it as a
speciality without geography. In some health economies the opposite has
happened with critical care being focused within the intensive care unit,
whereas in the UK critical care outreach is now a common and effective
tool to project critical care beyond the walls of the unit. Whether the
development of a new geography in the guise of an RCU is a way forward
remains to be seen, but if anyone wants to build one in Virchester then I’d
almost certainly welcome it with open arms. Staffed by critical care and EM
clinicians, based in the ED and offering high level care to patients combined
with great training it might be the future.
Until then, we will cope in resus with a team of ED clinicians interested in
critical care, and a team of critical care clinicians interested in working with
EM.
My belief is that there probably is data out there from this group. A simple
description of a novel concept is unlikely to change that many people no
matter how good it may seem. We really need data and I hope that we might
see that sometime soon. UPDATE – Cindy Hsu has been in touch to point
out that there is data out there in this paper from JAMA showing better
survival and decreased ICU usage (9) . I think that paper may be worth a
review in itself. Headline figures from the paper are that implementation of
an ED-based ICU was associated with reductions in risk-adjusted 30-day
mortality among ED patients, from 2.13% to 1.83%, and ICU admissions,
from 3.2% to 2.7% of all ED visits. One for a closer critical appraisal I
think…..
Simon Carley
References
1. Carley S. JC: ED RSI. St Emlyn’s. http://www.stemlynsblog.org/jc-ed-rsi-can-st-emlyns/. Published 2016. Accessed 2019.
2. Kerslake D, Oglesby A, Di R, et al. Tracheal intubation in an urban emergency department in Scotland: a prospective,
observational study of 3738 intubations. Resuscitation. 2015;89:20-24. https://www.ncbi.nlm.nih.gov/pubmed/25613360.
3. Leibner E, Spiegel R, Hsu CH, et al. Anatomy of resuscitative care unit: expanding the borders of traditional intensive care
units. Emerg Med J. April 2019:364-368. doi:10.1136/emermed-2019-208455
4. Cavallazzi R, Marik PE, Hirani A, Pachinburavan M, Vasu TS, Leiby BE. Association Between Time of Admission to the ICU
and Mortality. Chest. July 2010:68-75. doi:10.1378/chest.09-3018
5. Cardoso LT, Grion CM, Matsuo T, et al. Impact of delayed admission to intensive care units on mortality of critically ill
patients: a cohort study. Critical Care. 2011:R28. doi:10.1186/cc9975
6. Chalfin DB, Trzeciak S, Likourezos A, Baumann BM, Dellinger RP. Impact of delayed transfer of critically ill patients from
the emergency department to the intensive care unit*. Critical Care Medicine. June 2007:1477-1483.
doi:10.1097/01.ccm.0000266585.74905.5a
7. Safar P, Grenvik A. Critical Care Medicine. Chest. May 1971:535-547. doi:10.1378/chest.59.5.535
8. Safar P. Critical care medicine—quo vadis? Crit Care Med. 1974;2(1):1-5. https://www.ncbi.nlm.nih.gov/pubmed/4815738.
9. Gunnerson KJ, Bassin BS, Havey RA, et al. Association of an Emergency Department–Based Intensive Care Unit With
Survival and Inpatient Intensive Care Unit Admissions. JAMA Netw Open. July 2019:e197584.
doi:10.1001/jamanetworkopen.2019.7584
. CATEGORY: #FOAMed, Critical Care, ED Management, Journal Club, Resus & Crit Care
. TAG: FOAMed, resuscitation, Resuscitative Care Unit

Chapter 13
CLOT’S THE PROBLEM? VENA

CAVA FILTERS IN TRAUMA
PATIENTS
No one likes getting a pulmonary embolism. Or a deep vein thrombosis.

And because about 60% of all blood clots are associated with
hospitalisation for acute illness (1) , we take the idea of prophylaxis very
seriously. Emerging data suggests that this seriousness has reaped reward in
the UK (2) . We give information about mobilisation and hydration. We
sometimes use stockings. We risk assess patients early on and give
pharmacological thromboprophylaxis if they have a low risck of bleeding.
And we keep our eye on people. They still get clots sometimes, but they
seem to be getting less clots overall, which is good news for everyone.
But sometimes, patients can be very complicated. This is particularly true of
polytrauma patients, who often have a complex pelvic injury (putting them
at high risk of VTE) alongside a traumatic brain injury (putting them at high
risk of a complication from thromboprophylaxis) as well as a critical care
admission (putting them at high risk of VTE) in addition to a splenic injury
(putting them at…… you get the idea). These cases are challenging. And
when things are challenging, people often start to champion a solution with
face validity but not much hard evidence. “We’ll never get the evidence!”.
“We must take action!”. “Lives are at stake!” I am sure you have heard
them cry.
Arise the Inferior vena caval (IVC) filter. What’s not to like about the idea
of an umbrella in a big proximal vein that will stop any clot travelling to the
cardiorespiratory system, where it can potentially kill. You can even put it
in yourself these days…. However, the absence of data supporting this
intervention is concerning (3) . As are the reports of fragmentation,
thrombosis and complication. You will perhaps have noted that NICE have
recently removed all reference to IVC filters (4) from their updated
prophylaxis guideline in 2018. You may also have seen this comparative
effectiveness study reporting increased harm with filter use (5) .
But what this issue needs is a randomised controlled trial, yes? In the right
patients, with appropriate methodology and reported transparently? Of
course it does. And hats off to the author group for tackling this challenging
issue head on. The abstract is below, but as we always say, please go readit
for yourself (6).
Available at https://www.nejm.org/doi/full/10.1056/NEJMoa1806515
The background
The paper quotes initially that pulmonary embolism accounts for 12% of all
deaths after major trauma. A quick point on that figure; firstly, that came
from a single centre study of an intensive care population (by the same
authors), automatically excluding pre-hospital deaths and deaths from
haemorrhage. Secondly, that 12% was equal to 16 patients of the 143 that
died in total. Thirdly, it used an autopsy diagnosis of PE to ascertain it as
the cause of death. This may be perhaps unnecessarily pedantic; just an
opportunity to remind us to check references and quoted figures.
Nonetheless, there is no debate that the research topic is important and
relevant.
What was the question?

In trauma patients with a contraindication to pharmacological
thromboprophylaxis, does the insertion of a retrievable IVC filter in the first
72 hours result in a lower incidence of pulmonary embolism (PE), when
compared to no filter.
How did they set out to answer it?

In an interesting way. This was a multicentre open label randomised
controlled trial across 4 tertiary hospitals in Australia. Great. Patients were
included if they were aged over 18, had an estimated injury severity score
(ISS) >15 (denoting ‘major’ trauma in most modern systems) and a
contraindication to pharmacological thromboprophylaxis within the first
72hrs. Patients were excluded if there was suspicion of imminent death, a
confirmed PE on admission, pregnancy, or if no interventional radiologist
was available to insert the IVC filter. Interesting already I am sure you will
agree – they don’t specify in the manuscript what they considered to be a
contraindication to anticoagulation, so it’s tricky to tell if this was
subjective or objective. Clearly, there are contraindications and
contraindications, if you know what I mean. Also, the lack of an available
interventional radiologist as an exclusion criteria introduces a degree of
selection bias, or convenience sampling. Providing allocation concealment
was maintained up to the point of randomisation, there should be limited
impact from this. But still something to bear in mind.
Patients were randomised to receive either an IVC filter or no filter, through
a permuted block central system across 4 sites. This should maintain
allocation concealment and minimise conscious or subconscious bias. All
patients were allowed intermittent pneumatic compression, although we
couldn’t clearly find out results on who got what. The protocol
recommended commencement of pharmacological thromboprophylaxis at
clinical discretion as soon as it was considered safe to do so. Very
subjective…
To minimise detection bias, the trial used a predefined criteria for
identifying PE. The intention here is good – you could easily envisage that
in an open label study, all patients randomised to control would worry
clinicians – as such they may scan anyone with any symptoms, detect a load
of asymptomatic PEs and quickly announce that filters were the best thing
since sliced bread. However, that doesn’t mean that the issue is foolproof. If
you read the supplementary appendix, you’ll see that the predefined trigger
for PE investigation was oxygen requirement of 5L to maintain target sats,
hypotension for more than 30 minutes or unexplained chest pain. If we are
talking about the same polytrauma patients that we see all the time in
Virchester and London, then a lot of them have pulmonary contusions, rib
fractures and all kinds of injuries that can cause those symptoms. As such,
you can make the argument that these patients are being screened for the
presence of PE and not necessarily investigated for symptomatic disease.
But it’s tricky to know without the granular data.
All patients had Doppler ultrasound of the legs at 2 weeks after enrollment,
as a safety measure to try and pick up big DVTs early in the control arm.
Again, this is screening, not diagnostics resulting from a clinical suspicion
or assessment.
The study used a composite primary end point of symptomatic PE, or all-
cause mortality at 90 days. This has raised eyebrows in the social media
sphere. Composite outcomes are frowned on, although I am sure we all
agree that it is vital to know when patients in a trial like this die of PE.
Could the authors have been more circumspect here, perhaps using an
independent adjudication committee to confirm death from, or potentially
related to PE? Perhaps. Many other thrombosis trials use this technique and
there are even recently published recommendations on it (7) , so it was quite
interesting not to see it here.
A key secondary end point was the incidence of symptomatic PE in patients
who survived to 7 days and did not receive pharmacological
thromboprophylaxis (due to ongoing contraindications). The authors also
looked at all cause mortality, major and non-major bleeding at 90 days
The study was powered to detect a 9% incidence of PE in the control group.
They assumed a negligible PE rate in those randomised to IVC filter
insertion, worked out as a 8.5% lower rate of PE with filters (0.5 vs 9%).
Data were analysed with intention to treat, which seems sensible. The study
predefined stopping criteria for the study which meant that If 4 fatal PEs
occurred in the control group then the trial would be stopped.
What did they find?

The trial was conducted over 2 years and screened 1740 patients, enrolling
240. This is immediately notable and demonstrates one of 2 things – either
these patients are rare, or that when pushed most of us will be comfortable
with the idea of using pharmacological thromboprophylaxis within 72h. 2
patients from each group crossed over treatment arms; It is understandable
that someone randomised to a filter would not get it for logistical reasons or
complications, but it is not as clear why someone randomised to no filter
would then get one. This is not really explained other than vague hints at
‘clinician discretion’ and ‘clear indication arising’.
The patient demographics were as you might expect from a trauma
population; predominantly male, around the ages of 20-40, with an ISS
around 25. The median GCS was lower in the IVC filter arm, but this did
not equate to a larger number receiving intracranial pressure monitoring.
57.5% of the patients had a form of intracranial haemorrhage (ICH), but
you have to go to the supplemental appendix to see that there were slightly
more ICH patients in the filter arm. The vast majority (95%) of patients
were also recruited through a single-centre; this raises alarm bells about
allocation concealment after all, and makes you wonder if this could (?
should) really be considered a single centre study. In the IVC filter group,
89% had the filter inserted within the first 24 hours.
There were 27 deaths in total in the study, of which one died from a fatal
saddle embolism (in the control arm). It is worth highlighting that this
patient died on day 16 after being on pharmacological thromboprophylaxis
for 8 days preceding. The study found no statistically significant difference
between groups for the composite outcome of symptomatic PE or death
(13.9 vs 14.4%) in the IVC filter group vs control respectively. In the pre-
specified subgroup that survived 7 days and had no chemoprophylaxis in
that time due to ongoing contraindication (a total of 80 patients only; 46
filter vs 34 control), 5 of the patients in the control group developed a
symptomatic PE, whilst there were none in the IVC filter group. The
authors present this as a hazard ratio for PE of 0 (0 to 0.55), which looks
potentially significant. There was no difference in the occurrence of DVT at
2 week screening, and no difference in transfusion requirements.
What else? Well, there was a higher rate of all cause death (13.1% vs 9.3%)
major bleeding (70.5% vs 66.1%), and non-major bleeding (23.8% vs
17.8%), in the IVC filter group. None of these results would be deemed
significant as secondary outcomes and also with the 95% confidence
intervals for the hazard ratio spanning 1.
What does this mean?

Like always, we think the meaning is probably in the eye of the beholder.
There is and will always be a degree of confirmation bias when reading
papers. When studies are underpowered it can lead to a wide number of
opinions. Those already opposed to IVC filters will read this as confirming
their beliefs given the lack of significant difference in the primary outcome
between groups. Those who favour the use of IVC filters will note the
absence of any symptomatic PEs in the IVC filter group compared to the 5
the presented in the control arm, along with the hazard ratio. Were these
PEs important? Not sure we know. Does prevention of these PEs justify
widespread use of an intervention that can potentially cause harm? Who’s to
say.
On that topic however, it is worth highlighting that multiple safety
endpoints were seen with filter use. These events included entrapped
thrombus within the filter at first removal (4.9% of cases) and adherence to
the caval wall requiring surgical removal (0.8% of cases). There is also
devil in the detail – if you look at the cox proportional hazards regression
analysis in the supplementary appendix, you will see that the risk of death
or PE appears to be worse with a filter as your ISS and age increase. Odd, in
that these are the sickest and most vulnerable patients who we would expect
to potentially benefit. They don’t appear to. They appear to do worse.
Following on from this, it is very much worth looking at the deaths in this
study, which are the main contributors to the primary outcome. Again, it’s
the supplementary appendix for these, but good of the authors to provide.
There is only 1 cause of death attributed to VTE directly; all others talk
about TBI, complications of multisystem trauma and multiorgan failure.
This reassures us that in >100 complex trauma patients with an initial
contraindication to pharmacological thromboprophylaxis who did not get an
IVC filter, <1% died as a result of VTE. Again, this one case of saddle PE
had also had 8 days of pharmacological thromboprophylaxis prior to dying
of PE.
A quick note on power and outcomes

Quite a few clinicians have commented on the power of this study and use
of a composite outcome. Some have even begun tinkering with the stats.
This can be dangerous.
Say you thought that the primary outcome in this trial should have been
symptomatic PE (as defined by the authors) and/or death attributed to PE, in
patients with an ongoing contraindication to thromboprophylaxis. It is fairly
straightforward to look at the event rate of 5 PEs in the control group and
compare it to 0 in the intervention group, then proudly announce an
absolute risk reduction of 14.7% and a NNT of 7. Well done everyone.
However, the variation around this estimate is unclear and any sample size
calculator will tell you to be cautious around interpreting data from an n=80
population, even if your risk reduction is as large as this one.
More importantly though, looking at the data this way ignores the risks and
potential harm caused by the intervention, through focusing solely on VTE
outcomes. What if putting filters in causes significant bleeding, or other
adverse events? These would not be captured by your filtered primary
outcome. How do you address this? By presenting all cause mortality, as the
authors have done here, and ensuring that major bleeding and complications
are weighted against the benefits of reducing VTE risk. Many other recent
thrombosis trials have (8) taken the same approach, or presented efficacy
and safety data side by side. It is all well and good that an intervention may
reduce morbidity or mortality from PE; but if it increases these outcomes
through another mechanism, that is essential to know.
What’s the take home?

Trauma is a heterogenous set of diseases; patients surviving haemorrhagic
shock are very different to those with significant intra-cranial haemorrhage.
To say that there is no role for IVC filters based on this paper would be
quite a punchy conclusion to make. This isn’t the first study to identify that
IVC filters are associated with lower rates of PE (9) (and potentially
mortality) and there remains a suggestion that in the right patients it may
reduce the development of symptomatic PEs.
But who is the right patient? That’s where we suspect there will be ongoing
debate. For some of us, this paper suggests that restricting IVC filter use
does not bring about death in this population, may avoid harm, will save
cost and resource and allow opportunity to focus on other things. For others,
it may look like it prevents symptomatic PE without causing additional
mortality. A quick point on the latter – if we are talking about preventing
symptomatic PE in the subgroup analysis of patients who did not recieve
pharmacological prophylaxis for >7 days, then this data suggests there is no
great rush to put the filter in. I can’t find any evidence that any patient got a
PE in the first 7 days from admission. That in itself is useful, as the logistics
of arranging this intervention quickly can be challenging outside of centres
with IR on site.
Are you a naysayer? I think I am (Dan). I have never been overly convinced
by the data on IVC filters. On our major trauma/neurosciences ICU I don’t
pursue them unless I asbolutely have to, in particularly complex cases with
ongoing super high VTE risk and continuing lengthy contraindication to
thromboprophylaxis. So I am starting from a position of scepticism. This
work does not change my mind. In fact it supports my opinion that there is
harm with filters, that despite complexity very few of these patients seem to
die of VTE, and that the more complex the patient actually the higher the
hazard of a filter. This latter point and the additional supplementary data
suggest to me that it could be the younger pelvic fractures, who are not
super sick, that have an ongoing contraindication to anticoagulation who
may stand to benefit the most from filter placement. But that’s just me.
What do you think? Are you a fan of the filter? If so does this work support
your beliefs?
What do you believe? And when do you change? Sounds like a good
presentation that (10) , if only someone could cobble something
together…..
Dan Horner @RCEMProf and Rich Carden
References
1. Movement WT. Know Hospital-Associated VTE. World Thrombosis Day. http://www.worldthrombosisday.org/issue/hospital-
associated-vte/. Published 2019. Accessed 2019.
2. Hunt BJ. Preventing hospital associated venous thromboembolism. BMJ. June 2019:l4239. doi:10.1136/bmj.l4239
3. Bikdeli B, Chatterjee S, Desai NR, et al. Inferior Vena Cava Filters to Prevent Pulmonary Embolism. Journal of the American
College of Cardiology. September 2017:1587-1597. doi:10.1016/j.jacc.2017.07.775
4. NICE N. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary
embolism. NICE. https://www.nice.org.uk/guidance/ng89. Published 2018. Accessed 2019.
5. Turner TE, Saeed MJ, Novak E, Brown DL. Association of Inferior Vena Cava Filter Placement for Venous Thromboembolic
Disease and a Contraindication to Anticoagulation With 30-Day Mortality. JAMA Netw Open. July 2018:e180452.
doi:10.1001/jamanetworkopen.2018.0452
6. Ho KM, Rao S, Honeybul S, et al. A Multicenter Trial of Vena Cava Filters in Severely Injured Patients. N Engl J Med. July
2019. doi:10.1056/nejmoa1806515
7. Kraaijpoel N, Tritschler T, Guillo E, Girard P, Le Gal G. Definitions, adjudication, and reporting of pulmonary embolism‐
related death in clinical studies: a systematic review. J Thromb Haemost. July 2019. doi:10.1111/jth.14570
8. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. N Engl J Med.
April 2014:1402-1411. doi:10.1056/nejmoa1302097
9. Haut ER, Garcia LJ, Shihab HM, et al. The Effectiveness of Prophylactic Inferior Vena Cava Filters in Trauma Patients. JAMA
Surg. February 2014:194. doi:10.1001/jamasurg.2013.3970
1. Carley S. What to Believe and when to Change. SMACC. https://smacc.net.au/2014/08/carley-simon-what-to-believe-when-to-
change/. Published 2016. Accessed 2019.
. CATEGORY: #FOAMed, Critical Care, Emergency Medicine, Journal Club, Resus & Crit
Care, thromboembolism, Trauma
. TAG: CC20, CC3, CMP3, FOAMed, HMP3, IVC, thrombosis, Vena Cava, vte
Chapter 14
CAN WE REALLY USE IO BLOOD

FOR ANALYSIS?
For as long as I can remember I’ve been told that it is possible to analyse
marrow from an intra-osseous (IO) needle. It’s been taught on lots of APLS
courses I’ve attended (Ed – in other words you’ve taught it!), but can it
really work? There are many recommendations suggesting good correlation,
but those who have read the evidence have suggested that the data in
critically unwell patients may not be that robust (1,2).
On the very few occasions that I’ve heard of marrow being sent to the lab it
has been rejected on the basis that it is potentially too particulate to go
through the automated analysers. I would also caution against putting it
through your departmental blood gas analyser without clearing that with
your lab team first. You can make them very unhappy if you block up the
mechanism with bits of bone!
So there are practical reasons why your lab might not accept a sample, but
what if they could? Is there evidence that the values obtained would be
reliable and thus helpful to your resuscitation practice?
This week we’ve found a systematic review on exactly this topic and the
results are bordering on #dogmalysis (3) . The abstract is below, but as
always please read the full paper yourself.
It’s a systematic review of papers looking at the reliability of IO samples as
compared to blood samples. This is a reasonable approach to investigating
the question, but of course the findings are highly dependent on the quality
of the papers found. The authors have performed a comprehensive search
across several databases, conference abstracts and by hand searching
through references. In my opinion the search strategy is pretty good and I
think it’s unlikely that they have missed any key trials.
Which papers did they find?
This is a key question and in this case a surprising one. For a practice
recommendation that has been rather pervasive over the last 20 years or so
the types of papers found. The authors looked at over 800 papers, but just
27 were relevant to the question. Of those, eight (30%) studies included
humans, 18 (67%) included animals and one (4%) study protocol included
both. Most importantly to me is the fact that only one study included
haemodynamically unstable patients. In other words only one of the papers
found focused on the sort of patient I see in the resus room (4) .
The sample sizes in the studies were small, typically 5-30 subjects. In the
human study of critically ill patients there were just 17 subjects (4) .
It’s also worth noting that the authors of the review have included one of
their own studies (that took place in healthy volunteers) (5) .
How did they compare IO with blood samples.
Each individual paper had its own methods, but in general samples were
analysed in the laboratory (though a few were point of care). In terms of
agreement it looks like many of the studies used simple correlation to assess
agreement, or even just a comparison of means. At St Emlyn’s that sort of
analysis worries us as it’s possible to show good correlation despite
significant numbers of disagreements which could be clinically important.
A few studies used the better method of using Bland-Altman plots which
take much better account of outliers (6) .
The heterogeneity of methods and analysis meant that the authors were
unable to pool results as a meta-analysis.
In brief there is very little evidence that IO samples match IV samples in
critically unwell patients. The main finding from this study is really the lack
of evidence of anything really. The authors suggest that potassium levels are
higher in IO samples, but even that is arguably not a particularly robust
recommendation.
Chris Connolly reminded me on twitter that marrow may be suitable for use
in blood cultures, and I agree that in my Paeds practice we do this for the
septic kids.
The clinical bottom line.
Unless someone out there can find better evidence (I could not) then we
should not rely on bone marrow analysis in critically unwell patients.
Although the only paper in critically unwell humans suggests that it might
have a role for some variables I am unwilling to rely on a study of just 17
patients (4) .
Having been told (and taught) hundreds of times that we can use IO
samples in resuscitation I think this paper is #dogmalysis (7) , and we love
that here at St Emlyn’s. Next month I’m teaching APLS in Virchester and I
suspect that I might be struggling in the IO practical session.
References
1. Nickson C. Intraosseous access. Life in the Fast Lane. https://litfl.com/intraosseous-access/. Published April 2019. Accessed
June 2019.
2. Reid C. iStat Intrasseous. resus.me. http://resus.me/istat-intraosseous/. Published 2014. Accessed June 2019.
3. Jousi M, Laukkanen-Nevala P, Nurmi J. Analysing blood from intraosseous access. European Journal of Emergency Medicine.
April 2019:77-85. doi:10.1097/mej.0000000000000569
4. Tallman C, Darracq M, Young M. Analysis of intraosseous blood samples using an EPOC point of care analyzer during
resuscitation. Am J Emerg Med. 2017;35(3):499-501. https://www.ncbi.nlm.nih.gov/pubmed/27998615.
5. Jousi M, Saikko S, Nurmi J. Intraosseous blood samples for point-of-care analysis: agreement between intraosseous and arterial
analyses. Scand J Trauma Resusc Emerg Med. September 2017. doi:10.1186/s13049-017-0435-4
6. Giavarina D. Understanding Bland Altman analysis. Biochem Med. 2015:141-151. doi:10.11613/bm.2015.015
7. Reid C. Dogmalysis. Resus:Me. http://resus.me/dogmalysis/. Published 2013. Accessed 2019
. CATEGORY: #FOAMed, Critical Care, Emergency Medicine, Journal Club, Resus & Crit
Care, resuscitation
. TAG: FOAMed, HMP2, HMP3, intraosseous, IO, resuscitation

Chapter 15
HOW EVENTS IN EMERGENCY

MEDICINE IMPACT DOCTORS
PSYCHOLOGICAL WELL-BEING
Ed – This blog by Laura Howard is based on her excellent work on the

impact of events on emergency care clinicians. We hope that you read this
alongside the other blogs and podcasts (1) the team has put together on
improving the working lives of clinicians.
Laura – We all have stories.
There are those we tell to our friends proudly. I saw a patient with this and I
diagnosed them with that disease, or I had a great shift today I got to do my
first ever [insert procedure of your choice here]. These stories we love, they
make us feel like we can help, like we have achieved something, we hold
our heads high with pride when we tell them. However it is rare that we
acknowledge the other side, the stories we choose not to tell. The stories
that give us nightmares, and make us feel hollow in side. We all know these
stories exist, though we may not understand what impact they have on us.
Where and when do we process these cases?
2016 was an important and life changing year for me, my entire world was
turned upside down, I was involved in three events I will never forget, the
most haunting of all a maternal death. This was a case I did not want to talk
about. It haunted me, it was everywhere and yet I stayed silent. The entire
department knew about it, colleagues came into my anaesthetic theatre just
to ask me what happened. The case was in the papers, and then of course
the case was in my head, day and night haunting me. I had what I recognise
now as an acute stress reaction, I was changed. I no longer thought I was
strong enough or good enough to be a doctor. I was crippled by fear, I was
scared of patients, especially sick ones. I wasn’t sleeping, I was all
consumed by these cases. The guilt, the feeling of responsibility and the
tragedy of them.
Once back on my feet and feeling well again I vividly remember finding a
colleague crying in the toilets after a cardiac arrest, and another telling me
they hadn’t slept all night because they think they should have scanned a
patients head the shift before. Fortunately for me I had the opportunity to
speak with Simon Carley, who put me in touch with Rick Body , from this
and many coffees later the research project was born. As always please read
the open access full text in the EMJ (2) .
What was the aim?
To discover how often those in Emergency Medicine are impacted long
term by stories that ‘haunt’ them with a goal of discovering strategies to
assist people in the future and normalise the experience. Using the
expertise of a Dr C Wibberly (a qualitative researcher at
MMU), Rick, Liz Crowe and I designed the research.
What did we do?

Qualitative research is perfectly placed to explore a participants’ experience
of something. Collecting rich data based on how an experience was
perceived, rather than an objective collection of facts. Narrative interviews
allow the interviewee to tell a story based on what they feel is important to
them based on their experience. During a narrative interview the participant
decides what to reveal in what order, based on their own priorities and
perspectives. My opening gambit for the start of all interviews was “Could
you tell me about a time when an event at work has continued to play on
your mind after the shift in which it occurred was over”. From there the
interviewee was in control.
All interviews were transcribed in real time, replacing names with
pseudonyms to ensure anonymity the transcripts were then sent to the
research team. With this method, we were able to establish when data
saturation had occurred. Once no new themes were emerging from the
interviews we were able to stop data collection.
In total, 17 interviews were performed, with all researchers agreeing data
saturation had been reached at 15 interviews. Every single interviewee had
a story to tell. Chris, Rick and I immersed ourselves in the rich context of
these interviews. Allowing themes to arise as we read and re-read them, we
had four priori set themes (a-priori) and four themes emerged as we read the
interviews (emergent themes). In this blog only the a-priori themes are
discussed.
What clinical events haunted physicians?
The clinical cases recounted by interviewees all fitted into one of four
themes.
Traumatic and young deaths

Traumatic and young deaths it may be assumed these are the ones we would
find most upsetting and due to the nature of emergency medicine, we almost
expect to encounter these cases. They were described in vivid detail, for
example “she was just about alive when brought to the hospital and she was
stabbed in the abdomen and guts were hanging out..” This highlighted to
me how stories can stick in our minds and we continue to picture and
experience them sometimes in gruesome horrific detail.
Events EPs can relate to their own lives

These are the times when we, encounter a patient and we can make a
personal connection. It leaves you thinking, that could have been me or my
son or my husband. These are the cases which put you in the patient shoes
in a way that is all too close to your reality. For some this feeling of
identification caused profound distress. For example once interviewee
said “I think it is when you can draw parallels with yourself … so
essentially the family circumstances were like my family similar ages, there
was a girl who was my age she was about to get married, her sister and her
dad…….so there was the mum and the 2 daughters to which I was like that
is me and my sister and having to break bad news to them “
Bearing witness to the consequences of death on relatives
For some it is not the patient’s death itself, it is seeing the impact of that
death on those around them. “When you are breaking bad news to families
and you see their emotional response I find that I take that home quite a-lot,
when you realise how loved that person is”. As we all know, death is the
only one inevitability about life, as health care professionals this is
something we are reminded of sometimes on a daily basis. Therefore, death
becomes normal to us, and it is not surprising that not every death haunts
us. However, we also are exposed to the very real consequence of death.
“he is on his own now for the rest of his life………..I think about that more
than the actual death”.
The burden of responsibility

As physicians we have a huge number of choices to make on the patients’
behalf. We choose what questions to ask when taking a history, what tests
to order, how to interpret those tests, the treatment they need and finally
where the patients goes after the emergency department. We try our best to
rule out MIs, PEs, sepsis, and many other high-stake diagnoses. Highstakes
as each choice can have life changing or life ending consequence for the
patient. This responsibility is an immense privilege, and can be a huge
burden. For some interviewees it was feeling the effects of this huge burden
on a daily basis, a daily cause of worry and anxiety. “I was dreaming about
patients and thinking about… have I checked her bloods? What if her
potassium is high? What if her amylase is this? I used to phone people in
the middle of the night.”.
For others, it was the constant ruminating following a negative outcome,
for which they were not responsible. The fear of a mistake having been
made despite the lack of evidence that there was any mistake. This is
illustrated by the following quotes; “I shouldn’t have sent that patient home
or I should have got them to come and see them coz I think regardless
whether you have written down on a bit of paper discussed with so and so,
it is still your patient and you have to take responsibility” and “I came in
the next day and unfortunately, he had died in the department, and that was
quite a big thing to happen. Obviously, I just thought I had done something
wrong”.
Conflict in the work place

As emergency physicians we have many interactions with colleagues, in a
wide multi-disciplinary team and from other specialities. Occasionally the
interactions with other specialities can become confrontational. It is these
interactions that haunted some interviewees. “Conversations with other
specialties at times can be fraught and there are certain times where that
has had a real impact on me.’
So what effect did these clinical cases have on the physician?
This section of the research was the hardest to listen to, the profound and
difficult emotions felt by each participant. Despite some of these cases
occurring many years prior to data collection, it was clear the lasting
haunting effect some of these cases had.
Psychological effects
For some this was a deep feeling of sadness or crying every day. There is
far more powerful using the words of the interviewees, so here are some
examples:
“I was driving to work in tears every day, driving home in tears every day”
“Just getting to the lowest point you can possibly get to or, or the lowest
point where you could not function”
For some this resulted in a loss of confidence and self-esteem in both their
home and work life.
“It had kind of a massive impact on my kind of self-esteem my self-
confidence….how worthwhile I felt I was and I got kind of in a really bad
way”
Alongside the emotion felt by the interviewees they also reported physical
symptoms in keeping with anxiety and stress, this included vomiting,
weight loss and diarrhoea. One interviewee said ‘I was actually
unwell….because I was going to the toilet all the time…I was losing weight
and I thought..actually…and I was being sick in the shower..”
Sleep Disruption
Problematic sleep was the most commonly reported symptom. This was
either in the form of problems getting to sleep, or being woken by intrusive
negative thoughts. For some this was a short term effect, for others it lasted
years.
“Some events were incredibly intrusive that you can’t get away from at all…
so there was one period in my life when I didn’t sleep properly for 6 months
which was due to clinical case which didn’t go well”
“At 3 o’clock in the morning I would be lying awake going over every
patient that I had seen that night or that day……and I would be second
guessing myself, I would be stressing myself out, worrying myself sick…
even about simple decisions that are well within my capabilities, or even
things that were simple”
“The net result of all that was, that I certainly didn’t sleep properly for three
and a half years, i thought about it probably every day”
Work events intruding on personal relationships

Not only did these cases effect the individuals own health and wellbeing,
interviewees also report the effect they had on personal relationships with
the people closest to them.
Interviewees reported that if they had family and friends who were non-
medical, they were less inclined to share haunting events they had
witnessed. For some there was a concern they would not ‘get it’.
“None of the people in my life outside of work have any kind of frame of
reference for any of this, this is all really weird and they don’t really know
what to say and its making everybody else feel very uncomfortable”
“I think it is difficult because like my family are not medical at all but I am
really close to my family but it is really difficult to talk to them about…oh I
saw this today and I’m a bit stressed because this happened because they
don’t really have that understanding of responsibility…they just go oh your
fine”
Others felt they should not be sharing these clinical cases with loved ones
who were not medical, because they wanted to protect them from such
confronting stories. “Because of the nature of emergency medicine we have,
we see, we do, we feel, we experience stuff which other people shouldn’t, so
I don’t impose those on people who are not in this particular club. In fact, I
don’t impose them on anybody.”
In order to process these clinical cases, interviewees often reported
becoming withdrawn from family and social life. “I was becoming more
withdrawn and I started to feel anxious at social events and gatherings
amongst my closest friends and family. I had to kind of retreat in.“.
Some thoughts
All the themes I have just described can be part of our daily lives in the
emergency department. While we do not know what one day has in store for
us, we can make some predictions. These cases do happen, we will at some
point in our careers experience one of them. Can we teach how to process
and deal with them when they do? Should we be educating our medical
students about acute stress reactions? How can we help people shoulder the
responsibility we carry so that it is manageable?
While reading this you may well be thinking about a case or cases that have
caused you some of the experiences described by interviewees. This
research has evidenced that , you are not alone. These cases happen and
when they do they are tough professionally and personally. If you find
yourself impacted by a case please recognise that your symptoms are
probably shared, talk to someone, seek help and care for yourself.
StEmlyn’s has some great podcasts on wellbeing with more to follow
Laura Howard @laurahoward10
References
1. Carley S. Wellbeing. St Emlyn’s. https://www.stemlynsblog.org/?s=wellbeing. Published 2019. Accessed 2019.
2. Howard L, Wibberley C, Crowe L, Body R. How events in emergency medicine impact doctors’ psychological well-
being. Emerg Med J. August 2018:595-599. doi:10.1136/emermed-2017-207218
1. CATEGORY: #FOAMed, Compassion, Emergency Medicine, Healthy Clinicians, Morale, Research, Teamwork, The
philosophy of EM, wellbeing, Workforce
2. TAG: CC15, CC24, CC8, error, FOAMed, medical error, psychological
Chapter 16
SHOULD WE USE CHEST

COMPRESSIONS IN TRAUMATIC
CARDIAC ARREST?
This is a question that we’ve addressed on the blog before and the evidence
has been a little conflicting (1–6) . From a pathophysiological perspective
the logic of using closed chest compressions in a patient who has no
circulating volume is clearly pointless. In order for CCC to work, then the
patient has to have an intravascular volume to pump around the circulation.
However, that’s just a pathophysiological argument and to date there has
been little evidence to support it.
This week there is a paper published which, although an experimental
model in pigs, might help enlighten the debate (7) . I actually saw this data
at a recent conference but it was (rightly) embargoed and so it’s great to see
it in e-print format. The abstract is below, but as always please read the
paper yourself and make your own mind up.
What type of paper is this?

We don’t usually cover this sort of experimental study on St Emlyn’s. As a
group we very much prefer to review, design and research practical and
pragmatic studies. However, for some topics that approach is pretty tricky
and a more experimental approach may give more insight.
So this is a very tightly controlled animal experiment study using pigs and a
haemorrhagic shock model.
What was done?

Five groups of pigs randomised to different strategies after receiving a bolt
injury to the thigh and then a 30% blood loss down to a MAP of 40mmHg
for 60 minutes.
Gp 1 – CCC
Gp 2 – Whole Blood
Gp 3 – 0.9% saline
Gp 4 – Whole Blood and CCC
Gp 5 – 0.9% saline and CCC
The results are summarised in this tweet from Karim Brohi below.
So in summary the group with the best outcomes were those who did not
get CCC and just whole blood. CCC appears to be detrimental to outcome.
Is this definitive?
Not at all. There are many caveats here. Phil Godfrey mentioned the major
issues with the design and transferability of the findings. I’d agree with him,
this is in pigs, and it’s small numbers. There are clearly reasons why that is,
but it does limit the transferability of the data.
Perhaps it’s about perspective here. If, like me, you believe the
pathophysiological argument then this all makes sense and it strengthens
your prior opinion. On the other hand, it’s a small number of pigs in a very
controlled setting.
Additionally, it reminds me of Caroline Leech‘s talk at SMACC on mimics
in traumatic cardiac arrest. I’ve certainly looked after patients in supposedly
traumatic cardiac arrest who were actually a medical arrest that led to
trauma (e.g. car accident after myocardial infarction). Similarly, impact
brain apnoea (8,9) may lead to what appears to be a traumatic arrest without
any signs of hypovolaemia. The bottom line is that if you are considering
whether or not to deliver CCC then the question you must ask is whether
this is hypovolaemic shock, or if there is another cause.
We must all be mindful about outcomes here. In the study a positive
outcome was ROSC, which is clearly important, but it’s not the sort of
outcome that we look for at St Emlyn’s. In many studies of this kind the
pigs are killed at the end of the experiment, and that means that we don’t
get any information on functional outcome (which is something we always
look for in Virchester).
Not delivering CCC is based on the fairly simple assumption that if the
heart is empty it will not be effective and it gets in the way of doing other
things which may be help. However, you really do have to be sure that
hypovolaemia is the main cause.
I’m also unclear whether this study helps in the patient with asystole. In the
asystolic patient it can be argued that there is no mechanism to generate any
blood flow and so logically it would make sense to fill the patient up and
then deliver CPR, or perhaps not, we just don’t know. It’s tricky to
extrapolate from this study as firstly, the pigs in this study were not
asystolic (so it can’t tell us), and secondly because I’m not sure whether it’s
possible to survive from an asystolic cardiac arrest that has arisen from
hypovolaemia. The second concern may mean that the question is
irrelevant, but it’s tricky to know. There are plenty of series with survivors
of TCA with asystole as the initial rhythm, but they may not have been the
hypovolaemic ones (10–12) . I cannot personally recall any survivors from
hypovolaemic asystole, but I’d be interested to hear if you have seen them
in your practice.
Human factors.
I stopped using CCC in hypovolaemic shock some time ago. However, it
can be challenging if you don’t carry your team with you. Many clinicians
have an almost brain stem reflex of ‘cardiac arrest = compressions’. If you
are in the stressful moment of managing a traumatic cardiac arrest patient
and then you suddenly decide to do something completely different it won’t
work.
You need to train for this. You need to carry your team (and that’s not just
the docs, but everyone in your resus room and in other specialities) if you
make that decision and if my experience is anything to go by, then you’ll
have to explain it several times over.
What about open vs closed compressions?

Rich Carden reviewed a paper back in 2016, which although was only small
numbers suggested that there was no benefit for open vs. closed
compressions (1).
Since we published this post Karim Brohi has added a really interesting
thread on open vs. closed compressions which is also worth a read. I would
recommend clicking the link below and following the discussion.
The bottom line
If you think that your patient is in hypovolaemic traumatic cardiac arrest
then CCC is unlikely to be helpful and may be harmful (but exclude other
causes before you abandon them).
References
1. Carden R. Push or cut in traumatic cardiac arrest. St Emlyn’s. http://www.stemlynsblog.org/jc-push-or-cut-traumatic-cardiac-
arrest/. Published 2016. Accessed May 2019.
2. May N. Traumatic Cardiac Arrest. St Emlyn’s. http://www.stemlynsblog.org/traumatic-cardiac-arrest/. Published 2012.
Accessed 2019.
3. Smith JE, Rickard A, Wise D. Traumatic cardiac arrest. J R Soc Med. January 2015:11-16. doi:10.1177/0141076814560837
4. Konesky KL, Guo WA. Revisiting traumatic cardiac arrest: should CPR be initiated? Eur J Trauma Emerg Surg. November
2017:903-908. doi:10.1007/s00068-017-0875-6
5. Bradley M, Bonds B, Chang L, et al. Open chest cardiac massage offers no benefit over closed chest compressions in patients
with traumatic cardiac arrest. J Trauma Acute Care Surg. 2016;81(5):849-
6. Barnard E, Hunt P, Lewis P, Smith J. The outcome of patients in traumatic cardiac arrest presenting to deployed military
medical treatment facilities: data from the UK Joint Theatre Trauma Registry. J R Army Med Corps. 2018;164(3):150-
7. Watts S, Smith JE, Gwyther R, Kirkman E. Closed chest compressions reduce survival in an animal model of haemorrhage-
induced traumatic cardiac arrest. Resuscitation. May 2019. doi:10.1016/j.resuscitation.2019.04.048
8. Wilson MH, Hinds J, Grier G, Burns B, Carley S, Davies G. Impact brain apnoea – A forgotten cause of cardiovascular
collapse in trauma. Resuscitation. August 2016:52-58. doi:10.1016/j.resuscitation.2016.05.007
9. Carley S. Impact Brain Apnoea. St Emlyn’s. http://www.stemlynsblog.org/impactbrainapnoea/. Published 2016. Accessed
2019.
10. Stifkens F, Dami F, Feiner A-S, Dubois M, Pasquier M. Prehospital Simple Thoracostomy for Traumatic Cardiac Arrest: Does
the Cardiac Arrest Rhythm Matter? The Journal of Emergency Medicine. April 2019:457. doi:10.1016/j.jemermed.2018.09.058
11. Leis CC, Hernández CC, Blanco MJG-O, Paterna PCR, Hernández R de E, Torres EC. Traumatic cardiac arrest. Journal of
Trauma and Acute Care Surgery. February 2013:634-638. doi:10.1097/ta.0b013e31827d5d3c
12. Lockey D, Crewdson K, Davies G. Traumatic cardiac arrest: who are the survivors? Ann Emerg Med. 2006;48(3):240-
1. CATEGORY: #FOAMed, Critical Care, Emergency Medicine, Journal Club, Prehospital Care, Resus
& Crit Care, Trauma
2. TAG: cardiac arrest, chest compressions, CMP2, HMP2, HMP3, hypovolaemic shock, Traumatic
cardiac arrest
Chapter 17
TRAUMATIC CARDIAC ARREST

(TCA) PODCAST WITH PROF
JASON SMITH RN
A few weeks ago we reviewed a paper on the management of traumatic

cardiac arrest. That paper specifically looked at the role of closed chest
compressions in traumatic cardiac arrest (TCA). I recently managed to
catch up with the lead author, an old friend of mine and an expert in the
management of this complex condition.
In this podcast we discuss the background to Jason’s research and discuss

the recent closed chest compression trial in some detail.
My take home messages were.
TCA is not a futile condition
Successful outcomes can be as good as for medical cardiac arrest in some
systems
Not every TCA is due to exsanguination
If the patient is in asystole we lack evidence of what to do (although the
outcomes are terrible in this group anyway)
in the UK TCA is not that common so we need to train our resus teams to
manage this e.g. through Sim sessions
Closed chest compressions can inhibit other interventions (such as rapid
infusion of blood)
There are a lot of myths, dogma and misunderstanding of TCA
management. We hope you find the podcast and the linked references
helpful (1–12).
References
1. Smith JE, Le Clerc S, Hunt PAF. Challenging the dogma of traumatic cardiac arrest management: a military perspective. Emerg
Med J. October 2015:955-960. doi:10.1136/emermed-2015-204684
2. Watts S, Smith JE, Gwyther R, Kirkman E. Closed chest compressions reduce survival in an animal model of haemorrhage-
induced traumatic cardiac arrest. Resuscitation. July 2019:37-42. doi:10.1016/j.resuscitation.2019.04.048
3. Vassallo J, Webster M, Barnard EBG, Lyttle MD, Smith JE. Epidemiology and aetiology of paediatric traumatic cardiac arrest
in England and Wales. Arch Dis Child. September 2018:437-443. doi:10.1136/archdischild-2018-314985
4. Barnard E, Yates D, Edwards A, Fragoso-Iñiguez M, Jenks T, Smith JE. Epidemiology and aetiology of traumatic cardiac arrest
in England and Wales — A retrospective database analysis. Resuscitation. January 2017:90-94.
5. Rickard AC, Vassallo J, Nutbeam T, et al. Paediatric traumatic cardiac arrest: a Delphi study to establish consensus on
definition and management. Emerg Med J. April 2018:434-439. doi:10.1136/emermed-2017-207226
6. Hillman CM, Rickard A, Rawlins M, Smith J. Paediatric traumatic cardiac arrest: data from the Joint Theatre Trauma
Registry. J R Army Med Corps. June 2015:276-279. doi:10.1136/jramc-2015-000464
7. Vassallo J, Nutbeam T, Rickard AC, et al. Paediatric traumatic cardiac arrest: the development of an algorithm to guide
recognition, management and decisions to terminate resuscitation. Emerg Med J. August 2018:emermed-2018-207739.
doi:10.1136/emermed-2018-207739
8. Barnard E, Yates D, Edwards A, Smith JE. Reply to Letter: Mortality in traumatic cardiac arrest. Resuscitation. April 2017:e23.
9. Barnard EBG, Hunt PAF, Lewis PEH, Smith JE. The outcome of patients in traumatic cardiac arrest presenting to deployed
military medical treatment facilities: data from the UK Joint Theatre Trauma Registry. J R Army Med Corps. October
2017:150-154. doi:10.1136/jramc-2017-000818
10. Smith JE, Rickard A, Wise D. Traumatic cardiac arrest. J R Soc Med. January 2015:11-16. doi:10.1177/0141076814560837
1. Carley S. Should we use closed chest compressions in traumatic cardiac arrest? St Emlyn’s. http://www.stemlynsblog.org/jc-
should-we-use-chest-compressions-in-traumatic-cardiac-arrest-st-emlyns/. Published 2019. Accessed 2019.
2. May N. Traumatic Cardiac Arrest. St Emlyn’s. http://www.stemlynsblog.org/traumatic-cardiac-arrest/. Published 2012.
Accessed 2019.
. CATEGORY: #FOAMed, Emergency Medicine, Resus & Crit Care, Trauma
. TAG: C3AP1a, FOAMed, HMP3, podcast, TCA, trauma, Traumatic cardiac arrest
Chapter 18
VIRTUAL REALITY FOR

DISTRACTION FROM
PAEDIATRIC PROCEDURAL PAIN
Ed – At the SMACC conference our good friend and simulation guru Jesse
Spurr (1) talked about virtual reality as a future technique for education
and for therapy. It’s an area that we’ve not really seen in practice (yet) and
so it was really interesting to see this paper published so soon after the
conference.
That takes us back to this week and thinking about children in the ED.
Procedures in children – particularly venepuncture and cannulation – are
tricky. It’s very easy to get into a spiral of paediatric distress, parental
anxiety and personal stress that seems to predict procedural failure. Much of
this occurs because children are scared, they’re irrational (at least by most
adult standards), and the fact that they are even in the Emergency
Department has been preceded by an illness or injury – a stressful event in
itself.
That said, it is in our interests to make things as smooth as possible,
particularly when it comes to procedures. Having a bad procedural
experience tends to predict future difficulties, so that investment of time in
preparation to make things go as smoothly as possible is not time wasted.
This is one of my favourite rants – you can read more in this earlier blog
post (2) about procedures and this one (3) about paediatric pain.
So, when I spotted this paper on the use of Virtual Reality (VR) for
distraction during painful procedures (4) , I was very interested. As always,
please take the time to read the paper yourself – it’s open access so there’s
no excuse!
What is this paper about?
This is a paper from Melbourne, in Victoria, Australia. The authors wanted

to see if VR could provide better distraction than standard distraction
techniques employed during needle-based painful procedures. To answer
this question, they recruited paediatric patients requiring venepuncture or
IV cannulation from two settings (the ED and pathology) and randomised
them to either VR or standard of care.
In this case, standard of care still involved some distraction techniques –
which is fair, as the study is not looking at distraction as a single entity but
specifically the benefits of interactive VR. Use of electronic screens, toys
and/or books was classed as standard of care. The interactive VR in
question was an aquatic environment in which the child could elicit a
“visual effect” by looking directly at virtual fish.
What did they do?
Subjects were “opportunistically identified”, which I took to mean a

convenience sample. They included children aged 4-11 years, with a
requirement for venepuncture or cannulation, with sufficient English
language skills to be able to provide comments and feedback. Exclusions
included critical illness or deteriorating state, along with medical conditions
precluding VR use (presumably epilepsy falls into this group).
Parents/carers gave consent while all participating children gave assent – a
nice touch not often seen in paediatric papers but vital in giving children
agency over what happens to them – powerlessness being a significant
distress factor.
Computerised random-number generation was used for randomisation in a
1:1 ratio, with the ED and pathology populations handled entirely
separately. Again, this seems appropriate as they are potentially quite
different settings with differing urgency and perceptions surrounding them.
The authors state that “blinding was not feasible” – I suppose to be
completely fair, they could have used VR headsets without the VR
displaying, however this wouldn’t really have been standard of care as other
methods of distraction could not have been concurrently employed – so it’s
hard to see how else they could have explored the effectiveness of VR
separately in a blinded fashion.
For outcomes, they powered the study around a primary outcome of change
in baseline pain between VR and standard of care using the Faces Pain
Scale-Revised (FPS-R) 5 . This is similar to the Wong-Baker Faces Scale
but rather than 0-5 (Wong-Baker) it runs from 0-10. It is a validated tool,
which is important, but I’m always a little wary of such subjective tools as a
primary outcome. Of course, pain is subjective, and it’s hard to think of a
more useful or reliable alternative primary outcome, particularly when we
don’t necessarily expect the VR to make the procedure faster or easier, just
to make the whole experience less unpleasant and traumatic for the child –
but that’s not necessarily all about pain. Something to ponder, perhaps.
What did they find?
Recruitment occurred over 7 months and involved randomisation of 123

subjects from ED (59 to standard of care, 64 to VR) and 131 from
pathology (68 to standard of care, 63 to VR). Two of the pathology patients
withdrew assent after randomisation to the standard of care group, but even
with these patients excluded the authors had achieved a sample size of more
than 114 in each setting.
Interestingly, most of the ED patients were for cannulation (100, vs 23 for
venepuncture) while all of the pathology patients were for venepuncture.
Most of the patients in both standard of care groups had some sort of
alternative distraction therapy (73% in ED, 86% in pathology).
In both groups, the authors found that VR decreased pain from baseline in
the ED and demonstrated a smaller increase in pain from baseline in
pathology, compared to standard of care, as shown below;
ED: Standard of Care: +0.39 (95% confidence interval -0.67 to 1.45)
ED: VR: -1.39 (95% confidence interval -2.42 to -0.36)
Pathology: Standard of Care: +2.76 (95% confidence interval 1.79 to 3.72)
Pathology: VR: +1.37 (95% confidence interval 0.50 to 2.23)
In fact, the results suggest that in the ED, VR actively reduced pain from
baseline whereas in all other circumstances the procedure increased pain
despite distraction with VR or other methods. This is interesting and a little
unexpected; I would have thought the rather more stressful environment in
the ED might have predicted an increase in pain in both groups more akin to
that seen in pathology, but perhaps there are other factors at play here that
we are struggling to capture. When we look at table 3 in more detail, there
doesn’t seem to be much difference between ED and pathology in number
of needle attempts, number of people restraining the child, or in caregiver’s
distress rating – so there’s no explanation here as yet. Another one to
ponder, perhaps.
The authors collected a lot of other data, all of which is interesting but as
the study was powered around the primary outcome of change from
baseline pain this is really where we should focus.
What is especially interesting is the qualitative data; contained in table 5,
there are a number of comments and reflections from the patients
themselves, their carers and those undertaking the procedure, addressing the
usefulness of VR for distraction, reduction of pain and reduction of distress,
the usefulness of VR in keeping the child still and calm, and suggestions for
improvement. There’s quite a spectrum of responses and, although most are
positive about the VR experience from all three perspectives, it’s interesting
how differently things are perceived. For example, a couple of carers
commented that the VR blocking the child’s view of the needle made them
more calm, while others felt that being able to see and understand what was
happening was more helpful to their child.
What does it all mean?

This is by no means a definitive study but it does provide some evidence
that VR could be a useful (albeit likely expensive) addition to our
distraction arsenal, improving paediatric patient experience in ED. It
contains some nice reminders about giving the child as much control and
agency as we can (encouraging them to assent to participation and perhaps
to give them the option of seeing the needle versus being completely
distracted) and is almost worth reading for these dimensions alone.
Christmas is coming (well… isn’t it always?) so on the offchance your
hospital has a charity looking for tangible and evidence-based ways to
improve patient experience in the ED, this is a nice little example you could
use. It might not be as useful as several new beds and a load of additional
nursing staff, though…
Natalie May @_nmay
References
1. Brazil V, Spurr J. Simulation Podcast. Simulcast. http://simulationpodcast.com/. Published 2017. Accessed 2019.
1. May N. It’s not OK. St Emlyn’s. https://www.stemlynsblog.org/its-not-ok/. Published 2017. Accessed 2019.
2. May N. Paediatric Pain and Sedation. St Emlyn’s. https://www.stemlynsblog.org/paediatric-pain-and-sedation/. Published
1. Chan E, Hovenden M, Ramage E, et al. Virtual Reality for Pediatric Needle Procedural Pain: Two Randomized Clinical
Trials. The Journal of Pediatrics. June 2019:160-167.e4. doi:10.1016/j.jpeds.2019.02.034
2. IASP I. Faces Pain Scale. International Association for the Study of Pain. https://www.iasp-pain.org/Education/Content.aspx?
ItemNumber=1519. Published 2001. Accessed 2019
. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Paeds, Pain
. TAG: FOAMed, paediatrics, pain, virtual reality

Chapter 19
SHOULD WE RAPIDLY
CARDIOVERT AF IN THE ED?
If I develop AF then I reckon I’d be able to spot it pretty quick, and I’d get
myself down to ED pronto so that I could get myself cardioverted having
read the excellent work of Stiell et al (1) . Why? Well I quite like to do
cardioversions and so it would be nice to give someone else the opportunity,
but more than that, it’s because I think it’s a good idea. But is it?
My belief is that the risks of cardioversion are low, and that the risks of
complications are higher if we wait to get it done. In other words my
‘belief’ is that earlier is better, but in truth that may not be the case. The
data that’s out there suggests that cardioversion is low risk up until 48 hours
(2) and so what’s the rush? Perhaps it’s because of this thought…..
There are two indications for any procedure. Either the patient needs it,
or you want to do it. Only one of these is valid and honourable.
St Emlyn (with HT to John Hinds)
We might just want to stop and think about how urgent new onset AF really
is. Maybe we can wait and see if the patient will spontaneously convert
back to sinus rhythm to avoid sedation, electricity or drugs? If so, then how
long should andcan we wait?
Thankfully, there is a paper that might help us in this dilemma (ably
reviewed on a newly found EM blog called the Breach (3) which is well
worth a look (4)). An RCT of early vs delayed cardioversion.
The abstract is below, but as we always say please read the evidence for
yourself (3) and come to your own conclusions
This is a randomised controlled trial which is an appropriate design for an
intervention trial. Specifically, it is described as a non-inferiority trial which
seeks to demonstrate that the difference between two treatments is no more
different than a prespecified amount (in this case a 10% difference). The
10% difference is arguably a rather large one. In such a common condition
we should perhaps be looking for a rather more robust analysis of
equivalence. Patients were randomised in a 1:1 ratio to either a wait-and-see
policy or for chemical cardioversion.
Who was studied?
Patients with new onset AF. Aged >18 and who were cardiovascularly
stable. They had to be within a 48 hour window of onset of symptoms, so
pretty much the group that we could either watch and wait or proceed to
cardioversion in the ED.
This paper enrolled 327 patients in 15 hospitals. Specifically this was in the
cardiology departments but that might reflect how things are organised in
the Netherlands. In the ED most of these patients would be in the ED or
under the care of the acute medical teams (our cardiologists in Virchester
are selective in what type of heart problems they take).
What did they do?
In the wait-and-see group, patients were administered a variety of rate-
control medications, so not really a true wait-and-see approach.
The cardioversion group were preferentially treated with pharmacological
cardioversion (flecainide where possible) or with electrical cardioversion if
that was not possible.
So, this was not really a trial of nothing vs cardioversion, but rather a rate-
control approach vs. cardioversion.
Primary outcome
The primary outcome was whether the patient was in AF at 4 weeks post
intervention. To me this is not really the outcome measure that matters
acutely. I’m more interested in whether the patient gets out of AF in the
early phase of the disease.
Main results
In terms of the 4 week outcome there was no real difference between the
groups. 91% were in sinus rhythm in the delayed group vs. 94% in the
cardioversion group.
What is interesting is the number of people who spontaneously cardioverted
in the watch-and-wait group. 69% of patients got themselves back into sinus
rhythm with just rate control medications. That’s a lot of patients who
essentially sorted themselves out.
So what does this mean for practice?
When I first read the title and some of the buzz around it, I did think that
this paper would change my practice, but now I’m not so sure. In
Virchester, when a patient with new onset AF arrives we don’t usually go
straight for electrical cardioversion. If there are no contraindications we
start pharmacological interventions first whilst making arrangements for
DC cardioversion to take place within the 48 hours from onset window. If
the patient cardioverts within that time then of course we cancel the DC
cardioversion.
Does this new evidence mean that we should not give pharmacological
agents in this group? I don’t think it does, but it certainly takes any pressure
off us to DC cardiovert as soon as the patient arrives. It also means that in
those patients who are unsuitable for pharmacological intervention
(flecainide is contraindicated in many patients), that a delayed approach to
DC cardioversion is appropriate, for example by planning to do this after a
period of observation rather than straight away.
Just be careful with timings though – remember that you do want to
cardiovert your patient within 48 hours if possible. So, if your patient
presents at 40 hours, and it’s nearly midnight, then you need to be super
slick to make sure that they have the opportunity for cardioversion within
the remaining 8 hours. System issues may mean that on balance a DC
cardioversion right now might be the best option for that patient.
This will disappoint some clinicians. DC cardioversions in the ED are fun
(for us, but not the patient) and in procedure-based systems there may be
resistance to not ‘doing stuff’.
What this study cannot tell us (as it was not designed to and is not powered
enough to) is whether there are advantages to early cardioversion in terms
of complications such as thrombosis, sedation issues and others. Is there an
argument that the earlier you cardiovert the better it is? My reading of the
data out there is that this has not been shown within the 48 hour window,
but please do get in touch and post in the comments section if you’ve seen
differently. The authors clearly thought the same as they excluded those
presenting at >36 hours from symptom onset.
What I don’t get from this paper is any information that might guide me in
predicting who is likely to spontaneously convert. Data from 1998 suggests
that early presentation is a predictor of conversion 5 , but that does not
really help me (Ed- interestingly that paper also found that roughly two
thirds of patients spontaneously converted as they did in this trial). For
example, my approach to a 65 year old overweight, hypertensive, smoker
might be very different from that of a 22 year old who ends up in AF after a
weekend of alcohol and drug excess.
Also remember that you must manage the stroke risk in these patients post
cardioversion. In this study they used the EMERG-AF 6 approach but still
had 2 patients suffer strokes. You may use something different, but you
should be using something. As the accompanying editorial suggests 7 , it
may be a sprint race to get the patient back into sinus rhythm, but it’s often
the start of a long term treatment marathon for the patient.
This is a pretty well-conducted study that certainly adds to the literature on
AF management so well done to the authors on putting this together.
The bottom line
In patients who present to the ED within 48 hours there is probably no panic
to cardiovert the patient. It’s fine to delay DC cardioversion to try a period
of either rate control, or (as we will continue to do) an attempt to
pharmacologically cardiovert them.
If you want to go straight for a DC cardioversion then that’s probably also
fine, but just make sure you balance the risks of the procedure against time,
space and convenience.
References
1. Stiell I, Clement C, Rowe B, et al. Outcomes for Emergency Department Patients With Recent-Onset Atrial Fibrillation and
Flutter Treated in Canadian Hospitals. Ann Emerg Med. 2017;69(5):562-
571.e2. https://www.ncbi.nlm.nih.gov/pubmed/28110987.
2. Weigner M, Caulfield T, Danias P, Silverman D, Manning W. Risk for clinical thromboembolism associated with conversion to
sinus rhythm in patients with atrial fibrillation lasting less than 48 hours. Ann Intern Med. 1997;126(8):615-
3. Pluymaekers NAHA, Dudink EAMP, Luermans JGLM, et al. Early or Delayed Cardioversion in Recent-Onset Atrial
Fibrillation. N Engl J Med. April 2019:1499-1508. doi:10.1056/nejmoa1900353
4. Stevenson B. should we cardiovert everyone with recent onset AF. The Breach. https://the-breach.com/should-we-cardiovert-
everyone-with-recent-onset-fast-af/. Published 2019. Accessed 2019.
5. Danias P, Caulfield T, Weigner M, Silverman D, Manning W. Likelihood of spontaneous conversion of atrial fibrillation to
sinus rhythm. J Am Coll Cardiol. 1998;31(3):588-592. https://www.ncbi.nlm.nih.gov/pubmed/9502640.
6. Coll-Vinent B, Martín A, Sánchez J, et al. Benefits of Emergency Departments’ Contribution to Stroke Prophylaxis in Atrial
Fibrillation: The EMERG-AF Study (Emergency Department Stroke Prophylaxis and Guidelines Implementation in Atrial
Fibrillation). Stroke. 2017;48(5):1344-1352. https://www.ncbi.nlm.nih.gov/pubmed/28389612.
7. Healey JS, McIntyre WF. The RACE to Treat Atrial Fibrillation in the Emergency Department. N Engl J Med. April
2019:1578-1579. doi:10.1056/nejme1902341
1. CATEGORY: #FOAMed, Cardiology, Emergency Medicine, Journal Club, Med Ed
2. TAG: #Cardiology, cap25, CC3, CC5, FOAMed, hap23, journal club

Chapter 20
WHICH AGENT AS SECOND LINE IN

PAEDIATRIC STATUS EPILEPTICUS?
I first heard about the EcLiPSE trial into second-line agents for paediatric status epilepticus back
in 2012 when the proposed trial protocol was presented at the APEM meeting in Bristol, UK:
It wasn’t long before EcLiPSE’s Australasian cousin, ConSEPT, was registered at ANZCTR
(August 2013, to be exact (1) ) – and after what has felt like a long wait, both studies’ findings
were published together in the Lancet earlier this month.
You can find EcLiPSE here (2) (it’s open access) and ConSEPT here (3) (not open access) and
as always we would encourage you to read the original articles and form your own appraisal and
opinions before reading further.
What are these trials all about?
Both EcLiPSE and ConSEPT are interested in the pharmacological agent used as a second-line
medication in paediatric status epilepticus.
Traditionally in the “fitting child” algorithm, benzodiazepines are the first line medication used in
an attempt to stop the seizure. The algorithm differs slightly between APLS UK (the 6th edition
algorithms aren’t open access online but a reproduction is included in this policy document from
Leicester (4)) and APLS Australia (5) , predominantly in the timings used between doses.
Midazolam, diazepam or lorazepam are given via IV, IO, IM, buccal or intranasal routes with a
second dose either five (for IV/IO administration) or ten (for buccal, rectal or intranasal routes)
minutes later in Australia, and five minutes later irrespective of route on the UK 6th edition of
APLS. Following the second dose of benzodiazepine, the algorithm prompts the clinician to start
preparing a second line agent – which, in both cases, is phenytoin if intravenous or intraosseous
access has been obtained.
Quite aside from these differences, there are other issues with the way that status epilepticus
management plays out in paediatric patients in both the Emergency Department and in the
prehospital setting.
Some patients do not receive prehospital benzodiazepines at all; others receive more than two
doses either prehospital or in ED or between the two – presumably this is deliberately undertaken
because phenytoin is not available, but repeated doses come with a corresponding increase in
associated respiratory depression. In other cases there are long delays between doses, far larger
than those advised in the algorithm. It’s reasonable to think that either circumstance might lead to
an increased likelihood of intubation and ventilation, and that certainly corresponds to my
experiences. This open access paper from a UK PICU (6) focused particularly on issues with
benzodiazepine administration exactly as described above.
Phenytoin is a bit of a pain to administer, as our ED nursing colleagues can readily tell us. It can
only be administered by infusion (maintenance of which has its own challenges in the fitting
child) over 20mins; there are concerns about cardiovascular side effects of faster infusion rates
although the evidence base for this is not particularly robust (7) .
Harder to evidence is the omission of phenytoin altogether, but it is certainly my experience that
this occurs (and I have heard this echoed by colleagues in NETS NSW, for whom I work casually
as a paediatric retrieval registrar). Whether it is the trickiness of administration, or a perception
that the child has been fitting “too long already”, or a belief that if benzos haven’t worked then
only RSI will be successful, I am aware of a number of cases where a second line agent has been
omitted and the team has moved straight to induction of anaesthesia and intubation.
Enter levetiracetam, or Keppra (the trade name by which it is often known and which is far easier
to spell and pronounce). Since levetiracetam’s introduction onto the market we have seen its use
expanding into spaces traditionally filled by phenytoin or other antiepileptic drugs, particularly
for adult patients.
So what happened in these studies?
In my own appraisal of these studies, I’ve put together a simple abstract-type summary of each
paper (a hangover from FRCEM exams). Hopefully these highlight the methodological
differences between the two papers and their results.
EcLiPSE 2
Design: open-label, multi-centre (30 UK Emergency Departments though the PERUKI network
(8)), randomised controlled trial
Objective: to determine which is more effective and safer as a second line agent
Population: 6months-18yrs, convulsive status (generalised tonic-clonic, generalised clonic, focal
clonic) requiring second-line agent. Excluded if: other seizure type, pregnancy, renal failure, had
received second line agent already, previously enrolled. Also excluded after randomisation if
seizure stopped and treatment was not given.
Computer generated randomisation, blocks of 2-4. No blinding.
Interventions: randomly assigned to 40mg/kg keppra over 5mins vs phenytoin 20mg/kg over
20mins via IV route only
Primary outcome: time from randomisation to cessation of convulsive activity, determined by
clinician.
Key Results: 152 received keppra, 134 received phenytoin
Terminated by Keppra in 106 (70%) and phenytoin in 86 (64%)
Median time from randomisation to commencement of second line agent: 11min for Keppra (IQR
8-15), 12min for phenytoin (IQR 8-17)
Median time to cessation of seizure from randomisation: 35 min for Keppra (IQR 20 to ??),
45min for phenytoin (IQR 24-??)
Authors’ Conclusions: did not show Keppra to be superior, however in combination with other
data and ease of administration it may be an appropriate alternative
ConSEPT 3
Design: open-label, multi-centre (13 Emergency Departments in Australia and New Zealand),
randomised controlled trial
Objective: to determine which is better second-line treatment for emergency management of
convulsive status epilepticus
Population: 3months-16years, convulsive status with two doses benzodiazepines given. Excluded
if: previously enrolled, on maintenance of either agent, second line agent in last 24h,
management plan excluding phenytoin, allergy/contraindication to either agent, head injury,
eclampsia.
Computer generated randomisation, blocks of 2-4. No blinding.
Intervention: randomly assigned to 40mg/kg keppra over 5mins vs phenytoin 20mg/kg over
20mins IV or IO
5mins after completion, if still seizing, other drug was given
If still seizing 5mins after other drug, RSI performed.
Primary outcome: clinical cessation of seizure activity five mins after completion of infusion of
the first trial drug (10mins for Keppra, 25mins for phenytoin).
Key Results: 119 received Keppra, 114 received phenytoin
Cessation within five mins – 68 (60%) phenytoin group, 60 (50%) Keppra group
Authors’ Conclusions: Keppra is not superior to phenytoin. Consider sequential use to reduce
failure rates.
What do the results mean?
The two papers both found insufficient evidence to demonstrate levetiracetam’s superiority over
phenytoin as a second-line agent in that small group of patients who continue to fit after
benzodiazepines. It’s worth noting that this really is a subgroup; for example, the EcLiPSE study
had 1432 patients presenting in status epilepticus and potentially eligible for inclusion, but only
404 made it to randomisation. This also doesn’t capture the patients whose fits stopped before
arrival into hospital, so the need for a multi-centre trial over a long recruitment period is easily
explained.
There was slightly different methodology between the two papers and their results weren’t
directly comparable: EcLiPSE looked at time from randomisation to seizure cessation, while
ConSEPT looked at proportions stopping seizing within five minutes of completion of the
infusion. With different infusion rates between the two agents, this is an interesting take and
would theoretically give phenytoin longer to have an effect (since the infusion takes longer to
administer). That does rather leave us with the question: if levetiracetam’s quicker administration
is an advantage, how long do we wait before deciding it hasn’t worked? Traditionally in APLS
guidelines, the phenytoin administration time was used to prepare for RSI as the next step. I think
that in the real world, it’s unlikely that a clinical team will be ready to perform an RSI five
minutes after starting levetiracetam. It’s interesting that the time to administration is similar for
both agents in the EcLiPSE trial as this somewhat contradicts my perception that phenytoin is a
pain to give, but I wonder whether this is Hawthorne effect/selection bias (more below).
Ummm… Superiority?!
There’s a misconception around superiority trials (which both of these studies were). Superiority,
non-inferiority and equivalence trials are different beasts and the burden of statistical “proof” is
different for each entity. In practical terms, this means that different numbers of subjects are
required; the trade-off (and a common misunderstanding) is that when a superiority trial has a
non-significant result, we cannot conclude either equivalence or non-inferiority. For these two
studies, this means that the insufficient evidence of superiority of levetiracetam does not mean it
is “as good” as phenytoin.
This paper (9) is a bit intense but the abstract summarises the difference nicely:
When the aim of the randomized controlled trial (RCT) is to show that one treatment is
superior to another, a statistical test is employed and the trial (test) is called a superiority trial
(test). Often a nonsignificant superiority test is wrongly interpreted as proof of no difference
between the two treatments. Proving that two treatments are equal in performance is
impossible with statistical tools; at most, one can show that they are equivalent. In an
equivalence trial, the statistical test aims at showing that two treatments are not too different in
characteristics, where “not too different” is defined in a clinical manner. Finally, in a non-
inferiority trial, the aim is to show that an experimental treatment is not (much) worse than a
standard treatment.
Lesaffre, E. Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt
Dis. 2008;66(2):150-4.
If this is still too much for you, there’s a more plain-language example here. And if your head is
still spinning after that, take a moment to appreciate the role of statisticians in clinical research!
So Should We Change Practice?
So, we have insufficient evidence of levetiracetam’s superiority – is there anything else that
might influence our decision of which agent to use?
Crucially, levetiracetam is easier to administer to phenytoin; it is compatible with either saline or
5% dextrose and while most documentation suggests it should be given over 15min, both
EcLiPSE and ConSEPT administered the drug over 5mins. Access in children can be difficult at
the best of times, let alone with ongoing seizure activity, so being able to give an infusion quickly
while a line is patent is a definite advantage (if you don’t believe me, ask your nursing colleagues
– or think of how many times you’ve been told halfway through an aciclovir infusion that the
cannula has stopped working).
Theoretically, the difference in administration should translate to a longer time to administration
of phenytoin in the studies. While the evidence for this isn’t in the papers, I suspect that’s at least
in part because the departments were set up to administer phenytoin. We can almost see this as a
selection bias or Hawthorne effect within the paper – for a child to be included in the trial, they
had to be in status epilepticus in an ED that was prepared to administer IV phenytoin. And from
my (anecdotal) experience, the difficulty around administration of phenytoin is often prohibitive
to its administration at all, with an often articulated belief that “it doesn’t work” (both of these
studies certainly show that it does work!). We see clinicians skipping the second-line agent and
moving straight to RSI – which is not necessarily a smooth process for those same departments
who are unprepared to administer phenytoin, unused to its administration or for whom this is a
rarely encountered situation. Perhaps these department are more comfortable with paediatric RSI
– but it’s a reasonably rare event even for prehospital services like the one I work for 10 , so I
would be surprised if this was true.
For clinicians working in prehospital care, as I do, the difference between administering
levetiracetam and phenytoin is not trivial and perhaps that is why I hold these opinions; my
colleagues at Sydney HEMS are undoubtedly more comfortable with the care of adult patients
and in trauma and a case discussion at our joint HEMS/NETS education day around a child in
status epilepticus exposed the magnitude of the degree of discomfort.
I am not saying that these papers provide evidence that levetiracetam is safer, but I do think that
the practicalities of using these agents in the prehospital environment or in smaller centres should
be debated, probably more openly than they have been so far.
So I’m left with these questions:
How often do we fail to follow the fitting child protocol, either by giving more benzodiazepines
(which leads to respiratory depression and presumably increases intubation rates) or by
omitting a second line agent and moving straight to intubation?
Is this scenario more likely in non-paediatric centres?
Does it cause harm, either because of complications during RSI or because of delays to
appropriate therapy?
Would having an easier, quicker-to-administer agent negate some of these harms – and if so, is
that agent levetiracetam?
I’m not sure the answers to these questions will be forthcoming any time soon – but I suspect we
will start to see clinicians reaching for levetiracetam as a second line agent (if they are giving
one!) and hopefully more conversation around this particularly sticky problem now that the
studies are out.
Finally, hats off to the research teams for trying to answer a relevant but tricky clinical question
and giving us plenty of food for thought.
More FOAMed Takes on the Papers
If you want to read more appraisals and opinions on these two papers, try:
Justin Morgenstern’s take at First10EM
ConSEPT and EcLiPSE – Levetiracetam versus Phenytoin for Status Epilepticus
Don't Forget the Bubbles
ConSEPT Trial: Phenytoin vs. Levetiracetam in Status Epilepsy

Broome Docs
Natalie May @_nmay
References
1. ANZCTR – Registration. ANZCTR. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364600&isReview=true. Published 2013. Accessed May 3,
2019.
2. Lyttle MD, Rainford NEA, Gamble C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a
multicentre, open-label, randomised trial. The Lancet. April 2019. doi:10.1016/s0140-6736(19)30724-x
3. Dalziel SR, Borland ML, Furyk J, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-
label, multicentre, randomised controlled trial. The Lancet. April 2019. doi:10.1016/s0140-6736(19)30722-6
1. Management of Paediatric Status Epilepticus. Leicester Royal
Infirmary. https://secure.library.leicestershospitals.nhs.uk/PAGL/Shared%20Documents/Status%20Epilepticus%20UHL%20Childrens%20Medical%20Guideline.pdf.
Published 2019. Accessed May 3, 2019.
2. Status Epilepticus. APLS Australia. https://www.apls.org.au/sites/default/files/uploadedfiles/Algorithms%20-%20Status%20Epilepticus.pdf. Published 2018.
Accessed May 3, 2019.
1. Chin RFM. Inappropriate emergency management of status epilepticus in children contributes to need for intensive care. Journal of Neurology, Neurosurgery &
Psychiatry. November 2004:1584-1588. doi:10.1136/jnnp.2003.032797
2. Guldiken B, Rémi J, Noachtar S. Cardiovascular adverse effects of phenytoin. J Neurol. December 2015:861-870. doi:10.1007/s00415-015-7967-1
3. PERUKI (@PERUKItweep) on Twitter. PERIUKI. https://twitter.com/PERUKItweep. Published 2019. Accessed May 3, 2019.
4. Lesaffre E. Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis. 2008;66(2):150-154. https://www.ncbi.nlm.nih.gov/pubmed/18537788.
5. Watterson JB, Reid C, Burns BJ, Regan L. Pre-hospital advanced airway management in children: a challenge that training can handle. Scand J Trauma Resusc
Emerg Med. December 2017. doi:10.1186/s13049-017-0432-7
1. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Paeds, Resus & Crit Care, resuscitation
2. TAG: CC20, CC21, CC3, ConSEPT, critical appraisal, EcLiPSE, FOAMed, FOAMped, journal
club, levetiracetam, paediatrics, phenytoin, PMP6, status epilepticus
Chapter 21
THE BEAUTY OF SIMPLICITY. ANDROMEDA-SHOCK
For many years, we have enjoyed discussing the concept of euboxia in

critical care (1) . If something has a normal range, and abnormality is bad,
surely using medical interventions to restore it to the norm can only be
helpful? Lactate has been fed, saddled and ridden all the way to the races on
this. It remains a key component of international screening metrics and
clinical guidelines (2,3) . There are opposers to this logic (4) and we
certainly believe at St Emlyns that lactate is often misunderstood and poorly
applied as a point of care test (5) . Make of this what you will. Either way, a
lot of scientific attention (6) has been paid to the baseline level and the
speed and success of lactate clearance, as a proxy marker of successful
resuscitation
Do we need this? What about good old fashioned clinical assessment of
shock resolution? Shock windows were described many years ago (7) and
feature heavily in textbooks; the skin is one such window, and capillary
refill time (CRT) following direct pressure is taught on most life support
courses as a central tenet of shock assessment. However, it is subjective,
operator dependent and potentially subject to bias. Not like the good old
objective number spat out by whatever flavour of gas machine you invest in
at your ‘shop’.
How do the 2 compare? Well, helpfully, JAMA proposes to have the answer
for us. A recent ambitious study seeking to compare objective numerical
values to a subjective clinician dependent interpretation, to guide
resuscitation during early septic shock 8 . Interesting stuff and hats off to
the Latin America Intensive Care Network for completing and publishing
this work.
What did they do?
The alternative hypothesis for the study, was that resuscitation guided by
peripheral perfusion would be superior to that guided by lactate level
targeted resuscitation in patients with early septic shock. The authors
conducted a large randomised controlled trial to answer this question.
Are your eyebrows raised already? If not, they should be. Why on earth do
we think capillary refill time (CRT) would be superior to lactate clearance?
How did they do it?
This was an open label, multicentre RCT across 28 South American
Centres. The authors convened a Trial Steering Committee and a Data
Monitoring and Events Committee which is good practice for a study of this
size. The protocol and analysis plan were pre registered and published,
which is all good stuff as well. Central randomisation via permuted block at
patient level was used, which should have maintained allocation
concealment; an important factor in the context of an open label trial.
This study was set in the ICU which has several important implications I
think. Firstly, this affects the generalisabilty of the findings to other acute
care areas. Secondly, would you use CRT on your unit when you have
access to arterial line monitoring, central venous pressure, focussed echo
etc? Would it be drowned out by other information, or if these study results
were positive, would you be happy to go back to basics? I’m not sure I
would (Ed – but in many health economies where invasive monitoring is
limited this strategy might well be a realistic alternative).
The inclusion criteria seem straightforward – suspected infection, lactate
>2, vasopressors needed for a MAP 65 following 20ml/kg fluid. We can
debate the details, but I think most of us would agree this group to be a
pragmatic representation of septic shock. Exclusion criteria were pretty
standard also; bleeding and DNR orders, although I was a bit surprised to
see severe ARDS in here.
What about the intervention?

Following randomisation, there was an 8 hour intervention period. Patients
were assigned to one of the following:
CRT – pressure was applied to the right index finger with a glass
microscope slide, maintained for 10 seconds after blanching. The refill
time was assessed using a chronometer. >3s was defined as abnormal.
This was assessed every 30 minutes until normalisation, then every hour.
I assume a chronometer is a watch/clock. I cannot see why they have
used extra letters here, other than to befuddle me with long words.
Lactate blood levels, assessed every 2 hours. A 20% decrease was
considered to be evidence of effective resuscitation, with an aim to
normalise.
Abnormal results from either strategy triggered an interesting cascade of
intervention, on top of baseline critical care for sepsis. Assessment of fluid
responsiveness, tailored fluid therapy, trial of a higher MAP target and
inodilator use. The supplements describe baseline and increasing levels of
care.
It is undoubtedly a strength of the study that the authors tried to structure
the response to inadequate resuscitation. However, they also allowed local
variation at the discretion of treating physicians and surviving sepsis
campaign guidelines were also endorsed. The latter have received a lot of
recent criticism (4) as highlighted above. These issues have the potential to
introduce bias and affect validity.
And the outcomes?
The authors chose a primary outcome of mortality at 28 days. Follow up by
phone or death register. There were lots of secondary outcomes.
The sample size calculation suggested a need for 420 participants. This
provided 90% power to detect a 15% ARR with an alpha of 0.05. I can’t
resist getting into this right now, and I don’t think it would be going too far
to suggest that this ARR is crazy. A NNT of 7 for CRT guided resus,
compared to lactate guided? A relative risk reduction of 50%? Better than
the NNT for appropriate and early empirical antimicrobial therapy? (9) I
have no idea how they made this leap – although the cynic in me would
suggest that might have done the sample size (10) after the event.
It is also worth pointing out again here that the authors determined CRT as
their intervention, with lactate as the control. This was also a superiority
trial. I have no idea why they were so confident about all this. And I am not
sure why this was not a non-inferiority trial (11) ; I would have been very
interested to see simply that CRT guided resuscitation is no worse than
lactate guided. A genuine result on this could still save a lot of blood gases.
The DMEC also had no stopping rules I can see, although I appreciate
many study groups don’t publish these in the central manuscript.
The Results
They cracked this in a year, recruiting and randomising 424 participants,
which is excellent work. However, the consort diagram raises a few early
concerns. 68% of assessed patients were excluded during this year, with 102
deemed to be eligible but not enrolled. The excuses here are pretty thin –
logistic issues, physician preference, lack of consent etc…. 102 is >just shy
of a quarter of the trial. In essence, this makes the data look more like a
convenience sample, which introduces further risks of bias.
No patients were lost to follow up and all were included in the ITT analysis,
which is good, but perhaps represents the follow up methods of death
register and telephone follow up, which are not great. Baseline
characteristics were mostly comparable between intervention groups
suggesting success of the randomisation process, although a gender
difference of 8% is quite high. The mean APACHE 2 score was 22 in both
groups – much higher than the mean of 18 in the PROMISE trial 12 for
example, showing how international sepsis trials can struggle for
generalisability.
There were protocol deviations in over 10% patients. Mostly around
deviation from the suggested resuscitation algorithim I think. This raises
some questions of internal validity. And there are questions already.
Questions on questions….
And the primary outcome?
For the key result of death within 28 days, results were as follows: 34.9%
(CRT guided) vs 43.4% (lactate guided). A Hazard ratio for death of 0.75,
but with the 95% CI crossing 1. A p value of 0.06. Close, but no cigar.
Or is there a cigar? Peripheral perfusion is a cheap reliable and easy method
of assessment in septic shock. Although these results don’t prove it is
significantly better than lactate clearance, the likelihood of it being as good
if not better is very high indeed. Had these results been statistically
significant, we would be talking about an absolute risk reduction of 8.5%,
with a NNT of 12. Just think about what this result suggests – to save one
life, you would need to abandon a resuscitation strategy guided by lactate
clearance and rely on one guided principally by peripheral perfusion
assessment in only 12 patients. What’s not to like about that?
There were some interesting secondary outcomes. Significantly less organ
dysfunction at 72h and less fluid administration were highlighted in the
CRT group. However, these variables are more continuous; as such it is
often easier to show a statistical difference but the question of clinical
significance remains. The SOFA score was reduced at 72 hours by 1 and the
fluid admin by 408mls mean. I am not sure I buy this as clinically
remarkable.
In the prespecified subgroup analysis, patients with a baseline SOFA score
of <10 seemed to do significantly better with peripheral perfusion. This is
quite interesting. Why would a lack of reliance on lactate clearance in the
less sick lead to better outcomes? Perhaps because you are not then forced
to resuscitate as aggressively? Perhaps you give less fluids? These are
uncomfortable conclusions that make us try and face up to the fact that our
sepsis care can often be overzealous, to the later detriment of the patient.
Hypothesis generating only, but food for thought. Once the SOFA score is
>10 the HR levelled off at 0.98 implying no difference in outcome between
intervention groups.
All very interesting. Any concerns with the design or results?
Unfortunately, there are quite a few. This doesn’t negate the value of
information provided by the study. But some common issues are worth
digging into.
The failure to achieve statistical significance could well be a type 2
error here. Had they powered looking for half the proposed ARR, they
would have required 1580 patients; a study of this size could well have led
to a more convincing result. Have a go with a sample size calculator – you
will be amazed at the margins that lead to far higher recruitment figures.
There are lots of questions on generalisability – is Argentinian sepsis the
same as that in the UK? Is ICU sepsis the same as ED sepsis? Mortality
rates were quite high with both interventions I thought; the mortality in the
recent PROMISE study 13 was 29% in both groups for example. As
highlighted previously, the baseline APACHE 2 was lower in PROMISE so
this outcome may simply reflect the severity of illness.
I still have questions about the CRT intervention – what about those with
peripheral poor perfusion, known vasculopathy, Raynauds disease etc…
Can this intervention really be standardised? I would also ask questions
about the timing of review – as well as a different method of assessment,
this study also randomised assessment to 30 minutes (CRT group) and 2
hour intervals (lactate group). Although you may tell an intensivist to just
check the CRT at 30 minute intervals, you will not stop her sneaking a
cheeky look at the latest gas, UOP, CVP, art line trace, HR etc…. This type
of repeated frequent clinical assessment can only ever be beneficial.
Perhaps this is one of the lessons from the study; that providing you
regularly reassess, simple assessment measures are just as good if not better
than objective numerical goals.
As discussed, the number of exclusions and protocol deviations make this
more of a convenience than a consecutive sample. As such there is a decent
risk of bias in the outcome. The study was also open label and as such
introduces conscious and subconscious bias. The authors tried to reduce this
risk through a hard outcome measure and standardised protocol, but also
allowed clinician preference on several measures.
What else is interesting?
Trials of hypertensive therapy achieved resuscitation targets 40% of the
time when instituted. That is another hypothesis generating subgroup result,
implying further that there may indeed be a role for individualised MAP
targets. I like the design of this aspect, with hypertensive therapy as a trial
only to be continued in the event of objective improvement.
We have already mentioned that CRT guided resuscitation resulted in less
fluid administration and appeared to be even better in the less sick. Worth
reiterating that maybe these issues are intertwined. The sepsis police won’t
like this, but the sepsis revolution will…
Death at 90 days continued to adjust after the primary outcome, with more
patients in the CRT group meeting their end over the following 2 months – I
am not sure this can be attributed to the interventions within the first 72h.
Does it reflect some of the baseline imbalances between groups/
No subgroup analysis favoured lactate clearance to guide resuscitation. All
markers of lower severity favoured a CRT guided strategy; lactate <4,
SOFA <10 and APACHE2 <25. A lactate guided strategy did not come out
of this looking good, no matter how you dressed it up.
And the take home?
Well, in my opinion this trial was clearly underpowered, is difficult to
generalise, had issues with recruitment and was at risk of bias in several
domains . I am not alone in those views. There is a great interactive tool to
examine the sample size issue here.
However, it is hard to read this without acknowledging that the cheaper,
easier and more globally transferable assessment of resuscitation
effectiveness outperformed the blood test. And it did so principally by
mandating regular review (which is cheap and easy to do) and limiting the
fluid administered (which is cheap and easy to do).
What would you want to see before you use this intervention to guide your
care? More trials in your population? Statistical significance? Blinded data?
I am not sure you need it.
I for one am going to dust off my use of CRT, standardise my application,
pay more attention to it and try to increase the frequency of my clinical
reviews. This trial suggests to me another source of harm resulting from the
quest for euboxia.
I also think research like this can sometimes remind us about the power of
rational repeated clinical assessment and rigorous application of basic
principles.
But that’s just me. What do you think?
The Bottom Line

Rebel EM
EMCrit
References
1. 1.Nickson C, Chris NicksonFCICM FACEM BSc(Hons) BHB MBChB MClinEpid(ClinTox) DipPaeds DTM&H
GCertClinSim Chris is an Intensivist at the Alfred ICU in Melbourne and is an Adjunct Clinical Associate Professor at Monash
University. He is also the Innovation Lead for the Australian Centre for Health Innovation and the Chair of the Australian and
New Zealand Intensive Care Society (ANZICS) Education Committee. He has a passion for helping clinicians learn and for
improving the clinical performance of individuals and collectives. After finishing his medical degree at the University of
Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne.
He has since completed further training in emergency medicine, clinical toxicology, clinical epidemiology and health
professional education. He coordinates the Alfred ICU’s education and simulation programmes and runs the unitâ€™s
education website, INTENSIVE. He created the “Critically Ill Airway” course and teaches on numerous courses around the
world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of
Lifeinthefastlane.com, the RAGE podcast, the Resuscitology course, and the SMACC conference. His one great achievement is
being the father of two amazing children. On Twitter, he is @precordialthump. A. Euboxia and (Ab)Normality • Life in the
Fast Lane • LITFL • Medical Blog. Life in the Fast Lane • LITFL • Medical Blog. https://lifeinthefastlane.com/ccc/euboxia-
abnormality/. Published 2019. Accessed March 21, 2019.
2. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med. April 2018:925-
928. doi:10.1007/s00134-018-5085-0
3. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med. April 2018:925-
928. doi:10.1007/s00134-018-5085-0
4. Weingart S. Petition to retire the surviving sepsis guidelines. EMCRIT. https://emcrit.org/pulmcrit/ssc-petition/. Published
5. Richard C. Lactate Lacthate. St Emlyn’s. https://www.stemlynsblog.org/lactate-lacthate/. Published 2015. Accessed 2019.
6. Jones AE. Lactate Clearance for Assessing Response to Resuscitation in Severe Sepsis. Kline J, ed. Acad Emerg Med. July
2013:844-847. doi:10.1111/acem.12179
7. Vincent J-L, Ince C, Bakker J. Clinical review: Circulatory shock – an update: a tribute to Professor Max Harry Weil. Crit
Care. November 2012. doi:10.1186/cc11510
8. Hernández G, Ospina-Tascón GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status
vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock. JAMA. February 2019:654.
doi:10.1001/jama.2019.0071
9. Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic Review and Meta-Analysis of the Efficacy of
Appropriate Empiric Antibiotic Therapy for Sepsis. Antimicrobial Agents and Chemotherapy. August 2010:4851-4863.
doi:10.1128/aac.00627-10
10. Medscape M. The sample size samba. Medscape. https://www.medscape.com/viewarticle/584026. Published 2008. Accessed
2019.
1. Gertelhamer G. Non-inferiority. Slideshare. https://www.slideshare.net/simonledinek/non-inferiority. Published 2012. Accessed

2019.
1. Mouncey PR, Osborn TM, Power GS, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med. April
2015:1301-1311. doi:10.1056/nejmoa1500896
2. Mouncey PR, Osborn TM, Power GS, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med. April
2015:1301-1311. doi:10.1056/nejmoa1500896
1. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Resus & Crit Care
2. TAG: cap refill, capillary refill, CC20, FOAMed, lactate, septic shock, shock
Chapter 22
TIME TO PUT THE REBOA

BALLOON AWAY? MAYBE,
MAYBE NOT…
The management of the critically hemorrhaging trauma patient has seen

a large amount of change over last decade, from bringing care far forward
to the field to early use of blood products to civilian translation and
application tourniquets to name a few.
The reality unfortunately is that there is still a subgroup of patients who
continue to suffer early mortality from hemorrhage, primarily because they
are bleeding in the torso. This is particularly challenging for both
prehospital and in-hospital clinicians to manage as these areas do not allow
control through direct compression.
Enter resuscitative endovascular balloon occlusion of the aorta (REBOA) –
a technique that builds on principles from vascular surgery and sees the
placement of a balloon catheter into the aorta via the femoral artery. Acting
as an internal tourniquet, it temporarily occludes flow to the bleeding vessel
thus providing circulatory support and precious time to get the patient to
definitive care.
With the alternative being death from hemorrhage, REBOA came as a
breath of fresh air – a minimally invasive means of achieving hemorrhage
control in these extremely sick patients. There were innovators and early
adopters and reports of fantastic saves – patients were surviving who would
never have survived before.
But then came the reports of complications, primarily limb ischemia and
multisystem organ failure. The initial equipment was also cumbersome and
risky to place, and so many sat on the sidelines watching these early
adopters do their thing. With time came improvements in the equipment,
and more centers joined the bandwagon, some even pushing this
prehospital. Of course, on the flip side, there remain the staunch nay-
sayers.
Continued debate is good (and necessary) especially for a high-stakes
procedure like REBOA. You only have to turn to Twitter to see how much
controversy and angst this procedure still brings up – the reality is there are
still few clear answers or (completed) high quality trials answering
questions like: who is the right patient; how long can the balloon remain up
in humans; what is the right setting to do this in; what are the actual
outcomes when compared to usual care?
This week we saw the publication in JAMA Surgery of a paper by Dr.
Joseph et al from the United States. He had presented the initial data at the
AAST meeting held in September 2018, and the full paper was eagerly
awaited. The real important aspect of this study, in my mind, is that it was
designed to compare REBOA to “standard care” – more on this later.
The abstract is below but it is, as always, very important to read the actual
paper in full and ultimately decide for yourself what it tells us.
This is a retrospective case-control analysis of data in the American College
of Surgeons-Trauma Quality Improvement Program (ACS-TQIP) database.
This program works to ensure quality standards amongst US trauma
centers, and includes data from over 800 hospitals. Individual centers can
compare how they are doing in accordance to national standards.
What did the authors do?
The authors looked through the database from 2015-2016, and identified
adult trauma patients who received REBOA within one hour of presentation
to the trauma center. They excluded patients arriving in arrest, those that
were transferred, those with missing physiologic data, and those who
underwent thoracotomy.
Of almost 594,000 patients (primarily suffering blunt injury), they were
able to find 140 patients who underwent REBOA. These patients were
more likely to have lower presenting blood pressures, higher injury severity
scores, and lower GCS than non-REBOA patients overall.
They then propensity-matched a cohort of patients with similar
demographics, severity score, vital signs, injury mechanism, injury pattern,
and injury severity scores in a 1:2 ratio, to obtain 280 patients in the control
group – these received “standard care”. The table shows they did a pretty
reasonable job at this. Click on the link through to JAMA and then look at
figures/tables on the right hand side to see this in more detail.
Click the link to the paper and then view tables on the right hand side to see
table 2 in detail.
The primary outcomes they sought were mortality in the ED, at 24 hours,
and after 24 hours, with secondary outcomes of transfusion requirements (at
4 and 24 hours), complications in-hospital (to include deep vein thrombosis,
pulmonary embolism, stroke, renal failure, myocardial infarction,
compartment syndrome or amputation of the limb, and unplanned return to
the operating room), ICU length of stay (LOS) and hospital LOS.
What did they find?
The headline figures are that there was significantly higher 24-hour
mortality (26.4% vs 11.8 p=0.01), rates of acute kidney injury (10.7% vs
3.2% p=0.02) and lower limb amputation (3.6% vs 0.7% p=0.04) in the
REBOA group than the no-REBOA group. There was no significant
difference in blood transfusion requirements at 4 and 24 hours, nor in ICU
or hospital LOS. All other secondary outcome measures also showed no
significant difference.
An additional finding was that time from ED to intervention (either
interventional radiology angioembolization or laparotomy) appeared
significantly longer in the REBOA group.
Finally, they reported on the subgroup of REBOA patients who survived
against those who subsequently died. The survivors had significantly
higher mean SBP (114 vs 98mmHg p=0.006) and GCS (15 vs 3 (p=0.04),
and lower heart rate (99 vs 109 beats/minute p=0.02), lower ISS (27 vs 38
p=0.043) and blood product requirements (24-hour PRBC requirement 1U
vs 14U p<0.001) – or in other words those who died in this subgroup were a
much more critically injured bunch.
What do the authors conclude – and can we take that at face value?
[SR1]
The authors conclude that “placement of REBOA in severely injured
trauma patients was associated with higher mortality compared with a
similar cohort of patients who did not undergo REBOA placement.” They
go on to highlight the higher complication rates in the REBOA group.
Some have touted this study as a nail in the coffin for REBOA. But is this
really what we can conclude – in 2019 – from this study? Personally, I feel
the headlines on this article in social media and elsewhere are not fully
supported by the study for these reasons:
The ACS:TQIP database is a fantastic tool – but it only records initial
blood pressure and heart rate. Hence the response to initial resuscitation
cannot be measured from that dataset, nor was it in this study. Even
though the authors go to great pains to propensity match a cohort of
patients with similar initial vital signs, if that patient then goes on to
respond to a liter of fluid or a unit of blood, they are no longer a non-
responder, and hence are no longer a patient in whom REBOA is
indicated. There is no way for us to determine that responder group from
this paper. The authors, to their credit, do acknowledge this limitation,
but this to me is the biggest flaw in the methodology.
There was no means to determine duration of aortic occlusion. This is a
critical piece of information – occlusion times, especially in zone 1, need
to be kept to a minimum. Inevitably, those with prolonged occlusion
times will suffer ill effects downrange. It is impossible to identify this
from the dataset used, and yet this information is vital to have a clear
understanding of the outcomes from REBOA.
The time period the authors looked at (2015-2016) reflected a very
different way REBOA was implemented to what it is in 2019 (albeit we
are still in many ways defining the use). Importantly, the big move in the
US about mid-2016 was to go from the large (at least 12-French) sheath
and device to the lower profile 7-French system. This smaller system
only got approval from the US Food and Drug Administration (FDA) in
October 2015, and it took several months for it to then come into use at
centers doing REBOA. We know that smaller sheath devices lead to
lower (though not negligible) access site and limb ischemic
complications, and so it is not that surprising to see the higher limb
ischemic complications in the REBOA cohort of this paper.
If you look at the patients who got REBOA, you have to question why
those with SBP>80mmHg were even getting this. Likely these people did
not need REBOA and this can certainly skew outcomes
The subgroup of patients who got REBOA and died was a lot sicker
cohort than those who got it and lived. There are significant differences
in initial SBP, GCS, and blood product requirements. Did these people
die because of REBOA – or did they die because their injuries were so
severe from the outset? Or was it something else completely? The
presented data makes it difficult to conclude which factor may be most
responsible.
The majority of patients included suffered blunt injuries. Would a group
that had a primarily penetrating mechanism of injury have fared
differently – again difficult to conclude from this dataset and not
accounted for by the study.
Despite contributions to the ACS:TQIP database from almost 800 centers
and almost 594,000 individual patient records, only 140 had undergone
REBOA. It is unfortunate that the sample size is so low. However, again
reflecting practice in 2015, the majority of REBOA procedures were
being done at a very small number of centers, and this certainly skews the
data in this paper.
The use of REBOA in general in 2019 is much different than it was in
2015-2016. Not only are more centers utilizing it, but newer concepts
such as partial REBOA are being implemented, and this may ameliorate
some of the complications highlighted in this paper.
I do however applaud the authors for undertaking this study and I think we
can take away some important points:
It is imperative that we continue to study this evolving technique – but we
must develop well-conducted multicenter trials to do so
I was glad to see the comparator being “standard care” in this study – this
is what we need. Prior trials comparing to resuscitative thoracotomy, for
example, can be somewhat misleading. Thoracotomy has its own unique
indications and REBOA is not a complete replacement of it.
One of the interesting data points from this study was the increased time
to intervention in the REBOA group. This is important and needs to be
considered by individual centers. In some scenarios, it may be prudent to
utilize those extra minutes to provide temporary hemorrhage control in a
patient who would otherwise imminently exsanguinate and die. However,
in some patients it will clearly be to their detriment to delay movement to
definitive care (especially if the indication for placement has not been
correctly considered). This goes back again to our discussion around
appropriate patient selection
We need to focus more on our post-procedure management of these
patients. When REBOA is truly indicated, does our post-procedure
management affect morbidity and mortality? Are we being cautious
enough about monitoring for limb ischemia, removing the sheath
appropriately, managing the peri-operative and early intensive care phases
of these patients well?
So “nail in the coffin” for REBOA this study is not – but rather a call to
arms that if we are to continue using this modality (and it looks like we are
for now), then we should continue the debate and support development of
high-quality trials to, as the authors state, “clearly define when and in which
patient population REBOA has benefit.”
Zaf Qasim @resusone

Editorial note: This article was originally submitted to the REBEL EM site.
It is dual published here with permission from both editorial teams.
References
1. Harris T et al. The evolving science of trauma resuscitation. Emerg Med Clin North Am 2018:85-106 PMID 29132583
2. Morrison JJ, Rasmussen TE. Noncompressible torso hemorrhage: a review with contemporary definitions and management
strategies. Surf Clin North Am 2012:843-858 PMID: 22850150
3. Gamberini E et al. Resuscitative endovascular balloon occlusion of the aorta in trauma: a systematic review of the literature.
World J Emerg Surg 2017 PMID: 28855960
4. Davidson AJ et al. The pitfalls of resuscitative endovascular balloon occlusion of the aorta: Risk factors and mitigation
strategies. J Trauma Acute Care Surg 2018:192-202 PMID: 29266052
5. Joseph B et al. Nationwide analysis of resuscitative endovascular balloon occlusion of the aorta in civilian trauma. JAMA Surg
2019 PMID: 30892574
6. Teeter WA et al. Smaller introducer sheaths for REBOA may be associated with fewer complications. J Trauma Acute Care
Surg 2016:1039-1045 PMID: 27244576
7. Brohi K et al. Why are bleeding trauma patients still dying? Intensive Care Med 2019 PMID 30741331
8. Qasim ZA, Sikorski RA. Physiologic considerations in trauma patients undergoing resuscitative endovascular balloon
occlusion of the aorta. Anesth Analg 2017:891-894 PMID: 28640785
1. CATEGORY: Emergency Medicine
2. TAG: CC20, CC23, FOAMed, REBOA, trauma, traumaresearch

Chapter 23
DO WE NEED SCRIBES IN THE

ED?
Editorial note: this blog is co-authored by Chris Gray and Katie Walker.
Katie was lead author on the study. Chris Gray is well known to you as a
St Emlyn’s author and editorial board member. I have indicated where
comments are limited to Chris (as critical appraisal lead) or Katie (as
author). Both authors have reviewed the manuscript and are happy with
the content.
Help a patient, write your notes, help a patient, write your notes. Rinse and
repeat ad infinitum.
Unwittingly, we might have just condensed the entirety of medicine into
just two actions. Hmm. Anyway, thinking about it further, with the increase
in allied health professionals such as advanced nurse and clinical
practitioners, emergency practitioners and physician associates there is
more and more support available for the “help a patient” side of the
profession. Emergency medicine however remains one of those specialties
where clinicians of all grades still have to write their own notes for each
patient they see. Medical or surgical consultants generally have junior
doctors to scribe on the ward round, secretaries to type up dictated clinic
letters, assistants to write the op note. Down in the ED, even the professors
have to put their own (usually more fancy) pen to paper, or finger(s) to
keyboard depending on how much your department has evolved.
There may be a solution – scribes.
What’s a scribe?
A scribe is a clerical assistant whose primary role is to complete the
medical record. They accompany the clinician, documenting history,
examination, recording procedures, results of investigations, further
consultations or re-evaluations. They also have access to computer systems
and patient records and are able to order investigations, book follow up
appointments or complete referral letters. Whilst scribes are usually also
health workers in training, such as medical students, they are not healthcare
providers, and so are unable to carry out procedures such as giving
medication, or tending to hygiene needs.
In 2014, Nat May and Damian Roland wrote a journal club review1,2 here
at St Emlyn’s of a before and after study looking at the introduction of
scribes into an American emergency department. They also discussed they
ways that they take notes in their own practice and some valuable opinions
on the pros and cons of scribes in the ED. It’s a great read and provides a lot
of background information too, which I won’t repeat again here, so make
sure you take a look!
The paper we’re going to be taking a look at today was published in the
BMJ only a couple of weeks ago at the end of January 20193, looking at
whether ED scribes could improve productivity and patient throughput. As
ever we’d advise you to read the evidence for yourself to form your own
opinion.
Tell me about the paper.
This is a prospective, multicentre, randomised controlled trial performed
over five hospitals in Victoria, Australia over a little more than a two year
period. They randomised emergency physicians to shifts with or without a
scribe, then compared productivity between these shifts.
Of course, it would be difficult to blind such a study, and likely lead to an
unfortunate situation in court a few months down the line where a lack of
notes from the encounter would finally make you realise that that patient
was in the ‘placebo’ arm. Not ideal. However, what is ideal is performing
an RCT to assess the impact of an intervention here.
What’s the background?

Before undertaking this RCT, Katie Walker (who co-authored this blog) and
her team undertook a feasibility study to assess the costs of training medical
scribes, at the lead hospital in Melbourne. It was published in the EMJ and I
wrote a brief commentary on this paper over at the EMJ blog in 2016. It is
this training programme that nurtured the scribes who took part in today’s
paper.
If you want to read more about the cost analysis, and information on the
training process for the scribes, have a look at that paper.
Who were the patients?

Well, this study is slightly different, as it wasn’t patients that were
randomised to the treatment, but rather the clinicians/scribes. Trained
scribes were allocated what appears to be two weeks in advance to
participating clinicians (88 in total) by random number generator. Full
details are in the paper, but this seems a fair way to decide this whilst still
ensuring rotas were distributed in a timely fashion.
Clinicians signed up voluntarily, and only included consultants, though an
exception was made to include very senior trainees at the two smaller
hospitals. There were no scribes allocated on night shifts or bank holidays.
Patients were not randomised, and the clinicians had no restrictions on who
they could see, though of course consultants were free to adjust their own
workload and select patients to see based on workflow and clinical priority
needs.
What did they do?

Scribes accompanied the clinician for the full shift, documented the
encounter, and performed other appropriate tasks. The medical record was
checked by the clinician before sign-off. Emergency consultants (or
occasionally advanced trainees) were recruited and trained scribes were
randomised to their clinical shifts (or not). Junior doctors and night shifts
were excluded.
The primary outcome measure was productivity, defined as patients per
doctor per hour.
Secondary outcomes were primary patients per doctor per hour (i.e. patients
the doctor had seen from start to end rather than handovers), productivity in
various parts of the ED, door-to-doctor times, and emergency department
length of stay.
They also looked at patient safety events related to the scribe, and
completed another cost evaluation.
Was the study big enough?

The study was powered to detect a 15% increase in productivity using
scribes which seems a lot, but actually (assuming an 8-10 hour shift and
using their previous work which found on average doctors see 0.83 patients
per hour) only equates to one extra patient per shift. Their power
calculations are given in the paper, but look reasonable and you can read
more about how they work on Simon’s intro to power calculations blog.
They met the required numbers of patients for their calculations.
What were the results?
Overall, 589 scribed and 3263 unscribed shifts were analysed. Each site
needed to provide 100 scribed and non-scribed shifts
The team found a 15.9% increase in the number of patients seen overall per
doctor per hour when a scribe was present. In real terms this is an increase
from 1.13 to 1.31 patients per hour or around 1-2 patients per shift. Primary
patient productivity increased from 0.83 to 1.04 patients per hour (25.6%).
The most gains were obtained when a scribe was placed with a senior
doctor in triage, however there were a low number of encounters here.
There was no change in door-to-doctor time, though ED length of stay
decreased by an average of 19 minutes per patient.
Chris Gray on unresolved questions and concerns?
Chris: This is a well powered study and has set out its objectives well.
Overall, it’s a good study. However, there may be a few issues, mainly
relating to selection bias.
Chris: The clinicians in the study all volunteered, which may mean a
particular type of doctor. Potentially those already enthusiastic about
scribes, maybe those who have already worked with or trained those scribes
at the centres. Maybe consultants who are a bit slower with
technology/typing (if they even exist…) and leapt at the chance for
someone else to do the computer work. We don’t know. However, this is
probably the population who would use scribes day-to-day anyway, but it’s
all self-selective, so could bias the results. We also know that in another
study (also by Katie) increases in productivity did not always increase
financial gains4 (but that was in a smaller, single centre study).
Chris: I was surprised to see that only day shifts were taken into account,
however there were a small number of scribes, so this seems reasonable.
During the day though, there are often more people around, with less
pressure on the system. Could this have affected the study? On nights and
bank holidays, would scribes make even more of an impact?
Chris: Consultants followed their usual work pattern, so were able to select
patients to see if needed based on their clinical judgement. It’s possible that
the case mix they elected to see varied depending on whether they had a
scribe or not (see also the Hawthorne effect), though of course it’s hard to
determine this from these data.
Chris: Due to the randomisation of scribe-clinician pairings, there also
wasn’t the opportunity for working relationships to form, which could
improve productivity more.
What’s the take home?
This is the first study of its type to have been performed, and although it
was done over in Australia, it does suggest that scribes could improve
things in the ED. We believe that we can extend that to say that it suggests
that scribes could improve the productivity of some clinicians.
Many clinicians, us included, may find that writing things down helps us to
consolidate the patient story, ensuring we’ve asked all the questions we
need to, and allowing ourselves to repeat it back to them so that we can both
make sure we haven’t missed something important out.
In the UK there may be more systematic issues that could be addressed
within our EDs that could allow us to see one extra patient a shift, before
thinking about scribes.
Chris: I have worked mainly in dual paper/electronic-based departments
though, so my opinion may change in the future as we see more electronic
medical record software take the forefront in the emergency department.
Scribes haven’t yet been evaluated in the UK as far as we know. However,
we do know that patients tolerate scribes well5 and that emergency doctors
really like working with scribes6 (85% don’t want to work another shift
without a scribe). We also suspect that the scribes learn a tremendous
amount that stands them in good stead for their future careers and we know
that they like being paid to undertake meaningful work at the bedside as an
embedded team member.
Ed – So Katie is obviously an advocate for scribes and we can see that in
the paper and commentary. As for Chris as an impartial reviewer, what’s
your bottom line?
Chris: I would certainly give scribes a go, to enable to me to see if it would
help my practice. It would be interesting to hear if anyone in the UK has
any experience of medical scribes as well! Let us know.
Katie: Thanks Chris. As an Australian researcher it’s really interesting to
her the UK view on our paper. If anyone is seriously interested in evaluating
scribes in the UK, I would be interested in partnering with them and helping
them get the study off-the-ground and delivered. I’d love to understand
whether scribes should be implemented in the NHS. You can contact me by
email at katie_walker01@yahoo.com.au
Chris (aka @graydoc) and Katie

Katie is an emergency physician at Cabrini Hospital, Melbourne; where she
is the director of emergency medicine research. She is an adjunct clinical
associate professor at Monash University. Her undergraduate degree was
from Bristol University, UK.
You can read more about this paper on Salim Reazzaie’s REBELEM blog
written by Melanie Stephenson (7_
Hate Using Electronic Hospital Records? An Evaluation of Medical Scribes
in Emergency Departments.
References
1. May N. JC: Time to Scribe? Introducing Scribes into the ED. St.Emlyn’s. https://www.stemlynsblog.org/jc-scribes-
ed/. Published May 23, 2014. Accessed February 21, 2019.
2. Bastani A, Shaqiri B, Palomba K, Bananno D, Anderson W. An ED scribe program is able to improve throughput time and
patient satisfaction. The American Journal of Emergency Medicine. May 2014:399-402. doi:10.1016/j.ajem.2013.03.040
3. Walker K, Ben-Meir M, Dunlop W, et al. Impact of scribes on emergency medicine doctors’ productivity and patient
throughput: multicentre randomised trial. BMJ. January 2019:l121. doi:10.1136/bmj.l121
4. Walker KJ, Ben-Meir M, Phillips D, Staples M. Medical scribes in emergency medicine produce financially significant
productivity gains for some, but not all emergency physicians. Emergency Medicine Australasia. March 2016:262-267.
doi:10.1111/1742-6723.12562
5. Dunlop W, Hegarty L, Staples M, Levinson M, Ben-Meir M, Walker K. Medical scribes have no impact on the patient
experience of an emergency department. Emergency Medicine Australasia. June 2017:61-66. doi:10.1111/1742-6723.12818
6. Cowan TL, Dunlop WA, Ben-Meir M, et al. Emergency consultants value medical scribes and most prefer to work with them, a
few would rather not: a qualitative Australian study. Emerg Med J. September 2017:12-17. doi:10.1136/emermed-2017-206637
7. Hate Using Electronic Hospital Records? An Evaluation of Medical Scribes in Emergency Departments. – REBEL EM –
Emergency Medicine Blog. REBEL EM – Emergency Medicine Blog. http://rebelem.com/hate-using-electronic-hospital-
records-an-evaluation-of-medical-scribes-in-emergency-departments/. Published February 21, 2019. Accessed March 1, 2019.
1. CATEGORY: #FOAMed, Administration, ED Management, Emergency Medicine, Human
factors, Technology
2. TAG: administration, CC15, CC25, CC8, FOAMed, scribes

Chapter 24
SHOULD WE CONTINUE
VENTILATIONS DURING RSI?
Over the last few years there has been much effort and a fair bit of
#FOAMed activity around ensuring that RSI in critical environments is as
safe and efficient as possible. Concepts such as first pass success(1),
apnoeic oxygenation(2–4), positioning(5), bougies(6,7) and more have all
aimed to promote safe practice. An overarching principle behind these
innovations and adaptations is the aim of preventing peri-intubation
hypoxia and hypotension.
Hypoxia is always a risk for our critically unwell patients. The RSI
sequence arguably promotes hypoxia through the use of paralytics that
cause apnoea. The apnoea between induction, to laryngoscopy, to
intubation, to then ventilation, make hypoxia likely in a group of patients
who are often difficult to pre-oxygenate, who have less physiological
reserve than the average routine theatre case and who may have excessive
oxygen demands (think agitated delirium(8)). Hypoxia is more common in
the ED and the ICU, and the consequences may be significant.
Why then do we stop ventilating during the apnoea phase of RSI?

For many years I have seen some of my colleagues routinely ventilate
patients at risk of desaturation in the time between induction and paralysis
taking effect. We typically do this using a Water’s circuit with a bit of PEEP
applied (that’s a Mapleson C circuit) which we use for pretty much all RSIs
in Virchester). In pre-hospital care there is a preference for the BVM as it
still works even if you lose your O2 supply. It’s done gently and carefully to
avoid gastric insufflation, but it’s always felt a little odd as we I was
originally taught that ventilating at this stage of the RSI was forbidden and
dangerous. Notably because it was felt that it could induce aspiration. On
the other hand there are the risks of desaturation, hypoxia and the associated
consequences of cardiovascular instability and potential end organ damage.
Thus the debate about whether ventilating the patient in the time between
induction and intubation has been controversial and debated for years(9–
12).
To get some clarity here, think of a patient who is already on the edge of
desaturation, the septic patient with pneumonia who is really struggling.
The best you can get their O2 is 95% before you start and they are clearly
working hard (with a presumed high O2 demand). Even with good apnoeic
oxygenation adjuncts, good pre-oxygenation and other first pass
optimisation techniques you know that this patient may well crash their O2
saturations on induction. Should you really stop ventilating that patient for
the 20-60 seconds it’s going to take for the paralytics to take effect PLUS
the time it then takes you to get an airway and then ventilate the patient?
Realistically this person may have a ventilatory pause of 60-120 seconds.
Hang on, they look a bit tricky to intubate too. Maybe that 120 seconds will
be an ambitious target……..
Does a prolonged ventilatory pause seem such a good idea now?

This week we have a paper that hopes to answer the question of whether
there are potential advantages, and also whether there are any potential
harms to ventilating a patient throughout the RSI induction
process. Published in the NEJM(13), the abstract is below, but as always we
strongly advise you to read the full paper, perform your own critical
appraisal and make your own mind up.
It’s a randomised controlled trial. As this is a study of an intervention this is
the best design to test this.

This study is a multicentre study of ICU patients in the US. Adults were
included in the paper who required endotracheal intubation in the ICU for
whatever reason. The common exclusions (such as pregnancy and
prisoners) applied.
What was the intervention?

Patients in the study group were ventliated using a bag mask valve (BVM)
with a PEEP valve in the interval between induction and laryngoscopy. The
control group did not receive ventilations. Ventilations were gentle (just to
see the chest rise) and at a rate of about 10/minute.
Interestingly in the UK we tend to use the BVM less and the Water’s circuit
more. The amount of PEEP applied using a Water’s circuit is a bit of an art
rather than a science and certainly does not allow a quantifiable value.
The rest of the RSI was not standardised and pretty much left to the
discretion of the physician, although there were few differences in terms of
medications used.
What were the outcomes?

The key outcome was the median lowest oxygen saturation (as defined by
an SaO2 of <90%) after induction and up to 2 minutes post intubation.
They also looked for any evidence of aspiration at laryngoscopy and from
looking at new opacities on the chest Xray within 48 hours of the
procedure.
What are the main results?
The authors recruited 401 patients into the trial. The patients were pretty
similar at baseline but there were statistically more patients with pneumonia
and GI bleeds in the no ventilation group. This may be important as
pneumonia patients are at particular risk of desaturation during induction.
Patients in the BVM group had more BVM ventilation pre induction as
compared to the non-ventilated group. Presumably because once enrolled
the airway operator in the BVM group would have had the device in their
hands and ready to go. It is unclear then if pre-induction BVM may have
influenced the results.
For the primary outcome of median lowest oxygen saturation then patient’s
did better in the BVM group with a median O2 sats of 96% as compared to
93% in the non ventilated group.
However, when I look at trials like this I am less interested in average
scores as to be honest if all patients stayed at >92% I’d probably be arguing
that it’s clinically not important. What I am interested in is the number of
patients who have significant desaturations during RSI.
There was more desaturation below 90% in the non ventilation group
(40.1%) as compared to the BVM group (29.5%). However, the image
below from the paper, and released on twitter is really the key to
understanding just how different the groups were.
The key point is the increased number of patients who have very significant
desaturations between the two techniques. The increased number of extreme
desaturations is, for me, the strongest argument of the paper and also a
reminder that looking at the raw data wherever possible and not just the
summary statistics is an important part of critical appraisal. If you prefer
your data as a bar chart then here you go.
Again, this data suggests that there were far fewer clinically significant
desaturations in the BVM group.
There were no increase in the number of complications (aspiration) in the
BVM group.
So we should all bag away with gay abandon during an RSI then?
There are always caveats. The data here is by far the best that we have so
far but we need to be thoughtful if we wish to adopt this. Patients in the
BVM group may have been more effectively pre-oxygenated (through use
of BVM) as much as by BVM in the apnoeic phase and this needs to be
taken into account, but personally I think that’s likely to be less of a factor.
The technique of BVM in this study was carefully applied and gentle. This
needs skill and care and is may not be in the skill set of all airway
practitioners (sorry, but it’s true). Face mask ventilation is not that easy
(although many people think it is). In this study a two person, two handed
technique was used and so it’s not just a case of putting a BVM on the face
and expecting similar results. Use of the Water’s circuit, as we do in
Virchester, raises the skill levels required even further.
In the UK we generally use Water’s circuits more often than BVM. On
those occasions when we do use BVM then we often don’t have PEEP
valves. Would we therefore get the same results with those technique
modifications as compared to the paper? Probably, but we don’t really
know. Personally I think that PEEP is probably as important as the
ventilation in these patients. PEEP maintains alveolar recruitment which
may be the key pathophysiological mechanism underpinning the difference
in the results.
I would strongly recommend, in fact I would insist that if you are thinking
of adopting this in your practice then you read the excellent blog by Josh
Farkas on the EMCRIT site(14). It gives an excellent explanation of this
trial and the underlying physiological principles. Please read this before
concluding your thoughts on this trial.
Finally, as an ED clinician it’s important to remember that these are critical
care patients and whilst they will share similar characteristics to the patients
I see in the ED, they are not quite the same.
Should we adopt this practice?

So in Virchester, for those patients in whom desaturation is a risk/concern,
and where some additional precautions are possible (e.g. head up
positioning) then I would advocate very gentle ventilatory support during
the period between induction and laryngoscopy.
Although this study used a BVM with PEEP valve I will continue to do this
using a Water’s circuit with a ‘bit’ of PEEP, during both the preoxygenation
and post intubation phases of RSI.
References
1. Sakles JC, Chiu S, Mosier J, Walker C, Stolz U. The Importance of First Pass Success When Performing Orotracheal
Intubation in the Emergency Department. Reardon RF, ed. Acad Emerg Med. January 2013:71-78. doi:10.1111/acem.12055
2. Semler MW, Janz DR, Lentz RJ, et al. Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the
Critically Ill. Am J Respir Crit Care Med. February 2016:273-280. doi:10.1164/rccm.201507-1294oc
3. Carley S. JC: Apnoeic Oxygenation (again). St.Emlyn’s • St Emlyn’s. St.Emlyn’s. https://www.stemlynsblog.org/jc-apnoeic-
oxygenation-again-st-emlyns/. Published August 16, 2017. Accessed February 20, 2019.
4. Caputo N, Azan B, Domingues R, et al. Emergency Department use of Apneic Oxygenation Versus Usual Care During Rapid
Sequence Intubation: A Randomized Controlled Trial (The ENDAO Trial). Miner J, ed. Acad Emerg Med. September
2017:1387-1394. doi:10.1111/acem.13274
5. Weingart S. EMCrit Podcast 226 – Airway Update – Bougie and Positioning. EMCrit Project. https://emcrit.org/emcrit/bougie-
and-positioning/. Published June 13, 2018. Accessed February 20, 2019.
6. Driver BE, Prekker ME, Klein LR, et al. Effect of Use of a Bougie vs Endotracheal Tube and Stylet on First-Attempt
Intubation Success Among Patients With Difficult Airways Undergoing Emergency Intubation. JAMA. June 2018:2179.
doi:10.1001/jama.2018.6496
7. Carley S. JC: Don’t blame it on the Bougie. St Emlyn’s • St Emlyn’s. St.Emlyn’s. https://www.stemlynsblog.org/jc-dont-blame-
it-on-the-bougie-st-emlyns/. Published May 20, 2018. Accessed February 20, 2019.
8. Gray C. Managing Acute Behavioural Disturbance • St Emlyn’s. St.Emlyn’s. https://www.stemlynsblog.org/acute-behavioural-
disturbance/. Published May 20, 2016. Accessed February 21, 2019.
9. El-Orbany M, Connolly LA. Rapid Sequence Induction and Intubation. Anesthesia & Analgesia. May 2010:1318-1325.
doi:10.1213/ane.0b013e3181d5ae47
10. Divatia J, Myatra S, Ahmed S, et al. The All India Difficult Airway Association 2016 guidelines for tracheal intubation in the
Intensive Care Unit. Indian J Anaesth. 2016:922. doi:10.4103/0019-5049.195485
11. Higgs A, McGrath B, Goddard C, et al. Guidelines for the management of tracheal intubation in critically ill adults. Br J
Anaesth. 2018;120(2):323-352. https://www.ncbi.nlm.nih.gov/pubmed/29406182.
12. Schwartz D, Matthay M, Cohen N. Death and other complications of emergency airway management in critically ill adults. A
prospective investigation of 297 tracheal intubations. Anesthesiology. 1995;82(2):367-
13. Casey JD, Janz DR, Russell DW, et al. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med.
February 2019. doi:10.1056/nejmoa1812405
14. Farkas J. PulmCrit: Is pure RSI a failed paradigm in critical illness? The primacy of pressure. EMCrit
Project. https://emcrit.org/pulmcrit/pressure-rsi/. Published February 19, 2019. Accessed February 21, 2019.
1. CATEGORY: #FOAMed, Emergency Medicine, respiratory, Resus & Crit Care, resuscitation
2. TAG: airway, anaesthesia, BVM, C3AP6, CC21, FOAMed, foamed. FOAMed, rsi, ventilation
Chapter 25
WHY DO BLEEDING TRAUMA

PATIENTS DIE?
Just a quick JC blog chapter to point you to an editorial written by Karim

Brohi and John Holcomb on why, and when, patients die of trauma. The
editorial appears in Intensive Care Medicine(1) and is currently open
access. As always we recommend you read the article yourself in order to
form your own opinion. It’s a short article, but well worth a read IMHO.
This is something I’ve chatted to Karim about several times over the last
year or so and it’s really interesting stuff. Firstly it’s important that we
recognise that we have seen a reduction in the number of deaths from
trauma. That’s a great thing of course, but we should not be complacent. It’s
also worth looking at where and how patients die. The key graph from the
editorial is shown below and is based on data from the Royal London
Hospital(2).
The data seems to be suggesting that changes to how we manage trauma
have altered where, and perhaps why people die.
Overall we are getting better at the resuscitation phases of trauma
management. Prehospital care improvements, such as the use of prehospital
blood3, has led to an increase in the number of patients reaching hospital
alive4. Improvements in our resuscitation practice, such as TXA5 and the
regionalisation of trauma6,7 seem to suggest a signifcant difference in
prehopsital deaths, but more people arriving in hospital alive means that a
greater number of patients die in the first few hours.
Improved surgical techniques and better surgical practice have resulted in

more patients reaching the ICU alive with fewer patients who survive the
first 3 hours dying on the first day and making it to the ICU.
However, getting to the ICU is not an end point for these patients. In this
editorial Karim and John show how we now have an increase in later
deaths. The data here is really interesting and perhaps surprising. Despite
patients arriving in the ICU in better condition than previously there are still
significant numbers of patients dying ‘late’ from complications of bleeding.
We now also know that the mortality from trauma laparotomy is essentially
unchanged for many years8,9, the new TELA study is specifically
addressing this10.
The editorial explores potential reasons for these late deaths. Describing a
complex mixture of cardiovascular failure in the first few hours or days and
leading to progressive requirements for inotropes and organ support. The
second group of deaths occurs later and is described as persistent
inflammation, immunosuppression and catabolism syndrome11,12.
It’s worth following the conversation on twitter too regarding this editorial
as others suggest potential mechanisms and reasons, but the bottom line is
that we don’t yet fully understand the mechanism of late death in many
patients.
What does this mean for us?
My first take home message from this paper is that we to remind ourselves
that it is trauma ‘systems’ that make a difference and that we need to
consider how changes in one area might impact another. The increase in
early hospital deaths is probably a result of improved prehospital care, and
is perhaps one of the reasons why the Royal London Hospital had terrible
outcomes reported by the TARN network for many years13. The RLH
received patients from London HEMS who were miles ahead of prehospital
practice as compared to the rest of the UK for many, many years. As a
result a greater number of patients arrived at RLH alive as compared to
other hospitals. My assumption is that TARN is unable to account for this
and so bizarrely may attribute better hospital scores to localities with less
advanced pre-hospital services.
In recent years we have perhaps been complacent about how trauma care
has improved with a significant focus on the early phases of the disease.
This editorial points out that there is still work to do in both understanding
the pathophysiology of trauma and also in the search for new solutions and
therapies that might reduce the number of late deaths.
References
1. Brohi K, Gruen RL, Holcomb JB. Why are bleeding trauma patients still dying? Intensive Care Med. February 2019.
doi:10.1007/s00134-019-05560-x
2. Rehn M, Weaver A, Brohi K, et al. Effect of Pre-Hospital Red Blood Cell Transfusion on Mortality and Time of Death in
Civilian Trauma Patients. SHOCK. April 2018:1. doi:10.1097/shk.0000000000001166
3. Lyon RM, de Sausmarez E, et al. Pre-hospital transfusion of packed red blood cells in 147 patients from a UK helicopter
emergency medical service. Scand J Trauma Resusc Emerg Med. 2017;25(1). doi:10.1186/s13049-017-0356-2
4. Griggs JE, Jeyanathan J, et al. Mortality of civilian patients with suspected traumatic haemorrhage receiving pre-hospital
transfusion of packed red blood cells compared to pre-hospital crystalloid. Scand J Trauma Resusc Emerg Med. 2018;26(1).
doi:10.1186/s13049-018-0567-1
5. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant
haemorrhage (CRASH-2): a randomised, placebo-controlled trial. The Lancet. 2010;376(9734):23-32. doi:10.1016/s0140-
6736(10)60835-5
6. Grayson A. Trauma in the UK, who cares? St Emlyn’s • St Emlyn’s. St.Emlyn’s. https://www.stemlynsblog.org/trauma-in-the-
uk-who-cares-st-emlyns/. Published December 31, 2018. Accessed February 13, 2019.
7. Moran CG, Lecky F, Bouamra O, et al. Changing the System – Major Trauma Patients and Their Outcomes in the NHS
(England) 2008–17. EClinicalMedicine. 2018;2-3:13-21. doi:10.1016/j.eclinm.2018.07.001
8. Marsden M, Carden R, Navaratne L, et al. Outcomes following trauma laparotomy for hypotensive trauma patients. Journal of
Trauma and Acute Care Surgery. May 2018:1. doi:10.1097/ta.0000000000001988
9. Harvin JA, Maxim T, Inaba K, et al. Mortality after emergent trauma laparotomy. Journal of Trauma and Acute Care Surgery.
2017;83(3):464-468. doi:10.1097/ta.0000000000001619
10. Carden R. What’s the bleeding problem with trauma laparotomies?! • St Emlyn’s.
St.Emlyn’s. https://www.stemlynsblog.org/whats-the-bleeding-problem-with-trauma-laparotomies/. Published December 28,
2018. Accessed February 13, 2019.
11. Mira JC, Brakenridge SC, Moldawer LL, Moore FA. Persistent Inflammation, Immunosuppression and Catabolism
Syndrome. Critical Care Clinics. 2017;33(2):245-258. doi:10.1016/j.ccc.2016.12.001
12. Efron PA, Mohr AM, Bihorac A, et al. Persistent inflammation, immunosuppression, and catabolism and the development of
chronic critical illness after surgery. Surgery. 2018;164(2):178-184. doi:10.1016/j.surg.2018.04.011
13. TARN – Main Hospital Details. Trauma Audit and Research Network. https://www.tarn.ac.uk/Content.aspx?
ca15&c=2897&hid=8003&pcid=3056. Published February 13, 2009. Accessed February 13, 2019.
1. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Prehospital Care, Resus & Crit
Care, Trauma
2. TAG: CC20, CMP3, Coagulopathy, FOAMed, HMP3, mortality, trauma, Trauma Research
Chapter 26
SHOULD WE PREMEDICATE FOR

KETAMINE SEDATION?
Here in Virchester we believe that we were early pioneers of conscious

sedation in the UK. It’s something we adopted as a routine procedure back
in the 90s, in both adults and children, and so over the years we have tried
to refine and adapt our techniques as the evidence changed. If you want to
read more about our philosophical approach to sedation in the emergency
department then you can read this blog and listen to the
podcast on the concept of ‘balanced sedation’.
One question that often arises is whether to give patients pre-treatment with
midazolam in order to smooth emergence and decrease side effects. In
children, and via the BestBets methodology we developed here our view is
that it probably does not work, but what about adults? I will admit that I did
go through a phase of using small doses of midazolam (1-2mg) before the
procedure, in particular when the patient appeared anxious. However, in
recent years I’ve used it less and less. I’ve also had the experience of
dealing with some really disturbing emergence phenomena. I remember
deciding to use ketamine for the sedation of an elderly patient with a
significant limb injury. All went well, but on recovery she became
psychotic, believing that she was dead and that we were all dying. It was
rather chaotic and distressing for all involved, so if there is something we
might do to avoid this then all the better.
This month there is a randomised controlled trial in the Annals of
Emergency Medicine that addresses this question, not only looking at the
use of midazolam as a pre-treatment, but also in the use of haloperidol in
patients undergoing ED ketamine sedation. The abstract is below, but as we
always say, please read the full paper and make up your own mind about the
strength of the evidence.

It’s an RCT which is entirely appropriate. We are looking at an intervention
and so an RCT is the best design.
What did they do?
Patients over the age of 18 undergoing procedural sedation were recruited.
There is a long list of entirely reasonable exclusions for the study, although
interestingly there are a lot of patients in the list who I still use ketamine
with – e.g. hx of alcoholism). This is a single centre study in a relatively
small US emergency department. Patients were randomised using block
randomisation, and then I think an envelope sequence of packs to dictate the
next allocation with prepacked syringes of either haloperidol, placebo, or
midazolam in blinded syringes, together with an unblinded syringe of
ketamine.
The premeds were given five minutes before the ketamine which is a
reasonable length of time to ensure that they would have had an effect. The
ketamine dose was standardised at 1mg/kg which is a fairly robust dose for
sedation in my opinion (my practice is to titrate to effect), but it’s in keeping
wth standard recommendations. However, I wonder if some patients may
have received more ketamine than they need as midazolam or concurrent
analgesia may reduce the required ketamine dose.
What were the outcome measures?
So the key points here were the use of the Richmond Agitation Score at 5,
10 and 50 mins post ketamine, and then the Pittsburgh Agitation
Score (PAS) during recovery which seems to be used in a variety of settings
notably dementia(?).
And the main results?
They randomised 185 patients in total, with pretty good follow-up as you
would expect in a trial that takes place entirely within the ED. 185 is a
pretty small number for a three-armed trial. The power calculation was
based on a five-fold decrease in the incidence of agitation at a score of 3 on
the PAS. A score of 3 is defined in the paper as disruptive behaviour though
if you look at the scoring system it’s arguably a fairly low level (as the PAS
goes from 0-16) There were no major differences between in the groups in
statistical terms, but with small numbers it’s difficult to tell.
In terms of sedation as measured on the RASS score the results suggest that
patients with placebo were less sedated and sedated for less time. Indeed
recovery time was significantly longer in the haloperidol and midazolam
groups. Recovery time for placebo was 18 mins on average compared to 35
mins for midazolam and 50 mins for haloperidol (Ed – wow!). That’s a big
difference in recovery times in my opinion. An important point if you are
thinking about doing this.
In terms of agitation then the authors state that there is less agitation in the
midazolam and haloperidol groups, and that looks to be the case. Agitation
scores were only really seen in the placebo group with a median of 3 and an
IQR of 0-5 (so still fairly low). Interestingly the overall level of agitation as
defined in the study was just under 64% in the placebo group vs 25% for
midazolam and 20% for haloperidol (defined as a PAS>2). This outcome is
the one used for their power calculation. Clinician satisfaction was the same
with all agents.
I do find it interesting to reflect on how we commonly report studies of this

type where analysis is often targeted at differences in average scores.
Arguably this is less important than looking at the number of patients who
have very severe reactions. It’s a similar argument in studies about average
pain scores, where I might be more interested in reducing the number of
patients with severe pain as opposed to very small (arguably
inconsequential) differences in average scores. In this study that finding is
there in the adverse events data where there was a 10% risk of severe
agitation (PAS>8) in the placebo group, but no severe agitation in the
others. That’s an interesting finding, but the number is small and does not
reflect my experience in using ketamine in the ED.
Any limitations?
The authors do a fair job in highlighting the limitations of this study. It’s a
small single centre study which is always a bit of an issue with
generalisability. The RCT design is good, but I wonder how effective the
blinding will have been with the very different emergence times recorded
(after a while I think we could have worked out who had placebo as they
would have recovered far faster). The reported changes in agitation are
interesting, but seem rather higher than in my practice which perhaps
reflects the threshold of what was considered a significant change on the
PAS (a score of 3 being regarded as important). I am interested in the
apparent higher number of severe agitations in the placebo group, but the
data here is not conclusive.
We would also look at the 60 min limit on data collection. Although this
seems a long time it is pretty close to the average sedation time for
haloperidol and so it might be possible that some patient outcomes may
have occurred after data recording stopped.
What is really missing is the patient perspective. Does it matter if the
patient is a bit agitated on emergence but that they have no memory of it?
We can’t decide in this study, but my experience is that ketamine is a
fabulous amnesic agent and so we may be pursuing something that does not
matter from a ‘patient orientated outcome’ perspective. The PAS is a
measure of expressed emotion/distress which may not be the same as the
patients’ experienced emotion/distress. This is a subtle but important
distinction that should be addressed in future trials
So what’s the bottom line?
This is a good paper, it’s a good design and the patients are seemingly
similar to those in my practice, but is it enough for us all to adopt midaz or
haloperidol? I’m not so sure at the moment. It’s important that we weigh up
the potential for less agitation against the much longer recovery times.
However, there may well be a group of patients whom I might feel are at
risk of emergence phenomena where I might think that trade off is worth it.
Paradoxically though, those might well encompass many of the patients
who were excluded from inclusion in this trial. Such are the difficulties and
vagaries of trying to practise EBM.
So well done to @pooya_mehr and co-authors for moving the evidence on.
I agree with them that larger and multicentre studies would help clarify
those questions that remain.
References
1. Balanced Sedation in the ED. St.Emlyn’s http://www.stemlynsblog.org/balanced-sedation-in-the-ed-st-emlyns/
1. Midazolam use in children undergoing ketamine sedation to reduce emergence reaction https://bestbets.org/bets/bet.php?
id=3044
1. Richmond Agitation Score https://www.mdcalc.com/richmond-agitation-sedation-scale-rass
2. Pittsburgh Agitation Score https://www.researchgate.net/publication/230557061_The_Pittsburgh_Agitation_Scale_A_User-
Friendly_Instrument_for_Rating_Agitation_in_Dementia_Patients
1. Premedication With Midazolam or Haloperidol to Prevent Recovery Agitation in Adults Undergoing Procedural Sedation With
Ketamine: A Randomized Double-Blind Clinical Trial.Akhlaghi N1, Payandemehr P2, Yaseri M3, Akhlaghi
AA4, Abdolrazaghnejad A5. https://www.ncbi.nlm.nih.gov/pubmed/30611640
1. JC: Intranasal Ketamine vs. Fentanyl for kids. St. Emlyn’s https://www.stemlynsblog.org/jc-intranasal-ketamine-vs-fentanyl-
for-kids-st-emlyns/
2. JC: K is Good For You – Subdissociative Ketamine vs Morphine in the ED https://www.stemlynsblog.org/jc-ketamine/
1. JC: Is Ketofol worth the hassle? St.Emlyn’s https://www.stemlynsblog.org/jc-is-ketofol-worth-the-hassle-st-emlyns/
2. Is Ketofol the milk of human kindness for procedural sedation. St.Emlyn’s https://www.stemlynsblog.org/ketofol-milk-human-
kindness-procedural-sedation-st-emlyns/
1. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Pain, Resus & Crit Care, Sedation
2. TAG: agitation, C3AP6, CC20, CC21, CC3, FOAMed, haloperidol, journal

club, ketamine, midazolam, sedation
Chapter 27
PULMONARY EMBOLISM,
AMBULATORY CARE AND THE
GODDESS OF THE HUNT
This post covers a talk I was asked to give at the recent RCEM CPD
conference in Belfast. A great event, and well hosted in spite of the LOC
chair becoming indisposed by imminent fatherhood.
Background
I was asked principally to talk about the new British Thoracic Society
guidelines for the outpatient management of pulmonary embolism (1) , but
thought I would add a dusting of NICE guideline revision and a few
cherries of recent literature, which should all directly impact how we
provide care to these patients.
Why are we talking about this? Well, PE lends itself very well to the topic
of ambulatory care. It is a potentially serious condition with significant
morbidity and mortality, and it often presents insidiously. So we think about
it. And we look hard for it. And this is good. But our increasing vigilance in
tandem with better scanners, keener radiologists and patient awareness has
resulted in a dilute pretest probability of around 5%. So we need to think
carefully about how we balance resource use and time. And what we hope
to achieve through hospital admission. That’s why it’s one of the top 5
conditions on the RCEM ambulatory toolkit (2) .
Emergency Medicine has been ahead of the game here I think. This paper
was published in Manchester 3 back in the days when I was an F3 just
scratching my chin about the idea of a career in EM. The authors ambulated
425 patients with suspected PE attending the ED, with disease confirmed in
5% and an adverse event rate of <0.5%. How did you get on the pathway?
HR <100 RR <20 SPO2 >95%. Simples.
There are lots of other options now. What do you do? Do you ambulate
suspected disease? Do you ambulate confirmed disease? How do you
decide? Are you confident in your pathway?
New guidelines
The British Thoracic Society noted variation in the management of this
disease back in 2015 and felt a consensus multispecialty guideline would
add value. They went about it well I think, inviting representation from the
Society of acute medicine, RCEM, British Society of Haematology and
,many others including NICE methodologists. They also had the advantage
of not being quite as hamstrung by randomised trial and economic data as
NICE can be. The concept was to provide an evidence review and best
practice consensus to support outpatient management with associated
quality standards.
What is it not? This is not a diagnostic pathway. The NICE CG144 update
released later this year will I suspected cover PERC, age adjusted d-dimer
and all the other things that are crying out for national guidance. It is also
not entirely about ambulatory care; there are sections here that refer to
PESI48 4 and the idea of early discharge after a short period of inpatient
care. It is also not a pathway for someone who worries you. I am a big fan
of guidelines guide and clinicians decide, and you are the latter. If you think
someone does not tick the box for ambulatory care but you can’t quite put
your finger on why, then they don’t tick the box.
The guideline tries to embed this logic in the exclusion criteria. These are
obvious but important. I for one am certainly seeing increasing problems
with reluctance to admit patients where ambulatory care is feasible, even if
they are sick or complex. These criteria offer a good line of defence against
the overzealous medical registrar.
Key issues – risk stratification

What are the big take home points from this guideline? Well the first
concerns risk assessment. This is the HOLY GRAIL OF VTE CARE if you
like; a complex disease that can range from the probably doesn’t need any
treatment, to the immediately life threatening, with very little in the way of
physiological derangement in between. We need some help to decide where
people sit on this spectrum.
How can we risk assess? Multiple scores have now been externally
validated in data on >40,000 patients 5 . It is worth highlighting that these
scores are different, but most have been designed to identify patients at
higher risk of death, recurrence or haemodynamic collapse. As such they
are screen in tools, assuming that the default is ambulatory care. This is ok
provided you understand the design. The commonest tools in use are
the PESI 6 , SPESI and HESTIA 7 score. A low risk on any of these scores
reduces the chance of adverse events to <2%.
The first thing to ask with regard to prognostic scoring systems, is whether
they add value to gestalt. Surely I can decide who is low risk and who is
high? Surely you can? Well, there is some emerging literature on the
variation in gestalt by grade and interest. Sure enough, it’s been looked at
for ambulatory PE within this paper from 2017 8 . Here we see the SPESI
outperform all clinicians across multiple attending and registrar grades with
regard to sensitivity at ruling out a poor outcome. We also see a variety in
low risk classification ranging from 20 to 40%. We can’t all be right….
The second thing to ask is if scores are good, then which score is best? This
is a bit more goldilocks. PESI is complex but ordinal, and so can provide
information on low risk, while also identifying those at higher risk for
complication. SPESI is simple and dichotomous, with good prognostic
characteristics but includes cancer as a variable that limits application to a
degree. HESTIA purports to identify more patients as low risk, but again is
dichotomous and has less external validation. There are papers like this one
comparing 2 scores in small cohorts 9 , but no definitive evidence of
superiority. The take home from the guideline is that any of these options
are reasonable, as long as they are used in the manner intended and with
insight into the pro’s and cons.
Key issues – advanced prognostic markers.

We don’t just have scores though. We have a plethora of advanced
prognostic tools at our twitchy and tech loving fingertips. Want
biomarkers? BNP 10 , NT BNP 11 , trop and HS trop for you madam. Want
RV imaging? Perhaps some CT RV:LV ratio data 12 , focussed echo 13 or
PAP estimation sir. Want bleeding risk scores? I recommend HASBLED 14
or VTE bleed 15 to while away the rest of your evening….
But does any of this add benefit? David Jiminez has looked fairly
extensively at the cumulative value of prognostic information; his study
from 2014 suggests that SPESI outperforms the vast majority of these tests
16 . Essentially, with a validated score you are reducing the chances of an
adverse event to <2%. Additional markers of PE severity may perhaps
further reduce this risk, although potentially at the cost of reducing the
number of overall patients suitable for outpatient management with only
minimal further risk reduction. Further measurements may also add to time
and cost. Are you sure you want the second course??
It is worth a specific mention that several of the respiratory physicians on
this guideline felt negative biomarkers may have a role to play in
identifying a small subset of patients who have PE and signs of RV strain
on CT, but are still safe to consider ambulatory care. This is pretty
individualised I think. It would certainly take an interesting set of
circumstances for me to send home anyone with RV strain on the day of
diagnosis.
Key issues – treatment and follow up

We should tackle follow up first really as it’s an interesting and under
researched area. Whilst we are good at conducting research which proves
ambulatory care in certain conditions does not kill people, we tend to be
very bad at studying what information and support needs patients actually
have. However, if we are going to believe the evidence here and apply it
appropriately, then it seems clear we need to model the pathways within the
trials.
What did the original and applicable randomized trials do? Quite a lot
actually. The Aujesky 17 and Beam studies 18 provide some good data
here, discharging patients with written and verbal guidance on the risks of
recurrence, major bleeding and other adverse events. But not only this; they
ensured routine follow up within the first week either by face to face
appointment or by phone contact. Think about the value of this. How are
you feeling? Are you taking your meds? Have you had any bleeding? Are
you more breathless? Do you know who to call or where to come if you
have a problem? This type of early safety netting and follow up is vital for
expedient ambulatory care, and as such is endorsed within this guideline.
And then there is treatment. What should we use in suspected disease?
What should we use in confirmed? What should we use in cancer patients?
Well, this guideline is the first to endorse the use of a single agent DOAC
pathway in the first 2 situations. If your hospital is anything like mine, I am
sure there has been resistance to the idea of prescribing DOACs for patients
with suspected disease. I have heard all combinations of licensing,
compliance, reversibility and adverse event concerns. The same criticisms
can easily be made of any form of LMWH. DOAC agents are now cheaper
(in the short term) and arguably more effective in straightforward cases than
other forms of anticoagulation. A recent SR/MA published in blood 19
looking specifically at their performance in treatment of VTE, suggests the
Factor Xa DOAC agents have a lower rate of major bleeding, Intracranial
bleeding and fatal bleeding, with non inferior rates of VTE recurrence. Not
bad for a few pills, when previously we required a series of injections and a
district nurse.
What about DOACs compared to LMWH though? That’s what we have
always used in suspected disease? Well, I would suggest that whenever you
compare 2 treatments for a condition where 95% of patients do not actually
have the condition, you’ll be unlikely to definitively prove any result. As
such we just won’t get data on suspected disease. However, given it’s
supposed improved clinical effectiveness in cancer patients, there is now
data comparing LMWH to DOACs in this group for treatment of confirmed
VTE. A SR/MA by a Canadian team published this year 20 suggests the
balance is a bit trickier, with lower rates of recurrence on DOAC therapy,
but higher rates of bleeding. Not clear really.
As such, we need to look at practicality, cost, convenience. I think the take
home is that there are multiple options. Offer your patients the choice. But
remember the concerns and contraindications. And if you want to use a
single agent DOAC pathway, your choice in suspected disease is limited to
rivaroxaban, apixaban. The others require a 5 day LMWH lead in.
Key issues – special circs

Worth a nod to the specialist group comments within this guideline, which
highlight a few key differences. Intravenous drug users are determined to be
a higher risk group overall, both regarding compliance and risk for
recurrence. As such an inpatient pathway is recommended.
Cancer patients are noted to be at slightly higher risk overall, and it should
also be noted that SPESI automatically excludes everyone with cancer –
therefore you might want to use HESTIA in this group to stratify risk. The
mortality with cancer patients is significantly higher and that puts some
people off the idea of ambulatory care in general. But I think I would ask
you what you hope to achieve by admitting these patients to hospital. Is it
for their benefit? Or for yours? Probably one for shared decision making.
Lastly, this is the first guideline I have seen that is clear about the fact that it
still applies to pregnant patients. This is a real step forwards. Often, these
patients are excluded from trials and guidelines using the rationale of safety
and concerns on generalisability of the evidence. What this unfortunately
leads to is an evidence free zone of people doing whatever they please. The
committee were keen that pregnant patients could be offered the
opportunities associated with outpatient care, but with reference to the
caveats. First – risk scores cannot be applied to this group. Second – DOAC
agents are contraindicated in this group. Third – MDT discussion should be
encouraged, with regard to shared obstetric and haematology services.
The hunt is on (for the needle in the haystack)

Whilst we’re talking about suspected PE in pregnancy, it would be remiss
of us not to highlight the recent progress in the literature. March 2019 saw
the publication of ARTEMIS in the New England Journal of Medicine 21 ;
this followed the HTA funded Diagnosis of PE in Pregnancy (DIPEP)
project 22 , published across a variety of haematology and obstetric journals
last year; this followed Marc Righin 23 i’s earlier study in Annals of
Internal Medicine and this followed lots of smaller studies and clinical
practice reviews 24 . We must have the answer by now? Unfortunately not –
these studies offer conflicting conclusions.
ARTEMIS was a multicentre prospective observational cohort study
looking at 498 patients with suspected PE in pregnancy. These women were
managed according to a pregnancy adjusted YEARS algorithim, which is a
decision tool containing only 3 dichotomous variables – haemoptysis, signs
of DVT and is PE the most likely diagnosis? After this you applied a
probability adjusted cutpoint to your d-dimer level. Patients with a d-dimer
below the individualized cutpoint were discharged without imaging. This
strategy avoided CTPA in somewhere between 30-60% patients, no PEs
were seen during 3 month follow up and a composite VTE event rate
overall of 0.21% was noted, with a conclusion that this algorithm appeared
safe and effective.
DIPEP was quite different. This was an observational cohort with added
positive cases from UK Obstetric Surveillance Service. Approx 300 cases
were prospectively recruited with supplemented cases of positive VTE.
Only 6.5% of these patients were in the first trimester, compared to double
that in ARTEMIS. The results from this study were less positive about the
roles of clinical prediction or biomarkers; no prediction rule could be
gleaned from the data and no biomarker exceeded an AUROC value of 0.7.
The conclusions supported going straight to imaging without any messing
around.
Interesting stuff. Why the disparity? Well, I suspect it’s a combination of
low pretest probability, inclusion criteria, confounding and gestalt. The
studies are quite different really. There are very few patients in the first
trimester within DIPEP, whereas ARTEMIS highlights that this group are
exactly where the highest efficiency of their algorithm was found. This
discrepancy in results doesn’t really solve the problem, but does provide a
further evidence base that you can look at in light of your current practice
and lab assays. Personally, I am buoyed on by ARTEMIS; I think it
probably highlights a group where gestalt is low who are suitable for d-
dimer measurement. DIPEP reminds us that if you need to image or have
any doubts/concerns – get on and do a CTPA. The background radiation is
not as terrifying as we have always suspected.
How does this all help

I am sure many of you have been ambulating PE for years. But these
guidelines and this recent literature provide support to some of the greyer
areas and create national templates to support delivery of care that you
know is right, but have been struggling to deliver. I think the key areas are
as follows:
1. There is now clear guidance supporting the use of risk scores and which
ones are preferable
2. Clear exclusion criteria to defend a decision to refer for inpatient care
3. First guideline to advocate a single DOAC pathway as an option; this will
help you with your medicines management committees.
4. First guideline to even suggest that ambulating pregnant patients is an
option, although complex as we have seen.
5. First guideline to provide a template for follow up care
Quality standards are coming that will lend further support to development
in this area. Need buy in, funding, staff or resources to deliver any of the
above? Lever this national guidance and quality standards to get it.
Anything else to add?

There’s lots of other stuff out there to look at. NICE guidelines will be out
for consultation this summer. More literature will come I am sure. And the
BTS guidelines will drive care, which will create a lot of quality
improvement work. Look at the papers highlighted above and try the
following resources below if you want more.
RCEM learning
Thorax article – who to thrombolyse and who to discharge 25
Hope that helps. Good luck with your ambulating. Let these guidelines help
you; but don’t let anyone tell you what to do. You are the clinician. You
decide.
References
1. Howard LS. BTS guidelines for the initial outpatient management of pulmonary embolism: there’s no place like home. Thorax.
June 2018:607-608. doi:10.1136/thoraxjnl-2018-211646
1. RCEM Guidance – Ambulatory Care. RCEM . https://www.rcem.ac.uk/RCEM/Quality-
Policy/Clinical_Standards_Guidance/RCEM_Guidance.aspx?WebsiteKey=b3d6bb2a-abba-44ed-b758-
467776a958cd&hkey=862bd964-0363-4f7f-bdab-89e4a68c9de4&RCEM_Guidance=3. Published 2019. Accessed April 20,
2019.
1. Hogg K. Outpatient diagnosis of pulmonary embolism: the MIOPED (Manchester Investigation Of Pulmonary Embolism
Diagnosis) study. Emergency Medicine Journal. February 2006:123-127. doi:10.1136/emj.2005.027110
2. Moores L, Zamarro C, Gómez V, et al. Changes in PESI scores predict mortality in intermediate-risk patients with acute
pulmonary embolism. Eur Respir J. June 2012:354-359. doi:10.1183/09031936.00225011
3. Elias A, Mallett S, Daoud-Elias M, Poggi J-N, Clarke M. Prognostic models in acute pulmonary embolism: a systematic review
and meta-analysis. BMJ Open. April 2016:e010324. doi:10.1136/bmjopen-2015-010324
4. Pulmonary Embolism Severity Index (PESI) – MDCalc. MDCALC. https://www.mdcalc.com/pulmonary-embolism-severity-
index-pesi. Published 2019. Accessed April 20, 2019.
5. Simplified PESI (Pulmonary Embolism Severity Index) – MDCalc. MDCALC. https://www.mdcalc.com/simplified-pesi-
pulmonary-embolism-severity-index. Published 2019. Accessed April 20, 2019.
6. Jiménez Castro D, Barrios D, Morillo R, Nieto R, Guerassimova I, Gomez V. Clinical gestalt and the prognosis of pulmonary
embolism. In: Pulmonary Circulation and Pulmonary Vascular Disease. European Respiratory Society; 2017.
doi:10.1183/1393003.congress-2017.pa2357
7. Crobach MJT, Dolsma A, Donker ML, et al. Comparison of two methods for selection of out of hospital treatment in patients
with acute pulmonary embolism. Thromb Haemost. 2013:47-52. doi:10.1160/th12-07-0466
8. Coutance G, Le Page O, Lo T, Hamon M. Prognostic value of brain natriuretic peptide in acute pulmonary embolism. Critical
Care. 2008:R109. doi:10.1186/cc6996
9. Coutance G, Le P, Lo T, Hamon M. Prognostic value of brain natriuretic peptide in acute pulmonary embolism. Crit Care.
2008;12(4):R109. https://www.ncbi.nlm.nih.gov/pubmed/18721456.
10. Ghuysen A. Computed tomographic pulmonary angiography and prognostic significance in patients with acute pulmonary
embolism. Thorax. November 2005:956-961. doi:10.1136/thx.2005.040873
11. Pavlidis A, Kallistratos M, Karamasis G, et al. Diagnosis and risk stratification in acute pulmonary embolism: the role of
echocardiography. Rev Cardiovasc Med. 2013;14(1):56-65. https://www.ncbi.nlm.nih.gov/pubmed/23651987.
12. Kooiman J, van Hagen N, Iglesias del Sol A, et al. The HAS-BLED Score Identifies Patients with Acute Venous
Thromboembolism at High Risk of Major Bleeding Complications during the First Six Months of Anticoagulant Treatment.
Garcia de Frutos P, ed. PLoS ONE. April 2015:e0122520. doi:10.1371/journal.pone.0122520
13. Barco S, Konstantinides S, Klok F. External validation of the VTE-BLEED score for predicting major bleeding in stable
anticoagulated patients with venous thromboembolism. Thromb Haemost. 2017:1164-1170. doi:10.1160/th16-10-0810
14. Jiménez D, Kopecna D, Tapson V, et al. Derivation and Validation of Multimarker Prognostication for Normotensive Patients
with Acute Symptomatic Pulmonary Embolism. Am J Respir Crit Care Med. March 2014:718-726. doi:10.1164/rccm.201311-
2040oc
15. Aujesky D, Roy P-M, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an
international, open-label, randomised, non-inferiority trial. The Lancet. July 2011:41-48. doi:10.1016/s0140-6736(11)60824-6
16. Beam DM, Kahler ZP, Kline JA. Immediate Discharge and Home Treatment With Rivaroxaban of Low-risk Venous
Thromboembolism Diagnosed in Two U.S. Emergency Departments: A One-year Preplanned Analysis. Hiestand BC, ed. Acad
Emerg Med. June 2015:788-795. doi:10.1111/acem.12711
17. Li A, Garcia DA, Lyman GH, Carrier M. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for
treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thrombosis Research. January
2019:158-163. doi:10.1016/j.thromres.2018.02.144
18. Li A, Garcia D, Lyman G, Carrier M. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for
treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res. 2019;173:158-
19. van der Pol LM, Tromeur C, Bistervels IM, et al. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected
Pulmonary Embolism. N Engl J Med. March 2019:1139-1149. doi:10.1056/nejmoa1813865
20. Goodacre S, Horspool K, Shephard N, et al. Selecting pregnant or postpartum women with suspected pulmonary embolism for
diagnostic imaging: the DiPEP diagnostic study with decision-analysis modelling. Health Technol Assess. 2018;22(47):1-
21. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of Pulmonary Embolism During Pregnancy. Ann Intern Med. October
2018:766. doi:10.7326/m18-1670
22. Simcox LE, Ormesher L, Tower C, Greer IA. Pulmonary thrombo-embolism in pregnancy: diagnosis and
management. Breathe. December 2015:282-289. doi:10.1183/20734735.008815
23. Condliffe R, Elliot CA, Hughes RJ, et al. Management dilemmas in acute pulmonary embolism. Thorax. December 2013:174-
180. doi:10.1136/thoraxjnl-2013-204667
1. CATEGORY: #FOAMed, Acute Medicine, Ambulatory Care, Clinical Guidelines, Emergency

Medicine, Research, thromboembolism
1. TAG: CAP6, CAP7, CC1, CC21, CC5, FOAMed, pulmonary embolus, thromboembolism
Chapter 28
DO YOU SEE THE LIGHT?

SERUM NEUROFILAMENT
LIGHT CHAIN FOR
PROGNOSTICATION
FOLLOWING OOHCA
I’ve been meaning to do a blog on this paper for some time now. Paul
Young, who’s opinion I have a lot of time for, seemed clearly excited about
its release. And in December at the ICSSOA 2018 Celia Bradford selected
it as one of her top 5 neuro papers of the year. It also got a cheeky nod from
Alasdair Proudfoot in the top 5 cardiovascular papers. Evidence enough that
people are sitting up and taking notice.
This attention is not surprising when the paper concludes that “(serum
neurofilament light chain) performs better (at predicting neurologic
outcome after cardiac arrest) than other biochemical, clinical, neuroimaging
and electrophysiological methods.” This is quite the claim. And it is a claim
regarding an area that we all struggle with. Neuroprognostication following
cardiac arrest has changed over recent years; we all want to be clear about
who has any chance of a good outcome, and who doesn’t, but this is not
black and white. What does a ‘good outcome’ mean to you, and what does
it mean to your patient? What does a ‘trial of therapy’ mean? What duration
of time is enough to be confident in your prognosis of a poor outcome, in
those failing to improve? And are you sure this is a good use of the
bed/staff/morale/equipment when the chances of survival are down to the
low single digits?
Any paper like this which seems to offer us a dichotomous objective test to
inform this type of tricky decision making is always going to be very
attractive to clinicians. Our moral compass can point straight and true if we
withdraw life sustaining treatment because the test told us to do it. As such,
we have an immediate issue that we want this test to be a good one. That
affects the way we read the paper. There is a risk of focussing effect,
anchoring and/or confirmation bias.
Luckily St Emlyns is on hand for you to break it down. Although let’s
remember, as a neurointensivist, I am likely to be biased in my appraisal.
But I’ll try not to be.
As always, we would recommend downloading this paper and reading it in
full. I don’t think this is FOAMed in the classic sense, but this really is one
worth the hassle of dropping your librarian an email. Other summaries can
be found here if you already think I’ve been going on for too long.
Tell me about the paper.

This is essentially an international multicentre prospective observational
cohort study of 717 patients presenting with ROSC after cardiac arrest, who
had serum biomarkers collected at several intervals and underwent
protocolised neuroprognostication if still comatose at 108 hours post arrest.
The authors then describe follow up data at 6 months using the Cerebral
Performance Scale, dichotomised to a good (CPC 1 or 2) and bad (CPC 3,4
or 5). Prognostic test characteristics are then described, such as the
sensitivity, specificity and PPV of this test to predict a bad outcome.
What on earth is serum neurofilament light chain (NFL)

That’s a good question. Took me right back. Light chains are proteins
produced by plasma cells. NFL appears to be a major protein component of
the neuroaxonal cytoskeleton, providing structural support for axons and
regulating diameter, which influences conduction velocity. In axonal
damage, these proteins are released into CSF and subsequently peripheral
blood. Early pilot work started looking at NFL levels in CSF through
lumbar puncture. This current work centres on the theory that serial LPs are
inconvenient and introduce risk, therefore serum NFL could offer a more
practical and reproducible way of assessing axonal injury after cardiac
arrest.
It is worth highlighting that NFL appears to be a general biomarker for
axonal injury – work is ongoing to look at clinical relevance in multiple
other disease states, including multiple sclerosis. A troponin of the brain, if
you will. And troponin, as we know, can be released due to a variety of
myocardial infarction states depending on the underlying pathological
process.
Is this a new study

No. Let’s be clear about that from the outset. This is a subset of patients
from the previously published randomised controlled TTM trial, who had
serum samples sent to a biobank. These patients were recruited between
2010 and 2013. With 6 months follow up, one wonders why it took 4 years
to write up and publish these data. The TTM lead authors are on the paper,
so clearly have approved the analysis. I couldn’t find any mention of this
study in the prespecified analysis plan for the TTM trial, but that may be an
issue to do with tech development?
Who were the patients?

TTM recruited out of hospital cardiac arrest patients who remained
unconscious on arrival to hospital. Their specific inclusion and exclusion
criteria can be found here – it is of specific note that TTM excluded the
following patients:
1. Obvious or suspected pregnancy
2. Known bleeding diathesis (medically induced coagulopathy (e.g.
warfarin, clopidogrel) does not exclude the patient).
3. Suspected or confirmed acute intracranial bleeding
4. Suspected or confirmed acute stroke
5. Unwitnessed cardiac arrest with initial rhythm asystole
6. Known limitations in therapy and Do Not Resuscitate-order
7. Known disease making 180 days survival unlikely
8. Known pre-arrest Cerebral Performance Category 3 or 4
9. >4 hours (240 minutes) from ROSC to screening
10. Temp <30C on admission
11. Systolic blood pressure < 80 mm Hg in spite of fluid
loading/vasopressor and/or inotropic medication/intra aortic balloon pump
As such any results from this subgroup analysis are not generalizable to
these populations above. This is a particularly depressing point for those of
us working in neuro centres, as it seems that anyone with a significant brain
injury of any kind would have been excluded. As such, we don’t have any
idea about what serum NFL tells us in these situations.
360 patients (50.2%) had a poor neurologic outcome at 6 months as per
their prespecified definition.
What did they do?

All patients recruited to the biobank arm of the study were supposed to have
serum NFL samples sent at 24, 48 and 72h post ROSC. Of 963 recruited to
TTM, 819 were engaged in the biobank arm, 782 patients were deemed
eligible for this study and then for some reason only 717 samples were
available for NFL analysis. The authors report 65 exclusions for sample
problems or missing outcome data, but don’t really tell us what happened to
the other 181 patients.
They compared different levels of serum NFL against 6 month outcome as
planned, and then also against other tools used for prognostication. These
other tools included currently available biomarkers, neuroimaging,
electroencephalography and somatosensory evoked potentials.
Outcome was determined by CPC score as noted, but it is worth considering
the neuroprognostication protocol within the TTM trial so we can be clear
about how this was done. Essentially, this supported initial targeted
temperature management with mandatory sedation (at either 33 or 36
degrees C depending on randomisation) for 28 hours, followed by cautious
rewarming at 0.5degrees C per hour until back to 37, tapering/cessation of
sedation at 36h and then fever control (<37.5 degrees C) for a total of 72h
post ROSC. At this stage, a blinded physician performed a clinical
assessment of those patients who remained unconscious and a decision on
WLST was taken clinically, but supported by a variety of criteria as listed in
the supplementary appendix. Ongoing care was at the discretion of the
clinical treating team.
How did they plan to analyse the data?

The authors wanted to look at specificity primarily, with the rationale that a
false positive test in this situation (a raised biomarker predicting futility
when actually the patient might have survived) would be the worst possible
result. In other words, they wanted to rule in a poor outcome (SpIN) – ‘if
the biomarker is high, you are likely to die. If the biomarker is low, then
onwards we go’. I suppose this fair is enough, but then they decided to
report cut points that would provide specificities between 95-100%. As
soon as we drop from 100 here, we are starting to see false positives.
Bearing in mind that this test is taken early on in the disease process, this
makes me anxious.
There was also no sample size calculation and there was lots of talk of
comparison and regression models in this section. However, we should bear
in mind that these analyses could only be performed in patients who had the
additional tests (which was always clinician directed and not 100%). So the
additional analyses are only hypothesis generating really.
What were the results

First off, not everyone had the relevant serum NFL levels and so data is
reported on all patients but with >5% of cases missing 2 timepoint
measurements. But the first headline is that serum NFL was significantly
higher at all three intervals in those patients with a poor outcome, compared
to those with a good one. And by some stretch; well into 4 digits in the poor
outcome group, compared to 2 in the good. This significant effect remained
after adjustment for target temperature, age and sex. The rise in serum NFL
also seemed to correlate with the severity of outcome, such that a higher
CPC score was associated with a higher NFL. Face validity – check.
The authors then looked at prognostic performance and report an area under
the receiver operating curve of 0.94. This is very high indeed and implies an
excellent diagnostic test. These data were compared to other recognised and
established biomarkers and other well used tests in neuroprognostication
such as neuroimaging, somatosensory evoked potentials and clinical
examination of brainstem reflexes. Their headline was of serum NFL
outperforming all other investigations – The AUC values knock the other
biomarkers out of the park, and NFL appeared to have improved sensitivity
over all other adjunctive tests. For the latter comparisons they used matched
specificity cut points, which is a little confusing – this implies that they
were selecting bespoke cupoints to match the specificity of CT for example,
then reporting on differences in other test characteristics. This is a bit
naughty – they could have chosen a suggested cut point and then compared
specificity of other tests as an alternative method I think.
The authors also looked at the additional value of serum NFL when added
to features such as clinical information and bedside neurological testing.
The AUC values increased quite remarkably but it was a little unclear as to
the timepoints of these assessments.
Wow – sounds too good to be true?

Well, these are certainly exciting results. Table 2 in particular highlights
potential cut off values mapped to diagnostic test characteristic data and
reveals just how useful this test could potentially be. For instance, at
24hours after ROSC, a cut off level of 12,317 for serum NFL resulted in
100% specificity for prediction of a poor outcome, with 0 false positive
results in 693 patients. Of this large cohort, this corresponds to 178 patient
families being informed within 24h that the outcome looks poor and 0
families being told this in error. Of the remaining 500 odd patients, 164
with a NFL lower than the cut point go on to have a bad outcome, but 351
with a low value have a good outcome. At 48 and 72 hours the sensitivity
just keeps getting better when the authors maintain a cut point producing
100% specificity.
When they look at cut points with any less than 100% specificity, then of
course you start to get false positives. Even then however, the figures
remain interesting. If you enjoy likelihood ratios, then you can convert the
figures provided in table 2 – for example, serum NFL at 24h with a cutpoint
of 641pg/mL and specificity of 99% would correspond to a positive
likelihood ratio of >50 and a negative likelihood ration of <0.5. These really
are excellent likelihood ratios for a prognostic test.
There must be a kicker though?

There is. Well there are 2 really.
Firstly, this ‘test’ is one of many in critical care which has a high risk of
being a self fulfilling prophecy. Although a specificity of 99% would
usually be deemed excellent, what that means in this cohort is that if we
rely on the test individually, we will tell 4 families (out of 693) that their
loved one has little chance of a good outcome incorrectly. This will often
lead to discussions on futility, preference and withdrawal of life sustaining
treatment. Thus, we have very little opportunity to correct our mistake.
These patients do not represent, or ask for second opinions. And worse still,
we will never know that we made a mistake.
Second, the authors of this paper do not propose a cut point for NFL. Their
data presents prognostic information based on the outcomes from this
dataset, but at no point do they validate this externally or suggest a figure
that could be used in clinical practice. The implication is that a really high
NFL is a bad prognostic sign. But how high is really high? How high does it
have to be before you are certain of futility?
Any other concerns?

Yes, a few minor ones. We have already mentioned the decline in
participants from TTM recruitment, to biobanking, to analysis. This study is
presented under the banner of the TTM trial, but it is not the same cohort
overall. Are the results therefore generalisable?
In addition, 2 of the lead authors are cofounders of the tech. We should be
thinking about this like pharmaceutical research really. Often industry gets
away with minimal declarations if it is not drug related. However, the same
biases and concerns exist. Although this study is presented clearly and
methodically, the authors have pecuniary interest in the success of the
biomarker.
Lastly, the powering is interesting here. They could have powered this on
test characteristic data. They chose instead to try and derive a cut point.
There is also a bit of logistic regression in there, some bootstrapping and
mention of AUROC data. This is a relatively small group of patients to do
all this on, which screams the need for further independent validation
studies in my eyes.
And the take home?
Like everyone else, I wanted this to be the test that absolves me of personal
accountability and the need for careful examination, ancillary testing and
balanced judgement in this cohort. I do not think it is that test.
Personally I think the authors overstate the conclusions. Although this test
appears exciting, we need to be absolutely explicit about the fact it has no
role at present for anyone with any kind of brain injury, and that the authors
have not as yet externally validated the results or defined a cut point for
practical clinical use.
Certainly, if these results are validated then in an uncomplicated post
cardiac arrest patient, high serum NFL values at 24/48/72 hours will add to
my clinical impression of a likely poor outcome. But I will certainly use this
only alongside my standard ESICM endorsed pathway of multimodality
prognostication. And I will be careful in my discussions with families.
If we think there is any chance whatsoever of functional recovery in these
patients, then we owe it to them to be cautious, objective and gentle in our
prognostication. Often this involves several days anyway, as care is
delivered, sedation cleared, clinical examination repeated and end of life
discussions commenced. How much does a biomarker add to this pathway?
Potentially a reasonable amount of supporting information. But I do not
think this is an overt game changer and I would never rely on a biomarker
in isolation for these patients.
Maybe that’s just me. What about you?
References
1. ICSSOA Day 3
1. Serum Neurofilament Light Chain for Prognosis of Outcome After Cardiac Arrest.
https://www.ncbi.nlm.nih.gov/pubmed/30383090
1. TTM Trial https://www.stemlynsblog.org/whats-target-temperature-oohca-cooling-st-emlyns/
1. CATEGORY: #FOAMed, Emergency Medicine, Journal Club, Resus & Crit

Care, resuscitation, Science
2. TAG: C20, cardiac arrest, CC21, CMP2, HMP2, neurofilament, OOHCA, prognosis, TTM
Chapter 29
TAKING THE PESIT – HOW

COMMON IS PE AMONG ED
PATIENTS WITH SYNCOPE?
You might remember the tremendous stink around PE prevalence caused by

the outcomes of the Pulmonary Embolism in Syncope Italian Trial (PESIT)
(1) from when it was published back in 2016; we covered it here at St
Emlyn’s(2), and there are other appraisals in the FOAM community – over
at REBELEM(1,3), EMLitOfNote(4) and EMCrit(5) to name a few. The
paper was pretty controversial in EM circles, not least because it seemed to
conclude with a prevalence of PE of a huge 17% in patients who had
presented with syncope – far higher than fits with the experiences of
Emergency Physicians the world over, particularly when talking about our
typical undifferentiated syncope patient population. There were other
criticisms too – read the original paper here, then the appraisals above, and
make your own mind up.
Other studies have since called these findings into question – Frizell et
al(6) performed a retrospective secondary analysis of patients presenting to
the ED with syncope and found a far lower prevalence at 1.4% of the 348
patients enrolled. Ryan Radecki covered this paper over
at EMLitOfNote(7).
Last month, Annals of Emergency Medicine added an article in proof,
which throws even more doubt at the original PESIT findings. Have a read
of the article first(8), then read on more below.
https://www.annemergmed.com/article/S0196-0644(18)31535-X/fulltext
What is this paper about?
In this paper, the authors are interested in identifying the 30-day prevalence
of PE among patients who attend the Emergency Department with a
presenting complaint of syncope. This wasn’t a new data collection but an
analysis of prospectively-collected data as part of a larger multi centre study
looking at diagnoses in patients presenting with syncope. The authors have
pooled data from two different prospective studies – one in Canada, one in
the US – in order to get a better idea of how common PE is as a finding
among these patients.
What do we even mean by syncope?
This is a really interesting question. It’s essential to define this term in order
to collect data about it, and it seems as though this was done relatively
sensibly. The authors tell us that patients were screened if they had a
presenting complaint of “syncope, presyncope, fainting, blackout, loss of
consciousness, fall, collapse, seizure, dizziness, or lightheadedness.” It’s
easy to see from the outset that these entities are not the same, but patients
rarely arrive at the ED describing their symptoms using completely accurate
terminology – and in any case there’s a reasonable chance that two
clinicians witnessing the same event might use different descriptors.
What matters here is initially capturing those attendances, then honing the
group down to include only those actually presenting with syncope. Patients
with prolonged loss of consciousness (more than five minutes) were
excluded, along with those who had witnessed seizures or head injuries, or
whose mental status [presumably this means conscious level] did not return
to baseline after the event in question.
Were the original studies conducted in the same way?
Yes and no. Both studies looked at 30-day outcomes for patients with
syncope, defined as loss of consciousness lasting less than 5 minutes (we
know this because patients with prolonged loss of consciousness lasting
more than 5 minutes were specifically excluded).
The Canadian study enrolled any adult patient (>16 years), while the US
study enrolled only those >60 years; quite different populations.
Both studies tried hard to identify the diagnosis of PE within 30 days of the
ED visit. They did this through chart analysis and telephone follow-up, with
adjudication in both studies for ambiguous cases (a panel of three blinded
clinicians in the Canadian study, a single independent clinician in the US
study). The adjudication component is important; it may sound
straightforward to ascertain a diagnosis from medical notes but in my
experience that is not always the case – it very much depends on who is
doing the documentation!
There were differences in data collection too; D-dimer usage was not
recorded as part of the US study.
What did they find?
The headline results were as follows:
9091 patients were analysed between the two studies; 547 were investigated
for PE as part of their workup and 55 had PE identified, plus one additional
patient who was picked up during the 30-day telephone follow-up. This
gave an overall prevalence of 0.6% (95% confidence interval 0.5%-0.8%).
The results are broken down further in the paper, which gives some more
food for thought.
41 patients (0.5% of total) had their PE identified in ED, 8 (0.1% of the
total) had PE identified during inpatient admission, and 7 (0.1% of total)
had PE identified on 30-day follow-up after index visit and were not
investigated for PE during the index visit.
11/56 patients with PE also had another non-PE serious outcome (eg
arrhythmia, MI, aortic dissection.
4/56 patients diagnosed with PE died within 30 days of index visit, coded in
the paper as “PE leading to death” in Table 1 – it’s unclear how much
overlap there is with those with concomitant non-PE diagnoses but I think
these are separate patients.
There are some other interesting things we can draw from the results, too.
In the Canadian cohort, 183 patients had a negative d-dimer (of the 278 who
had non-age-adjusted d-dimer performed) and 18 of those patients were
further investigated anyway; 1 with VQ scan, 17 with CTPA. I’m not
completely sure what we are to make of that use of d-dimer…!
The authors also did some modelling around worst-case scenarios – they
looked at what might happen among the patients who weren’t investigated
for PE and those lost to follow-up/with deaths from an unknown cause,
estimating a maximum total diagnoses of PE of 381 patients (4.1% of total;
95% confidence interval 3.7%-4.5%).
What does all this mean?
For me, this data is pretty reassuring, at least in part. The prevalence rates
among patients with syncope – even in worst case scenarios – are lower
than found in the PESIT trial, and this has at least face validity in my
practice.
The authors conclude that the prevalence is likely lower than that reported
in PESIT, thus reducing the emphasis on syncope as a primary presenting
complaint suggesting PE and necessitating that syncope patients should
have PE investigations. There are more patients in this combined cohort
than in PESIT, which also sits in its favour.
What the study doesn’t tell us is how other risk factors or prediction tools –
like PERC or Well’s scores – are affected by this data, because risk factors
weren’t collected in the original investigation. Likewise, there is no data
around location of the clots; we don’t know how many of these diagnosed
PEs were subsegmental and thus of limited clinical relevance – so-called
lung fluff or lung lint(9) (with credit to Casey Parker(10) and Seth
Trueger(9)), exactly the kind of incidental findings where risks of treatment
are likely to outweigh benefits, and which the PERC score is designed to
help us avoid diagnosing in the first place.
I think for now we can return to where we were before PESIT kicked up an
unpleasant smell in the ED. We can flush PESIT’s uncomfortably high
prevalence from our minds and consider PE in conjunction with evidence-
based diagnostic aids like PERC and Well’s scoring, rather than exposing
everyone who faints to a big dose of radiation or the risks of
anticoagulation.
Natalie May @_nmay
References
1. The PESIT Trial: Do All Patients with 1st Time Syncope Need a Pulmonary Embolism Workup? – REBEL EM – Emergency
Medicine Blog. REBEL EM – Emergency Medicine Blog. http://rebelem.com/the-pesit-trial-do-all-patients-with-1st-time-
syncope-need-a-pulmonary-embolism-workup/. Published October 24, 2016. Accessed February 19, 2019.
2. Carley S. JC: Prevalence of PE in patients with syncope. St.Emlyn’s • St Emlyn’s.
St.Emlyn’s. http://www.stemlynsblog.org/prevalence-of-pe-in-patients-with-syncope-st-emlyns/. Published October 20, 2016.
Accessed February 19, 2019.
3. Prandoni P, Lensing AWA, Prins MH, et al. Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope. N
Engl J Med. October 2016:1524-1531. doi:10.1056/nejmoa1602172
4. The Impending Pulmonary Embolism Apocalypse. Emergency Medicine Literature of Note. http://www.emlitofnote.com/?
p=3640. Published October 20, 2016. Accessed February 19, 2019.
5. Spiegel R. EM Nerd-The Case of the Incidental Bystander. EMCrit Project. https://emcrit.org/emnerd/the-case-of-the-
incidental-bystander/. Published October 20, 2016. Accessed February 19, 2019.
6. Frizell A, Fogel N, Steenblik J, Carlson M, Bledsoe J, Madsen T. Prevalence of pulmonary embolism in patients presenting to
the emergency department with syncope. The American Journal of Emergency Medicine. February 2018:253-256.
doi:10.1016/j.ajem.2017.07.090
7. There Are (Almost) No PEs in Syncope, Actually. Emergency Medicine Literature of Note. https://www.emlitofnote.com/?
p=3997. Published August 25, 2017. Accessed February 19, 2019.
8. Thiruganasambandamoorthy V, Sivilotti MLA, Rowe BH, et al. Prevalence of Pulmonary Embolism Among Emergency
Department Patients With Syncope: A Multicenter Prospective Cohort Study. Annals of Emergency Medicine. January 2019.
doi:10.1016/j.annemergmed.2018.12.005
9. Trueger S. Guest Glossary Term: Little Bitty PE. mdaware. http://mdaware.blogspot.com/2012/10/guest-glossary-
term.html. Published 2018. Accessed February 19, 2019.
10. Casey Parker (@broomedocs) on Twitter. Casey Parker. https://twitter.com/broomedocs. Published 2019. Accessed February
19, 2019.
1. CATEGORY: #FOAMed, Acute Medicine, Emergency Medicine, Journal Club, thromboembolism
2. TAG: CAP32, FOAMed, HAP5, jc, journal club, pulmonary embolism, pulmonary embolus
Chapter 30
CAN HEMS IMPROVE PATIENT

OUTCOME IN TRAUMATIC
CARDIAC ARREST?
This week we are briefly looking at an interesting paper that suggests that
HEMS services have much to offer in the management of traumatic cardiac
arrest (TCA).
We know that outcomes from TCA are poor, though arguably similar to the
outcomes in medical cardiac arrest, but there is the possibility of very
positive outcomes in a population which is often young and with great
potential. In the prehospital population traumatic cardiac arrest presents
significant difficulties relating to the availability of people, equipment and
skills. In addition, TCA is not that common and may be widely
geographically distributed, whilst also being a time critical condition.
Unsurprisingly then, helicopter emergency medical services (HEMS) teams
have developed systems and processes to try to get the right team to the
patient as fast as possible with the hope that the patients will benefit, but do
they really benefit and do HEMS interventions make a difference?
This month we have a paper in the Resuscitation journal that addresses this
question for a UK based HEMS service. The abstract is below, but as
always please read the full paper and make up your own mind as to its
quality and message.
This is a database analysis of a retrospective cohort of patients treated by
the Kent, Surrey and Sussex air ambulance in the UK. Data is collected
routinely on all patients treated by the service.
Who was studied
The authors have interrogated the database between 2013 and 2018,
searching for any cases where a traumatic cardiac arrest was recorded. It’s
important to note that the KSS air ambulance service covers quite a large (in
UK terms) geographical area which is predominantly rural. This is in
marked contrast to some other services, such as London HEMS, which
serve a predominantly urban population. This leads to significant
differences in case mix, with penetrating trauma forming a much smaller
proportion of patients as described in urban or military reports.
What were they looking at?
This paper is written by the HEMS service itself and so focuses on what
they do. Essentially they are primarily looking at the processes and
procedures of the HEMS service in response to the call to attend TCA
patients. The focus is therefore on what they have done in terms of things
like RSI, thoracostomy, thoracotomies, use of blood etc.
They have also tried to look at whether these interventions make a
difference to patients in terms of ROSC or survival. This has been done by
analysing the data using a logistic regression model to see if any of the
HEMS interventions are associated with ROSC.
Tell me about the patients
Over the 5-year period the authors identified 263 patients with TCA, so
roughly one a week which demonstrates the relative rarity of the event for
the service and for any individual within it. Patients were predominantly
male (75%) and mostly the victims of blunt trauma (86%). Read the paper
for a full description of the patients but it is largely as you would expect.
Patients were severely injured with significantly deranged physiology.
What are the main results?
This paper is largely about process and it’s clear that the majority (88%) of
these patients receive complex resuscitation interventions that can only be
delivered by a HEMS team in the prehospital setting. In addition, all
patients had other interventions delivered by ground based paramedic teams
(e.g. intubation without drugs).
So in terms of process these patients were deemed to require significant
interventions to try to achieve ROSC.
51 patients had a sustained ROSC, and of those just 7 survived to hospital
discharge. That’s a lower proportion than in other studies, but this may be
because of the smaller number of penetrating cases in this cohort and also
the significant geographical distances involved (the assumption being that
outcome is improved in patients with penetrating trauma and short response
times).
So does HEMS make a difference?
The authors make the case, and I think the data supports this, that a HEMS
service has a number of procedures that can be delivered to patients
following traumatic cardiac arrest, but that’s not as important as considering
whether it makes a difference to outcome. It’s less than clear in this study. If
we look at the number of patients who obtain ROSC then there appears to
be an association between some interventions and ROSC. These are BVM,
RSI, thoracostomies and blood products, although it is unclear whether
these were performed pre- or post-ROSC.
This is important as the matter becomes much less clear when we look at
the patients who survive to hospital discharge, which I believe is a far more
important outcome than ROSC. Amongst those 7 patients it is clear that all
achieved ROSC before the arrival of the HEMS team. To be clear, 28
patients had ROSC before the arrival of HEMS and all hospital survivors
had ROSC before HEMS arrival, though all of them subsequently had a
HEMS intervention post ROSC. What we don’t know is anything about the
functional outcome of the patients who survived. What we really want to
see is something like a Glasgow Outcome Score. We might be able to
determine the value of HEMS interventions in hospital survivors if there
was more detail, but in the paper the data is limited (though they may well
have made a difference).
The authors rightly point out that the diagnosis of cardiac arrest is difficult
in trauma patients and they relied on the ground crew to determine this. It is
possible that those who achieved ROSC before HEMS may have been in
low-flow states as opposed to absent circulation.
Ultimately this study shows that some HEMS procedures are associated
with ROSC, but fails to demonstrate a benefit in terms of patient survival. It
also demonstrates that survival to hospital discharge only occurred if ROSC
was achieved before the arrival of the HEMS team. Neither of these facts
tell us whether HEMS makes a difference to the final outcome in this very
seriously injured group of patients. Some interventions have an association
with ROSC, but association does nor equal causality. Additionally the
number of hospital survivors is too few, and the details too limited to draw
meaningful conclusions.
What appears to be the case, but something that is not highlighted in the
paper is that the most important factor in determining whether a patient will
survive to discharge is if they regain a circulation before HEMS arrive. My
basic calculations suggest that the odds ratio of pre arrival ROSC as a factor
to survival is essentially infinite (as no survivors in one arm), with a p value
in the region of 0.012. This was calculated using statpages online
calculator (which is pretty nifty by the way). The table below has survival
as the condition, and presence or absence of a circulation pre- or post-
HEMS as the test.
It is reasonable to argue that ROSC is an essential component on the way to
future survival and positive long term morbidity and mortality benefits, but
as we have seen in other critical care prehospital studies (such
as PARAMEDIC2) an increased survival may be at the expense of
increased morbidity. Unfortunately, the low incidence of TCA in the UK
means that further evidence, or any form of trial is likely impossible. We
should also be mindful that this is the data from one service and we should
be cautious in extrapolating to other services which may have very different
patient and logistical characteristics.
Although my personal belief is that there is likely to be a benefit in a very
small number of patients, the data presented here does not confirm this.
Whilst it is possible that HEMS are influential in the small number of
survivors, it is also possible that much time, expense and effort is being
delivered by the service for marginal, or perhaps even futile gains.
Simon Carley
References
1. TCA cardiac arrest stats: http://www.stemlynsblog.org/jc-uk-traumatic-cardiac-arrest-stats-st-emlyns/
2. Epidemiology and aetiology of traumatic cardiac arrest in England and Wales — A retrospective database
analysis EdBarnardab DavidYatesc AntoinetteEdwardsc MarisolFragoso-Iñiguezc TomJenksc Jason
E.Smithbd https://doi.org/10.1016/j.resuscitation.2016.11.001
3. Traumatic Cardiac Arrest: Who Are the Survivors? DavidLockey,
KateCrewdson,GarethDavies, https://doi.org/10.1016/j.annemergmed.2006.03.015
1. St Emlyn’s resources on Cardiac Arrest http://www.stemlynsblog.org/tag/cardiac-arrest/
1. CATEGORY: #FOAMed, Critical Care, Emergency Medicine, Journal Club, Resus & Crit
Care, Trauma
2. TAG: CC20, CMP2, CMP3, FOAMed, HEMS, HMP2, HMP3, TCA, Traumatic cardiac arrest
Chapter 31
TOP 10 EM PAPERS 2018-2019 FOR #RCEM

ANNUAL SCIENTIFIC CONFERENCE
In October 2019 the St Emlyn’s team headed to Gateshead for the Royal College of Emergency Medicine’s annual
scientific conference. This year I’ve been tasked with putting together the top 10 (plus 1) papers of the year.
This is always a bit of a random presentation as what do we mean by ‘Top’? Ask 5 different professors of
emergency medicine and you’ll probably get 5 different answers. For me it’s papers that might make a change to
clinical practice. Either by changing what we do, or by reinforcing something that we currently do. So the papers
below are entirely my choice. You can argue with them and that’s fine. In fact if you think I’ve missed something
please suggest your favourite paper in the comments. If the paper you published yourself is not here, then I
apologise, I’m sure it was fabulous but I may have just missed it 😉
In truth I did not select these on my own. I asked the St Emlyn’s team and fellow bloggers around the world,
notably Chris Hicks, Scott Weingart, Ken Milne, Cliff Reid, Salim Rezzaie and more.
Let’s crack on and in no particular order…..

Paper 1: Do we need to shock AF early?
I’m an enthusiast about cardioverting AF in the ED. For patients coming in with acute onset AF and no reason for
not sedating then I’m really keen to get the anaesthetic drugs out in order to deliver a bit electricity to get them
back into sinus and on their way. The question is whether we need to do that as urgently as I would like? In this
RCT from the US patients were randomised to either early (asap) electrical cardioversion or a delayed approach
where they aimed to cardiovert within the 48 hour window.
In
the paper the main outcome was whether patients were still in sinus rhythm at 90 days and the result there was that
there was no difference. So their argument was it makes no difference.
More interestingly for me was the number of patients who spontaneously cardioverted in the delayed treatment
arm of the trial. Roughly two thirds of them spontaneously went back into sinus rhythm. Thus my conclusion is
that it’s fine to watch and wait. The argument for asap cardioversion can be made from a in patient bed availability
perspective, but that needs to be balanced against the potential risks of sedation and cardioversion.Paper 2
Paper 2: Ventilation during RSI.

For
many years I have seen some of my colleagues routinely ventilate patients at risk of desaturation in the time
between induction and paralysis taking effect. We typically do this using a Water’s circuit with a bit of PEEP
applied (that’s a Mapleson C circuit) which we use for pretty much all RSIs in Virchester). In pre-hospital care
there is a preference for the BVM as it still works even if you lose your O2 supply. It’s done gently and carefully to
avoid gastric insufflation, but it’s always felt a little odd as we I was originally taught that ventilating at this stage
of the RSI was forbidden and dangerous. Notably because it was felt that it could induce aspiration. On the other
hand there are the risks of desaturation, hypoxia and the associated consequences of cardiovascular instability and
potential end organ damage. Thus the debate about whether ventilating the patient in the time between induction
and intubation has been controversial and debated for years.
This paper is an ED based RCT showing that it is safe and advantageous to ventilate patients between induction
and laryngoscopy. Far fewer patients desaturated and there was no increase in complications (aspiration and
pneumonia). Read more about the paper here.
Paper 3: Cricoid pressure in RSI
This is an RCT in patients undergoing RSI in theatre. Patients were randomised to cricoid or sham cricoid (no
pressure) with outcomes of evidence of aspiration at laryngoscopy or on chest Xray. Secondary outcomes were on
the difficulty of aspiration.
The bottom line was that there was no difference in terms of airway soiling (0.6% vs. 0.5%), but it was clear that
there was evidence of increased difficulty if the patient had cricoid.
Although this is not an EM trial and there were exclusions (e.g. small bowel obstruction) it’s yet more evidence
that cricoid may do more harm than good.
Paper 4: Magnesium in AF
This has been a long running debate. Should we give magnesium to patients in fast AF in the ED. This RCT
randomised ED patients to adjuvant MgSO4 together with their usual rate/rhythm control drugs. Patients got
placebo, 4.5g MgSO4 or 9g MgSO4.
The bottom line is that adjuvant MgSO4 made a real difference, but the higher dose offered no advantages but
more side effects. So go with adjuvant MgSO4 for your AF patients.
Paper 5. Levetiracetam vs. Phenytoin for second line treatment in paedaitric epilepsy
This RCT randomised children to children who were still fitting after first line benzos. We reviewed this trial in
depth here on the blog, so read that if you want the detailed analysis. Bottom line is that there was little difference,
perhaps with a signal that phenytoin was slower to get control.
For us at St Emlyn’s we believe that Levetiracetam is a preferred option as it’s easier to make up and has a better
safety profile.
We reviewed this paper on the blog earlier in the year. You can read a full review of the paper (both Eclipse and
Concept) here. An RCT of Levetiracetam vs. Phenytoin for children in status epilepticus. The bottom line in the
trial was that there was no difference.
Although not a primary aim of the study it’s likely that Phenytoin takes longer to act and in our opinion it’s more
tricky to make up and has more side effects. Sadly I’ve been involved in a few drug errors with Phenytoin and so I
think there are pragmatic reasons why we might want to move to Levetiracetam.
Paper 6: Does POCUS make a difference in Cardiac Arrest?
I’m a big fan of ultrasound in the emergency department and have been on record as saying it’s an essential skill
for the resus room (it was a bit controversial and lost me some friends), but in truth the evidence to underpin my
assertions has been fairly scant. In cardiac arrest patients I use it to look for treatable causes and in those patients
with electrical activity I use it to assess whether there is any associated mechanical contraction. But does it make a
difference?
The SHOCK ED3 trial aimed to answer this. There are lots of biases in this observational single centre trial but it
is evidence of how POCUS might change resus room management.
Yes it’s retrospective, yes it’s single centre and retrospective but the results are interesting. POCUS frequently
changes management as evidenced by additional procedures AND it is associated with increased rates of ROSC.
Sadly the increased rates of intervention were not associated with increased survival and if you are a USS skeptic
I’m sure that you’ll find that the most important outcome (Ed – because it is), but for me it is evidence of the need
for USS skills by EM docs.
Paper 7. Are vasopressors contraindicated in haemorrhagic shock?

The answer, if you are in the UK at least, is yes. This is something that we don’t do in the early phases of
haemorrhagic shock. However, when we did a simulation competition at the EuSEM conference in Glasgow we
were surprised to find that many of our European colleagues do use vasoconstrictive inotropes far earlier than we
do. This year there is an interesting paper in JAMA, an RCT in fact, looking at the early use of Vasopressin in
trauma patients.
Interestingly the trial found improved outcomes in those treated with Vasopressin. However, the outcomes were
around the use of blood products rather than more patient orientated outcomes like death (which was 12% in both
groups).
Paper 8: Early vasopressors in septic shock
The Censor trial comes on the back of a general move towards earlier use of vasopressors in septic shock. This is
something that many sepsis afficionados have been pushing for several years. In Virchester we start considering
vasopressors after 2L of IV fluids, or at least we think we do. Whilst we imagine that the days of 6-10L of IV
fluids for the septic shock patient in the first few hours are gone, we are not naive enough to think that it never
happens, especially in those patients who are not heading straight to ICU.
In this RCT, 310 patients were randomised to early noradrenaline vs. placebo. Although this was single centre and
in Cambodia, factors which limit the applicability of the findings, they are interesting.
Patients with early noradrenaline had less shock and less pulmonary oedema than those receiving placebo. Sadly
the trial was not big enough to definitively find a mortality benefit, but it was better in the noradrenaline group.
Paper 9: Does every cardiac arrest patient need to go to the cath lab?
In
the ED we often focus out learning and skills on improving our ability to get ROSC, but what next? If we get
ROSC should the patient go to ICU, CCU or direct to the cath lab? This is a real question as moving patients to the
cath lab is not always straightforward as they be quite unstable and in some centres it may be tricky to manage
things like temperature control.
For those patients who have ST elevation on the post ROSC ECG I don’t think there is any argument – they go
straight to the cath lab. What about those without ST elevation though?
The COACT trial looked specifically at this. An RCT of 552 patients randomised to either immediate cath lab
transfer or a more delayed approach.
So the bottom line appears that there is no real need to go direct to cath lab in this group. Probably because they
represent a broad range of pathologies and that’s important because this does not mean that in practice none of
these patients should be directly transferred. It does mean that you should stop and think. For example, the patient
with prior ischaemic symptoms is different from the 24 year old athlete who collapsed whilst playing football. The
first should go, the second maybe not just yet.
Paper 10: Diagnosing PE in pregnancy
The pregnant patient with a potential PE is a diagnostic conundrum. We know that tests such as d-dimers are not as
helpful in this group and yet the patients are at higher risk and the consequences potentially awful. I’ve seen a
variety of approaches to this over the years, but at the moment it usually involves bloods, a chest x-ray, ultrasound
for DVTs and then a chat. V/Q is then the way to go with CTPA reserved for a small number of cases.
In some health economies I think CTPA is more common in this group and is may be rising as access to CTPA
becomes easier, even though few people think more CTPAs in this group is a good idea!
The YEARS study looked to exclude PE in patients who had no signs of DVT, no haemoptysis and in whom the
clinician felt that PE was an unlikely diagnosis. This study adapted the YEARS algorithm for use in pregnant
women and then followed 496 patients through to determine the utility of the approach.
Overall the sensitivity was good, although there were small numbers of positive patients in the trial. In terms of
CTPA use this study showed a reduction, but be cautious on this. It’s only a reduction if you did lots before. In my
practice I would worry that this may increase usage.
Paper 10: The Zero Point Survey
Cheekily I added the zero point survey paper that I co-authored in 201831–33. Why you may ask? It’s because of
all the things I’ve done this year it’s the easiest, quickest, cheapest and most effective to deliver in practice.
We don’t have the evidence yet, but it makes sense and I’d strongly recommend you consider putting it into your
practice. Read more about the ZPS here.
Thanks for getting this far. For those in the audience I hope you enjoyed the talk and the emojis.
References
1. Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation https://www.nejm.org/doi/full/10.1056/NEJMoa1900353

2. Effect of Cricoid Pressure Compared With a Sham Procedure in the Rapid Sequence Induction of AnesthesiaThe IRIS Randomized Clinical
Trial https://jamanetwork.com/journals/jamasurgery/fullarticle/2708019
1. Bag mask ventilation during tracheal intubation of critically ill
patients. https://www.nejm.org/doi/full/10.1056/NEJMoa1812405#targetText=These%20results%20suggest%20that%20for,severe%20hypoxemia%20in%20one%20patient.&targetText=It%20has%
1. Low-dose Magnesium Sulfate Versus High Dose in the Early Management of Rapid Atrial Fibrillation: Randomized Controlled Double-blind Study (LOMAGHI
Study). https://www.ncbi.nlm.nih.gov/pubmed/30025177
2. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised
trial. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30724-X/fulltext
1. Does Point-of-care Ultrasound Use Impact Resuscitation Length, Rates of Intervention, and Clinical Outcomes During Cardiac Arrest? https://www.cureus.com/articles/18740-does-point-of-
care-ultrasound-use-impact-resuscitation-length-rates-of-intervention-and-clinical-outcomes-during-cardiac-arrest-a-study-from-the-sonography-in-hypotension-and-cardiac-arrest-in-the-
emergency-department-shoc-ed-investigators
1. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients with Trauma and Hemorrhagic Shock: A Randomized Clinical Trial (AVERT
Shock). https://www.thebottomline.org.uk/summaries/avert-shock/
2. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. https://www.ncbi.nlm.nih.gov/pubmed/30704260
3. Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. N Engl J Med. March 2019. doi:10.1056/nejmoa1816897
4. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism https://www.nejm.org/doi/full/10.1056/NEJMoa1813865
5. Zero Point Survey. https://www.stemlynsblog.org/jc-the-zero-point-survey-optimising-resuscitation-teams-in-the-ed-st-emlyns/
. CATEGORY: #FOAMed, Acute Coronary Syndromes, Acute Medicine, Critical Care, Emergency Medicine, Research, Resus & Crit
Care, resuscitation, Science, The philosophy of EM, thromboembolism, Trauma
. TAG: EBM, evidence based medicine, FOAMed, RCEM, RCEMASC, top 10

Chapter 32
TOP 10 TRAUMA PAPERS 2018-

2019 FOR TRAUMA-UK
CONFERENCE
I’m back in the Midlands at the excellent and great value TraumaUK
conference. If you’ve not been to this conference then I’d strongly suggest
you do next year. It’s an amazing program and incredible value for money.
As usual I’m in the emergency medicine stream bringing together the top 10
trauma papers from 2018-2019.
As ever it’s a bit disappointing to find relatively few papers to talk about as
I try and focus on those papers that might lead to a change in practice.
Although there are a lot of publications out there, once you start applying
the filters of applicability, quality and interest that number plummets.
So here is my top 10 list based entirely on my own opinion. There is some
repetition from past posts, but I’m OK with that as we can call it spaced
repetition(1).
Paper 1. PAMPER trial

Paper 1 is the PAMPER trial that looked at the use of prehospital plasma in
patients suffering major trauma. The idea here is that we need to manage
coagulopathy in the seriously injured and by getting ahead of the curve by
giving FFP early. This large RCT based in the US showed a 9.8% increase
in survival which is incredible. It is the sort of treatment effect that is so
large that I’d like to see it repeated. You can read more about the PAMPER
trial on the Bottom Line Website here.(2,3)
Paper 2: Bougie use in the ED

Paper 2 is an RCT comparing the routine use of a bougie in the ED against
the use of a stylet. This is an important study for me as I’ve advocated the
routine use of a bougie for as long as I can remember. However, others have
suggested it takes more time, that it might cause injury or that a stylet (or
nothing at all) is better.
This paper demonstrates that not only is the bougie safe, but also that it is
quicker and easier to use. This is true irrespective of whether you think it’s
going to be a difficult airway. The bottom line is use a bougie in most cases.
(4,5)
Paper 3: Ventilation during RSI.

For many years I have seen some of my colleagues routinely ventilate
patients at risk of desaturation in the time between induction and paralysis
taking effect. We typically do this using a Water’s circuit with a bit of PEEP
applied (that’s a Mapleson C circuit) which we use for pretty much all RSIs
in Virchester). In pre-hospital care there is a preference for the BVM as it
still works even if you lose your O2 supply. It’s done gently and carefully to
avoid gastric insufflation, but it’s always felt a little odd as we I was
originally taught that ventilating at this stage of the RSI was forbidden and
dangerous. Notably because it was felt that it could induce aspiration. On
the other hand there are the risks of desaturation, hypoxia and the associated
consequences of cardiovascular instability and potential end organ damage.
Thus the debate about whether ventilating the patient in the time between
induction and intubation has been controversial and debated for years.
This paper is an ED based RCT showing that it is safe and advantageous to
ventilate patients between induction and laryngoscopy. Far fewer patients
desaturated and there was no increase in complications (aspiration and
pneumonia). Read more about the paper here.(6,7)
Paper 4: Is hypotensive resuscitation evidence based?

Paper 4 is a systematic review of the principles of hypotensive resuscitation
in trauma patients. The benefit of hypotensive resuscitation in trauma
patients is a widely held belief and there are good pathophysiological
arguments to support it. Is it a strategy with a strong evidence base though?
This year there have been two systematic reviews of the evidence base
(8,9) and it’s a bit of a surprise really. In my head I had imagined that there
was a very strong evidence base in the literature, but having read the papers
I’m less assured.
Across 722 papers reviewed the authors in one review found only 5 RCTs.
One of these, and by far the largest is the Bickell trial from 1994 when
trauma care was a little different and where the patients were all victims of
penetrating trauma(10).
Although the authors conclude that there is a benefit to hypotensive

resuscitation strategies it’s unclear what the magnitude of the effect is. I am
a little concerned that most of the evidence is historical and from a very
different patient group to the one I see.
Paper 5: Late presenters with head injury. Do they need a scan?

No doubt you will be familiar with the NICE guidelines on the management
of head injury11. They’ve been around for a while and they are well
embedded in our practice. In practice I see them applied to all patients with
head injury, even those who present late. However, most head injury
guidelines were derived from patient cohorts that limited themselves to
patients who presented within 24 hours of injury.
The bottom line is that we have far less evidence for patients who present
late which has led to some interesting ideas around how we deal with them.
We can of course use the guideline, or in some opinions the fact that the
patient has survived 24 hours is an indicator in itself that they are fine.
Remember that most of these patients are ‘walk-ins’ in the minor end of the
department, presenting with relatively mild symptoms such as nausea,
vomiting and headache.
NICE guidelines for head injury
Paper 5 looks at patients presenting after 24 hours to a UK trauma centre

with a head injury12. They compared the CT incidence of significant injury
with that of patients who were scanned within 24 hours. They identified 650
patients in the late presentation cohort. Note that they only included patients
who had a scan, it is highly likely that some patients will have presented
late and not received a CT scan. That may bias the results.
The bottom line is that the incidence of significant CT findings was the
same (well slightly more) in the late presentation group. Over 10% of the
patients presenting late (and who had a CT scan) had a significant finding,
and several ended up with neurosurgical intervention (3%). What this
means is that we cannot dismiss late presenting patients simply on the basis
of time.
Paper 6: Trauma laparotomy mortality.

Paper 6 covers a really interesting paper that looks at mortality following
trauma laparotomy. Whilst we all think that we’ve made great progress in
trauma care (13,14) there is a group of patients in whom mortality does not
seem to be improving (15,16).
Data from the Royal London and also from the UK military database shows
that mortality has remained the same despite all the advances that we know
have taken place. I think this paper links well with Karim Brohi’s paper on
why trauma patients die (17,18). That showed a shift to later deaths on the
ICU as a result of as yet unknown mechanisms. The bottom line is that
there is still work to be done in the management of torso trauma, and
especially in non-compressible torso haemorrhage. Interesting to listen to
Ed Barnard on exactly that issue of non compressible bleeding at the
conference today.
Paper 7: Hypothermia in head injury

Hypothermia should work for lots of critical illness, but it doesn’t seem to
in practice. Whilst lab data suggests and demonstrates the neuroprotective
effect of hypothermia we’e failed to demonstrate it in several different areas
(notably post cardiac arrest). What about head injury though? On the ICU
the Eurotherm trial showed that it did not make a difference in patients with
raised ICP, but that was criticised as the hypothermia was started late. What
happens if we start it early?
In the POLAR trial patients were randomised as soon as possible to
hypothermia after head injury (19,20). In this large RCT there was little
difference in outcome and more complications in the hypothermia group.
Once again hypothermia fails to live up to the promise although it’s still
unclear why. Read more on the blog here.
Paper 8: Beta blockers in the management of traumatic brain injury

We’ve reviewed a whole bunch of papers on the blog that aim to improve
outcomes from medical or traumatic causes of brain injury. Hormones
(21,22), hypothermia (20,23–25), EPO (26,27) and more have been tried,
but they have been disappointing. In fact there has been very little progress
in the ICU/medical management of serious TBI.
One therapy that I was not familiar with is the use of Beta blockers for this
group of patients. Paper 8 is an observational study that looks at outcomes
related to Beta Blocker use in critical care patients in the US (28).
In 15 US trauma centres and 2337 patients there was an association of beta
blocker use and survival. The mechanism for this is a bit uncertain but may
be related to control of catecholamine effects. Catecholamines surge post
TBI and the magnitude of the rise is associated with outcome.
Catecholamines cause inflammation and apoptosis with effects lasting for
over a week. There is therefore some logic in the use of Beta Blockers in
the management of these patients.
What they found is that there was a 4% difference in mortality and an
unadjusted difference in GOS (favouring no BB).
There are always problems with observational studies of this type. There are
many confounding factors and bias that may influence the result. Most
notably here that patients who are suitable to receive a beta blocker may not
have as much cardiovascular instability as those who do not (and with the
associated mortality as a result). They did try to address this by adjusting
for known factors, but that’s never perfect.
Having said that there is a fairly strong association between use and
survival and also use and positive functional scores.
What we need is an RCT of this therapy to find out whether the association
found in this paper is actually a causal relationship.
Paper 9: Paediatric Splenic Injury

Paper 9 is a paediatric paper looking at splenectomy results in UK trauma
centres (29). Using the TARN database the authors compared splenectomy
rates between hospitals that were dedicated paediatric major trauma centres
and those that are not. The results are really quite stark with almost a 5-fold
difference in operative rates.
Now you might think that this is because patients in the non Paeds MTC
were too sick to travel and thus more likely to need operative management.
The authors helped explore this by comparing rates dependent on the
severity of splenic injury as defined by AIS score.
So the bottom line here is that the differences exist irrespective of the
splenic injury. That suggests that injury severity is not the main factor. Ross
Fisher, our friend and resident paediatric surgeon has suggested that
splenectomy rates can be used as a quality marker for the surgical
management of major trauma (30). On the basis of this paper he may well
be right.
Paper 10: The Zero Point Survey

Cheekily I added the zero point survey paper that I co-authored in 201831–
33. Why you may ask? It’s because of all the things I’ve done this year it’s
the easiest, quickest, cheapest and most effective to deliver in practice.
We don’t have the evidence yet, but it makes sense and I’d strongly
recommend you consider putting it into your practice. Read more about the
ZPS here.
References
1. Carley S. Educational theories you must know. Spaced Repetition. St.Emlyn’s • St Emlyn’s.
St.Emlyn’s. https://www.stemlynsblog.org/better-learning/educational-theories-you-must-know-st-emlyns/educational-theories-
you-must-know-spaced-repetition-st-emlyns/. Published 2015. Accessed March 6, 2019.
1. PAMPer. The Bottom Line. https://www.thebottomline.org.uk/summaries/em/pamper/. Published August 3, 2018. Accessed
March 6, 2019.
1. Sperry JL, Guyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for
Hemorrhagic Shock. N Engl J Med. July 2018:315-326. doi:10.1056/nejmoa1802345
2. Driver BE, Prekker ME, Klein LR, et al. Effect of Use of a Bougie vs Endotracheal Tube and Stylet on First-Attempt
Intubation Success Among Patients With Difficult Airways Undergoing Emergency Intubation. JAMA. June 2018:2179.
doi:10.1001/jama.2018.6496
3. Carley S. JC: Don’t blame it on the Bougie. St Emlyn’s • St Emlyn’s. St.Emlyn’s. https://www.stemlynsblog.org/jc-dont-blame-
it-on-the-bougie-st-emlyns/. Published May 20, 2018. Accessed March 6, 2019.
4. Casey JD, Janz DR, Russell DW, et al. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med.
February 2019:811-821. doi:10.1056/nejmoa1812405
5. Carley S. JC: Should we continue ventilations during RSI? St Emlyn’s • St Emlyn’s.
St.Emlyn’s. https://www.stemlynsblog.org/jc-ventilation-during-rsi-st-emlyns/. Published February 22, 2019. Accessed March
6, 2019.
6. Tran A, Yates J, Lau A, Lampron J, Matar M. Permissive hypotension versus conventional resuscitation strategies in adult
trauma patients with hemorrhagic shock. Journal of Trauma and Acute Care Surgery. May 2018:802-808.
doi:10.1097/ta.0000000000001816
7. Tran A, Yates J, Lau A, Lampron J, Matar M. Permissive hypotension versus conventional resuscitation strategies in adult
trauma patients with hemorrhagic shock: A systematic review and meta-analysis of randomized controlled trials. J Trauma
Acute Care Surg. 2018;84(5):802-808. https://www.ncbi.nlm.nih.gov/pubmed/29370058.
8. Bickell W, Wall M, Pepe P, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso
injuries. N Engl J Med. 1994;331(17):1105-1109. https://www.ncbi.nlm.nih.gov/pubmed/7935634.
9. Overview | Head injury: assessment and early management | Guidance | NICE.
NICE. https://www.nice.org.uk/guidance/cg176. Published 2019. Accessed March 6, 2019.
10. Marincowitz C, Allgar V, Townend W. CT head imaging in patients with head injury who present after 24 h of injury: a
retrospective cohort study. Emerg Med J. April 2016:538-542. doi:10.1136/emermed-2015-205370
11. Moran CG, Lecky F, Bouamra O, et al. Changing the System – Major Trauma Patients and Their Outcomes in the NHS
(England) 2008–17. EClinicalMedicine. August 2018:13-21. doi:10.1016/j.eclinm.2018.07.001
12. Grayson A. Trauma in the UK, who cares? St Emlyn’s • St Emlyn’s. St.Emlyn’s. https://www.stemlynsblog.org/trauma-in-the-
uk-who-cares-st-emlyns/. Published December 31, 2018. Accessed March 6, 2019.
13. Marsden M, Carden R, Navaratne L, et al. Outcomes following trauma laparotomy for hypotensive trauma patients. Journal of
Trauma and Acute Care Surgery. May 2018:1. doi:10.1097/ta.0000000000001988
14. Carden R. What’s the bleeding problem with trauma laparotomies?! • St Emlyn’s.
St.Emlyn’s. http://www.stemlynsblog.org/whats-the-bleeding-problem-with-trauma-laparotomies/. Published December 28,
2018. Accessed March 6, 2019.
15. Carley S. JC: Why do bleeding trauma patients die? St Emlyn’s • St Emlyn’s. St.Emlyn’s. https://www.stemlynsblog.org/jc-
why-do-bleeding-trauma-patients-die-st-emlyns/. Published February 13, 2019. Accessed March 6, 2019.
16. Brohi K, Gruen RL, Holcomb JB. Why are bleeding trauma patients still dying? Intensive Care Med. February 2019.
doi:10.1007/s00134-019-05560-x
17. Carley S. JC: What’s the target temperature for OOHCA cooling. St.Emlyn’s • St Emlyn’s.
St.Emlyn’s. https://www.stemlynsblog.org/whats-target-temperature-oohca-cooling-st-emlyns/. Published November 18, 2013.
Accessed March 6, 2019.
18. Cooper DJ, Nichol AD, Bailey M, et al. Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among
Patients With Severe Traumatic Brain Injury. JAMA. December 2018:2211. doi:10.1001/jama.2018.17075
19. Carley S. JC: Progesterone’s pleiotropic failure in head injury. St.Emlyn’s • St Emlyn’s.
St.Emlyn’s. http://www.stemlynsblog.org/jc-progesterones-pleiotropic-failure-head-injury-st-emlyns/. Published December 29,
2014. Accessed March 6, 2019.
20. Wright DW, Kellermann AL, Hertzberg VS, et al. ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic
Brain Injury. Annals of Emergency Medicine. April 2007:391-402.e2. doi:10.1016/j.annemergmed.2006.07.932
21. Carley S. JC. Pre-hospital therapeutic hypothermia: The RINSE trial. St.Emlyn’s • St Emlyn’s.
St.Emlyn’s. http://www.stemlynsblog.org/pre-hospital-therapeutic-hypothermia-the-rinse-trial-st-emlyns/. Published September
13, 2016. Accessed March 6, 2019.
22. Bernard SA, Smith K, Finn J, et al. Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a
Rapid Infusion of Cold Saline. Circulation. September 2016:797-805. doi:10.1161/circulationaha.116.021989
23. Horner D. JC: EuroTHERM or EuroBURNED. St.Emlyn’s • St Emlyn’s. St.Emlyn’s. http://www.stemlynsblog.org/jc-
eurotherm-or-euroburned-st-emlyns/. Published November 7, 2015. Accessed March 6, 2019.
24. Cariou A, Deye N, Vivien B, et al. Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest. Journal of
the American College of Cardiology. July 2016:40-49. doi:10.1016/j.jacc.2016.04.040
25. Carley S. JC: Does EPO improve OOHCA outcomes? St.Emlyn’s • St Emlyn’s. St.Emlyn’s. http://www.stemlynsblog.org/jc-
epo-improve-oohca-outcomes-st-emlyns/. Published July 3, 2016. Accessed March 6, 2019.
26. Ley EJ, Leonard SD, Barmparas G, et al. Beta blockers in critically ill patients with traumatic brain injury. Journal of Trauma
and Acute Care Surgery. February 2018:234-244. doi:10.1097/ta.0000000000001747
27. Warwick AM, Jenks T, Fisher R, Garrett‐Cox R, Lecky F, Yates D. Disparities in the management of paediatric splenic
injury. Br J Surg. October 2018:263-266. doi:10.1002/bjs.10996
28. Development P. Ross Fisher on the management of UK Paediatric trauma. St Emlyn’s
podcast. https://www.stemlynspodcast.org/e/ross-fisher-on-the-management-of-uk-paediatric-trauma/. Published 2016.
Accessed March 6, 2019.
29. Carley S. JC: The Zero Point Survey. Optimising resuscitation teams in the ED. St Emlyn’s • St Emlyn’s.
St.Emlyn’s. https://www.stemlynsblog.org/jc-the-zero-point-survey-optimising-resuscitation-teams-in-the-ed-st-
emlyns/. Published September 30, 2018. Accessed March 6, 2019.
30. Zero point survey: a multidisciplinary idea to STEP UP resuscitation effectiveness. Clin Exp Emerg
Med. https://www.ceemjournal.org/upload/pdf/ceem-17-269.pdf. Published 2018. Accessed March 6, 2019.
31. Reid C, Brindley P, Hicks C, et al. Zero point survey: a multidisciplinary idea to STEP UP resuscitation effectiveness. Clin Exp
Emerg Med. September 2018:139-143. doi:10.15441/ceem.17.269
1. CATEGORY:#FOAMed, Emergency Medicine, Head injury, Resus & Crit Care, The philosophy of
EM, Trauma
2. TAG: #FOAMed, FOAMed, resuscitation, TBI, trauma, traumaUK

THE ST EMLYN’S EDITORIAL
TEAM
Alan Grayson
Alan Grayson MB ChB, FRCEM is a consultant Emergency Physician in Manchester. He is an
honorary senior lecturer at the University of Manchester and associate academic lead for the year 5
MBChB programme. He is Honorary Senior Clinical Lecturer, Centre for Effective Emergency Care,
Manchester Metropolitan University
All Posts Website
Ashley Liebig
Ashley Voss-Liebig, RN, BSN, CCRN is the Division Chief for Clinical Performance and Education
in Travis County Texas. She is a senior flight nurse and helicopter rescue specialist with STAR
Flight. Her reseach interests include Medical Education, POCUS, Human Performance. She is
@ashleyliebig on twitter
All Posts Website
Charlie Reynard
MB. ChB, Academic Clinical Fellow, President's Doctoral Scholar, Honorary Lecturer, TERN
regional representative. Manchester, Greater Manchester, United Kingdom
All Posts Website
Chris Gray
Dr Chris Gray BSc(Hons) MBBS MRCP(UK) MRCEM AICSM is an ST6 in Emergency Medicine
and Intensive Care Medicine, training in Manchester and the North West. He is also an ALS, APLS,
and ETC instructor and keen educator. He is @cgraydoc on twitter
All Posts Website
Craig Ferguson
Dr Craig Ferguson MB ChB, FRCEM, PhD is an Editorial Board Member of the St Emlyn’s blog and
podcast. He is a Consultant in Emergency Medicine in Manchester where is operational lead for the
emergency department. His research interest include diagnostics, heart failure, human factors and
EBM. You will find him on twitter as @doccjf
All Posts Website
Dan Horner
Dr Daniel Horner BA MBBS MD PgCert MRCP (UK) FRCEM FFICM is an editorial board member
on the St Emlyn’s blog and podcast. He is Professor of Emergency Medicine of the Royal College of
Emergency Medicine. He is a consultant in Emergency Medicine and Intensive Care at Salford Royal
NHS Foundation Trust. He is chair of the national exemplar centre Thrombosis Committee and
Regional lead for Injuries and Emergencies on the NIHR Clinical Research Network. He is a Senior
clinical lecturer at the University of Manchester and collaborator with the University of Sheffield.
You can find him on twitter as @RCEMProf
All Posts
Gareth Roberts
Dr Gareth Roberts MB/ChB FRCEM MAcadMed is an editorial board member of the St Emlyn's
blog and podcast. He is a senior trainee in Emergency Medicine at Manchester University Foundation
Trust. His research interests are in communicable disease, public health, resuscitation and emergency
medicine. You can find him on twitter as @drgarethroberts
All Posts Website
Iain Beardsell
Dr Iain Beardsell. MBChB (Birm) FRCEM is section lead for podcasts. Editorial Board Member St
Emlyn’s blog and podcast. He is a Consultant in Emergency Medicine at University Hospital
Southampton and a Consultant in Pre Hospital Emergency Medicine. Iain qualified in 1998 and over
the past 20 years has trained and practiced medicine in major teaching hospitals both in the UK and
overseas. He has been a consultant at University Hospital Southampton for the past ten years,
including a three year term as the unit’s Clinical Director. UHS is the main Major Trauma Centre for
the South Coast region of England as well as the eighth largest hospital in the UK. Iain is also a
highly regarded advisor to television medical dramas, including Casualty and Good Karma Hospital.
An acclaimed speaker, Iain has spoken at international conferences in Australia, Ireland, Austria and
Germany as well as across the UK. You will find him on twitter as @docib
All Posts
Janos Baombe
Dr Janos Baombe MD, FRCEM, FEEBEM, PgCert, MSc is section editor and editorial board
member on the St Emlyn's blog and podcast. He is a consultant in emergency medicine in Manchester
and visiting senior lecturer at Manchester Metropolitan University. His research interests include
infectious disease, European emergency medicine networks, ultrasonogaphy, toxicology, HIV/AIDS,
EBM. You can find him on twitter as @baombejp
All Posts Website
laura howard
Laura Howard. MBChB, MRCEM is an Editorial Board Member on the St Emlyn’s blog and
podcast. She is an emergency physician trainee and clinical and doctoral (PhD) fellow in Emergency
Medicine Manchester Metropolitan University. She co-founded the ED Spa Project (@edspa_mcr).
She was the RCEM Young Investigator of the Year 2016. Her reseach interests include emergency
medicine, wellbeing, compassionate care, triage. She is regularly invited to speak on the topic of
well-being. Her PhD is on triage (funded by the Manchester Triage Group) and she is a member of
the Wellbeing Committee at the Royal College of Emergency Medicine. You can find her on twitter
as @laurahoward10
All Posts Website
Liz Crowe
Ms Liz Crowe BachSW, PhD(Candidate) is section lead for Wellbeing and Editorial Board Member
on the St Emlyn’s blog and podcast. She is a wellbeing counsellor and educator. She works as an
Advanced Clinician Paediatric Social Worker in the Paediatric Intensive Care Unit at Queensland
Children’s Hospital. She is the author of “The Little Book of Loss and Grief You Can Read While
You Cry”and “When a Child Dies – A Guide to Working with Bereaved Parents after the Death of a
Child from Illness. She is currently completing a Doctoral Thesis in Staff Wellbeing in the critical
care context. Examining risk and protective factors with a view to designing interventions that build
capacity, psychological flexibility and resilience for staff proactively and reactively. She is an
internationally renowned speaker on paediatric loss, grief, crisis and bereavement work. Her research
interests include staff wellbeing, loss, grief, crisis and bereavement work in critical care, paediatric
sepsis, moral distress, clinical debriefing following a critical incident, end of life care and advance
care planning. You can find her on twitter as @lizcrowe2
All Posts Website
Natalie May
Dr. Natalie May, MBChB, MPHe, MSc, PGCert Medical Education, FRCEM, FACEM is section
lead for paediatrics and medical education. She is an Editorial Board Member of the St Emlyn’s blog
and podcast. She is a specialist in Emergency Medicine (Australia) and a Specialist in Emergency
Medicine with Paediatric Emergency Medicine (UK). She works as Staff Specialist in Prehospital
and Retrieval Medicine with the Ambulance Service of New South Wales (aka Sydney HEMS). She
also works as aStaff Specialist, Emergency Medicine, St George Hospital (South Eastern Sydney
Local Health District). Her research interests include medical education, particularly feedback;
gender inequity in healthcare; paediatric emergency medicine. You can find her on twitter as
@_NMay
All Posts
Niall Morris
Dr Niall Morris MB ChB, MCEM is an emergency physician in Manchester. He is currently working
on his PhD in cardiac diagnostics.
All Posts Website
Nick Smith
Nick Smith RN is a registered nurse and head of clinical teaching & assessments for undergraduate
medical education for a hospital Manchester. He has a background in intensive care medicine, EM
and resuscitation training. Nick is a technical guru who supports the St Emlyn's team with audio
visual needs. He regularly wins awards for teaching excellence at the University of Manchester.
All Posts
Pete Hulme
Dr Peter Hulme MB ChB, FRCEM, DTM&H, is a consultant in adult and paediatric emergency
medicine in Central Manchester. His interests include tropical medicine, trauma, quality
improvement, audit and medical education.
All Posts Website
Richard Carden
Dr Richard Carden MBChB MSc BSc (Hons) PGCert FHEA MAcadMEd RAMC(V) Dr Richard
Carden MBChB MSc BSc (Hons) PGCert FHEA MAcadMEd RAMC(V) is an Emergency Medicine
Trainee in London. He is currently a PhD Candidate in Trauma Sciences at the Centre for Trauma
Sciences. He is a Major in the British Army with 335 Medical Evacuation Regiment. He is a Co-
Founder of the National Trauma Research and Innovation Collaborative and Module Lead for the
MSc in Emergency and Resuscitation Medicine at QMUL. You can find him on twitter as
@richcarden
All Posts Website
Rick Body
Professor Richard Body MB ChB, FRCEM, PhD is Professor of emergency medicine in Manchester.
He is honorary Consultant in Emergency Medicine at Manchester Foundation trust. He is also the
director of the Manchester Diagnostics and Technology Accelerator (DiTA) and Research Director of
the Emergency Medicine and Intensive Care Research Group (EMERGING). His research interests
include diagnostics, cardiac disease and the philosophy of emergency medicine. He is an acclaimed
international speaker on cardiac diagnostics . He can be found on twitter as @richardbody
All Posts Website
Robert Lloyd
Dr Robert Lloyd MBChB is an emergency medicine trainee in the UK. He is an NHS Innovation
fellow with research interests in new technologies and healthcare. You can find himon twitter as
@ponderingEM
All Posts Website
Ross Fisher
Mr Ross Fisher MBChB MPhil MSc FRCS RCPS (Paediatric Surgery) is section lead (presentation
skills) and editorial board member on the St Emlyn's blog and podcast. He is a Consultant Paediatric
Surgeon at the Sheffield Children’s Hospital, Sheffield. He is chairman of the Paediatric Trauma
Audit and Research Network (TARNlet). He is an internationally acclaimed presentation expert and
founder p cubed presentations http://ffolliet.com, His research interests include Paediatric, Neonatal,
and Oncological Surgery and Paediatric Trauma Management. You can find him on twitter as
@ffolliet
All Posts Website
Rusty Carroll
Rusty Carroll PgC, DipIMC (RCS Ed), MCoP is a paramedic working in primary care in Manchester
and a trainee Advanced Clinical Practitioner. You can find him on twitter as @paramedrusty.
All Posts
Simon Carley
Professor Simon Carley MB ChB, PGDip, DipIMC (RCS Ed), FRCS (Ed)(1998), FHEA, FAcadMed,
FRCEM, MPhil, MD, PhD is Creator, Webmaster, owner and Editor in Chief of the St Emlyn’s blog
and podcast. He is Professor of Emergency Medicine at Manchester Metropolitan University and a
Consultant in adult and paediatric Emergency Medicine at Manchester Foundation Trust. He is co-
founder of BestBets, St.Emlyns and the MSc in emergency medicine at Manchester Metropolitan
University. He is an Education Associate with the General Medical Council and is an Associate
Editor for the Emergency Medicine Journal. His research interests include diagnostics, MedEd,
Major incidents & Evidence based Emergency Medicine. He is verified on twitter as
@EMManchester
All Posts Website
Stevan Bruijns
Dr Stevan Bruijns is a South African/ British emergency physician (dual trained). His interests
include quality improvement, emergency care development and research access in African low-
resourced settings. He is honorary associate professor of emergency medicine with the University of
Cape Town and the chief editor of the African Journal of Emergency Medicine. Stevan is a person of
action and like for things he does to be useful to others. He has worked in a number of settings,
including resource-rich and resource-poor ones. Stevan currently works at Yeovil District Hospital in
Somerset, UK. He also serves on the Royal College of Emergency Medicine's Global Emergency
Medicine committee.
All Posts Website
Steve Jones
Dr Steve Jones MD, MRCP, FRCSEd, FCEM, FFICM is an Emergency and intensive care consultant
in Manchester. He is a registered specialist in both Intensive Care and Emergency Medicine. In
addition to his clinical work he has a research interest in the evaluation and implementation of
technology in healthcare. You can find him on twitter at @CDoftheED
All Posts
Zaf Qasim
Dr Zaf Qasim is an attending physician in Emergency Medicine and Critical Care based at the
University of Pennsylvania in the United States. He has particular interests in trauma, prehospital
care and advanced resuscitation and is widely regarded as an expert in practical resuscitation
procedures. You can find him on Twitter as @ResusOne
All Posts

ST Emlyns Critical Appraisal 2019

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ST Emlyns Critical Appraisal 2019

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FOREWORD

Simon Carley and Liz Crowe

Dr Richard Carden MBChB MSc BSc (Hons) PGCert FHEA MAcadMEd

Dr Chris Gray BSc(Hons) MBBS MRCP(UK) MRCEM AICSM is an ST6

Dr Daniel Horner BA MBBS MD PgCert MRCP (UK) FRCEM FFICM is

Laura Howard. MBChB, MRCEM is an Editorial Board Member on the St

Dr. Natalie May, MBChB, MPHe, MSc, PGCert Medical Education,

Dr Zaf Qasim is an attending physician in Emergency Medicine and Critical

Tell me about the patients.

What did they do.

What about the outcomes?

Tell me the results.

So they are the same then?

Global health perspective

The bottom line

5. Farkas J. Rare and Catastrophic complications. EMCRIT. https://emcrit.org/pulmcrit/rare-catastrophic-complications/.

1. Cook T. NAP 6. National Airway Project. https://www.nationalauditprojects.org.uk/NAP6home. Published 2019. Accessed

2. TAG: airway, C3AP6, CC3, FOAMed, rapid sequence induction, suxamethonium

PSEUDO PEA IN THE ED

What were the main results?

–Therapeutic approach to Pseudo-PEA

-Prognosis of patients in pseudo-PEA

What’s the bottom line?

Pete Hulme @tropdocpete

RISK SCORES FOR CARDIAC

What did we find?

Risk scores listed in order of results

Enough waffle: what does this mean?

Global health perspective

Charlie Reynard @Reynard_EM

2. TAG: CAP7, CC5, chest pain, Manchester, TMACS, troponin

LEVEL PEGGING? THE PEGED

How was this trial designed?

Who was involved?

What was the primary outcome?

A word on d-dimer testing

Ok, tell me about the patients recruited?

And what are the headline results?

All sounds very impressive. Any concerns?

Bottom line – Do you think we should adopt this?

Any last messages?

Dan Horner @RCEMProf

1. CATEGORY: #FOAMed, Acute Medicine, Ambulatory Care, Emergency Medicine, Journal

2. TAG: CAP7, CC5, FOAMed, NEJM, pe, PEGeD, pulmonary embolus

INTRANASAL FENTANYL VS.

Last year we reviewed a pilot RCT comparing IN Fentanyl vs IN Ketamine

Tell me about the patients.

What did they do?

What were the main results?

Global health perspective (Steven Bruijns)

Simon Carley @EMManchester

. CATEGORY: #FOAMed, Acute Medicine, Ambulatory Care, Emergency Medicine, Journal

. TAG: CAP7, CC5, FOAMed, NEJM, pe, PEGeD, pulmonary embolus

Here at St Emlyn’s we’ve always prided ourselves on being reflective

So what exactly did they do?

What did they find?

So what does this mean?

TRANEXAMIC ACID (TXA) IN

By Hywell Roberts for LSHTM https://vimeo.com/user23820206

Tell me about the patients.

What did they do?

So what did they find?

Talk to me about timings.