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The Management of Sepsis

Christine A. Zawistowski, MD

Management of sepsis in the pediatric patient is guideline


driven. The treatment occurs in two phases, the first hour being
the most crucial. Initial treatment consists of timely recognition
of shock and interventions aimed at supporting cardiac output
and oxygen delivery along with administration of antibiotics.
The mainstay of treatment for this phase is fluid resuscitation.
For patients in whom this intervention does not reverse the
shock medications to support blood pressure should be started

and respiratory support may be necessary. Differentiation


between warm and cold shock and risk factors for adrenal
insufficiency will guide further therapy. Beyond the first hour of
treatment patients may require intensive care unit care where
invasive monitoring may assist with further treatment options
should shock not be reversed in the initial hour of care.
Curr Probl Pediatr Adolesc Health Care 2013;43:285-291

Introduction

The seminal study for early goal-directed therapy


was published in 2001.4 Adult patients with septic
uidelines were developed for the management
shock were randomized upon presentation to the
of sepsis when it was noted that mortality from
emergency department to early goal-directed therapy
sepsis had not improved in a decade. Pediatric
or conventional therapy. Those in the study arm had
specic guidelines rst appeared in 2002.1 These were
arterial and central venous catheters placed for monthen updated in 2007 and again in 2013.2,3 The general
itoring. Therapeutic goals for treatment included mainprinciples of resuscitation follow those of the pediatric
taining the central venous pressure, mean arterial
advanced life-support program.
pressure, and superior vena cava saturations within
specic parameters. In-hospital mortality was signiBackgroundEarly Goal-Directed
cantly less in the goal-directed therapy group (30.5%
Therapy
vs. 46.5%, p 0.0009). This was the rst large-scale
study that showed a reduction in mortality from sepsis
Resuscitation should commence in the emergency deand demonstrated the importance of early recognition
partment once sepsis is suspected. The mainstay of initial
and aggressive resuscitation.
therapy is early aggressive treatment to restore the balance
4
Further studies continued to
between oxygen delivery and demand.
show
the benets of early recogEarly therapy aims to improve preload,
The
mainstay
of
initial
nition and aggressive treatment
afterload, and contractility. This is
therapy
is
early
aggressive
of sepsis. A meta-analysis of 21
accomplished through the use of uids,
randomized controlled trials of
treatment to restore the
vasoactive substances, oxygen, antibiotics, and optimization of ventilation.
balance between oxygen sepsis showed a 23% mortality
difference between control and
Targeted end points look for improvedelivery and demand.
protocol groups in severely ill
ment in perfusion, taking into account
patients (control group patients
vital signs, examination ndings, and
with 420% mortality) when
laboratory ndings. Early studies showed the survival
patients with acute critical illness are treated early to
benet of early aggressive uid resuscitation, which was
4,5
achieve goals prior to organ failure.6 A retrospective
also found to be true in adult patients.
analysis of 91 infants and children showed a greater than
9-fold increased odds of survival with prompt recogniFrom the Department of Pediatrics, Division of Pediatric Critical Care,
NYU School of Medicine, New York, NY.
tion and treatment of shock.7 In 2002 the rst pediatric
Curr Probl Pediatr Adolesc Health Care 2013;43:285-291
guidelines for the management of pediatric and neonatal
1538-5442/$ - see front matter
patients in septic shock were published.1 The guidelines
& 2013 Mosby, Inc. All rights reserved.
were time based with the rst 60 min being the most
http://dx.doi.org/10.1016/j.cppeds.2013.10.005

Curr Probl PediatrAdolesc Health Care, November/December 2013

285

crucial. Goals and parameters were dened by both


clinical and oxygen-utilization variables. Goals of therapy included capillary rell less than 2 s, urine output of
at least 1 mL/kg/h, normal pulses without a differential
between peripheral and central pulses, a mixed venous
oxygen saturation greater than 70%, declining lactate
and base decit, and an improved level of consciousness.
The guidelines were developed from the best data
available and many recommendations are expert consensus of that data due to the small numbers of studies
and small sample sizes within the studies. Data collected
as a result of the 2002 guidelines demonstrated that they
were useful, effective, and caused no evidence of harm.2
The guidelines were updated in 2007 and again in 2013
and have remained largely unchanged due to lack of new
evidence to the contrary.

Management (Tables 1 and 2)


The management of sepsis is divided into that for the
rst hour and then subsequent care. The initial hour of
resuscitation often occurs in the emergency department, as that is often the entry point into the healthcare
system for patients in septic shock.

Time 05 min
The timeline for treatment starts in the rst 5 min
with the recognition of shock and should ideally be
prior to the onset of hypotension. Clinical signs of
shock include an alteration of body temperature with
hypothermia or hyperthermia, alteration in mental
status, and peripheral vasodilation (warm shock) or

TABLE 1. Algorithm for time sensitive goal-directed, stepwise management of shock in infants and children2

Time
Recognition
05 min

Shock not reversed


Initial resuscitation
515 min

Shock not reversed


Fluid-refractory shock
1560 min

Shock not reversed


Catecholamine-resistant shock
460 min
Pediatric Intensive Care Unit
Monitor CVP, SCVO2470%
Cold shock with normal BP
1. Titrate uid and epinephrine SVCO2 470% and
Hgb 410 g/dL
2. SVCO2 o70%, add vasodilator with uid loading,
consider levosimendan

Shock not reversed


Persistent catecholamine-resistant shock

Shock not reversed


Refractory shock

Intervention
1. Recognize shock: decreased mental status and perfusion
2. Begin high-ow oxygen
3. Establish IV/IO access

1. Push boluses of 20 ml/kg isotonic saline or colloid 460 ml/kg until perfusion
improves or rales or hepatomegaly develop
2. Correct hypoglycemia
3. Correct hypocalcemia
4. Start antibiotics

1.
2.
3.
4.

Begin inotrope via IV/IO


Obtain central access and airway if needed
Cold shock: titrate dopamine, if resistant titrate epinephrine
Warm shock: titrate norepinephrine

Begin hydrocortisone if at risk for adrenal insufciency

Cold shock with low BP


1. Titrate uid and epinephrine SVCO2 470%
and Hgb 410 g/dL
2. BP still low, consider norepinephrine
3. SVCO2 o70%, consider milrinone or
levosimendan

Warm shock with low BP


1. Titrate uid and norepinephrine
SCVO2 470%
2. BP still low, consider vasopressin
3. SCVO2 o70%, consider low-dose
epinephrine

1. Rule out/correct: pericardial effusion, pneumothorax, and elevated intra-abdominal


pressure
2. Consider advanced monitoring tools to guide therapy with goal CI 43.3 and
o6.0 L/min/m2

ECMO

CI, cardiac index.

286

Curr Probl Pediatr Adolesc Health Care, November/December 2013

TABLE 2. Medications used to treat shock

Agent

Clinical effect

Dose

Dopamine

Increased cardiac output, increased inotropic effects, increased heart


rate, and arterial vasoconstriction
Increased heart rate, decreased stroke volume, and increased cardiac
output
Vasoconstriction and increased mean arterial pressure
Increased myocardial contractility, increased venous and arterial
dilation, decreased preload, and decreased systemic vascular
resistance
Increased systemic vascular resistance and vasoconstriction
Suppress production of cytokines; increase sensitivity of the
cardiovascular system to catecholamines, improving contractility,
stroke volume, and systemic vascular resistance; replace insufcient
endogenous steroids
Increase blood calcium level
Increase blood calcium level
Increase blood glucose level

2 mcg/kg/min titrated up to 10 mcg/kg/min

Epinephrine
Norepinephrine
Milrinone

Vasopressin
Hydrocortisone

Calcium chloride
Calcium gluconate
Dextrose

constriction (cold shock). Heart rates outside the


normal range are a good early indicator of shock.
Threshold heart rates found to be associated with an
increased mortality in critically ill infants were less
than or equal to 90 beats per minute (bpm) or more
than 160 bpm; in critically ill children, they were found
to be less than 70 bpm or greater than 150 bpm.8
Within the rst 5 min after recognition of shock, highow oxygen via a face mask should be started and
intravenous or intraosseous access obtained. For
patients who do not maintain oxygen saturations 494% on high-ow face mask oxygen and/or
exhibit increased work of breathing high-ow nasal
cannula (HFNC) or nasopharyngeal continuous positive airway pressure (CPAP) should be instituted to
increase functional residual capacity and decrease
work of breathing.

Time 515 min


The next 10 min of management (time 5 min through
15 min) is aimed at restoration of normal mental status,
threshold heart rates, peripheral perfusion (capillary
rell o2 s), palpable distal pulses, and normal blood
pressure for age. The mainstay therapy for this stage of
resuscitation is uid administration done as a push over
5-min intervals. Isotonic saline or colloid in aliquots of
20 mL/kg is rapidly administered manually. Emergency medicine research has shown that this can be
done either through a peripheral intravenous catheter or
central venous catheter.9 Fluid is administered up to or
more than 60 mL/kg. Initial therapy usually requires
4060 mL/kg but can be as much as 200 mL/kg.5

Curr Probl PediatrAdolesc Health Care, November/December 2013

0.05 mcg/kg/min titrated up to 1 mcg/kg/min


0.051 mcg/kg/min
0.51 mcg/kg/min

0.032 mU/kg/min
250 mg/kg/d

10 mg/kg
100 mg/kg
24 mL/kg; 12.5% dextrose if o2 months,
24 mL/kg; 25% dextrose if 42 months

There has traditionally been a concern that large


volumes of uid resuscitation for acute stabilization
increase the incidence of acute respiratory distress
syndrome, but this has shown to not be the case.5,10
Likewise, there is no correlation between large volumes of uid resuscitation and cerebral edema.5,11
There is also no difference in the efcacy of crystalloids (normal saline, and Lactated Ringer's) vs. colloids (dextran, gelatin, and 5% albumin) as the choice
of uid for acute volume resuscitation.1214 After each
administered bolus, the patient should be assessed for
improvement in perfusion, rales, increased work of
breathing, hypoxemia, and hepatomegaly.
During this stage of resuscitation glycemic status and
calcium status should be checked and corrected to
maintain metabolic homeostasis. Hypoglycemia
can cause neurologic damage when missed. Glucose
infusion rates of 68 mg/kg/min in newborns or
46 mg/kg/min in non-newborns should be targeted.
This need can often be met by providing 10% dextrose
in addition to saline as maintenance intravenous uids.
Patients with liver failure require higher glucose
infusion rates to meet the body's needs. Conversely,
hyperglycemia should be avoided as well, as levels 4140 mg/dL were found to be a risk factor for
mortality.15 Hypocalcemia, dened as an ionized
calcium o1.025 mmol/L or total serum calcium o8.5 mg/dL, should also be quickly identied and
corrected as it is a frequent contributor of reversible
cardiac dysfunction.16,17 Calcium can be repleted
either using calcium chloride at a dose of 10 mg/kg
or calcium gluconate at a dose of 100 mg/kg. Centrallined administration is preferred for calcium chloride

287

as extravasation of calcium can result in severe


necrosis and tissue sloughing. Both preparations can
be given as an intravenous push over 35 min or as an
infusion over 1-h. The goal of therapy should be to
maintain a normal ionized calcium concentration via
intravenous calcium supplementation.
The nal cornerstone of this stage of resuscitation is
administration of broad-spectrum antibiotics once appropriate cultures have been obtained. The initial antibiotics
should be broad enough to cover the most likely
pathogens and have adequate penetration into the
presumed primary source of infection. Clinicians should
be aware of specic susceptibility patterns in the
community and institution to help guide initial therapy.
Possible combinations of antibiotics include an extended
spectrum penicillin or third- or fourth-generation cephalosporin or carbapenem aminoglycoside vancomycin. At the end of the initial 15-min period, if
shock is not reversed a second peripheral intravenous
catheter should be inserted and inotrope therapy started.

fold. Fluid-refractory shock is best managed with


invasive hemodynamic monitoring, which in an uncooperative potentially coagulopathic patient is best
accomplished by sedation and immobilization, requiring intubation and mechanical ventilation for optimal
control. Intubation and mechanical ventilation is also an
important intervention for any patient whose cardiovascular function is not rapidly stabilized with uid and
inotropes. Up to 40% of cardiac output may be needed
to support the work of breathing and this can be
unloaded by providing mechanical ventilation. In
addition, the increased intrathoracic pressure provided
by mechanical ventilation reduces left ventricular afterload, which may be benecial to patients with a low
cardiac index and high systemic vascular resistance. In
patients with elevated pulmonary vascular resistance,
ventilator-controlled mild hyperventilation can compensate for metabolic acidosis. Finally, in any patient
with evidence of respiratory failure or impaired mental
status, there should be no hesitation to proceed with
intubation and the initiation of mechanical ventilation.

Time 1560 min


At time point 15 min, if shock is not reversed it is
considered to be uid refractory and inotropes should
be started. The original guidelines published in 2002
recommended obtaining central venous access prior to
starting therapy. It was found that mortality increased
with delay in time to inotropic use due to lack of
central venous access and subsequent guidelines recommended beginning this therapy via an intravenous
or intraosseous catheter. Medications should be titrated
to maintain adequate perfusion. At this point, central
venous access and if needed, an airway, should be
obtained. Ketamine and atropine are the recommended
agents to use for sedation for these procedures. Ketamine is a central N-methyl-D-aspartate (NMDA)
receptor blocker, which blocks nuclear factor B
transcription and reduces systemic interleukin-6 production. Ketamine does not affect the adrenal axis or
cardiovascular stability, making it an ideal agent for
use in patients in shock.18 Atropine is a competitive
antagonist of the muscarinic acetylcholine receptor.
It is administered prior to intubation for one of two
reasons: either to block the action of the vagus nerve,
which can be stimulated with direct laryngoscopy,
especially in small infants or to counteract the sialogogue action of ketamine through its direct antimuscarinic action. Indications for intubation and
mechanical ventilation in a patient in shock are several

288

Cold Shock
Cold shock is a consequence of poor cardiac output and
is evidenced by poor peripheral perfusion with cool
extremities, delayed capillary rell, and diminished or
absent peripheral pulses. Low cardiac output (cold shock)
has been shown to be associated with mortality in
pediatric patients.19,20 Vasoactive agents suitable for the
treatment of cold shock include dopamine and epinephrine administered into the central circulation.21 The dosing
range for dopamine should fall within 59 mcg/kg/min;
at this dose, it works as an inotrope to improve contractility.22 In instances when dopamine is ineffective,
epinephrine in a dosing range of 0.050.3 mcg/kg/min
should be used; in this dosing range, it acts predominantly as a -adrenergic agonist with a resulting increase
in heart rate and stroke volume. It should be noted that
epinephrine stimulates gluconeogenesis and glycogenolysis and inhibits the action of insulin, leading to an
increase in blood glucose. Epinephrine also promotes
increased delivery of lactate to the liver (to be used as a
substrate for glucose production), with a resulting
increase in blood lactate concentration.

Warm Shock
Warm shock is caused by low systemic venous
resistance. Patients in this state appear overly well

Curr Probl Pediatr Adolesc Health Care, November/December 2013

perfused, with ash capillary rell, bounding peripheral


pulses, and a ushed appearance. The vasoactive agent
of choice for this state is centrally administered norepinephrine in a dosing range of 0.051 mcg/kg/min.
Norepinephrine is a potent -adrenergic agonist, which
increases mean arterial pressure as a result of vasoconstriction with little change in heart rate.

pressure, cardiac output, and maintaining oxygen


carrying capacity. At this point, the patient should be
in an intensive care unit and invasive monitoring
should guide further treatment. If not already done, a
central venous catheter should be placed and a central
venous pressure (CVP) recorded and trended. The
optimal CVP for each patient will be dictated by their
clinical condition. Although a CVP of 510 cm H2O is
Time 60 min
considered within normal range, some patients may
require higher levels to maintain cardiac output.
The rst 60 min after the recognition of shock is
Observing the relationship between the CVP and blood
considered the golden hour during which time therapressure (i.e., when the CVP is 18 cm H2O, the patient
pies need to be initiated to reverse the shock. Carcillo
has
normal BP for age, when it drops to 12 cm H2O the
et al.5 showed an improved survival
patient becomes hypotensive)
in patients receiving 440 mL/kg of
will guide the clinician as to what
uid in the rst hour of treatment in a
CVP a patient requires. Vasoacgroup of 34 patients presenting to the
The rst 60 minutes after tive agents and uid should be
emergency department in shock. Han
the recognition of shock is titrated to maintain a normal
et al.7 have shown that for every
mean arterial pressure (MAP)
considered the golden
additional hour of persistent shock,
CVP, which range between 55 for
hour during which time
there is a 42-fold increased odds of
a term newborn and 65 for
therapies need to be
mortality in pediatric patients with
patients who are 2 years of age
septic shock. At time point 60 min, if
initiated to reverse
and older. Mixed venous oxygen
the patient does not have evidence of
the shock.
saturation (SCVO2), an indirect
reversal of shock, they fall into the
indicator of the adequacy of carcategory of having catecholaminediac output to meet tissue metaresistant shock and hydrocortisone therapy should be
bolic demand, should be checked periodically with a
initiated if the patient is at risk for absolute adrenal
goal of maintaining saturations 470%. Normal arterial
insufciency. A patient with purpura fulminans and
oxygen saturation is 100% and mixed venous saturaWaterhouseFriderichsen syndrome, one who has pretion is 470%. In concert with maintenance of cardiac
viously received steroid therapies for chronic illness and
output, hemoglobin concentration is an important
one with pituitary or adrenal abnormalities are all at risk
determinant of oxygen delivery. Maintaining a hemofor adrenal insufciency. A peak cortisol concentratioglobin concentration 410 g/dL is of utmost imporn o18 mcg/dL obtained after corticotropin stimulation
tance in a patient in shock.4,23 For patients with a
is indicative of adrenal insufciency. This test may be
SCVO2 o70% adding a vasodilator with uid loading
helpful to perform in centers with the capability to obtain
can improve oxygen delivery. Agents that can be used
results in a timely fashion (i.e., 30 min or less) but in
are nitrovasodilators, such as sodium nitroprusside,
patients with catecholamine-resistant shock and risk
nitroglycerine, and milrinone. The nitrovasodilators
factors for adrenal insufciency, steroids should not be
recruit microcirculation and reduce ventricular afterwithheld due to lack of results. The dose of steroid can
load, which allows better ventricular ejection and
be titrated over a wide dosing range to achieve resolution
overall improvement in cardiac output. Milrinone
of shock, using between 2 and 50 mg/kg/d of hydroimproves contractility and lowers systemic vascular
cortisone given as a continuous infusion or via interresistance by inhibiting type III phosphodiesterase,
mittent dosing. The hydrocortisone should be weaned off
which in turn increases intracellular cAMP by blocking
as tolerated to minimize toxicity.
its hydrolysis. It is not receptor mediated and is useful
if adrenergic receptors are down regulated or desensitized. Because normal renal function is needed for
Beyond the First Hour
milrinone clearance, the dose should be lowered in
patients with signs of renal insufciency. Milrinone
Beyond the rst hour of treatment, the treatment goal
has a long half-life compared to the other medications
is to improve oxygen delivery by supporting blood

Curr Probl PediatrAdolesc Health Care, November/December 2013

289

and o6.0 L/min/m2, which has been associated with


used to support blood pressure ( mean half-life 2.3 h)
and can cause hypotension, which can be treated with
the best outcomes in septic shock patient.22 For those
norepinephrine or vasopressin. An alternative agent to
patients not aided by these tools, extracorporeal
consider is levosimendan, which exerts a positive
membrane oxygenation (ECMO) should be considinotropic effect by increasing calcium sensitivity of
ered. Survival rates in septic shock patients placed on
myocytes by binding to cardiac troponin C in a
ECMO are 73% for newborns and 39% for older
calcium-dependent manner. It also has a vasodilatory
children.26
effect by opening adenosine-triphosphate-sensitive
Guidelines for the management of shock in children
potassium channels in vascular smooth muscle. Thus,
have been in effect for the last 10 years. They are time
in the endotoxin-induced heart dysfunction of septic
based and can be enacted in whatever setting shock is
shock, levosimendan treats the
rst recognized. The interventions
source of the problem.24 In
are designed to quickly improve
oxygen delivery through mainteinstances where these measures
All practitioners who care nance of cardiac output and timely
are not successful, vasopressin
for pediatric patients are
administration of antibiotics. Since
should be added. Vasopressin is
the original guidelines were puba peptide hormone that increases
encouraged to become
lished, two revisions have been
peripheral vascular resistance via
familiar with these
made, but the content has remained
the V1 receptors found on vasguidelines
as
they
are
clear,
largely unchanged. Many studies
cular smooth muscle of the systemic circulation. It has been concise and can save lives. have tested the recommendations of
the original guidelines. There is
shown to increase systemic vasample evidence that the guidelines
cular resistance, mean arterial
25
are effective and do not cause harm.7,2731 All practiblood pressure, and urine output in septic shock. There are some instances in which the patient remains
tioners who care for pediatric patients are encouraged
in shock despite all of the aforementioned intervento become familiar with these guidelines as they are
tions. After initial assessment for correctable causes,
clear, concise, and can save lives.
such as pericardial effusions, pneumothoraces, and
intra-abdominal hypertension, more advanced tools
must be employed to guide therapy. Pulmonary artery
References
(PA) catheters can assist in the identication of
1. Carcillo JA, Fields AI, American College of Critical Care
selective left ventricular dysfunction and can determine
Medicine Task Force Committee Members. Clinical practice
the relative contribution of right and left ventricular
parameters for hemodynamic support of pediatric and neonatal
work. The measured and derived values that are
patients in septic shock. Crit Care Med 2002;30(6):136578.
2. Brierley J, Carcillo JA, Choong K, et al. Clinical practice
obtained can allow the clinician to titrate medications
parameters for hemodynamic support of pediatric and neonatal
and interventions that affect preload, afterload, and
septic shock: 2007 update from the American College of
contractility and follow-up with subsequent PA cathCritical Care Medicine. Crit Care Med 2009;37(2):66688.
eter measurements to assess the effects of treatment.
3. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis
Pulse index contour cardiac output catheters (PICCO)
campaign: international guidelines for management of severe
estimate global end-diastolic volume in the heart,
sepsis and septic shock: 2012. Crit Care Med 2013;41(2):
580637.
extravascular lung water, and assess adequacy of
4. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed
preload. PICCO catheters were developed as a lesstherapy in the treatment of severe sepsis and septic shock.
invasive way to obtain much of the same information
N Engl J Med 2001;345(19):136877.
that PA catheters provide. The measurements from a
5. Carcillo JA, Davis AL, Zaritsky A. Role of early uid
PICCO catheter allow the clinician to assess cardiac
resuscitation in pediatric septic shock. J Am Med Assoc
1991;266(9):12425.
function and volume status and titrate therapies accord6. Kern JW, Shoemaker WC. Meta-analysis of hemodynamic
ingly. Follow-up measurements are then obtained to
optimization in high-risk patients. Crit Care Med 2002;30(8):
evaluate treatment. Femoral artery thermodilution
168692.
catheters and Doppler ultrasound can also aid in the
7. Han YY, Carcillo JA, Dragotta MA, et al. Early reversal of
assessment of cardiac output. These devices can help
pediatric-neonatal shock by community physicians is associguide therapy to achieve a goal cardiac index of 43.3
ated with improved outcome. Pediatrics 2003;112(4):7939.
290

Curr Probl Pediatr Adolesc Health Care, November/December 2013

8. Pollack MM, Ruttimann UE, Getson PR. Pediatric risk of


mortality (PRISM) score. Crit Care Med 1988;16(11):11106.
9. Stoner MJ, Goodman DG, Cohen DM, et al. Rapid uid
resuscitation in pediatrics; testing the ACCM guidelines. Crit
Care Med 2005;33:A68.
10. Zadrobilek E, Hackl W, Sporn P, Steinbereithner K. Effect of
large volume replacement with balanced electrolyte solutions
on extravascular lung water in surgical patients with sepsis
syndrome. Intensive Care Med 1989;15(8):50510.
11. Powell KR, Sugarman LI, Eskenazi AE, et al. Normalization of
plasma arginine vasopressin concentrations when children with
meningitis are given maintenance plus replacement uid
therapy. J Pediatr 1990;117(4):51522.
12. Ngo NT, Cao XT, Kneen R, et al. Acute management of
dengue shock syndrome: a randomized double-blind comparison of 4 intravenous uid regimens in the rst hour. Clin
Infect Dis 2001;32(2):20413.
13. Cochrane Injuries Group Albumin Reviewers. Human albumin
administration in critically ill patients: systematic review of
randomized controlled trials. Br Med J 1998;317(7153):23540.
14. Oca MJ, Nelson M, Donn SM. Randomized trial of normal
saline versus 5% albumin for the treatment of neonatal
hypotension. J Perinatol 2003;23(6):4736.
15. Lin JC, Carcillo JA. Increased glucose/glucose infusion rate
ratio predicts anion gap acidosis in pediatric sepsis. Crit Care
Med 2004;32(suppl 20):A5.
16. Cardenas-Rivero N, Chernow B, Stoiko MA, Nussbaum SR,
Todres ID. Hypocalcemia in critically ill children. J Pediatr
1989;114(6):94651.
17. Roberton NR, Smith MA. Early neonatal hypocalcaemia. Arch
Dis Child 1975;50(8):6049.
18. Yli-Hankala A, Kirvel M, Randell T, Lindgren L. Ketamine
anaesthesia in a patient with septic shock. Acta Anaesthesiol
Scand 1992;36(5):4835.
19. Pollack MM, Fields AI, Ruttimann UE. Sequential cardiopulmonary variables of infants and children in septic shock. Crit
Care Med 1984;12(7):5549.
20. Pollack MM, Fields AI, Ruttimann UE. Distributions of
cardiopulmonary variables in pediatric survivors and nonsurvivors of septic shock. Crit Care Med 1985;13(6):4549.
21. Perkin RM, Levin DL. Shock in the pediatric patient. Part II.
Therapy. J Pediatr 1982;101(3):31932.

Curr Probl PediatrAdolesc Health Care, November/December 2013

22. Ceneviva G, Pashcal JA, Eckstein J, et al. Hemodynamic


support in uid refractory pediatric septic shock. Pediatrics
1998;102:e19.
23. de Oliveira CF, de Oliveira DS, Gottschald AF, Moura JD,
Costa GA, et al. ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with
and without monitoring central venous oxygen saturation.
Intensive Care Med 2008;34(6):106575.
24. Matejovic M, Krouzecky A, Radej J, Novak I. Successful
reversal of resistant hypodynamic septic shock with levosimendan. Acta Anaesthesiol Scand 2005;49(1):1278.
25. Liedel JL, Meadow W, Nachman J, Koogler T, Kahana MD.
Use of vasopressin in refractory hypotension in children with
vasodilatory shock: ve cases and a review of the literature.
Pediatr Crit Care Med 2002;3(1):158.
26. Skinner SC, Iocono JA, Ballard HO, et al. Improved survival
in venovenous vs venoarterial extracorporeal membrane oxygenation for pediatric noncardiac sepsis patients: a study of the
Extracorporeal Life Support Organization registry. J Pediatr
Surg 2012;47(1):637.
27. Wills BA, Nguyen MD, Ha TL, et al. Comparison of the three
uid solutions for resuscitation in dengue shock. N Engl J Med
2005;353:87789.
28. Maitland K, Pamba A, English M, et al. Randomized trial of
volume expansion with albumin or saline in children with
severe malaria: preliminary evidence of albumin benet. Clin
Infect Dis 2005;40:53845.
29. Ninis N, Phillips C, Bailey L, et al. The role of healthcare
delivery on outcome of meningococcal disease in children:
Case control study of fatal and non-fatal cases. Br Med J
2005;330:1475.
30. de Oliveira CF, de Oliveira DS, Gottschald AF, et al. ACCM/
PALS haemodynamic support guidelines for paediatric septic
shock: an outcomes comparison with and without monitoring
central venous oxygen saturation. Intensive Care Med 2008;
34:106575.
31. Karapinar B, Lin JC, Carcillo JA. ACCM guidelines use,
correct antibiotic therapy, and immune suppressant withdrawal are associated with improved survival in pediatric
sepsis, severe sepsis, and septic shock. Crit Care Med 2004;
32(12 suppl 3):A161.

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