II. Signs

  1. Fever or Hypothermia
    1. Temperature > 101.3 F (38.5 C)
    2. Temperature < 96.8 F (36.0 C)
    3. Contrast with adult fever definition of >100.4 (38.0 C)
  2. Tachycardia
    1. See Heart Rate for age-based normal range
  3. Tachypnea
    1. See Respiratory Rate for age-based normal range
  4. Peripheral Vasoconstriction (cold, pale extremities)
    1. Most children under age 12 years with Septic Shock will compensate with marked increase in SVR (Cold Shock)
  5. Hypotension
    1. Ominous, late sign preceding imminent cardiovascular collapse
    2. Systolic Blood Pressure is typically maintained >70 mmHg + (2 * age) with very high Systemic Vascular Resistance
  6. Abnormal appearance
    1. Irritability
    2. Increased crying
    3. Lethargy
  7. Increased or decreased sleep
  8. Decreased feeding
  9. Petechiae or Purpura

III. Evaluation: Tools

  1. Most tools were established before Immunizations and GBS testing and prophylaxis
    1. Haemophilus influenzae B Vaccine (Hib Vaccine) reduced HIB Meningitis rates 99%
    2. Pneumococcal Conjugate Vaccine (Prevnar) has dramatically reduced invasive pneumococcus disease
  2. Rules that may still apply in unimmunized children
    1. See Rochester Criteria for Febrile Infant 0 to 60 days
    2. See Philadelphia Criteria for Febrile Infant 29-60 days
    3. See Boston Criteria for Febrile Infant 28-89 days
    4. See Yale Scale for Febrile Child 3 to 36 months

IV. Labs

  1. Blood Cultures
  2. Urinalysis
  3. Lumbar Puncture
  4. Complete Blood Count
    1. Neither sensitive nor specific to adequately rule-in or rule-out serious infection
  5. Acute phase reactants and Bacterial Infection markers
    1. Insufficiently sensitive to exclude serious infection (decision to perform LP should not be based on these markers)
    2. C-Reactive Protein (CRP)
    3. Procalcitonin

V. Imaging

VI. Types

  1. Warm Shock
    1. Accounts for 20% of children under age 12 years (esp. if indwelling lines), most adults and teens over age 12 years
    2. High or normal Cardiac Output (CO)
    3. Low Systemic Vascular Resistance (SVR)
  2. Cold Shock
    1. Accounts for 80% of children under age 12 years
    2. Low Cardiac Output (CO)
    3. Systemic Vascular Resistance (SVR)
      1. Increased SVR (60% of children)
      2. Decreased SVR (20% of children)

VII. Diagnosis

  1. Sepsis
    1. Systemic Inflammatory Response Syndrome (SIRS) and
    2. Suspected or proven infection
  2. Severe Sepsis
    1. Sepsis and
    2. Organ dysfunction (one of the following)
      1. Cardiovascular organ dysfunction (see criteria below) or
      2. Acute Respiratory Distress Syndrome (ARDS) or
      3. Two or more organ dysfunctions (see criteria below)
  3. Septic Shock
    1. Sepsis and
    2. Cardiovascular organ dysfunction (see criteria below)
  4. Organ Dysfunction criteria
    1. Cardiovascular dysfunction
      1. Dysfunction despite NS or LR fluid bolus >40 ml/kg in 1 hour
      2. Criteria (requires 1 for diagnosis)
        1. Systolic Blood Pressure <2 SD below normal for age or <5th percentile or
        2. Pressors required to maintain adequate Blood Pressure
          1. Dopamine >5 mcg/kg or
          2. Dobutamine, Epinephrine or Norepinephrine
        3. Two of the following
          1. Metabolic Acidosis (Base Deficit >5.0 mEq/L) without other explanation
          2. Arterial Lactic Acid >2 times the upper normal limit
          3. Oliguria (Urine Output <0.5 ml/kg/h)
          4. Prolonged Capillary Refill >5 seconds
          5. Difference between core Temperature and peripheral Temperature >3 C (5.4 F)
    2. Respiratory dysfunction
      1. PaO2 per FIO2 <300 mmHg (not due to cyanotic heart disease or preexisting lung disease) or
      2. PaCO2 >65 or 20 mmHg over baseline PaCO2 or
      3. FIO2 >0.5 required to maintain Oxygen Saturation >92% or
      4. Mechanical Ventilation required non-electively (invasive or noninvasive)
    3. Neurologic dysfunction
      1. Glasgow Coma Scale: 11 or less or
      2. Acute change in mental status with a fall in GCS 3 points or more from an abnormal baseline
    4. Hematologic dysfunction
      1. Platelet Count <80k mm3 or
      2. Platelet Count with 50% decline in Platelet Count from highest recorded value in the last 3 days (chronic hematology, oncology patients) or
      3. INR >2
    5. Renal dysfunction
      1. Serum Creatinine >2 times normal for age or 2 fold increase over baseline Serum Creatinine
    6. Hepatic dysfunction
      1. Total Serum Bilirubin >4 mg/dl (not newborn Bilirubin) or
      2. Serum ALT >2 times normal for age

VIII. Management

  1. Precautions
    1. Do not be satisfied with a normal Blood Pressure (in the face of other signs of poor perfusion)
      1. Blood Pressure is frequently normal in children despite severe Sepsis and cardiac dysfunction
        1. Children age <12 years maintain BP by increasing Systemic Vascular Resistance (SVR)
        2. However, children cannot significantly increase Cardiac Output
          1. Blood Pressure fall is an ominous sign
      2. Manage based on signs of poor perfusion despite a normal Blood Pressure (see below)
      3. Start with aggressive hydration (20 cc/kg boluses up to 60 cc/kg cummulatively)
        1. Move rapidly to Vasopressors if indicated
    2. Lab markers are not sufficient to exclude serious infection
      1. Decide whether to perform complete evaluation including LP with aggressive management
        1. Based on overall clinical assessment, risks and whether clear source is identified
    3. Monitor closely with frequent re-evaluation after each intervention until stable
    4. Do not delay pressors when indicated for central access
      1. Administer pressors for up to 4 hours until central access is available
      2. Risk of extravasation is outweighed by the risk of overall worse outcome
      3. Central access is more difficult and time consuming to obtain in children and often requires sedation
  2. Target goals for interventions: Counteract markers of poor perfusion
    1. Tachycardia
    2. Lactic Acid >4 mg/dl
    3. SVO2 <70%
    4. Poor Capillary Refill
    5. Lethargy or poor responsiveness
    6. Avoid Blood Pressure as a marker of adequate perfusion (typically misleadingly normal in children)
      1. However, a fall in Blood Pressure is an ominous sign and requires aggressive management
      2. Age 0 to 3 months old: Maintain mean arterial pressure (MAP) > Gestational age + weeks of life
      3. Age 3 to 12 months old: Maintain systolic Blood Pressure > 70 mmHg
      4. Age >1 year old: Maintain systolic Blood Pressure >70 mmHg + (2 * age)
  3. Step 1: Immediate
    1. Provide high flow Supplemental Oxygen
    2. Obtain intravenous or Intraosseous Access within 5-10 minutes
    3. Obtain initial lab studies including Blood Culture
  4. Step 2: Initial Resuscitation
    1. NS or LR 20 cc/kg bolus, repeated up to 60 ml/kg until response or Fluid Overload
      1. Ongoing evaluation for Fluid Overload by Ultrasound (e.g. RUSH Exam, IVC Ultrasound for Volume Status)
      2. Ongoing evaluation for Fluid Overload by examination (e.g. pulmonary rales or Hepatomegaly)
    2. Correct Glucose and Calcium
      1. Correct Hypoglycemia
      2. Correct Hypocalcemia
    3. Administer brioad-spectrum empiric antibiotics early (associated with best outcomes)
      1. See Neonatal Sepsis for age <1 month
      2. See Neutropenic Fever
      3. Cover for Pneumococcus, Group A Strep, MRSA (as well as N Meningitidis, and the rare H. Influenzae)
      4. Cefotaxime 50 mg/kg IV q8h or Ceftriaxone 100 mg/kg IV q24h (or Zosyn 75 mg/kg IV q6h) AND
      5. Vancomycin 15 mg/kg IV q6h (or Linezolid 10 mg/kg IV q8h)
      6. (2015) Sanford Guide to Antibiotics, accessed IOS app on 4/20/2016
    4. Order first line Vasopressor to be available at bedside (see agent selection under Step 3)
  5. Step 3: Fluid resistant shock management
    1. Determine if fluid resistant shock within the first 15-30 minutes
    2. Obtain central Intravenous Access when able (but do not delay pressors in refractory shock)
      1. See precautions above
      2. Start Vasopressors via peripheral access (or IO may be used, but less ideal)
      3. Epinephrine may be preferred over Dopamine in Cold Shock (if central Intravenous Access)
        1. Ventura (2015) Crit Care Med 43(11):2292-302 +PMID:26323041 [PubMed]
    3. Start inotrope (Catecholamine) and titrate to signs of improved perfusion (see above)
      1. Cold Shock (most children under age 12 years)
        1. Agent 1: Dopamine (preferred pressor in children, esp. if no central access)
          1. Start Dopamine 5 mcg/kg/min
          2. Titrate Domamine to 10 mcg/kg/min
        2. Agent 2: Epinephrine (add to Dopamine if refractory, or consider as first-line if central access)
      2. Warm Shock (most teens and adults)
        1. Agent 1: Norepinephrine (preferred pressor in age over 12 years old)
        2. Agent 2: Vasopressin (or consider Terlipressin, Angiotensin)
    4. Consider intubation
  6. Step 4: Inotrope (Catecholamine) resistant shock management
    1. Consider Hydrocortisone IV for Adrenal Insufficiency
    2. Central monitoring directs next step
      1. Central Venous Pressure
      2. Mean arterial pressure
      3. SVO2 (>70% is goal)
      4. Rapid Ultrasound in Shock (RUSH Exam)
  7. Step 5: Central monitoring directed management
    1. See shock type definitions above (warm and Cold Shock)
    2. Goal SvO2 >70% (Hemoglobin >10g/dl)
    3. Cold Shock with normal Blood Pressure
      1. First: Titrate crystalloid, Dopamine and Epinephrine to goal SvO2 >70%
      2. Next: Add Vasodilator if SvO2 <70% (e.g. Milrinone, a Phosphodiesterase Inhibitor)
        1. Do not add Milrinone until Blood Pressure and perfusion are improved
        2. Prematurely starting Milrinone with its potent vasodilation and long Half-Life can worsen perfusion that is difficult to counter
    4. Cold Shock with low Blood Pressure
      1. First: Titrate crystalloid, Dopamine and Epinephrine to goal SvO2 >70%
      2. Next: If persistent Hypotension, consider adding norepinephine
      3. Next: Add Vasodilator if SvO2 <70% (e.g. Milrinone, Dobutamine) if Blood Pressure corrects
        1. See precautions above regarding not starting vasodilators prematurely
    5. Warm Shock with low Blood Pressure
      1. First: Titrate crystalloid, Norepinephrine to goal SvO2 >70%
      2. Next: If persistent Hypotension, consider adding Vasopressin, Terlipressin, Angiotensin
      3. Next: Consider low dose Epinephrine

IX. References

  1. Claudius and Melendez in Herbert (2014) EM:Rap 14(7): 6-8
  2. Fuchs and Yamamoto (2011) APLS, Jones and Bartlett, p. 104-13
  3. Orman and Sloas in Herbert (2014) EM:Rap 14(11): 6-7
  4. Brierly (2009) Crit Care Med 37: 666-88 [PubMed]
  5. Goldstein (2005) Pediatr Crit Care Med 6:2-8 [PubMed]

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