SSC Children 2026 — Part 4: Corticosteroids, Metabolic & Adjunctive Therapies

This section covers corticosteroids, metabolic management, and adjunctive therapies in pediatric sepsis and septic shock, including hydrocortisone use, temperature management, sodium bicarbonate, calcium, thyroid hormone, vitamins C, B1, and D, fluid balance optimization, renal replacement therapy and high-volume hemofiltration, plasma exchange for thrombocytopenia-associated multiple organ failure (TAMOF), extracorporeal blood purification, ECMO, management of immunosuppressive therapies, and intravenous immunoglobulin. These recommendations apply to pediatric patients from 37 weeks gestational age at birth through 18 years of age.

1. Corticosteroids

Recommendation 40 — Hydrocortisone When Hemodynamically Stable

For children with septic shock whose hemodynamic stability can be restored with fluid resuscitation and vasoactive therapy, we suggest against the routine use of intravenous hydrocortisone.

Conditional recommendation, low certainty evidence

Change from 2020: No change (reviewed, not changed).

Rationale: In children who achieve hemodynamic stability with standard fluid and vasoactive management, the addition of hydrocortisone has not been shown to improve outcomes and may carry risks including secondary infections, hyperglycemia, and suppression of the hypothalamic-pituitary-adrenal axis. Corticosteroids should be reserved for situations where hemodynamic instability persists despite adequate resuscitation (see Recommendation 41) or where there is suspected or documented adrenal insufficiency.

Recommendation 41 — Hydrocortisone for Refractory Shock

For children who remain hemodynamically unstable despite adequate fluid resuscitation and vasoactive therapy, there is insufficient evidence to recommend for or against intravenous hydrocortisone.

No recommendation (insufficient evidence)

Change from 2020: Updated.

Rationale: The evidence for corticosteroids in refractory pediatric septic shock remains conflicting. A recent meta-analysis of 45 RCTs (9,563 adult and pediatric patients) found that corticosteroids probably reduce short-term mortality overall (RR 0.93; 95% CI 0.88-0.99) and increase the rate of shock reversal (RR 1.24; 95% CI 1.11-1.38, high certainty). However, when analyzed specifically in children, no difference in mortality was demonstrated.

Most pediatric observational studies have shown an association between corticosteroid use and increased mortality, though this likely reflects confounding by indication (sicker children are more likely to receive corticosteroids). The PERSEVERE-II biomarker-based risk stratification score showed that high-risk children receiving corticosteroids had worse outcomes, raising the possibility that corticosteroid response may vary by sepsis subphenotype.

Remarks: Routine use of hydrocortisone for refractory septic shock is not recommended based on current evidence. However, stress-dose corticosteroids (hydrocortisone 50 mg/m2/day or 1-2 mg/kg/day in divided doses) should be administered to children with suspected or documented adrenal insufficiency, including those with a history of chronic corticosteroid therapy, known adrenal or pituitary disorders, or purpura fulminans suggestive of adrenal hemorrhage.

2. Temperature Management

Recommendation 42 — Fever Management

For children with sepsis or septic shock, there is insufficient evidence to recommend targeting normothermia or taking a permissive approach to fever.

No recommendation (insufficient evidence)

Change from 2020: Updated.

Rationale: One pilot RCT compared a restrictive fever treatment strategy (treat at greater than or equal to 37.5 degrees C) with a permissive strategy (treat only when temperature exceeded 39.5 degrees C). The trial achieved only a small separation in mean body temperature between groups (0.5 degrees C) and found no differences in mortality, duration of mechanical ventilation, or need for cardiovascular or kidney support.

Fever may be a beneficial adaptive response to infection by enhancing immune function and inhibiting microbial growth, but it also increases metabolic demand and oxygen consumption. Antipyretic therapy provides symptomatic relief and may reduce metabolic stress but could blunt the immune response.

“In our practice”: 25% of panel members always and 44% often treat fever in children with sepsis, reflecting the uncertainty in the evidence base and the prevailing tendency toward active treatment.

3. Metabolic Therapies

Recommendation 43 — Sodium Bicarbonate

For children with sepsis or septic shock, there is insufficient evidence to recommend for or against the use of sodium bicarbonate.

No recommendation (insufficient evidence)

Change from 2020: New recommendation.

Rationale: Two large retrospective studies including 7,460 children evaluated sodium bicarbonate use in pediatric sepsis. Propensity-matched analyses showed no overall association with mortality. A subanalysis identified a possible benefit of bicarbonate administration in the setting of hyperchloremia with a low anion gap (less than 6) (adjusted OR 0.52; 95% CI 0.34-0.79), suggesting that the potential benefit may be limited to a specific metabolic phenotype. These findings require confirmation in prospective studies before a recommendation can be made.

Recommendation 44 — Calcium

For children with sepsis or septic shock, there is insufficient evidence to recommend targeting normal blood calcium levels or tolerating hypocalcemia.

No recommendation (insufficient evidence)

Change from 2020: No change (carried over).

Rationale: Ionized hypocalcemia is common in critically ill children and may contribute to myocardial dysfunction and vasopressor hyporesponsiveness. However, calcium administration has been associated with adverse effects in some observational studies, and no pediatric RCT has established the optimal calcium management strategy in sepsis.

Recommendation 45 — Levothyroxine

For children with sepsis or septic shock and sick euthyroid syndrome (low triiodothyronine, low thyroxine, normal thyroid-stimulating hormone), we suggest against the routine use of levothyroxine.

Conditional recommendation, low certainty evidence

Change from 2020: No change (carried over).

Rationale: Sick euthyroid syndrome is a common adaptive response to critical illness and typically resolves with treatment of the underlying condition. Thyroid hormone replacement in the absence of true hypothyroidism has not been shown to improve outcomes and may increase metabolic demand and oxygen consumption during a period of physiological stress.

Recommendation 46 — Vitamin C (Ascorbic Acid)

For children with sepsis or septic shock, we suggest against the use of intravenous vitamin C (ascorbic acid).

Conditional recommendation, very low certainty evidence

Change from 2020: No change (reviewed, not changed).

Rationale: Two pediatric RCTs have evaluated intravenous vitamin C in pediatric sepsis. The RESPOND PICU trial (60 children) and the VITACiPS RCT (218 children) both showed no differences in primary outcomes. These results are consistent with the larger body of adult evidence, including the LOVIT and VICTAS trials, which failed to demonstrate benefit. High-dose intravenous vitamin C carries risks including oxalate nephropathy, interference with point-of-care glucose measurements, and hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

Recommendation 47 — Thiamine (Vitamin B1)

For children with sepsis or septic shock, we suggest against the routine use of intravenous thiamine (vitamin B1).

Conditional recommendation, very low certainty evidence

Change from 2020: No change (reviewed, not changed).

Rationale: Thiamine is an essential cofactor for aerobic metabolism, and deficiency may contribute to lactic acidosis and organ dysfunction. However, evidence for routine thiamine supplementation in pediatric sepsis is insufficient to support a recommendation.

Remarks: Routine use is not recommended, but consideration of thiamine replacement in children with suspected or documented deficiency is reasonable. Risk factors for thiamine deficiency include malnutrition, chronic illness, prolonged parenteral nutrition without supplementation, and excessive diuretic use.

Recommendation 48 — Vitamin D

For children with sepsis or septic shock, we suggest against acute repletion of vitamin D in the absence of clinical deficiency.

Conditional recommendation, very low certainty evidence

Change from 2020: No change (carried over).

Rationale: While vitamin D deficiency is prevalent among critically ill children and has been associated with worse outcomes in observational studies, RCTs of acute vitamin D supplementation in critical illness have not demonstrated clinical benefit. Vitamin D repletion should be undertaken according to standard pediatric guidelines when documented deficiency is present, but acute high-dose supplementation as a treatment for sepsis is not supported.

4. Fluid Balance Management

Recommendation 49 — Fluid Balance After Hemodynamic Stability

After hemodynamic stability is achieved, it is reasonable to prevent excessive fluid accumulation, monitor total fluid intake, and consider active fluid removal if fluid overload develops, while monitoring hemodynamic changes to avoid compromising end-organ perfusion.

Good practice statement (new)

Change from 2020: New GPS.

Rationale: Fluid overload is independently associated with prolonged mechanical ventilation, longer PICU length of stay, and increased mortality in critically ill children. Once initial resuscitation is complete and hemodynamic stability has been achieved, attention should shift to preventing further fluid accumulation and, where indicated, achieving a negative fluid balance. Active fluid removal strategies (diuretics, ultrafiltration during RRT) should be used judiciously, with close monitoring to ensure that negative fluid balance does not compromise perfusion.

“In our practice”: 64% of panel members reported targeting a negative fluid balance once hemodynamic stability is achieved, consistent with the growing recognition that post-resuscitation fluid overload is harmful.

5. Renal Replacement Therapy

Recommendation 50 — High-Volume Hemofiltration

For children with septic shock requiring renal replacement therapy, we suggest high-volume hemofiltration (HVHF; greater than 35 mL/kg/hr) over standard-volume hemofiltration (less than or equal to 35 mL/kg/hr).

Conditional recommendation, low certainty evidence

Change from 2020: Updated.

Rationale: A meta-analysis of 3 RCTs enrolling 195 children demonstrated that HVHF was associated with lower mortality (RR 0.58; 95% CI 0.34-0.98) and shorter duration of RRT compared with standard-volume hemofiltration. The mechanism may involve enhanced clearance of inflammatory mediators and improved hemodynamic stability.

Remarks: HVHF requires specialized equipment, trained staff, and appropriate anticoagulation. Filter life, replacement fluid management, drug clearance, and electrolyte monitoring require close attention. The evidence for HVHF is specific to children requiring RRT for clinical indications — this recommendation does not support initiating RRT solely for cytokine removal in children who do not otherwise meet indications for renal support.

6. Plasma Exchange

Recommendation 51 — Plasma Exchange for TAMOF

For children with sepsis-associated thrombocytopenia-associated multiple organ failure (TAMOF), there is insufficient evidence to recommend plasma exchange (PLEX).

No recommendation (insufficient evidence)

Change from 2020: No change (reviewed, not changed).

Rationale: TAMOF occurs in approximately 8% of children with sepsis and is mediated by reduced ADAMTS-13 activity, leading to microvascular thrombosis and organ dysfunction. Three studies were considered in the evidence review, including one showing lower 28-day mortality with PLEX (27% vs. 70%; p=0.004) in 42 children with TAMOF. While these results are encouraging, the small sample sizes, heterogeneous populations, and methodological limitations preclude a formal recommendation. Identification of TAMOF requires measurement of ADAMTS-13 activity or detection of schistocytes, which may not be routinely available.

7. Extracorporeal Blood Purification

Recommendation 52 — Extracorporeal Blood Purification

For children with sepsis or septic shock, there is insufficient evidence to recommend extracorporeal blood purification techniques.

No recommendation (insufficient evidence)

Change from 2020: New recommendation.

Rationale: Extracorporeal blood purification encompasses a range of techniques — including hemoperfusion, coupled plasma filtration adsorption, polymyxin B hemoperfusion, and cytokine adsorbers — aimed at removing inflammatory mediators and endotoxin from the circulation. An expert panel Delphi-based consensus supports the potential application of these techniques in refractory situations, but the pediatric evidence base is insufficient to support a recommendation. The heterogeneity of devices, targets, and patient populations makes it difficult to generalize findings.

8. Extracorporeal Membrane Oxygenation

Recommendation 53 — VV-ECMO for Refractory Hypoxia

For children with sepsis-associated refractory hypoxia present despite other therapies, we suggest the use of veno-venous (VV) ECMO.

Conditional recommendation, very low certainty evidence

Change from 2020: No change (carried over).

Rationale: VV-ECMO provides gas exchange support in severe respiratory failure refractory to conventional mechanical ventilation, prone positioning, and other rescue therapies. Its use should be considered when reversible lung pathology is present and the patient has no contraindications to anticoagulation. Outcomes depend on center experience, patient selection, and timely initiation before irreversible organ damage occurs.

Recommendation 54 — VA-ECMO for Refractory Shock

For children with septic shock refractory to all other treatments, we suggest the use of veno-arterial (VA) ECMO as rescue therapy.

Conditional recommendation, very low certainty evidence

Change from 2020: No change (carried over).

Rationale: VA-ECMO provides both cardiac and respiratory support and may serve as a bridge to recovery in children with severe myocardial dysfunction or combined cardiorespiratory failure that is unresponsive to maximal conventional therapy. Survival rates for pediatric septic shock on VA-ECMO are lower than for other indications, and patient selection remains challenging. VA-ECMO should be considered a rescue therapy of last resort, available only at specialized centers with appropriate expertise and infrastructure.

9. Immunosuppressive Therapy Management

Recommendation 55 — Tapering or Discontinuing Immunosuppressive Therapies

For children with sepsis or septic shock who are receiving immunosuppressive therapies, there is insufficient evidence to recommend tapering or discontinuing immunosuppressive therapy.

No recommendation (insufficient evidence)

Change from 2020: New recommendation.

Rationale: Children on immunosuppressive therapies — for malignancy, autoimmune disease, or solid organ or hematopoietic stem cell transplantation — are at high risk for sepsis and may have atypical presentations and pathogens. The decision to taper or discontinue immunosuppression during sepsis must balance the risk of uncontrolled infection against the risk of graft rejection, disease flare, or immune reconstitution inflammatory syndrome.

Recent adult evidence suggests that continuation of certain immunosuppressive regimens may be associated with improved outcomes in some transplant recipients with sepsis, potentially by modulating the dysregulated immune response. However, pediatric data are insufficient to guide this complex clinical decision, which should involve collaboration between intensivists, transplant specialists, and infectious disease consultants.

10. Intravenous Immunoglobulin

Recommendation 56 — IVIG

For children with sepsis or septic shock, we suggest against the routine use of intravenous immunoglobulin (IVIG).

Conditional recommendation, low certainty evidence

Change from 2020: No change (reviewed, not changed).

Rationale: A meta-analysis of 9 studies enrolling 3,973 infants with sepsis demonstrated no difference in mortality or disability with IVIG therapy. IgM-enriched IVIG formulations have shown lower mortality in meta-analysis (OR 0.41; 95% CI 0.32-0.55), but adult data do not support the routine use of standard or IgM-enriched IVIG for sepsis.

Remarks: Select patients with primary humoral immunodeficiencies or documented low immunoglobulin levels may benefit from IVIG replacement therapy. This recommendation addresses the routine, empiric use of IVIG as an adjunctive therapy for sepsis and does not apply to IVIG administration for specific indications (e.g., toxic shock syndrome, Kawasaki disease, primary immunodeficiency).

Quick Reference: Corticosteroids, Metabolic & Adjunctive Therapies

CORTICOSTEROIDS, METABOLIC & ADJUNCTIVE — AT A GLANCE (Recs 40-56)

1. CORTICOSTEROIDS
   ✓  Hemodynamics restored with fluids + vasoactives →             [Conditional, low CoE]
      suggest AGAINST routine hydrocortisone
   —  Refractory shock despite fluids + vasoactives →               [Insufficient evidence]
      hydrocortisone
      (NB: give stress-dose steroids for suspected/documented
       adrenal insufficiency)

2. TEMPERATURE & METABOLIC
   —  Normothermia vs permissive fever                              [Insufficient evidence]
   —  Sodium bicarbonate                                            [Insufficient evidence]
      (possible benefit in hyperchloremia + low anion gap)
   —  Targeting normal calcium vs tolerating hypocalcemia            [Insufficient evidence]
   ✓  Suggest AGAINST levothyroxine for sick euthyroid               [Conditional, low CoE]

3. VITAMINS
   ✓  Suggest AGAINST IV vitamin C                                   [Conditional, very low CoE]
   ✓  Suggest AGAINST routine IV thiamine (B1)                       [Conditional, very low CoE]
      (consider if suspected/documented deficiency)
   ✓  Suggest AGAINST acute vitamin D repletion                      [Conditional, very low CoE]
      (without clinical deficiency)

4. FLUID BALANCE
   GPS Prevent excess fluid; consider active removal after           [GPS]
       hemodynamic stability; monitor perfusion
       ("In our practice": 64% target negative balance)

5. RRT & EXTRACORPOREAL THERAPIES
   ✓  HVHF (>35 mL/kg/hr) over standard-volume for children        [Conditional, low CoE]
      on RRT (mortality: RR 0.58; 95% CI 0.34-0.98)
   —  PLEX for TAMOF                                                [Insufficient evidence]
   —  Extracorporeal blood purification                             [Insufficient evidence]

6. ECMO
   ✓  VV-ECMO for refractory hypoxia despite other therapies        [Conditional, very low CoE]
   ✓  VA-ECMO as rescue for shock refractory to all treatments      [Conditional, very low CoE]

7. IMMUNOSUPPRESSION & IVIG
   —  Tapering/discontinuing immunosuppressive therapies             [Insufficient evidence]
   ✓  Suggest AGAINST routine IVIG                                   [Conditional, low CoE]
      (consider for primary humoral immunodeficiency or
       documented low immunoglobulin levels)

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

References