What is the treatment approach for refractory septic shock in pediatric patients?

Treatment of Refractory Septic Shock in Pediatrics

For children with refractory septic shock unresponsive to fluid resuscitation and catecholamines, initiate ECMO support while simultaneously administering stress-dose hydrocortisone for suspected adrenal insufficiency, and consider vasodilator therapy if the hemodynamic profile shows low cardiac output with high systemic vascular resistance. 1

Initial Definition and Recognition

Refractory septic shock in pediatrics is defined as persistent hemodynamic instability despite:

• Aggressive fluid resuscitation (40-60 mL/kg or more) 1, 2
• High-dose catecholamine support with at least two vasopressors 1
• Appropriate antibiotic therapy within 1 hour 1

Critical pitfall: Do not continue fluid administration if hepatomegaly or rales develop—this signals fluid overload and mandates immediate transition to inotropic support rather than additional fluids. 1, 2

Hemodynamic Phenotyping and Targeted Therapy

Cold Shock (Low Cardiac Output, High SVR)

Add vasodilator therapy in addition to inotropes when blood pressure is normal but cardiac output remains low. 1

• Type III phosphodiesterase inhibitors (milrinone, amrinone) are preferred as they overcome receptor desensitization 1
• Alternative vasodilators include nitrosovasodilators, prostacyclin, and fenoldopam 1
• Levosimendan (calcium sensitizer) can be beneficial 1

Warm Shock (High Cardiac Output, Low SVR)

• Titrate central norepinephrine as the primary vasopressor 2
• Important caveat: While vasopressin and terlipressin have been described in case reports, two RCTs showed no benefit in pediatric septic shock, and safety data remain lacking 1

Corticosteroid Therapy

Administer hydrocortisone within 60 minutes for fluid-refractory, catecholamine-resistant shock with suspected or proven absolute adrenal insufficiency (Grade 1A). 1, 2

Dosing and High-Risk Populations

• Initial stress dose: 50 mg/m²/24 hours as continuous infusion 1
• May require up to 50 mg/kg/day for short-term shock reversal 1
• Approximately 25% of children with septic shock have absolute adrenal insufficiency 1

High-risk patients requiring empiric hydrocortisone:

• Severe septic shock with purpura 1
• Previous chronic steroid therapy 1
• Pituitary or adrenal abnormalities 1

Critical timing: Death from absolute adrenal insufficiency occurs within 8 hours of presentation—obtain serum cortisol at the time of empiric administration but do not delay treatment. 1

Nuance from older guidelines: The 2010 International Consensus noted insufficient evidence for routine use and mentioned increased risk of secondary infection in one study, but the 2012 Surviving Sepsis Campaign provides stronger Grade 1A recommendation for the specific population with catecholamine-resistant shock and suspected adrenal insufficiency. 1

Extracorporeal Membrane Oxygenation (ECMO)

Consider ECMO for refractory pediatric septic shock or respiratory failure (Grade 2C). 1, 2

Survival Data and Technical Considerations

• Survival: 73% for newborns, 39% for older children 1
• Venovenous ECMO has highest survival rates 1
• Venoarterial ECMO for refractory shock: 74% survival with central cannulation via sternotomy 1
• 41% survival for sepsis-associated respiratory failure requiring ECMO 1

Adjunctive Therapies for Refractory Shock

Blood Product Management

Target hemoglobin of 10 g/dL during resuscitation when superior vena cava oxygen saturation is <70%. 1, 2

• After stabilization and recovery from shock, lower target of 7.0 g/dL is reasonable (Grade 1B) 1
• Important caveat: A multicenter trial showed increased nosocomial sepsis in the severe sepsis subgroup with restrictive transfusion strategy 1

Plasma Therapies

Use plasma therapies to correct sepsis-induced thrombotic purpura disorders including: 1, 2

• Progressive disseminated intravascular coagulation 1
• Secondary thrombotic microangiopathy 1
• Thrombotic thrombocytopenic purpura 1

Toxic Shock Syndromes

Add clindamycin and anti-toxin therapies for toxic shock syndromes with refractory hypotension (Grade 2D). 1

Source Control and Reversible Causes

Evaluate and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock (Grade 1C). 1

• Implement emergent source control as soon as possible after diagnosis 2
• Remove intravascular access devices confirmed as infection source after establishing alternative access 2
• Early and aggressive source control is essential (Grade 1D) 1

Monitoring and Supportive Care

Goal-Directed Therapy

Protocol-driven therapy targeting superior vena cava oxygen saturation ≥70% may be beneficial (excluding cyanotic congenital heart disease). 1

• One Level 1 RCT showed improved survival to hospital discharge with this approach 1
• Titrate to clinical signs: capillary refill, urine output, blood pressure, mental status 1

Drug Toxicity Monitoring

Monitor drug toxicity labs closely as drug metabolism is reduced during severe sepsis, increasing risk of adverse events (Grade 1C). 1, 2

Fluid Overload Management

• Use diuretics to reverse fluid overload once shock resolves 1, 2
• If unsuccessful, initiate continuous venovenous hemofiltration (CVVH) or intermittent dialysis to prevent >10% total body weight fluid overload (Grade 2C) 1, 2

Time-Critical Algorithm for Refractory Shock

Within first hour:

• Complete aggressive fluid resuscitation (up to 60 mL/kg) 2
• Initiate peripheral inotropic support if fluid-refractory 1, 2
• Administer antibiotics 2

Within 60 minutes of catecholamine resistance:

• Administer hydrocortisone for suspected adrenal insufficiency 2
• Phenotype hemodynamics and adjust vasoactive therapy accordingly 1

If shock persists despite maximal medical therapy:

• Initiate ECMO consultation and preparation 1, 2
• Reassess for reversible causes (pneumothorax, tamponade, endocrine crisis) 1
• Consider vasodilator therapy if cold shock phenotype with normal BP 1