Pediatric Septic Shock

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Pediatric Septic Shock

• Steve Piecuch, MD, MPH
• Department of Pediatrics
• Lincoln Medical Center

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Definitions Confuse Rather than Clarify

• Fuhrmans 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 lt 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

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More Definitions

• Sharma S, Septic Shock, www.emedicine.com
• Systemic Inflammatory Response Syndrome (SIRS) 2
  or more of the following
• Temperature gt 38 deg C or lt 36 deg C
• Heart rate gt 90 BPM
• Respiratory rate gt 20 BPM or PaCO2 lt 32 mmHg
• WBC gt 12,000 per ml or lt 4,000 per ml or 10
  bands
• Sepsis SIRS in response to a documented
  infection
• Must also have at least 1 of the following
• Hypoxemia PaO2 lt 72 mmHg in FIO2 of 0.21
• Oliguria Urine output lt 0.5 ml/kg/hr
• Elevated plasma lactate
• Altered mental status

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Biochemical Pathogenesis of Septic Shock

• 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

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Anti-inflammatory Therapy in Septic Shock

• 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

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Definition of Septic Shock

• 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 gt 70
• Oxygen consumption gt 200 mL/min/m2

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Definition of Septic Shock (Continued)

• 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

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Adult vs. Pediatric Septic Shock

• 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

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Adult vs. Pediatric Septic Shock (Continued)

• 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 gt 200 mL/min/m2

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Initial Therapy of Septic Shock

• 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

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Management of Infection in Septic Shock

• 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

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Quality of Evidence in Clinical Decision-Making

• 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

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Recommendations American College of Critical
Care Medicine

• 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

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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

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Pediatric Septic Shock

• 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

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Perfusion

• 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

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Hydrocortisone

• 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 lt 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

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Initial Fluid Therapy of Septic Shock

• 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 lt 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

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CVP Monitoring 5-2 Rule

• Response of CVP to fluid bolus is important
• Fluid bolus is indicated and CVP lt 8 cm H2O
• Infuse 10-20 ml/kg bolus over 10 min
• Stop the infusion if the CVP increases by gt 5 cm
  H2O during the infusion
• After infusion If CVP has increased by gt 2 cm
  H2O but lt 5 cm H2O
• 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

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Initial Catecholamine Therapy of Fluid Refractory
Shock

• 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 lt 6-12 months old
  who may not have developed full complement of
  sympathetic vesicles
• Dopamine-resistant shock
• Warm shock Norepinephrine
• Cold shock Epinephrine

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Inotropes and Pressors in the Therapy of Shock

• Dopamine Dopaminergic, beta and alpha effects
• Stored catecholamine required for effect, may be
  ineffective in patients lt 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

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Inotropes and Pressors in the Therapy of Shock

• 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

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Dopamine-Resistant Shock

• Failure to respond to dopamine
• Inadequate intravascular volume
• Young age Inadequate NE-containing sympathetic
  vesicles in patients lt 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

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Vasodilators in the Therapy of Shock

• 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

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Septic Shock Refractory to Volume and
Catecholamines

• 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

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Persistent Refractory Shock

• 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

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ECMO in Pediatric Septic Shock

• 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

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Blood Pressure in Septic Shock

• 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

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Oxygen Delivery

• Adequate hemoglobin Patient in shock should have
  hemoglobin gt 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 gt 70
• No benefit to excessively high hemoglobin or
  excessively high MV O2 levels

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Summary Effective Therapy of Septic Shock

• 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