Pediatric Sepsis: A Comprehensive Lecture

Recognition and Screening

Implement systematic screening protocols in all acutely unwell children to enable timely recognition of septic shock and sepsis-associated organ dysfunction. 1

Clinical Assessment Priorities

Assess for key signs of sepsis: abnormal vital signs (tachycardia, tachypnea), altered mental status, decreased capillary refill (>2 seconds), diminished peripheral pulses, and changes in urine output 2
Do not rely solely on blood pressure as an endpoint for resuscitation—hypotension often occurs late in pediatric shock, making it an unreliable early indicator 2
Evaluate multiple clinical markers of perfusion simultaneously: heart rate, capillary refill, level of consciousness, and urine output 2
Systematic screening tools should be tailored to institutional resources and patient populations, with ongoing evaluation of effectiveness 1

Diagnostic Workup

Obtain blood cultures before initiating antimicrobials when this does not substantially delay treatment 1
Blood lactate measurement remains controversial—current guidelines cannot recommend using lactate values alone to stratify risk in pediatric sepsis 1
Implement a standardized protocol/guideline for management of children with septic shock or sepsis-associated organ dysfunction 1

Antimicrobial Therapy: Time-Critical Interventions

In children with septic shock, start antimicrobial therapy within 1 hour of recognition; in sepsis-associated organ dysfunction without shock, start within 3 hours. 1, 2

Initial Empiric Coverage

Use empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens 1, 2
For neonatal sepsis specifically: ampicillin (or amoxicillin or penicillin G) plus gentamicina as first-line empiric therapy 3
Optimize antimicrobial dosing based on published pharmacokinetic/pharmacodynamic principles, considering altered drug metabolism during severe sepsis 1, 2

Combination Therapy Considerations

In immunocompetent children without multidrug-resistant pathogen risk: avoid routine use of empiric multiple antimicrobials directed against the same pathogen for synergy 1
Exception: Group B streptococcal sepsis may warrant combination therapy for synergy 1
In immunocompromised children or those at high risk for multidrug-resistant pathogens: use empiric multi-drug therapy when septic shock or organ dysfunction is present 1

De-escalation Strategy

Perform daily assessment (clinical and laboratory) for de-escalation of antimicrobial therapy starting at 48 hours 1, 2
Once pathogen(s) and sensitivities are available, narrow empiric antimicrobial coverage 1
If no pathogen is identified, narrow or stop empiric therapy based on clinical presentation, site of infection, host risk factors, and clinical improvement in consultation with infectious disease experts 1
Determine duration of therapy according to infection site, microbial etiology, treatment response, and ability to achieve source control 1

Fluid Resuscitation: The First Hour

In healthcare systems with intensive care availability, administer up to 40-60 mL/kg in bolus fluid (10-20 mL/kg per bolus) over the first hour, titrated to clinical markers of cardiac output. 1, 2

Fluid Administration Protocol

Use crystalloids rather than albumin for initial resuscitation 2
Titrate fluid administration to clinical markers: heart rate, blood pressure, capillary refill, level of consciousness, and urine output 2
Discontinue fluid boluses immediately if signs of fluid overload develop: hepatomegaly, rales, or pulmonary edema 1, 2
Continuing fluid administration despite fluid overload signs significantly worsens outcomes 2

Critical Pitfall

Failure to switch from fluid resuscitation to inotropic support when hepatomegaly or rales develop leads to increased mortality 2
Begin peripheral inotropic support until central venous access can be obtained in children not responsive to fluid resuscitation 2

Hemodynamic Support: Vasoactive Medications

Begin inotropic therapy within 15 minutes for fluid-refractory shock; obtain central access and secure airway if needed. 2

Shock Phenotype-Directed Therapy

For cold shock (poor perfusion, cool extremities): titrate central dopamine or, if resistant, titrate central epinephrine 2
For warm shock (bounding pulses, flash capillary refill): titrate central norepinephrine 2
Begin peripheral inotropic support as a bridge until central venous access is established 2

Hemodynamic Targets

Target hemoglobin levels of 10 g/dL during resuscitation of low superior vena cava oxygen saturation shock 2
After stabilization, lower hemoglobin targets can be considered 2
Specific hemodynamic targets (>5th vs >50th percentile mean arterial pressure) remain an area requiring further research 1

Corticosteroid Therapy

Administer timely hydrocortisone therapy in children with fluid-refractory, catecholamine-resistant shock and suspected or proven absolute adrenal insufficiency. 2

Consider hydrocortisone within 60 minutes for catecholamine-resistant shock 2
This applies specifically to children at risk for adrenal insufficiency 2

Source Control

Implement emergent source control intervention as soon as possible after diagnosing an infection amenable to source control procedures. 1, 2

Specific Interventions

Remove intravascular access devices confirmed as the source of sepsis after establishing alternative vascular access, considering pathogen type and surgical risks/benefits 1, 2
Obtain specialist consultation (infectious diseases, surgery) to prioritize interventions needed for source control 1
Perform appropriate diagnostic testing to identify infection site and microbial etiology 1

Ventilatory Support

Use lung-protective ventilation strategies during mechanical ventilation for sepsis-induced pediatric acute respiratory distress syndrome 2

Intubation Considerations

Secure airway within 15 minutes if needed for fluid-refractory shock 2
The optimal timing of early versus delayed endotracheal intubation for refractory shock without respiratory failure remains an area requiring further research 1
Noninvasive ventilation modalities to identify need for early mechanical ventilation require further study 1

Metabolic and Supportive Care

Glucose Management

Control hyperglycemia with target <180 mg/dL 2
Accompany insulin therapy with glucose infusion in children 2
Correct hypoglycemia within 5 minutes of initial resuscitation 2

Calcium Homeostasis

Correct hypocalcemia within 5 minutes of initial resuscitation 2

Nutrition

Provide enteral nutrition when possible; use parenteral nutrition when enteral feeding is not feasible 2

Drug Monitoring

Monitor drug toxicity labs closely because drug metabolism is reduced during severe sepsis 2

Fluid Overload Management

Use diuretics to reverse fluid overload when shock has resolved; if unsuccessful, consider continuous venovenous hemofiltration or intermittent dialysis. 2

Early recognition of fluid overload features is critical 1
Preventing fluid overload improves outcomes 2

Advanced Therapies

Extracorporeal Support

Consider ECMO for refractory pediatric septic shock or respiratory failure 2

Plasma Therapies

Use plasma therapies to correct sepsis-induced thrombotic purpura disorders 2

Time-Sensitive Bundle: The Critical First Hour

Within 5 minutes:

Begin initial resuscitation with fluid boluses 2
Correct hypoglycemia and hypocalcemia 2
Start antibiotics 2

Within 15 minutes:

Begin inotrope therapy for fluid-refractory shock 2
Obtain central access if needed 2
Secure airway if needed 2

Within 60 minutes:

Consider hydrocortisone for catecholamine-resistant shock if at risk for adrenal insufficiency 2

Common Pitfalls and How to Avoid Them

Recognition Failures

Pitfall: Waiting for hypotension to diagnose shock in children 2
Solution: Assess multiple perfusion markers (capillary refill, mental status, pulses, urine output) rather than relying on blood pressure alone 2

Fluid Management Errors

Pitfall: Continuing fluid administration despite hepatomegaly or rales 2
Solution: Immediately switch to inotropic support when signs of fluid overload develop 2

Antimicrobial Delays

Pitfall: Delaying antimicrobial therapy to obtain all cultures 2
Solution: Start antibiotics within 1 hour for septic shock (3 hours for sepsis without shock), obtaining blood cultures only if this does not delay treatment 1, 2

Inadequate Reassessment

Pitfall: Failure to reassess frequently for clinical improvement and potential de-escalation 2
Solution: Implement daily assessment protocols starting at 48 hours for antimicrobial de-escalation 1, 2

Inotropic Support Delays

Pitfall: Underestimating the need for early inotropic support in fluid-refractory shock 2
Solution: Begin peripheral inotropic support within 15 minutes for fluid-refractory shock while establishing central access 2

Evidence Gaps and Future Directions

The 2020 Surviving Sepsis Campaign pediatric guidelines identified significant evidence gaps across 67 PICO questions, with many recommendations based on very low quality evidence 1. Key areas requiring further research include:

Optimal blood lactate thresholds for risk stratification 1
Specific hemodynamic targets (mean arterial pressure percentiles) 1
Choice of first-line vasoactive infusion 1
Balanced crystalloid versus 0.9% saline 1
Timing of mechanical ventilation in refractory shock without respiratory failure 1
Procalcitonin-guided antimicrobial therapy 1

Despite these evidence gaps, the available guidelines provide a clear framework for time-sensitive, protocol-driven care that prioritizes early recognition, rapid antimicrobial administration, judicious fluid resuscitation, and timely escalation to inotropic support—interventions that directly impact mortality and morbidity in pediatric sepsis. 1, 2

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