What is the management algorithm for a newborn with suspected sepsis (neonatorum)?

Management Algorithm for Neonatal Sepsis (Sepsis Neonatorum)

Begin immediate aggressive resuscitation with 10 mL/kg isotonic crystalloid boluses up to 60 mL/kg within the first 5 minutes, start empirical antibiotics (ampicillin plus gentamicin) immediately after obtaining blood cultures, and escalate to inotropic support with dopamine if shock persists after adequate fluid resuscitation. 1, 2, 3, 4

Initial Recognition (0-5 Minutes)

Recognize septic shock before hypotension develops by identifying any of the following clinical signs 1, 5:

• Tachycardia (>160 bpm) or bradycardia (<90 bpm) 5
• Capillary refill >2 seconds 1, 5
• Poor peripheral pulses with differential pulse quality 5
• Altered mental status (lethargy, decreased responsiveness, irritability) 1, 5
• Temperature instability 5
• Respiratory distress, tachypnea, grunting, retractions 1, 5
• Poor tone, poor color, poor feeding 1
• Cyanosis (especially with preductal-postductal O2 saturation difference >5%) 1

Critical pitfall: Waiting for hypotension to diagnose shock is dangerous—hypotension is a late finding indicating decompensated shock. 5

Immediate Actions (0-5 Minutes)

Airway and Breathing

• Maintain airway patency and begin high-flow oxygen 1
• Intubate if increased work of breathing, inadequate respiratory effort, or marked hypoxemia 1
• Volume load before intubation as positive pressure ventilation reduces preload 1

Vascular Access and Fluid Resuscitation

• Establish IV or intraosseous access immediately (umbilical venous or peripheral) 1, 2
• Push 10 mL/kg boluses of isotonic saline or colloid, repeating up to 60 mL/kg total until perfusion improves 1, 2
• Use crystalloid if hemoglobin >12 g/dL; transfuse packed red blood cells (10-15 mL/kg) if hemoglobin <12 g/dL 1
• Stop fluid boluses if hepatomegaly or rales develop (indicates fluid overload) 1

Metabolic Correction and Antibiotics

• Correct hypoglycemia and hypocalcemia immediately 1
• Obtain blood culture, then start empirical antibiotics within 5 minutes 1
• Ampicillin plus gentamicin is the standard empirical therapy for early-onset sepsis 3, 4, 6, 7
• Ampicillin dosing for neonates ≤28 days: 150 mg/kg/day divided every 8-12 hours depending on gestational and postnatal age 4
• Gentamicin is effective against Pseudomonas, Proteus, E. coli, Klebsiella-Enterobacter-Serratia, and Staphylococcus species 3

Monitoring Initiation

• Continuous monitoring: temperature, preductal and postductal pulse oximetry, intra-arterial blood pressure, ECG 1, 2, 5
• Serial capillary refill assessments every 5-15 minutes 5

Fluid-Refractory Shock (15 Minutes)

If shock persists after adequate fluid resuscitation (up to 60 mL/kg), begin inotropic support immediately. 1, 2

First-Line Inotropes

• Start dopamine 5-10 mcg/kg/min via central or peripheral access 1, 2
• Add dobutamine up to 10 mcg/kg/min if needed 2
• Obtain central venous access if not already established 1

Special Considerations for PPHN

• If preductal-postductal O2 saturation differential >5% or echocardiography confirms persistent pulmonary hypertension of the newborn (PPHN), start inhaled nitric oxide at 20 ppm 1, 2
• PPHN can cause right ventricular failure with right-to-left shunting causing cyanosis 1

Catecholamine-Resistant Shock (60 Minutes)

If shock persists despite dopamine/dobutamine and adequate fluid resuscitation, escalate therapy. 1, 2

Advanced Inotropic Support

• Titrate epinephrine 0.05-0.3 mcg/kg/min centrally 1, 2
• For refractory hypotension with adequate cardiac output, consider norepinephrine (maintain ScvO2 >70%) 1, 2

Hormonal Therapy

• Add hydrocortisone if adrenal insufficiency suspected (peak cortisol after ACTH <18 μg/dL, or basal cortisol <18 μg/dL in volume-loaded patient requiring epinephrine) 1
• Consider triiodothyronine if thyroid insufficiency present 1

Advanced Hemodynamic Monitoring

• Monitor central venous pressure and central venous oxygen saturation (target ScvO2 >70%) 1, 2
• Consider echocardiography, Doppler ultrasound, or superior vena cava flow measurement to guide therapy 2
• Target cardiac index 3.3-6.0 L/min/m² 1

Adjunctive Therapies

• Pentoxifylline (5-day, 6-hour per day IV course) can reverse septic shock in very low birth weight babies 1
• For poor left ventricular function with normal blood pressure, add nitrosovasodilators or type III phosphodiesterase inhibitors to epinephrine (volume load carefully) 1

Refractory Shock (Persistent Despite Maximal Medical Therapy)

Rule out and correct reversible causes before considering ECMO. 1

Exclude Occult Morbidities

• Pericardial effusion (perform pericardiocentesis) 1
• Pneumothorax (perform thoracentesis) 1
• Ongoing blood loss (blood replacement/hemostasis) 1
• Increased intra-abdominal pressure >12 mmHg (peritoneal catheter or abdominal release) 1
• Ductal-dependent congenital heart disease: Any newborn with shock plus hepatomegaly, cyanosis, cardiac murmur, or differential upper/lower extremity blood pressures/pulses should receive prostaglandin infusion until echocardiography rules out complex congenital heart disease 1
• Inborn errors of metabolism causing hyperammonemia or hypoglycemia (glucose/insulin infusion or ammonia scavengers) 1

ECMO Indications

• Consider ECMO for term newborns with refractory shock or PaO2 <40 mmHg after maximal therapy 1, 2
• Current ECMO survival rate for newborn sepsis is 80% 1
• Maintain ECMO flows ≤110 mL/kg/min to prevent hemolysis (keep free hemoglobin <10 μg/dL) 1
• Normalize calcium concentration in red blood cell pump prime (300 mg CaCl2 per unit of packed red blood cells) 1

Continuous Renal Replacement Therapy (CRRT)

• Initiate CRRT if inadequate urine output with ≥10% fluid overload despite diuretics 1
• Best performed on ECMO circuit in newborns 1

Therapeutic End Points (Continuous Goals)

Target the following parameters throughout resuscitation 1, 2:

• Capillary refill ≤2 seconds 1, 2
• Normal pulses with no differential between peripheral and central pulses 1, 2
• Warm extremities 1, 2
• Urine output >1 mL/kg/h 1, 2
• Normal mental status 1, 2
• Normal blood pressure for age 1, 2
• Normal glucose and ionized calcium concentrations 1, 2
• Preductal-postductal O2 saturation difference <5% 1
• Arterial oxygen saturation ≥95% 1
• Central venous oxygen saturation >70% 2

Antibiotic Management Beyond Initial Resuscitation

Duration and Modification

• Discontinue antibiotics at 48 hours if cultures negative and clinical probability of sepsis is low 7
• Continue for 10-14 days if cultures positive with minimal focal infection 6, 7
• Narrow antibiotic spectrum once pathogen identified (unless synergism needed) 6, 7
• Prolonged empirical treatment ≥5 days in preterm infants increases risks of late-onset sepsis, necrotizing enterocolitis, and mortality 7

Late-Onset Sepsis (>7 Days)

• Must cover early-onset organisms plus hospital-acquired pathogens (staphylococci, enterococci, Pseudomonas aeruginosa) 6
• Consider netilmicin or amikacin for nosocomial infections 6
• Add antistaphylococcal agents if vascular catheter present 6

Special Maternal Risk Factors

• Chorioamnionitis: All well-appearing newborns require limited evaluation (CBC, blood culture) and empirical antibiotics 1
• Maternal GBS colonization with inadequate intrapartum antibiotic prophylaxis: limited evaluation and 48-hour observation 1

Critical Pitfalls to Avoid

• Never delay fluid resuscitation or antibiotics while obtaining additional diagnostic tests 1, 2
• Do not assume adequate perfusion with normal blood pressure—compensated shock exists with normal BP but abnormal capillary refill 5
• Avoid over-reliance on laboratory tests—clinical signs mandate immediate intervention 8, 9
• Very low birth weight infants (<1000g, <32 weeks) require cautious fluid resuscitation due to intraventricular hemorrhage risk 5
• Maintain normoglycemia with D10%-containing isotonic IV solution at maintenance rate during resuscitation 1
• Monitor for fluid overload (hepatomegaly, rales) during aggressive resuscitation 1