Pediatric Septic Shock
Steve Piecuch, MD, MPH
Department of Pediatrics
Lincoln Medical Center
Definitions: Confuse Rather than
Clarify
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Fuhrman’s textbook: Pediatric Critical Care
– Bacteremia: Viable bacteria in the blood
– Septicemia: Systemic illness caused by spread of
microorganisms and/or associated toxins in the circulation
– Sepsis: Presence of pathogenic organisms somewhere in the
body with accompanying evidence of infection such as
tachycardia, tachypnea, hypothermia, hyperthermia
– Sepsis syndrome: Sepsis with evidence of altered organ
perfusion: E.g., PaO2/FIO2 < 280, lactic acidosis, oliguria
– Septic shock: Hypotension associated with sepsis
 All do not agree that hypotension is required for diagnosis
– Note: Positive blood culture not required for diagnosis of
sepsis/septic shock
More Definitions
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Sharma S, Septic Shock, www.emedicine.com
– Systemic Inflammatory Response Syndrome (SIRS): 2 or more
of the following:
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Temperature > 38 deg C or < 36 deg C
Heart rate > 90 BPM
Respiratory rate > 20 BPM or PaCO2 < 32 mmHg
WBC > 12,000 per ml or < 4,000 per ml or 10% bands
– Sepsis: SIRS in response to a documented infection
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Must also have at least 1 of the following:
– Hypoxemia: PaO2 < 72 mmHg in FIO2 of 0.21
– Oliguria: Urine output < 0.5 ml/kg/hr
– Elevated plasma lactate
– Altered mental status
Biochemical Pathogenesis of
Septic Shock
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Host inflammatory response is central in the pathogenesis of
septic shock
Initiate host inflammatory response:
– Endotoxin of cell wall of GN organisms
– Lipoteichoic acid of GP organisms
Sepsis-initiated inflammatory response has the potential to
involve multiple organs and metabolic pathways
– Impaired oxygen utilization by mitochondria
– Increased cardiac output and systemic vasodilatation
– Increased capillary permeability
– Myocardial depression
– ARDS
Anti-inflammatory Therapy in
Septic Shock
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A number of pathophysiologically-based therapies
designed to counteract the underlying causes of septic
shock are currently under active investigation
– Endotoxin binding and elimination
– Antagonists to specific inflammatory mediators
– Antagonists to leukocyte adhesion
 Leukocyte adhesion to endothelial cells is
necessary for maximal inflammatory effect
– Inhibitors of disordered coagulation
Definition of Septic Shock
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General definition: Evidence of infection associated with
evidence of impaired perfusion or impaired oxygen
delivery
– Presence of hypotension supports the diagnosis but is
not required for the diagnosis
Measures of perfusion, oxygen delivery and oxygen
consumption that are associated with a good prognosis:
– Cardiac index (CI) of 3.3 - 6.0 L/min/m2
– MV O2 saturation > 70%
– Oxygen consumption > 200 mL/min/m2
Definition of Septic Shock
(Continued)
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Hemodynamically: Reduction in perfusion pressure
below that required for organ perfusion
– Urine output a good index of organ perfusion
Clinical triad:
– Hypothermia or hyperthermia
– Peripheral vasodilatation (warm shock) or
peripheral vasoconstriction (cold shock)
– Altered mental status
Adult vs. Pediatric Septic Shock
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Predominant cause of mortality in adult septic shock is
vasomotor paralysis
– Myocardial dysfunction with decreased ejection fraction
present
– Compensate by tachycardia and/or ventricular
dilatation
 Failure to compensate associated with poor
prognosis
Pediatric septic shock associated with severe
hypovolemia
– Tend to respond well to vigorous volume resuscitation
Adult vs. Pediatric Septic Shock
(Continued)
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Predominant cause of mortality in pediatric septic shock is
low cardiac output
– Unlike adults where low systemic vascular resistance
is important
Major determinant of oxygen consumption in septic shock:
– Adults: Oxygen extraction
– Pediatrics: Oxygen delivery
Improved outcome in pediatric septic shock:
– Cardiac index (CI) of 3.3 - 6.0 L/min/m2
– Oxygen consumption > 200 mL/min/m2
Initial Therapy of Septic Shock
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Work quickly
Recognize presence of septic shock
Stabilize patient, place in oxygen, start intravenous lines,
send labs and cultures
Correct hypoglycemia and hypocalcemia if present
Start antibiotics
Decide if intubation indicated
– Indications for intubation: Severe respiratory distress,
significant carbon dioxide retention, physiologic instability
– Benefits of intubation: Secure the airway, prevent
aspiration, reduce the work of breathing, prevent
respiratory acidosis
Management of Infection in Septic
Shock
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Aggressively attempt to identify the source of infection
Drain abscesses
Use broad spectrum antibiotic regimen which is designed to
cover pathogens likely to be involved
– Regimen should cover resistant organisms that may be
involved
– Cefuroxime is usually not the drug of choice in critically ill
children
– Narrow the antibiotic coverage as the results of cultures
become available and the patient improves
Choose antibiotics intelligently but do not withhold an
antibiotic in a critically ill patient because of fears of inducing
resistance
Quality of Evidence in Clinical
Decision-Making
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References
– 1: Randomized controlled trials
– 2: Nonrandomized studies
– 3: Peer-reviewed state of the art articles, editorials,
substantial case series
– 4: Non-peer reviewed published opinions, such as textbook
statements or official organizational publications
Recommendations:
– 1: Convincingly justifiable on scientific evidence alone
– 2: Reasonably justifiable on scientific evidence and strongly
supported by expert opinion
– 3: Widely supported by available data and expert opinion
Recommendations: American
College of Critical Care Medicine
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Recommendations are primarily based on expert opinion and
consensus because only four randomized controlled trials
dealing with hemodynamic management of pediatric septic
shock were found
Many novel therapies not studied adequately to allow judgment
to be made regarding potential usefulness
– Preliminary evidence suggests a new therapy is useful:
 Tend to incorporate new therapy into clinical practice
before properly performed studies demonstrate its
effectiveness and safety
– Not unreasonable: Definitive studies may never be done but
must recognize potential for inadequately studied therapies
to actually be harmful
Recommendations Primarily Based
on Expert Opinion and Consensus

Expert opinion and consensus problematic:
– How do you define an expert
– How do you evaluate expert opinion: Opinion of one expert may
be more valuable than that of three other experts
– Consensus by a group of experts may result in general
agreement that a particular course of action is ideal
– On other hand: Consensus may result in a compromise which
all accept as reasonable but none considers ideal
– Expert consensus:
 Strength: May reflect experience of individuals who deal
with a difficult problem on a regular basis
 Weakness: Experience that is not supported by objective
data is potentially biased and flawed
Pediatric Septic Shock
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Incorrect to consider pediatric septic shock to be a high
output, hyperdynamic, vasodilated state
Pediatric septic shock: Hypovolemic but response
following volume loading may vary
– Mortality associated with low cardiac output
– Refractory shock: High systemic vascular resistance
with low cardiac output
Survival in pediatric septic shock
– Adequate volume resuscitation
– CI: 3.3-6.0 L/min/m2
– O2 consumption: 200 mL/min/m2
Perfusion
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Flow: (MAP – CVP)/Systemic Vascular Resistance
Organ-specific flow may vary
– Autoregulation may preserve flow to vital organs in
response to low overall systemic perfusion pressure
– Certain regional flows may be sacrificed to preserve
flow to other organs
 E.g., decreased perfusion of kidney and gut in order
to preserve flow to brain
Kidney: Second highest organ-specific blood flow
– Good urine output indicative of adequate systemic flow
Hydrocortisone
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Steroids not indicated in all patients with septic shock
Hydrocortisone is indicated in patients with septic shock who
have adrenal insufficiency
– Consider use in following circumstances:
 History of chronic steroid use
 Purpura fulminans/adrenal hemorrhage
 CNS pathology with impaired pituitary function
– Adrenal insufficiency: Cortisol level < 18 mg/dl
Dose unclear, recommendation varies from bolus of 1-2
mg/kg (stress dose) to 50 mg/kg (shock dose)
– Follow bolus with same dosage given as 24 hour infusion
Initial Fluid Therapy of Septic
Shock
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20 cc/kg boluses of isotonic crystalloid or colloid
– Whether crystalloid or colloid superior is unclear
– FFP only indicated if coagulopathy is present
– Blood may be indicated if hemoglobin < 10 gm/dl
Follow patients response to the fluid bolus and repeat as
indicated up to 60 ml/kg (or more) in first 60 min
– Desired response to volume loading: Improved blood
pressure, heart rate, perfusion, urine output, mental status
– Monitor for fluid overload: Respiratory distress, rales,
pulmonary vascular congestion, cardiomegaly
If multiple fluid boluses required: Consider CVP monitoring
Fluid-resistant shock: Failure to respond to 60 ml/kg in first 60
min
CVP Monitoring: 5-2 Rule
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Response of CVP to fluid bolus is important
Fluid bolus is indicated and CVP < 8 cm H2O
Infuse 10-20 ml/kg bolus over 10 min
Stop the infusion if the CVP increases by > 5 cm H2O during the
infusion
After infusion: If CVP has increased by > 2 cm H2O but < 5 cm
H 2O
– Observe the patient for 10 minutes
– During observation period if CVP remains greater than 2 cm
H2O greater than the starting value: No more fluid is given
– During observation period if CVP is or falls to below 2 cm
H2O above the starting value: Repeat the bolus
Initial Catecholamine Therapy of
Fluid Refractory Shock
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Dopamine: First line agent in fluid-refractory, hypotensive
shock in patient with low systemic vascular resistance
– Enhances cardiac function and at higher doses causes
vasoconstriction
– Dopamine acts by causing release of norepinephrine from
sympathetic vesicles
– May be ineffective in children < 6-12 months old who may
not have developed full complement of sympathetic
vesicles
Dopamine-resistant shock
– Warm shock: Norepinephrine
– Cold shock: Epinephrine
Inotropes and Pressors in the
Therapy of Shock
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Dopamine: Dopaminergic, beta and alpha effects
– Stored catecholamine required for effect, may be
ineffective in patients < 6-12 months of age or in patients
with depleted catecholamine stores
– May cause vasoconstriction which may result in impaired
perfusion
– May cause undesirable tachycardia
Dobutamine: Beta effect, may cause undesirable tachycardia
and vasodilatation
– Does not cause vasoconstriction and does not
compromise peripheral perfusion
Inotropes and Pressors in the
Therapy of Shock
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Epinephrine: Beta and alpha effects
Norepinephrine: Alpha effect
Phenylephrine: Pure alpha effect
– No beta effect
 No vasodilatation
 Does not enhance cardiac function
Vasopressin: Vasoconstriction by a non-alpha receptor
mediated mechanism
– May be useful in hypotensive patients who do not
respond to norepinephrine
Dopamine-Resistant Shock
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Failure to respond to dopamine:
– Inadequate intravascular volume
– Young age: Inadequate NE-containing sympathetic vesicles
in patients < 6-12 months
Alternatives in dopamine-resistant shock:
– Epinephrine
– Norepinephrine
Remember:
– Hypotension results in impaired perfusion
– But: Simply increasing blood pressure may not improve
perfusion and may actually impair perfusion
– Consider cardiac function and peripheral resistance as well
as vascular tone
Vasodilators in the Therapy of
Shock
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Vasodilators useful in patient who is hypodynamic despite
fluids and inotropes who has a high systemic vascular
resistance
Nitrovasodilators:
– Nitroglycerine
– Nitroprusside
Nitrovasodilator-resistant low output, high systemic
resistance failure or nitrovasodilator associated toxicity:
– Type 3 phosphodiesterase inhibitors which block the
hydrolysis of cAMP and potentiate the beta effect
 Amrinone
 Milrinone
Septic Shock Refractory to Volume
and Catecholamines
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Most common problem: Low cardiac output with high
systemic vascular resistance
Low blood pressure, warm shock:
– Titrate volume and norepinephrine
– Vasopressin acts independently of alpha receptor
 Potentially useful if patient does not respond to NE
Low blood pressure, cold shock:
– Titrate volume and epinephrine
Normal blood pressure, cold shock:
– Add nitrovasodilator: Nitroprusside or nitroglycerin
– Nitrovasodilator ineffective: Amrinone or milrinone
Persistent Refractory Shock
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Consider possibility of a persistent focus of infection
that needs to be drained
Rule out peumopericardium, pneumothorax
Reconsider whether hydrocortisone indicated
Consider placement of pulmonary artery catheter
– More precise characterization of physiologic
derangements and response to therapy
– E.g.: Can measure cardiac output
Consider ECMO
ECMO in Pediatric Septic Shock
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Extracorporeal membrane oxygenation (ECMO):
– Expensive
– Invasive
– Associated with potentially adverse effects
– Available only in a limited number of centers
ECMO definitely has a role in pediatric patients with
septic shock
– Especially in patients with low cardiac output states
– ECMO can provide circulatory support
Blood Pressure in Septic Shock
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Goal is to correct underlying physiologic derangements
Concerned about perfusion as well as blood pressure
It is possible to increase blood pressure without improving
perfusion or to increase blood pressure and at the same time
impair perfusion
– E.g.: Concerned that pressors may lead to impaired
perfusion of kidney or bowel
But: Adequate blood pressure required in order to maintain
organ perfusion
– Coronary perfusion dependent upon blood pressure
– Use of potent vasoconstrictors such as norepinephrine or
vasopressin may be associated with improved organ
perfusion
Oxygen Delivery
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Adequate hemoglobin: Patient in shock should have
hemoglobin > 10 gm/dl
Ideally want close to 100% saturation of hemoglobin
with oxygen
Mixed venous (or superior vena cava) oxygen
saturation an index of adequacy of oxygen delivery to
tissues
– Goal is MV (or SVC) O2 saturation > 70%
No benefit to excessively high hemoglobin or
excessively high MV O2 levels
Summary: Effective Therapy of
Septic Shock
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Work fast
Recognize condition, stabilize the patient
Start appropriate antibiotic therapy
Identify any collections that need to be drained
Aggressively restore intravascular volume with 20-60 ml/kg
(or more) of isotonic saline over the first 60 minutes
Consider invasive monitoring in patients who fail to respond
to fluid boluses with improved perfusion
Use inotropes and pressors intelligently
Understand the potential role of vasodilators
Be prepared to treat ARDS