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Pediatric Septic Shock

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Title: Pediatric Septic Shock


1
Pediatric Septic Shock
  • Steve Piecuch, MD, MPH
  • Department of Pediatrics
  • Lincoln Medical Center

2
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

3
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

4
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

5
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

6
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

7
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

8
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

9
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

10
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

11
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

12
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

13
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

14
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

15
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

16
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

17
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

18
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

19
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

20
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

21
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

22
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

23
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

24
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

25
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

26
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

27
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

28
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

29
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

30
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
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