REVIEW

CURRENT
OPINION ICU management based on big data
Stefano Falini a, Giovanni Angelotti b, and Maurizio Cecconi a,c

Purpose of review
The availability of large datasets and computational power has prompted a revolution in Intensive Care.
Data represent a great opportunity for clinical practice, benchmarking, and research. Machine learning
algorithms can help predict events in a way the human brain can simply not process. This possibility comes
with benefits and risks for the clinician, as finding associations does not mean proving causality.
Recent findings
Downloaded from https://journals.lww.com/co-anesthesiology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3hIW04IhZ9AvNyXiDskTJpGAYXztNG71dMzsxvxmZhgI= on 04/12/2020

Current applications of Data Science still focus on data documentation and visualization, and on basic
rules to identify critical lab values. Recently, algorithms have been put in place for prediction of outcomes
such as length of stay, mortality, and development of complications. These results have begun being
implemented for more efficient allocation of resources and in benchmarking processes, to allow
identification of successful practices and margins for improvement. In parallel, machine learning models
are increasingly being applied in research to expand medical knowledge.
Summary
Data have always been part of the work of intensivists, but the current availability has not been completely
exploited. The intensive care community has to embrace and guide the data science revolution in order to
decline it in favor of patients’ care.
Keywords
benchmarking, big data, clinical prediction model, data science, intensive care medicine

INTRODUCTION Attempts to improve patients’ safety via check-

We have been raised with the idea of increasingly
capable machines to help us with manual labor
because it is a phenomenon that had already largely
taken place before we were born. We have grown
accustomed with computers supporting us with cal-
culation power and storage capacity because it has
occurred gradually in the arc of a few decades. In
contrast, most of us are still skeptical to the perspec-
tive of artificial intelligence, likely because we feel it
has arrived too recently, and too abruptly. Mostly,
we cannot understand it: can machines provide us
with reasoning power? Could it mean they have
more to spare, more than we do?
Isaac Asimov’s first rule or robotics ‘A robot may
not injure a human being or, through inaction,
allow a human being to come to harm’ [1] is remark-
ably similar to the primum non nocere principle of
good clinical practice. As physicians, we swear not to
harm our patients [2]. Nevertheless, unintentional
mistreat happens frequently, with some statistics
reporting up to a third of hospital deaths linked
to some form of medical error [3]. Healthcare pro-
fessionals often make mistakes because they clearly
cannot see the information laid in front of their
eyes.
lists [4,5] have shown to improve outcomes, but this
approach cannot be applied to every single medical
diagnosis or treatment that physicians have to per-
form. Patients are different from each other, and
physiology is in a continuous state of change. A
resource capable of identifying the most relevant
information for ‘this patient, at this moment’ would
be extremely welcomed by clinicians at the bedside.
This is where the big hope for artificial intelligence
support for clinical practice stands. But where are we
today? And before artificial intelligence becomes a
standard tool in our ICUs, what can we do with the
available data?
It is ironic that despite the countless articles on
the subject, clinicians are still intimidated when the
topic of artificial intelligence is brought up. After all,
a
Department of Anesthesia and Intensive Care, bData Science Core
Facility, Humanitas Clinical and Research Center, Rozzano and cHuma-
nitas University, Milano, Italy
Correspondence to Stefano Falini, c/o Istituto Clinico Humanitas, Via
Alessandro Manzoni 56, 20089 Rozzano, Italy. Tel: +39 335 812 6498;
e-mail: stefano.falini@humanitas.it
Curr Opin Anesthesiol 2020, 33:162–169
DOI:10.1097/ACO.0000000000000834

www.co-anesthesiology.com Volume 33  Number 2  April 2020

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 In medicine, appreciation of data is key to gain real
knowledge. If properly trained, computer will enable us
to make sense of the overwhelming amount that we are
accumulating nowadays.
 The Intensive Care community has to embrace and
guide the Data Science revolution to provide better
care to critical patients and improve their outcomes.
 There is an urgent need for data sharing and common
data dictionaries: this will allow not only better training
of models, but also more generalizability and greater
external validation.
they have witnessed the breakthrough that the data
science revolution has brought in the latest years to
most other fields. The new thing machines are sup-
plying is novel insight into the data that we have
been collecting, better analytical power to interpret
patterns, and more efficiency at extrapolating
knowledge from our sources. It’s not that we hadn’t
grasped that data had value: it is that computers are
helping us understand its magnitude.
MAKING SENSE OF DATA: DATA SCIENCE
The realization that true knowledge can only be
achieved through effective measurement and
translation into data can be traced back for centu-
ries, and it was certainly evident to William Thom-
son, commonly known as Lord Kelvin. Beyond his
contributions on thermodynamics, he is famous
for stating: ‘I often say that when you can measure
what you are speaking about, and express it in
numbers, you know something about it; but when
you cannot [...] you have scarcely, in your
thoughts, advanced to the stage of science, what-
ever the matter may be’ [6]. The American statisti-
cian William Edwards Deming summarized these
concepts further: ‘Without data, you are just
another person with an opinion’ [7].
Additional meaning emerges when considering
large amounts of data at once. The expression ‘big
data’ is by now ostensibly familiar to everybody, yet
a formal definition has never been established and
the true concept often slips those who have not been
actively investing in the topic. A fairly practical and
intuitive way to describe it is by referring to datasets
whose size, complexity and dynamic nature are
beyond the scope of traditional analysis methods
[8]. The lack of structure of the information con-
tained in such datasets, its unruliness, and the fact of
not being immediately intelligible are all considered
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ICU management based on big data Falini et al.
implicit attributes, so it should not come as a sur-
prise that advanced mathematical models and com-
plex deciphering algorithms are required to make
sense of such tangled mess.
The discipline dedicated to the task is called data
science, and it draws concepts from mathematics,
statistics, informatics, and computer science. It
relies on machine learning, which is, in most cases,
just a fancier way to refer to statistical modelling
&&
[9 ]. In a broader sense, it defines the set of meth-
ods, processes, and algorithms aimed at extracting
knowledge from structured and unstructured data.
Machine learning models are basically frameworks
on which, by fitting certain parameters, the com-
puter tries to draw inference about the original
data. Fitting a model is similar to adapting the
equation of a straight line to impose its passage in
two points, by adapting the parameters of slope and
y-axis interception.
For most projects, innumerous models can be
trained and fit. Something can be read in this abun-
dance, i.e. that no method is inherently superior to
the others on all datasets. An algorithm may in fact
excel in certain contexts, but lack in others. Assess-
ing the performance of several models in relation to
the required goal, e.g. clinical prediction, becomes
&
paramount in order to choose the best one [10 ].
HISTORY OF MEDICAL DATA
The first documented medical record is inscribed
on papyrus and it is from Ancient Egypt, in the year
1600 BC [11]. By Hippocrates’ times, the idea of
recording data (in this case, notes) about single
patients was formed. Accordingly, the alleged
founder of medicine must have been already aware
of the value of keeping track of patients’ history and
vitals to provide them with better care, as he sug-
gested that such documents be stored and con-
sulted for future treatment of the same patient
[12]. Following this principle, medical charts have
kept growing, and with electronic health records
(EHRs) they nowadays record thousands of data
points per patient.
We are living a paradox in the evolution of
medical data: although in the past there was not
enough data recorded from the available informa-
tion, these days there is no readily intelligible
information from the overwhelming amount of
available data. Processing this data is our current
&&
challenge [13 ].
Medicine has distinguished itself from other
industries by being among the first to recognize
the value of data [14]. The past decades have marked
increasing belief in the need for experimental proof
to guide clinical practice and the birth of an entire
www.co-anesthesiology.com 163
Intensive care and resuscitation
movement of evidence-based medicine [15]. For
years, the imperative has been to only accept evi-
dence of the highest quality, that is randomized
controlled trials (RCTs) planned with statistical
rigor, thoroughly conducted, and possibly with an
ever-increasing number of participants. Unfortu-
nately, these expectations have proved hard to
meet: the proportion of clinical interventions based
on quality evidence rarely exceeds 50% [16], and
earlier estimates report figures even lower than 20%
[17]. Recently, the disadvantages of pursuing exclu-
sively this approach have been pointed out.
Although still considered the strongest study design
to eliminate confounders, RCTs have been criticized
for lacking external validity; also, they impose sig-
nificant costs and long periods of observation
&
[18,19 ]. Although it would be nice to test every
single intervention with trials, it is simply not feasi-
ble. They cannot represent the only framework for
advancing our knowledge.
EXTRAPOLATING KNOWLEDGE IN
MEDICINE
When, in the 1960s, the first prototype of EHR was
elaborated, the premise was to ease access to patient
information. Since then, advancements and avail-
ability of computing power, storage capacity and
networks have allowed EHRs to grow exponen-
tially, and become increasingly more advanced
and pervasive. Nowadays, they can capture many
aspects of patients’ physiology in a progressively
automated fashion [11]. These features, coupled
with their ongoing diffusion, have allowed massive
amounts of patient data to become available for
retrospective studies.
Longitudinal analysis of EHRs has reinstated the
once deprecated concept of observational studies
[20]. Until not so long ago, these used to be relegated
to small physiological studies, or to evaluate inter-
ventions in real-life scenarios, but have been
revamped after the criticism moved to RCTs, espe-
&
cially in ICU [21,22 ]. The innovation is that thanks
to the increasing adoption of EHRs, they can now be
run with very large samples. In comparison to RCTs,
observational studies are appealing for higher effi-
ciency, lower costs, limited research times,
and reproducibility.
On the other hand, they are by definition non-
randomized, and theoretically more prone to bias.
Indeed, association and causality can be difficult to
discriminate only by observations. During World
War II, statistician Abraham Wald helped the US
Navy solving the problem of reinforcing war air-
planes after air battles. Before his contribution, air-
crafts were being reinforced on wingtips and body,
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i.e. the parts where engineers had found most dam-
ages. Wald realized that this approach was flawed as
it focused only on the planes that made it the
ground, while the truly critical injuries had pre-
vented airplanes to land, making their data unavail-
able for inspection. Engineers were just making the
airplanes heavier without realizing where the real
problem was (engines and cockpit) [23].
Reversely, it is undeniable that with proper
observation and empirical testing improvement
can be achieved quickly. One of the first applica-
tions of Data Science that led from observations to a
precise intervention is the cholera outbreak in Broad
Street, London in 1854. Anesthesiologist and epide-
miologist John Snow was able to identify the asso-
ciation between cholera deaths and the use of water
from a specific water pump. His hypothesis found
confirmation when the simple intervention of
removing the water handle solved the outbreak [24].
Although there are reports of a very high degree
of correlation between findings of randomized and
nonrandomized trials [25,26], it would be a mistake
to get rid of RCTs. Research has to find a way to work
with observational studies and trials in a synergic
way [27]. Big Data needs to meet Big Trials. Data
Science could help stratify in a more precise fashion
the phenotypes of patients in which interventions
&
can be tested better and faster [28 ].
INTENSIVE CARE DATA
In general, EHRs mostly collect text data, such as
clinical notes, and, to a minor extent, structured
data, such as vital parameters and lab results. For
noncritical patients, the rate at which data is entered
into EHRs is relatively low, and only comprise rou-
tinely vitals check followed by an assessment note
from the clinician. On the contrary, in ICUs, where
patients’ health is at risk and must be judiciously
kept under surveillance, routine checks are espe-
cially frequent and vitals are continuously moni-
tored in high resolution [29].
For this reason, Intensive Care Medicine (ICM),
compared with other medical specialities, is partic-
ularly keen on generating large volumes of data.
True, it does not yet embed the -omic components
that oncology or haematology can boast, but it is
likely only a matter of time: studies that focus on the
different responses to therapies based on gene
expression profiling are already being published in
&
swarms [30,31 ,32]. Likewise, it does not offer as
much high-resolution imaging as radiology or
pathology. Yet the instability that characterizes
the typical ICU patient requires uninterrupted mon-
itoring of physiological parameters, frequent blood
sampling, multiple clinical examinations per day,
Volume 33  Number 2  April 2020

Table 1. Types of data recorded regarding ICU patients and their frequency
Type Density
Demographics Single value
Blood tests At least 1/day
Finger stick test 0–1 times/hour
Blood-gas analysis 1–12 times/day
Bedside radiology 2–7 times/week
Advanced imaging 0–3 times/week
Microbiology 1–5 times/week
Intermittent monitoring 0.5–12 times/hour
Continuous monitoring 1–30 times/second
Ventilatory settings 1–20 times/day
Bolus medication dose 1–6 times/day
Continuous infusion dose 1 times/minute
Clinical evaluation 3–12 times/day
Special interventions 0–5 times/week
and often even recurrent X-rays and scans. This
attitude results in a huge amount and variety of
data generated by every single patient, ranging from
notes to waveforms and structured data (Table 1).
This immense resource, is, as a matter of fact,
heavily underused. It appears in the fact that, on
average, humans can process no more than 3 or 4
independent variables at the time [33]. Decision
making in ICM is therefore limited to a relatively
small number of variables, indicated by clinical
guidelines or picked by physicians’ experience,
and ultimately chosen as key indicators of health
deterioration. This limitation does not hold for
computers. Indeed, machine learning shines in this
context, as it can see through thousands of variables
in a very short time, and could be of help with at
least two critical aspects in intensive care: prompt-
ness of response and feature selection.
BENCHMARKING INTENSIVE CARE
The term benchmarking originates from the field of
land surveying, where it refers to the practice of
carving horizontal marks in stone structures to form
a ‘bench’ for the placement of a levelling rod. Such
benchmarks ensure that levelling rods can be repo-
sitioned identically in future occasions, and conse-
quently that comparison between measurements
made at different times can be accurate. The expres-
sion has then spread to the business sector, where it
broadly indicates the custom of measuring the per-
formance of a company or its processes against those
of the competitors, and more typically of the indus-
try leaders, which are thus taken as reference. By
using a series of standardized indicators, it is aimed
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ICU management based on big data Falini et al.
Examples
Age, sex, height, BMI, comorbidities
Electrolytes, blood count
Glucose if decompensated diabetes
pH, PaCO2, PaO2, electrolytes, lactate levels
Chest X-ray
CT scan, MNR scan
Culture from specimens
Noninvasive blood pressure measurement, urine output
ECG, SpO2, temperature, invasive arterial pressure, ventilator curves
Mode of ventilation, end-expiratory pressure, respiratory rate
Antibiotics, proton pump inhibitors, corticosteroids
Noradrenaline, propofol, maintenance fluids
Doctor’s notes, nursing
Admission, discharge, CVC insertion, surgery
at identifying suboptimal processes and at generat-
ing ideas for improvement.
Similarly, experts and medical societies have
explicitly endorsed the adoption of quality indica-
tors and performance assessment of ICUs [34,35].
Intuitively, it is only by measuring performance that
upgrades from baseline can be appreciated, and thus
that the efficacy of certain interventions be recog-
nized and quantified [36]. Furthermore, there is
increasing evidence arguing that investments in this
direction are cost-effective and have been a major
force in improving outcomes of critical patients
by minimizing diagnostic error and therapeutic
&
harm [19 ].
Despite the positive trend toward better patient
outcomes, it appears in fact that the choice of func-
tional indicators for benchmarking is far from
straight-forward, and their implementation is rife
with challenges [37]. For example, standardized
mortality ratios have long been used for this pur-
pose, yet they rely on prognostic scores that have
ultimately failed to test for external validation, and
thus they have been criticized for substantial bias;
the same can be said about ICU length of stay, too
heavily influenced by the availability of step-down
units or extra-hospital postacute care facilities [38].
Big data tools, in the form of predictive models or
cluster analyses, are expected to improve this aspect
by allowing more accurate profiling of patients and
better corrections for the case-mix bias [39].
ISSUES IN THE IMPLEMENTATION
If it truly could be so helpful and in so many ways,
why is not machine learning already in use in ICU?
www.co-anesthesiology.com 165
Intensive care and resuscitation
The first issue is that algorithms need data to be
viable. For some models, especially those falling in
the ‘deep learning’ umbrella, data from millions of
patients. Such amounts are only now starting to be
available. Often all this data is collected exclusively
for administrative purposes in hospital servers, or is
secured by EHR manufacturers, and not made avail-
able to the extended research community. It is only
recently that the researchers have had the opportu-
nity to work with vast ICU databases, first among all
the Medical Information Mart for Intensive Care III
(MIMIC-III), developed by MIT’s Laboratory for
Computational Physiology in collaboration with
Beth Israel Deaconess Medical Center in Boston
[29]. MIMIC-III was a milestone in the field, offering
structured and waveform data from more than 40
000 ICU patients. Afterwards, other major databases
were publicly released, such as the eICU, with more
than 200 000 admissions from several hospitals
&&
around the United States [40 ]. Among the latest
releases is Amsterdam UMC’s database, providing a
&&
first insight into the European population [41 ].
A second, greater, bottleneck in the application
of machine learning in ICM is the lack of standardi-
zation. Different standards in data collection repre-
sent a steep barrier to overcome, and ultimately
translate into major difficulties when trying to
aggregate multiple data sets in a single workable
database. Realistically, a solution to this problem
can only be found by healthcare workers and data
scientists together. A shared infrastructure is yet to
be developed, but signs of progress can be seen in the
identification of standards for the exchange of clin-
ical data [42]. Common ICU dictionaries are
largely awaited.
The third issue, partly a consequence of the first
two, is the external validity of the analyses per-
formed on such databases. For example, MIMIC-
III only stores data collected between 2001 and
2012 (time constraint), in the Boston area (geo-
graphical constraint), and regarding mostly Cauca-
sian patients (variety constraint). It is hard to assess
if models trained on such data could be reliable in
other contexts, and it is likely that they would favor
patients with characteristics similar to those of the
original data. Only when both handicaps of quan-
tity and variety will be solved we will be able to talk
about true Big Data in ICU. The prospects are com-
pelling, major initiatives are being taken all around
the world, and the outlook is favorable as awareness
grows [43].
One final consideration regarding the aforemen-
tioned ‘correlation versus causation’ issue is due: as
already stated, when using observational data, it is
not possible to assert the causality of events,
but only correlation amongst those [44]. Model
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outputs must therefore be inspected with extra
care to make sure that learning is being done coher-
&
ently [45 ]. Hence, clinical input from physicians
will continue playing a major role for the full
development pipeline of artificial intelligence
algorithms, as in them resides the experience and
generalized knowledge that current technology
&&
cannot sustain [13 ,46].
USE CASES
Reports of machine learning algorithms in ICM have
so far been copious, but so far limited to research
&& & &
[47 ], with very few exceptions [48 ,49 ]. Indeed,
barriers to the prospective implementation of learn-
ing models are still holding strong, yet multiple
scenarios of application can be hypothesized.
Assuming unsupervised, supervised, and reinforce-
ment learning (Fig. 1), and data augmentation as the
major areas of machine learning research, some use
cases can be found for each.
Unsupervised models (Table 2) are used to find
patterns in data and differ from supervised models as
they don’t require any outcome. These algorithms
compute distances between observations and then
infer a degree of similarity amongst those. The
concept of distance here can take several different
meanings and formulations depending on the con-
text, but the key is to identify analogies between
observations. For instance, responses to medications
(i.e. vasopressors) are also a function of a patient’s
physiology, and not all patients respond in the same
manner. Clustering models could help in detecting
subgroups with similar responses to treatment,
based on additional covariates related to their
health history or parameters. Clusters would also
be of use to fine-tune doses and medications, thus
providing support to clinicians in the decision
process.
Supervised models, on the other hand, require
an outcome or classification to be trained on. They
answer questions like ‘how likely is this observation
to belong to class X?’, which can be easily turned in a
prediction framework. Examples of supervised mod-
els can be found in the yearly CinC/Physionet chal-
lenges on physiological data, such as the automatic
classification of ECGs, or prediction of severe hypo-
&&
tension and sepsis [50 ,51,52].
Reinforcement learning refers to a family of
models that falls somewhat in-between the previous
two. They learn from interacting in an environment
to take the action that yields to the highest reward.
In a recent example, the titular ‘AI clinician’ is
reported learning the best strategy to maximize
survival of a septic patient by choosing between
&&
supplying fluids and dosing vasopressors [53 ].
Volume 33  Number 2  April 2020
 ICU management based on big data Falini et al.

FIGURE 1. Three major types of machine learning paradigms. From top to bottom: in supervised frameworks the training set is
labelled and a prediction has to be made regarding a new value; unsupervised models find patterns in unlabeled data using
distances; in reinforcement learning, the agent tests actions and maximizes the reward function.

Finally, data augmentation models, namely gen- synthesized, and the generator, whose goal is
erative adversarial networks [54], leverage two com- deceiving the first. Ultimately, after training on
peting algorithms: the discriminator, whose goal is data, the generator should be able to create data
understanding if the output of the other is real or so similar to the original that the discriminator

Table 2. Paradigms of machine learning models and their application

Paradigm Techniques Scope Examples

Unsupervised learning K-Means Pattern discovery Identification of ICU patients with similar clinical trajectories
Hierarchical clustering Susceptibility of response to therapies
Biclustering Phenotypes of septic patients
Self-organizing maps
Supervised learning K-nearest neighbors Regression / prediction Prediction of hypotensive episodes
Linear regression Prediction of length of stay in ICU
Logistic regression Estimation of risk of mortality
Random forests Classification Assessment of sedation
X gradient boosting Prediction of survival
Neural networks
Reinforcement learning SARSA Policy discovery Weaning from mechanical ventilation
Deep Q network Optimal sepsis treatment
DDPG Antibiotic dosing strategy

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Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Intensive care and resuscitation
won’t be able to recognize it. The methodology may
be employed to augment data of any kind, such as
ECGs [55], to train models when the available data
are scarce.
Generative and reinforced models are expected
to see the greatest development in ICU data science,
thanks to their capabilities and yet uncovered
potential.
CONCLUSION
The data science revolution in ICM has started. As
shown, data can be used for benchmarking, clinical
decision support, and research. Machine learning
algorithms can identify hidden patterns in clinical
data. There are, as expected, both benefits and risks
in this opportunity, because finding associations
does not mean proving causality. There is an urgent
need for data sharing and common data dictionar-
ies. The intensive care community has to embrace
and guide the Data Science Revolution to improve
patients’ outcomes.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Asimov I. I, Robot. New York: Gnome Press; 1950.
2. Contributors to Wikimedia projects. Hippocratic oath. Wikipedia; 2002. https://
en.wikipedia.org/wiki/Hippocratic_Oath. Accessed 13 December 2019
3. Makary MA, Daniel M. Medical error-the third leading cause of death in the US.
BMJ 2016; 353:i2139.
4. Haynes AB, Weiser TG, Berry WR, et al. A surgical safety checklist to reduce
morbidity and mortality in a global population. N Engl J Med 2009;
360:491–499.
5. Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease
catheter-related bloodstream infections in the ICU. N Engl J Med 2006;
355:2725–2732.
6. Thomson W. Electrical units of measurement. In: Popular lectures and
addresses, Vol. 1: Constitution of matter. London, UK: Macmillan; 1889.
pp. 73–136.
7. Contributors to Wikimedia projects. W. Edwards Deming. Wikipedia; 2002.
https://en.wikipedia.org/wiki/W._Edwards_Deming. Accessed 13 December
2019
8. Docherty AB, Lone NI. Exploiting big data for critical care research. Curr Opin
Crit Care 2015; 21:467–472.
9. Cosgriff CV, Celi LA, Stone DJ. Critical care, critical data. Biomed Eng
&& Comput Biol 2019; 10:1179597219856564.
The present review remarks the necessity of quality data to produce robust AI
models for clinical purposes. Open databases for research and the development of
a collaborative form of clinical data science should be endorsed in this delicate
transition phase.
168 www.co-anesthesiology.com
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
10. Shah ND, Steyerberg EW, Kent DM. Big data and predictive analytics:
& recalibrating expectations. JAMA 2018; 320:27–28.
This viewpoint highlights 4 reasons for the longstanding hesitance to bring
predicting analytics into clinical practice: recurrent unfitness for risk-sensitive
decisions, failure to include calibration during model evaluation, hyped expecta-
tions from vendors, and heterogeneity of data formats.
11. Evans RS. Electronic health records: then, now, and in the future. Yearb Med
Inform 2016; 25:S48–61.
12. Dalianis H. The history of the patient record and the paper record. In:
Dalianis H, editor. Clinical text mining. Cham, Switzerland: Springer; 2018.
pp. 5–12.
13. Topol EJ. High-performance medicine: the convergence of human and arti-
&& ficial intelligence. Nat Med 2019; 25:44–56.
In this extensive review, best-selling author and prolific researcher Topol puts in
perspective both the potential and limitations of AI applied to healthcare. Review-
ing the achievements obtained in the different medical branches, he redimensions
the common hype and reminds the reader that the much-feared full automation is
unlikely to ever be implemented.
14. Murdoch TB, Detsky AS. The inevitable application of big data to healthcare.
JAMA 2013; 309:1351–1352.
15. Bothwell LE, Greene JA, Podolsky SH, Jones DS. Assessing the gold
standard–lessons from the history of RCTs. N Engl J Med 2016;
374:2175–2181.
16. Ebell MH, Sokol R, Lee A, et al. How good is the evidence to support primary
care practice? Evid Based Med 2017; 22:88–92.
17. Darst JR, Newburger JW, Resch S, et al. Deciding without data. Congenit
Heart Dis 2010; 5:339–342.
18. Frieden TR. Evidence for health decision making - beyond randomized,
controlled trials. N Engl J Med 2017; 377:465–475.
19. Niven AS, Herasevich S, Pickering BW, Gajic O. The future of critical care lies
in quality improvement and education. Ann Am Thorac Soc 2019;
&
16:649–656.
In this review, it is explained why investments in quality improvement, adherence to
standards and guidelines, and integration of evidence-based interventions repre-
sent the best way not only to boost patient outcomes, but also to reduce the noise
that confounds numerous RCTs.
20. Nair S, Hsu D, Celi LA. Challenges and opportunities in secondary analyses
of electronic health record data. In: MIT Critical data, editor. Secondary
analysis of electronic health records. Cham, Switzerland: Springer; 2016.
pp. 17–26.
21. Vincent J-L. We should abandon randomized controlled trials in the intensive
care unit. Crit Care Med 2010; 38:S534–S538.
22. Girbes ARJ, De Grooth H-J. Time to stop randomized and large pragmatic
& trials for intensive care medicine syndromes: the case of sepsis and acute
respiratory distress syndrome. J Thorac Dis 2020; 12:S101–S109.
Using Monte Carlo simulations, the authors demonstrate that syndrome-attribu-
table risks of ICM diagnoses are often overestimated, and how this phenomenon
leads to underpowering of RCTs and ultimately to their often negative results: a
renewed focus on mechanistic research is seeked.
23. Operations Evaluation Group. A Reprint of ‘A Method of Estimating Plane
Vulnerability Based on Damage of Survivors’ by Abraham Wald. Alexandria,
VA: Center for Naval Analyses; 1980.
24. Snow J. On the mode of communication of cholera. London, UK: John
Churchill; 1855.
25. Ioannidis JP, Haidich AB, Pappa M, et al. Comparison of evidence of treatment
effects in randomized and nonrandomized studies. JAMA 2001; 286:
821–830.
26. Schmidt AF, Rovers MM, Klungel OH, et al. Differences in interaction and
subgroup-specific effects were observed between randomized and nonran-
domized studies in three empirical examples. J Clin Epidemiol 2013;
66:599–607.
27. Angus DC. Fusing randomized trials with big data: the key to self-learning
healthcare systems? JAMA 2015; 314:767–768.
28. Timsit J-F, Aboab J, Parienti J-J. Is research from databases reliable? Yes.
& Intens Care Med 2019; 45:118–121.
This editorial addresses the potential uses of secondary analyses from databases:
although unfit to provide causal inference, they could be instrumental in raising new
hypotheses for RCTs, or in increasing levels of confidence and ensuring general-
izability of results.
29. Johnson AEW, Pollard TJ, Shen L, et al. MIMIC-III, a freely accessible critical
care database. Sci Data 2016; 3:160035.
30. Scicluna BP, van Vught LA, Zwinderman AH, et al. Classification of patients
with sepsis according to blood genomic endotype: a prospective cohort
study. Lancet Respir Med 2017; 5:816–826.
31. Antcliffe DB, Burnham KL, Al-Beidh F, et al. Transcriptomic signatures in
& sepsis and a differential response to steroids. From the VANISH Randomized
Trial. Am J Respir Crit Care Med 2019; 199:980–986.
This post-hoc analysis from the VANISH trial identifies an association between
transcriptomic sepsis response signatures and response to corticosteroids in
terms of mortality in septic patients. It is the first study addressing gene expression
profiling in critically-ill adults receiving steroids and adds experimental evidence to
the growing awareness that the ‘one size fits all’ approach is often not appropriate,
and possibly a cause of many negative trials.
Volume 33  Number 2  April 2020

32. Rello J, van Engelen TSR, Alp E, et al. Towards precision medicine in sepsis: a
position paper from the European Society of Clinical Microbiology and
Infectious Diseases. Clin Microbiol Infect 2018; 24:1264–1272.
33. Halford GS, Baker R, McCredden JE, Bain JD. How many variables can
humans process? Psychol Sci 2005; 16:70–76.
34. Rhodes A, Moreno RP, Azoulay E, et al. Prospectively defined indicators to
improve the safety and quality of care for critically ill patients: a report from the
Task Force on Safety and Quality of the European Society of Intensive Care
Medicine (ESICM). Intensive Care Med 2012; 38:598–605.
35. De Lange DW, Dongelmans DA, De Keizer NF. Small steps beyond bench-
marking. Rev Bras Ter Intens 2017; 29:128–130.
36. Peden CJ, Rooney KD. The science of improvement as it relates to quality and
safety in the ICU. J Intens Care Soc 2009; 10:260–265.
37. Woodhouse D, Berg M, van der Putten J, Houtepen J. Will benchmarking
ICUs improve outcome? Curr Opin Crit Care 2009; 15:450–455.
38. Salluh JIF, Soares M, Keegan MT. Understanding intensive care unit bench-
marking. Intens Care Med 2017; 43:1703–1707.
39. Salluh JIF, Chiche JD, Reis CE, Soares M. New perspectives to improve
critical care benchmarking. Ann Intensive Care 2018; 8:17.
40. Pollard TJ, Johnson AEW, Raffa JD, et al. The eICU Collaborative Research
&& Database, a freely available multicenter database for critical care research. Sci
Data 2018; 5:180178.
The article describes in detail the structure of the eICU Collaborative Research
Database, a US-based multicenter database with high granularity data for over 200
000 ICU admissions monitored by Philips Healtcare’s telehealth system. The
database is de-identified and publicly accessible for research purposes, and the
paper can be used as guidance for its interrogation.
41. Amsterdam UMC Database. Amsterdam Medical Data Science. https://amster-
&& dammedicaldatascience.nl/#amsterdamumcdb. Accessed 13 December 2019.
Officially released in November 2019, this is the first publicly accessible ICU
database from within the European Union, endorsed by the European Society of
Intensive Care Medicine, and containing de-identified data from tens of thousands
of ICU admissions.
42. Bender D, Sartipi K. HL7 FHIR: An Agile and RESTful approach to healthcare
information exchange. In: Pereira Rodrigues P, Pechenizkiy M, Gama J,
editors. Proceedings of the 26th IEEE International Symposium on Compu-
ter-Based Medical Systems (CBMS’13, Porto, Portugal, June 20-22, 2013).
Piscataway NJ: Institute of Electrical and Electronics Engineers; 2013.
43. Aboab J, Celi LA, Charlton P, et al. A ‘datathon’ model to support cross-
disciplinary collaboration. Sci Transl Med 2016; 8:333s8.
44. Bailly S, Meyfroidt G, Timsit J-F. What’s new in ICU in 2050: big data and
machine learning. Intens Care Med 2018; 44:1524–1527.
45. Roth JA, Battegay M, Juchler F, et al. Introduction to machine learning in
& digital healthcare epidemiology. Infect Control Hosp Epidemiol 2018; 39:
1457–1462.
In this review, the importance of adding machine learning to an epidemiologist’s
armamentarium is reviewed, in order to better exploit the potential of big data for
infection prevention and control, quality improvement, and optimal allocation of
hospital resources.
46. Bundy A. Preparing for the future of Artificial Intelligence. AI Soc 2017;
32:285–287.
0952-7907 Copyright ß 2020 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
ICU management based on big data Falini et al.
47. Shillan D, Sterne JAC, Champneys A, Gibbison B. Use of machine learning to
&& analyse routinely collected intensive care unit data: a systematic review. Crit
Care 2019; 23:284.
The present review is important as it reports the trends in research studies that
employ machine learning on routinely collected ICU data. It gives an overview of the
approaches, techniques and results: clinical prediction models are the most
common, they are rapidly increasing throughout the years, and mostly adopt
neural networks, support vector machines, and tree-based methods.
48. Roggeveen LF, Fleuren LM, Guo T, et al. Right Dose Right Now: bedside
& data-driven personalized antibiotic dosing in severe sepsis and septic shock -
rationale and design of a multicenter randomized controlled superiority trial.
Trials 2019; 20:745.
This trial is among the first ones to implement a real-time clinical decision support
system. In this case, a platform capable of guiding antibiotic dosing will be
evaluated prospectively in terms of pharmacometric and clinically relevant end-
points against standard practice.
49. McWilliams CJ, Lawson DJ, Santos-Rodriguez R, et al. Towards a decision
& support tool for intensive care discharge: machine learning algorithm devel-
opment using electronic healthcare data from MIMIC-III and Bristol, UK. BMJ
Open 2019; 9:e025925.
This study focuses on the validity of a clinical decision support system aimed at
optimizing discharge from ICU, a very useful topic in a time of increasing demand
and constrained resources. It employs two different databases (US- and UK-
based) yet finds consistent results.
50. Reyna MA, Josef CS, Jeter R, et al. Early prediction of sepsis from clinical data.
&& Crit Care Med 2019; 1. [Epub ahead of print]
The PhysioNet/Computing in cardiology challenge is an international competition
held annually in which participants submit novel algorithms of complex physiologic
signal processing for medical classification problems. For the 20th-year edition the
goal was to predict sepsis, hoping to contribute to the long-standing goal of early
detection for improved outcomes.
51. Moody G, Lehman L. Predicting acute hypotensive episodes: the 10th annual
PhysioNet/Computers in cardiology challenge. Comput Cardiol 2009;
36:541–544.
52. Clifford GD, Liu C, Moody B, et al. AF classification from a short single lead
ECG recording: the PhysioNet/Computing in cardiology challenge. Comput
Cardiol 2017; 44:065–469.
53. Komorowski M, Celi LA, Badawi O, et al. The Artificial Intelligence Clinician
&& learns optimal treatment strategies for sepsis in intensive care. Nat Med 2018;
24:1716–1720.
This original research article is of outstanding interest as the first adopting
reinforcement learning in ICM and among the first throughout all healthcare.
Moreover, it provides additional insight on the best policy to apply for the
hypotensive septic patient, helping to dissipate the perennial debate between
fluids and vasopressors. It is expected that this kind of modeling will reach notable
expansion in the following years.
54. Goodfellow I, Pouget-Abadie J, Mirza M, et al. Generative adversarial nets.
Adv Neural Inform Process Syst 2014; 27:2672–2680.
55. Esteban C, Hyland SL, Rätsch G. Real-valued (Medical) time series generation
with recurrent conditional GANs; 2017. http://arxiv.org/abs/1706.02633.
Accessed 13 December 2019.
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