SSC Children 2026 — Part 5: Long-Term Follow-Up & Prophylaxis

This section covers immune-modulating therapies, early rehabilitation, long-term follow-up, and prophylaxis topics in pediatric sepsis and septic shock, including immune stimulants for leukopenia and immunoparalysis, immunosuppressive therapies for hyperferritinemia syndromes, early rehabilitation bundles, targeted posthospital follow-up programs, post-sepsis morbidity screening, and prophylaxis domains deferred to other guidelines. These recommendations apply to pediatric patients from 37 weeks gestational age at birth through 18 years of age.

1. Immune-Modulating Therapies

Recommendation 57 — Immune Stimulants for Leukopenia or Immunoparalysis

For children with sepsis or septic shock who have leukopenia or immunoparalysis, there is insufficient evidence to recommend the use of immune stimulants.

No recommendation (insufficient evidence)

Change from 2020: New recommendation.

Rationale: Immunoparalysis — characterized by reduced HLA-DR expression on monocytes, impaired cytokine production, and functional immune suppression — is increasingly recognized as a contributor to secondary infections and late mortality in pediatric sepsis. Several immune-stimulating agents have been studied or are under investigation:

The American Society of Clinical Oncology (ASCO) Growth Factors Expert Panel recommends GM-CSF for the management of febrile neutropenia with comorbid cancer, but this indication is distinct from sepsis-associated immunoparalysis. Multiple large-scale RCTs evaluating immune stimulants in sepsis-associated immunoparalysis are ongoing, and their results may inform future guideline updates.

Recommendation 58 — Immunosuppressive Therapies for Hyperferritinemia

For children with sepsis or septic shock who have hyperferritinemia, there is insufficient evidence to recommend immunosuppressive therapies.

No recommendation (insufficient evidence)

Change from 2020: New recommendation.

Rationale: Hyperferritinemia (greater than 500 ng/mL) is a hallmark of secondary hemophagocytic lymphohistiocytosis (sHLH), macrophage activation syndrome (MAS), and cytokine storm syndromes, which may overlap with or complicate sepsis in children. Agents studied in these conditions include:

The evidence for these agents is derived primarily from the HLH/MAS literature rather than from sepsis populations specifically. Distinguishing between sepsis-driven hyperferritinemia and true sHLH/MAS has important therapeutic implications — the former may respond to antimicrobials and supportive care, while the latter may require targeted immunosuppression. Ferritin levels, fibrinogen, triglycerides, soluble IL-2 receptor, and NK cell function can help differentiate these conditions. Hematology or rheumatology consultation is recommended when sHLH/MAS is suspected.

2. Early Rehabilitation

Recommendation 59 — Early Rehabilitation Bundle

For children with sepsis or septic shock, we suggest implementing an individualized, early rehabilitation bundle during acute illness rather than not using one.

Conditional recommendation, very low certainty evidence

Change from 2020: New recommendation.

Rationale: An early rehabilitation bundle integrates multiple strategies to reduce the morbidity of critical illness and its treatment:

• Optimize comfort — structured pain and sedation assessment and management
• Reduce sedation — daily sedation assessment, targeted sedation goals, avoidance of excessive benzodiazepine use
• Prevent delirium — screening with validated tools (e.g., Cornell Assessment of Pediatric Delirium, pCAM-ICU), nonpharmacological prevention strategies
• Promote sleep — sleep hygiene protocols, noise reduction, clustering of care activities
• Facilitate ventilator liberation — daily spontaneous breathing trials, extubation readiness testing
• Engage families — family presence and participation in care, shared decision-making
• Encourage progressive mobility — early and progressive mobilization from passive range of motion to sitting, standing, and ambulation

The evidence base includes 1 RCT and 5 observational studies demonstrating reduced duration of mechanical ventilation, decreased risk of iatrogenic withdrawal syndrome (RR 0.65; 95% CI 0.49-0.87), and lower delirium incidence (RR 0.85; 95% CI 0.69-1.03) with early rehabilitation bundles.

Safety data: Early mobilization appears safe, with adverse events reported in only 5% of 1,473 mobilization events across 7 studies. Adverse events were predominantly transient and included desaturation, hemodynamic changes, and agitation — most resolved with cessation or modification of the activity.

3. Posthospital Follow-Up

Recommendation 60 — Targeted Posthospital Follow-Up

For children who survive sepsis, there is insufficient evidence to recommend targeted posthospital follow-up programs.

No recommendation (insufficient evidence)

Change from 2020: New recommendation.

Rationale: Up to one-third of children who survive sepsis will experience physical, cognitive, emotional, and/or social sequelae — collectively termed post-sepsis morbidity. Four RCTs conducted in general PICU populations (with approximately 8.7% of enrolled patients having sepsis) demonstrated that structured follow-up was associated with fewer behavioral health problems and improved mental health outcomes.

Despite these promising signals, the optimal modality, timing, frequency, duration, and content of posthospital follow-up for pediatric sepsis survivors remains unclear. Programs evaluated have included clinic-based assessments, telephone follow-up, digital health platforms, and multidisciplinary rehabilitation services. Further research is needed to define the most effective and cost-effective approaches for this population.

Recommendation 61 — Post-Sepsis Morbidity Screening

For children who survive sepsis, it is reasonable to: (1) assess risk factors for post-sepsis morbidity, (2) educate the patient, family, and clinicians on the symptoms of post-sepsis morbidity, and (3) evaluate for new, long-term sequelae after hospital discharge.

Good practice statement (new)

Change from 2020: New GPS.

Rationale: Children who survive sepsis are at risk for a broad range of long-term sequelae affecting multiple domains of health and function. Higher severity of illness, longer hospitalization, pre-existing chronic conditions, older age (particularly adolescents), and social vulnerabilities are risk factors for neurobehavioral and cognitive morbidity.

A structured approach to post-sepsis care should include:

1. Risk assessment at or before discharge — identification of children at elevated risk based on illness severity, duration of organ support, pre-existing conditions, developmental status, and social determinants of health
2. Education — providing patients, families, and primary care clinicians with information about the potential for post-sepsis sequelae and the importance of monitoring for new symptoms
3. Follow-up evaluation — systematic assessment for new physical, cognitive, emotional, and social problems in the weeks to months following hospital discharge, with appropriate referral for rehabilitation, mental health, or developmental services as needed

Post-Sepsis Sequelae in Children

The following table summarizes the domains of post-sepsis morbidity and their clinical manifestations in pediatric survivors.

High-risk populations for post-sepsis morbidity:

• Children with higher severity of illness (higher PRISM/PIM scores, longer PICU stay)
• Children requiring prolonged mechanical ventilation or ECMO
• Children with pre-existing chronic conditions or developmental delays
• Adolescents (particularly vulnerable to psychological and social sequelae)
• Children from socially vulnerable backgrounds (poverty, food insecurity, limited healthcare access)

4. Prophylaxis Topics Deferred to Other Guidelines

Several prophylaxis domains relevant to critically ill children with sepsis are addressed by other specialized guidelines and were not included in the scope of the SSC pediatric 2026 recommendations.

Stress Ulcer Prophylaxis

Stress ulcer prophylaxis in critically ill children is deferred to gastroenterology and critical care guidelines. The decision to initiate prophylaxis should consider the presence of risk factors for clinically significant gastrointestinal bleeding (mechanical ventilation, coagulopathy, traumatic brain injury, high-dose corticosteroids) and the potential adverse effects of acid-suppressive therapy (nosocomial infections, Clostridioides difficile).

Venous Thromboembolism (VTE) Prophylaxis

VTE prophylaxis in critically ill children is addressed in separate thrombosis and hematology guidelines. Central venous catheter-related thrombosis is the most common form of VTE in hospitalized children. Risk assessment, pharmacological prophylaxis (when indicated), and mechanical prophylaxis strategies should follow institutional protocols informed by the relevant specialty guidelines.

Nutrition

Nutritional support in critically ill children with sepsis is deferred to pediatric critical care nutrition guidelines. Key principles include early enteral nutrition when feasible, avoidance of overfeeding, protein delivery optimization, and monitoring for feeding intolerance. Parenteral nutrition should be reserved for children in whom enteral delivery is not possible or insufficient.

Blood Products

Transfusion management in pediatric sepsis is deferred to transfusion medicine and critical care guidelines. Restrictive hemoglobin thresholds (generally 7 g/dL in hemodynamically stable children) have been established in the general PICU population. Platelet and plasma transfusion triggers should be guided by clinical context, bleeding risk, and institutional protocols.

Quick Reference: Long-Term Follow-Up & Prophylaxis

LONG-TERM FOLLOW-UP & PROPHYLAXIS — AT A GLANCE (Recs 57-61)

1. IMMUNE-MODULATING THERAPIES
   —  Immune stimulants for leukopenia / immunoparalysis             [Insufficient evidence]
      (GM-CSF, IFN-gamma, anti-PD1 under investigation;
       ASCO recommends GM-CSF for febrile neutropenia + cancer)
   —  Immunosuppressive therapy for hyperferritinemia                [Insufficient evidence]
      (anakinra, etoposide, cyclosporine studied in HLH/MAS
       context, not sepsis specifically)

2. EARLY REHABILITATION
   ✓  Individualized early rehabilitation bundle                     [Conditional, very low CoE]
      • Comfort optimization, sedation reduction, delirium prevention
      • Sleep promotion, ventilator liberation, family engagement
      • Progressive mobility (safe: adverse events in only 5%)
      • Reduced MV duration, less withdrawal (RR 0.65),
        lower delirium (RR 0.85)

3. POSTHOSPITAL FOLLOW-UP
   —  Targeted posthospital follow-up programs                       [Insufficient evidence]
      (up to 1/3 of survivors have sequelae; 4 RCTs show
       structured follow-up associated with better mental health)
   GPS For sepsis survivors, it is reasonable to:                    [GPS]
      (1) Assess risk factors for post-sepsis morbidity
      (2) Educate patient, family, and clinicians on symptoms
      (3) Evaluate for new long-term sequelae after discharge

4. PROPHYLAXIS TOPICS (DEFERRED)
   • Stress ulcer prophylaxis → see GI/critical care guidelines
   • VTE prophylaxis → see thrombosis/hematology guidelines
   • Nutrition → see pediatric critical care nutrition guidelines
   • Blood products → see transfusion medicine guidelines

KEY: ✓✓ = Strong recommendation ("we recommend")
     ✓  = Conditional recommendation ("we suggest")
     GPS = Good practice statement
     —  = No recommendation / insufficient evidence
     CoE = Certainty of evidence

References