What is the algorithm for managing neonatal and pediatric sepsis?

Management Algorithm for Neonatal and Pediatric Sepsis

Immediate empiric antibiotic therapy with ampicillin plus gentamicin should be initiated within 1 hour of recognizing neonatal sepsis, while pediatric septic shock requires aggressive fluid resuscitation with 20 mL/kg isotonic crystalloid boluses up to 60 mL/kg in the first hour, followed by early inotropic support if fluid-refractory. 1, 2

Neonatal Sepsis Management (≤28 Days Postnatal Age)

Initial Recognition and Stabilization (0-5 Minutes)

• Recognize clinical signs: decreased perfusion, cyanosis, respiratory distress, weak cry, cool mottled extremities, altered mental status, oliguria, or bleeding at puncture sites 1, 3
• Maintain airway patency according to Neonatal Resuscitation Program guidelines and apply high-flow oxygen to maintain SpO2 >95% 1, 3
• Establish vascular access (IV/IO) immediately 1, 3

Fluid Resuscitation (5 Minutes)

• Administer 10 mL/kg boluses of isotonic saline or colloid, up to 60 mL/kg total, unless hepatomegaly develops 1, 3
• Correct metabolic derangements: hypoglycemia and hypocalcemia immediately 1, 3
• Begin prostaglandin infusion until ductal-dependent cardiac lesion is ruled out 1

Diagnostic Evaluation (Before or Concurrent with Antibiotics)

For any neonate with signs of sepsis:

• Full diagnostic evaluation including blood culture, CBC with differential and platelet count, chest radiograph if respiratory signs present, and lumbar puncture if stable enough and sepsis suspected 1
• Limited evaluation (blood culture and CBC only, no chest radiograph or lumbar puncture) for well-appearing neonates born to mothers with suspected chorioamnionitis 1
• Arterial or venous blood gas, glucose, ionized calcium, coagulation studies, and type/crossmatch 3

Antibiotic Therapy (Within 1 Hour)

First-line regimen:

• Ampicillin plus gentamicin is the safest and most effective empiric therapy 2, 4, 5, 6, 7
• Ampicillin dosing for neonates ≤28 days with bacterial meningitis/septicemia: 5
  • Gestational age ≤34 weeks, postnatal age ≤7 days: 100 mg/kg/day divided every 12 hours
  • Gestational age ≤34 weeks, postnatal age 8-28 days: 150 mg/kg/day divided every 12 hours
  • Gestational age >34 weeks, postnatal age ≤28 days: 150 mg/kg/day divided every 8 hours
• Gentamicin provides coverage against E. coli and gram-negative organisms 2, 4, 6

Alternative regimens when indicated:

• Ampicillin plus cefotaxime when meningitis is suspected or concern for gram-negative sepsis 2, 6, 7
• Amikacin plus cloxacillin for suspected resistant staphylococcal infection 2
• Vancomycin for suspected coagulase-negative staphylococcal infection in late-onset sepsis 2

Inotropic Support (15 Minutes if Fluid-Refractory)

• Dopamine 5-9 mcg/kg/min as first-line inotrope 1
• Add dobutamine up to 10 mcg/kg/min if shock persists 1

Escalation for Dopamine-Resistant Shock (60 Minutes)

• Epinephrine 0.05-0.3 mcg/kg/min for persistent shock 1
• Hydrocortisone if at risk for absolute adrenal insufficiency 1
• T3 supplementation for hypothyroidism 1
• Rule out and correct: pericardial effusion, pneumothorax 1
• Consider pentoxifylline if very low birth weight newborn 1
• Consider closing patent ductus arteriosus if hemodynamically significant 1

Refractory Shock Management

• ECMO for term newborns with refractory shock (current survival rate 80% for newborn sepsis) 1
• Continuous renal replacement therapy (CRRT) if inadequate urine output with ≥10% fluid overload despite diuretics 1

Therapeutic Goals

• Capillary refill ≤2 seconds 1
• Normal blood pressure for age 1
• Preductal and postductal O2 saturation difference <5% 1
• Central venous O2 saturation (ScvO2) >70% 1
• Superior vena cava flow >40 mL/kg/min or cardiac index >3.3 L/min/m² 1

Duration and De-escalation

• Discontinue antibiotics at 48 hours if cultures negative and clinical probability of sepsis is low 7
• Continue 10-14 days for confirmed sepsis with minimal focal infection 8
• Narrow therapy once pathogen identified and susceptibility testing available 2, 7
• Therapeutic drug monitoring should be performed for vancomycin and aminoglycosides 6

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Pediatric Sepsis Management (>28 Days to 18 Years)

Initial Recognition and Resuscitation (0-5 Minutes)

• Recognize signs: decreased mental status, impaired perfusion, tachycardia, tachypnea, altered temperature 1
• Begin high-flow oxygen to maintain adequate oxygenation 1
• Establish IV/IO access 1
• Push 20 mL/kg boluses of isotonic saline or colloid up to and over 60 mL/kg until perfusion improves, unless rales or hepatomegaly develop 1
• Correct hypoglycemia and hypocalcemia 1
• Begin antibiotics within 1 hour of sepsis identification 1

Diagnostic Evaluation

Full diagnostic evaluation for any child with signs of sepsis:

• Blood culture (obtain before antibiotics when possible, but do not delay antibiotics) 1
• CBC with differential and platelet count 1
• Chest radiograph if respiratory abnormalities present 1
• Lumbar puncture if stable enough and sepsis suspected (15-38% of early-onset meningitis have sterile blood cultures) 1

Antibiotic Therapy (Within 1 Hour)

Empiric therapy:

• Intravenous ampicillin and gentamicin (or another aminoglycoside based on local resistance patterns) for coverage of GBS, gram-negative organisms including E. coli, and other common pathogens 1
• Adjust empiric choice based on epidemic/endemic ecology (H1N1, MRSA, chloroquine-resistant malaria, penicillin-resistant pneumococci, recent ICU stay, neutropenia) 1
• Antimicrobials can be given IM or orally if tolerated until IV access available 1

Special situations:

• Clindamycin plus antitoxin therapy for toxic shock syndrome with refractory hypotension 1
• Enteral vancomycin for severe C. difficile colitis 1

Fluid-Refractory Shock (15 Minutes)

• Begin inotrope IV/IO using atropine/ketamine for sedation if needed 1
• Obtain central access and secure airway if needed 1
• For cold shock: titrate central dopamine or, if resistant, titrate central epinephrine 1
• For warm shock: titrate central norepinephrine 1

Catecholamine-Resistant Shock (60 Minutes)

• Begin hydrocortisone if at risk for absolute adrenal insufficiency 1
• Monitor CVP in PICU and attain normal MAP-CVP and ScvO2 1

Cold shock with normal blood pressure:

• Titrate fluid and epinephrine to achieve ScvO2 >70%, Hgb >10 g/dL 1
• If ScvO2 still <70%: add vasodilator with volume loading (nitrosovasodilators, milrinone) 1
• Consider levosimendan 1

Cold shock with low blood pressure:

• Titrate fluid and epinephrine to achieve ScvO2 >70%, Hgb >10 g/dL 1
• If still hypotensive and ScvO2 <70%: consider norepinephrine 1
• Consider low-dose epinephrine 1

Warm shock with low blood pressure:

• Titrate fluid and norepinephrine to achieve ScvO2 >70% 1
• If still hypotensive: consider vasopressin, terlipressin, or angiotensin 1

Persistent Catecholamine-Resistant Shock

• Rule out and correct: pericardial effusion, pneumothorax, intra-abdominal pressure >12 mmHg 1
• Consider advanced monitoring: pulmonary artery catheter, PICCO, FATD catheter, and/or Doppler ultrasound to guide therapy 1
• Goal cardiac index: 3.3-6.0 L/min/m² 1

Refractory Shock

• ECMO for refractory shock 1

Source Control

• Early and aggressive infection source control is paramount 1
• Immediate debridement/drainage for necrotizing pneumonia, necrotizing fasciitis, gangrenous myonecrosis, empyema, abscesses 1
• Repair perforated viscus with peritoneal washout 1
• Remove infected devices promptly 1

Therapeutic Goals

• First hour goals: restore heart rate thresholds, capillary refill ≤2 seconds, normal blood pressure for age 1
• Subsequent ICU goals: normal perfusion pressure (MAP-CVP) for age, central venous O2 saturation >70%, cardiac index >3.3 and <6.0 L/min/m² 1

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Critical Pitfalls to Avoid

• Never delay fluid resuscitation while obtaining vascular access—use IO route if needed 3
• Do not delay antibiotics beyond 1 hour of sepsis recognition; cultures can be obtained quickly but should not postpone treatment 1
• Avoid prolonged empirical antibiotic therapy (≥5 days) in preterm infants when cultures are negative and clinical probability is low, as this increases risk of late-onset sepsis, necrotizing enterocolitis, and mortality 7
• Do not use clindamycin for intrapartum prophylaxis without susceptibility testing, as ~20% of GBS isolates are resistant 1
• Never assume bleeding has stopped in neonates with shock and bleeding at puncture sites 3
• Monitor for fluid overload and hypothermia during aggressive resuscitation 3
• Do not overlook compartment syndrome in neonates with circulatory compromise 3
• Avoid administering boluses more rapidly than recommended (3-5 minutes for 250-500 mg ampicillin; 10-15 minutes for 1-2 g ampicillin) as this may result in convulsive seizures 5