Recommendations and Regimens for Pediatric Sepsis and Septic Shock

The definition of severe sepsis and septic shock in children is similar to that in adults. However, in pediatric patients, a systemic inflammatory response includes an abnormal temperature or abnormal leukocyte count as part of the clinical presentation. In addition, there are age-specific normative values for vital signs.[1] Time-sensitive, goal-directed therapy is the rule. Consensus guidelines and reviews are available.[2, 3] Most guidelines are available online through the Pediatric Sepsis Initiative.[4] The Pediatric Advanced Life Support (PALS) Pocket Reference Card provides a summary algorithm. [5] Details of early recognition and treatment of sepsis and septic shock are provided below. 1. Recognize signs of poor perfusion (0-5min) Decreased mental status Cold extremities Delayed capillary refill Weak pulses, differential central and peripheral pulses Low urine output Hypotension or low BP: Minimum systolic BP by age: < 1mo: 60 mmHg; 1mo to 10y: 70 + (2 age in years); 10y: 90 mmHg 2. Assess ABCs (0-5 min) Provide 100% oxygen at high flow rate (15L) Early intubation may be necessary in neonates and infants Breathing assistance as necessary, including mechanical ventilation 3. Establish IV access and place on monitor (0-5min)

2 large-bore peripheral IVs (PIVs) preferred: if difficult IV, place IO access per PALS guidelines; 1 PIV may be sufficient unless vasoactive drugs needed (see Step No. 6, below) Consider labs on IV placement: blood gas, lactate, glucose, ionized calcium, CBC, cultures (glucose check through finger stick preferred for rapid result) 4. Fluid and electrolyte resuscitation (5-15min) Fluids: Push 20 mL/kg fluid (isotonic crystalloid) IV/IO over 5-20min or faster if needed (reassess for signs of shock; see Step No. 11, below) Repeat 20 mL/kg bolus push of fluid (up to 60 mL/kg) until clinical symptoms improve or patient develops respiratory distress/rales/ hepatomegaly May continue to require additional fluid above 60 mL/kg (fluid refractory) (see Step No. 6, below) Fluid needs may approach 200 mL/kg in warm septic shock (warm extremities, flash capillary refill) Correct hypoglycemia: Glucose levels in hypoglycemia: Neonates < 45 mg/dL; infants/children < 60 mg/dL Glucose dosage: 0.5-1 g/kg IV/IO (max that can be administered through a peripheral vein is 25% dextrose in water) (see alternative treatments immediately below) Treatment options to provide 0.5-1 g/kg glucose: For infant/child: dextrose 25% in water: 2-4 mL/kg IV/IO; dextrose 10% in water: 5-10 mL/kg IV/IO; for neonate: dextrose 10% in water: 2-4 mL IV/IO; consider maintenance fluid containing dextrose Correct hypocalcemia for low ionized calcium: Calcium gluconate 100 mg/kg IV/IO (max 2g) PRN

Calcium chloride 20 mg/kg IV/IO PRN (Note: central line administration preferred over 60min in nonarrest situation) 5. Infection control (5-60min) Immediate considerations:

Administer antibiotics immediately after cultures obtained (blood, urine, +/- CSF/ sputum) Do not delay antibiotics because of delay in obtaining cultures; initial antibiotics should be given within 1h General treatment recommendations:

Empiric therapy should be used for unknown etiology of sepsis; Tailoring of therapy to address suspected pathogens or to achieve adequate drug penetration may be necessary; Broader initial coverage may be needed for initial stabilization Dosing varies by age and weight (see specific recommendations and dosages immediately below) Neonates < 2kg: Consult institution pharmacist and primary medication references for your institution practice and for preterm infants and neonates < 2kg Neonates >2kg:

Ampicillin plus gentamicin: Ampicillin for 0-7d: 50 mg/kg IV/IM/IO q8h; ampicillin >7d: 50 mg/kg IV/IM/IO q6h plus gentamicin (dosing institution dependent): 4mg/kg IV/IO/IM q24h (alternative for 07d: 2.5 mg/kg IV/IO/IM q12h; alternative for >7d: 2.5 mg/kg IV/IO/IM q8h) or Ampicillin plus cefotaxime: Ampicillin for 0-7d: 50 mg/kg IV/IM/IO q8h; ampicillin >7d: 50 mg/kg IV/IM/IO q6h plus cefotaxime 50 mg/kg IV/IO q8h Infants (>1mo) and children: Ceftriaxone 75 mg/kg (max 2g) IV/IO/IM q24h plus vancomycin 15mg/kg (max 1g) IV/IO q8h Immunosuppressed patients: Vancomycin 15 mg/kg IV/IO (max 1 g/dose) q8h plus cefepime 50 mg/kg IV/IO (max 2g/dose) q8h; consider antifungal therapy Duration of therapy:

Determined by ultimate source of infection; 7-10d is typically sufficient Above regimens may be empiric therapy for 48-72h, until cultures and sensitivities are known, so as to accurately tailor treatment If culture-negative sepsis, antibiotic choice and duration determined by severity of presentation and most likely pathogen Infectious disease consultation may be necessary 6. Fluid-refractory shock (persisting after 60 mL/kg fluid) (15-60 min) Continue fluid resuscitation and initiate vasopressor therapy titrated to correct hypotension/poor perfusion Central line placement and arterial monitoring if not already established; vasopressors should not be delayed for line placements Normotensive shock (impaired perfusion but normal blood pressure): Dopamine 2-20 mcg/kg/min IV/IO, titrate to desired effect; if continued poor perfusion, consider dobutamine infusion 2-20 mcg/kg/min IV/IO, titrate to desired effect (may cause hypotension, tachycardia) Warm shock (warm extremities, flash capillary refill): Norepinephrine 0.1-2 mcg/kg/min IV/IO infusion, titrate to desired effect Cold shock (cool extremities, delayed capillary refill): Epinephrine 0.1-1 mcg/kg/min IV/IO infusion, titrate to desired effect 7. Shock persists following vasopressor initiation (60 min)

Continued fluid replacement; obtain CVP measurement to guide SvO2 < 70% (cold shock): Transfuse Hgb >10 g/dL; optimize arterial saturation through oxygen therapy, ventilation; epinephrine 0.1-1 mcg/kg/min IV/IO infusion, titrate to desired effect SvO2 < 70% (normal BP but impaired perfusion): Transfuse Hgb >10 g/dL; optimize arterial saturation through oxygen therapy, ventilation; consider addition of milrinone 0.25-0.75 mcg/kg/min IV/IO (titrate to desired effect) ornitroprusside 0.3-5 mcg/kg/min IV/IO (titrate to desired effect) SvO2 >70% (warm shock): Norepinephrine 0.1-2 mcg/kg/min IV/IO infusion, titrate to desired effect; consider vasopressin 0.2-2 mU/kg/min infusion, titrate to desired effect 8. Fluid refractory and vasopressor-dependent shock) (60 min) Consider adrenal insufficiency Hydrocortisone 2 mg/kg (max 100mg) IV/IO bolus; obtain baseline cortisol level; if unsure, consider ACTH stimulation test; duration depends on response, laboratory evaluation 9. Continued shock Consider cardiac output measurement to direct further therapy Consider extracorporeal membrane oxygenation (ECMO) 10. Supplemental therapies Blood transfusion considered for Hgb < 10 g/dL (ideal threshold for transfusion unknown) Sedation/analgesia while ventilated Optimize oxygenation through ventilation IV immunoglobulin can be considered (unknown benefit; see Step No. 6 Infection Control for dosing information) 11. Therapeutic endpoints Clinical Heart Rate normalized for age Capillary refill < 2sec Normal pulse quality No difference in central and peripheral pulses Warm extremities Blood pressure normal for age Urine output >1 mL/kg/h Normal mental status CVP >8 mmHg Laboratory Decreasing lactate SvO2 >70%