Treatment of Sepsis and Septic Shock in Children

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] International guidelines, despite weak evidence for many therapies, have recently been updated. ^{[6, 7]}

Use of a triage protocol to recognize sepsis in children leads to more appropriate resuscitation management and shorter length of stay. ^[8] Additionally, clinician adherence to sepsis resuscitation guidelines also results in shorter length of stay for children. ^[9]

Recent reports question whether a fluid resuscitation – focused strategy is ideal in resource limited areas, ^[10] but resource-poor pediatric sepsis resuscitation data remain limited. ^[11]

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 0-7d: 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) or nitroprusside 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) ^[12]

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%