SSC 2026 — Part 5: Adjunctive & Supportive Therapies

This section covers adjunctive therapies specifically for the management of sepsis (corticosteroids, antipyretics, vitamin C, immunoglobulins, blood purification, vitamin D, XueBiJing) and additional supportive therapies pertinent to patients with sepsis but not prescribed specifically for sepsis treatment (stress ulcer prophylaxis, probiotics, active fluid removal, blood transfusion, nutrition, insulin therapy, renal replacement therapy, sodium bicarbonate, and VTE prophylaxis).

1. IV Corticosteroids

Recommendation 79 — IV Corticosteroids in Septic Shock

For adults with septic shock, we suggest using IV corticosteroids.

Conditional recommendation, low certainty evidence

Change from 2021: Revisited.

Rationale: Corticosteroids have been studied extensively in adults with multiple types of infection, including sepsis and septic shock, with a recent meta-analysis identifying 45 RCTs including 9,543 patients. Corticosteroids may result in a small reduction in 28-day mortality (RR 0.92; 95% CI, 0.83–1.01, low certainty) and long-term mortality at 60 days or later (RR 0.94; 95% CI, 0.88–1.00, low certainty), although these results are limited by imprecision and inconsistency.

Corticosteroids result in:

• Greater incidence of shock reversal at 7 days (RR 1.29; 95% CI, 1.13–1.46, high certainty)
• Increases in hyperglycemia (RR 1.19; 95% CI, 1.10–1.28) and hypernatremia (RR 1.64; 95% CI, 1.32–2.03, moderate certainty)
• Uncertain effect on neuromuscular weakness (RR 1.13; 95% CI, 0.48–2.65, very low certainty)

The panel judged most patients and clinicians would consider these potential adverse events to be outweighed by the potential benefits on mortality and shock reversal. Given the widespread availability and low cost of hydrocortisone, this recommendation is also applicable to low resource settings.

Dosing in practice: Among panel members who use IV corticosteroids, 90% prescribe 200 mg hydrocortisone-equivalent per 24-hour period, 86% as intermittent doses rather than continuous infusion. Timing varies: 34% initiate at NE < 0.2 µg/kg/min, 38% at 0.2–0.3 µg/kg/min, and 28% at > 0.3 µg/kg/min. 63% never provide concomitant fludrocortisone. When given solely for septic shock in a clinically improving patient, 61% stop steroids without a taper.

2. Antipyretics

Recommendation 80 — Antipyretic Therapy

For adults with sepsis or septic shock and fever, we suggest against the use of antipyretic therapy, either pharmacologic or surface cooling, for the purpose of improving clinical outcomes.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Remark: This recommendation does not apply to using antipyretic therapy for pain control, patient symptom control, or for patients with other indications for temperature control, such as neuro critical care patients or patients after cardiac arrest.

Rationale: Fever is a cardinal sign of infection and has been viewed as both a potentially adaptive and maladaptive response. A systematic review of 13 RCTs including 3,333 adults with infection evaluated pharmacologic agents (acetaminophen or non-steroidal anti-inflammatory agents) and/or surface cooling. Mortality at 28–90 days was uncertain (RR 1.02; 95% CI, 0.86–1.21, very low certainty). Three trials reported an uncertain effect on shock reversal (RR 1.20; 95% CI, 0.84–1.72, very low certainty), and there was an uncertain effect on LOS (MD −0.12 d; 95% CI, 0.72–0.49, very low certainty).

Given the additional work required for fever control (medication administration, cooling blankets, etc.) and the absence of clinical benefit, the panel made a conditional recommendation against use for the purposes of temperature control. The panel noted that worsening or new fever and infection may be missed with symptomatic treatment.

3. IV Vitamin C

Recommendation 81 — IV Vitamin C

For adults with sepsis or septic shock, we suggest against using IV vitamin C in patients with sepsis or septic shock.

Conditional recommendation, low certainty evidence

Change from 2021: Revisited.

Rationale: Updated two previous systematic reviews and identified 6 additional trials for a total of 55 RCTs evaluating IV vitamin C as monotherapy or in combination with thiamin and corticosteroids. Many trials were small, single-center, and at high risk of bias. Possibly no difference in mortality at 90 days in 7 RCTs at low risk of bias (RR 1.06; 95% CI, 0.95–1.18, low certainty). Among trials at a shorter endpoint (28–30 d), RCTs at low risk of bias showed no effect (RR 0.97; 95% CI, 0.82–1.13) while high risk of bias trials suggested a reduction (RR 0.85; 95% CI, 0.58–0.92). A low risk of adverse events was found, though the largest trial (LOVIT) proactively modified glucose monitoring strategies due to factitious hyperglycemia.

4. IV Immunoglobulin (IVIG)

Recommendation 82 — IV Immunoglobulins

For adults with sepsis or septic shock, we suggest against using IV immunoglobulins.

Conditional recommendation, low certainty evidence

Change from 2021: Revisited.

Rationale: No new large RCTs identified since the 2021 guidelines. IgM-enriched vs. non-enriched IgM, and high vs. low dose IVIG subgroups were also evaluated. Please see the 2021 SSC guidelines for rationale.

5. Blood Purification

Recommendation 83 — Blood Purification Techniques

For adults with sepsis or septic shock, we suggest against using blood purification techniques, including hemoperfusion, high-dose hemofiltration, or plasma exchange.

Conditional recommendation, very low certainty evidence

Change from 2021: Revisited.

Recommendation 84 — Polymyxin B Hemoperfusion

For adults with sepsis or septic shock, we suggest against using polymyxin B hemoperfusion.

Conditional recommendation, low certainty evidence

Change from 2021: Carryover.

Rationale: Updated existing systematic reviews of blood purification techniques, which included RCTs of hemoperfusion/hemadsorption (41 RCTs), hemofiltration (26 RCTs), and plasmapheresis (4 RCTs). Despite many RCTs, the panel was uncertain of the impact of blood purification on mortality. Although there is a signal for reduction in short-term mortality (28–30 d) with all three techniques:

The certainty of evidence is low due to varying factors for each technique (hemoperfusion: inconsistency, imprecision; hemofiltration: risk of bias, inconsistency; plasmapheresis: very serious imprecision). Few trials report on longer-term mortality outcomes. The substantial resource requirements and impacts upon health equity in the absence of clear benefit led to a conditional recommendation against any of these therapies.

6. Vitamin D

Recommendation 85 — Vitamin D Therapy

For adults with sepsis or septic shock, we suggest against the use of Vitamin D therapy for sepsis treatment.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Remark: This recommendation does not pertain to patients who are on lower doses of Vitamin D supplement for other indication or receiving it as part of standard nutritional practice.

Rationale: Updated an existing systematic review of vitamin D therapy in sepsis, including 11 RCTs. Uncertain effects on mortality (RR 0.84; 95% CI, 0.68, 1.04, from 9 trials of 2003 patients, very low certainty), duration of mechanical ventilation, and ICU LOS. The subgroup analysis in the VIOLET trial of patients with sepsis (350 patients) had a higher 90 mortality risk with high-dose enteral vitamin D supplementation (absolute risk increase 12.4%; 95% CI, 3.2–21.6%, very low certainty).

7. XueBiJing

Recommendation 86 — XueBiJing

For adults with sepsis or septic shock, we suggest against using XueBiJing injection outside of jurisdictions where it has regulatory approval.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Rationale: XueBiJing is an herbal product (containing Carthami Flos, Paeoniae Radix Rubra, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, and Angelicae Sinensis Radix) that was licenced in 2004 for treatment of sepsis in China. Although evidence from 30 RCTs (22 located) suggests that it may result in a large reduction in mortality at 28–30 days (RR 0.68; 95% CI, 0.45–1.32, low certainty), the panel had substantial concerns about risk of bias, and the applicability of evidence to sepsis populations outside of China where all trials were conducted. The two largest high-quality RCTs demonstrate high control group mortality rates despite recruiting relatively non-sick populations.

8. Stress Ulcer Prophylaxis

Recommendation 87 — PPIs for Stress Ulcer Prophylaxis

For adults with sepsis or septic shock, and who have risk factors for GI bleeding, we suggest the use of stress ulcer prophylaxis with proton-pump inhibitors over not using stress ulcer prophylaxis.

Conditional recommendation, moderate certainty evidence

Change from 2021: Revisited.

Rationale: Updated an existing systematic review with 12 RCTs, including the 2024 REVISE trial, evaluating the impact of PPIs on clinically important gastrointestinal bleeding:

Important risk factors for clinically important bleeding include acute kidney injury, male gender, coagulopathy, shock, and chronic liver failure. In the absence of PPIs, H2 receptor antagonists are a reasonable alternative. Since stress ulcer prophylaxis is widespread, available, and requires few resources, this recommendation is applicable to low resource settings.

9. Probiotics

Recommendation 88 — Probiotics

For adults with sepsis or septic shock, we suggest against using probiotics.

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Rationale: Identified 41 RCTs evaluating mortality, finding probiotics may have little to no impact on mortality (RR 0.95; 95% CI, 0.87–1.04, low certainty). Effects on VAP were uncertain. When restricted to trials at low risk of bias, including the large PROSPECT trial, improvements were no longer observed.

10. Active Fluid Removal

Recommendation 89 — Active Fluid Removal After Acute Resuscitation

For adults with septic shock after the acute resuscitation phase, we suggest using active fluid removal.

Conditional recommendation; very low certainty evidence

Change from 2021: New.

Remark: Acute resuscitation refers to escalating doses of vasopressors, ongoing high doses of vasopressors, or needing ongoing volume expansion. Active fluid removal refers to diuretics and, if diuretics are insufficient, ultrafiltration or extracorporeal fluid removal. Factors to be considered when deciding to initiate active fluid removal include cardiorespiratory function; vasopressor dose; clinical course; peripheral edema; weight; and fluid balance.

Rationale: Fluid overload in patients with sepsis and septic shock can lead to tissue edema, impaired oxygen delivery, and organ dysfunction. A meta-analysis of 13 RCTs (2,517 patients) demonstrated an uncertain effect of active fluid removal on mortality (RR 0.92; 95% CI, 0.81–1.04, very low certainty), with diuretics only having a potentially more favorable effect (RR 0.89; 95% CI, 0.78–1.01). This suggestion was influenced by input from patient representatives, who placed a high value on avoiding edema.

11. Blood Transfusion

Recommendation 90 — Restrictive Transfusion Strategy

For adults with sepsis or septic shock, we recommend using a restrictive transfusion strategy over a liberal transfusion strategy.

Strong recommendation, moderate certainty evidence

Change from 2021: Carryover.

12. Enteral Nutrition

Recommendation 91 — Early Enteral Nutrition

For adults with sepsis or septic shock, we suggest early (within 72 hours) initiation of enteral nutrition.

Conditional recommendation, very low certainty evidence

Change from 2021: Carryover.

13. Insulin Therapy

Recommendation 92 — Insulin Therapy for Hyperglycemia

For adults with sepsis or septic shock, we recommend initiating insulin therapy at a glucose level of ≥ 180 mg/dL (10 mmol/L).

Strong recommendation, moderate certainty evidence

Change from 2021: Carryover.

14. Renal Replacement Therapy

Recommendation 93 — RRT Without Definitive Indication

For adults with sepsis or septic shock and acute kidney injury, with no definitive indication for renal replacement therapy, we suggest against using renal replacement therapy.

Conditional recommendation, moderate certainty evidence

Change from 2021: Carryover.

Recommendation 94 — Continuous vs. Intermittent RRT

For adults with sepsis or septic shock and acute kidney injury warranting renal replacement therapy, we suggest either continuous or intermittent renal replacement therapy.

Conditional recommendation, low certainty evidence

Change from 2021: Carryover.

15. Sodium Bicarbonate

Recommendation 95 — Sodium Bicarbonate for Lactic Acidosis

For adults with septic shock and hypoperfusion-induced lactic acidemia, we suggest against using sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements.

Conditional recommendation, low certainty evidence

Change from 2021: Carryover.

Recommendation 96 — Sodium Bicarbonate for Severe Metabolic Acidemia

For adults with septic shock, severe metabolic acidemia (pH ≤ 7.2), and acute kidney injury (AKIN score 2 or 3), we suggest using sodium bicarbonate therapy.

Conditional recommendation, very low certainty evidence

Change from 2021: Carryover.

16. Venous Thromboembolism (VTE) Prophylaxis

Recommendation 97 — Pharmacologic VTE Prophylaxis

For adults with sepsis or septic shock, we recommend using pharmacologic venous thromboembolism (VTE) prophylaxis unless a contraindication exists.

Strong recommendation, moderate certainty evidence

Change from 2021: Carryover.

Recommendation 98 — LMWH Over Unfractionated Heparin

For adults with sepsis or septic shock, we recommend using low molecular weight heparin over unfractionated heparin for VTE prophylaxis.

Strong recommendation, moderate certainty evidence

Change from 2021: Carryover.

Recommendation 99 — Pharmacologic vs. Combined Mechanical + Pharmacologic

For adults with sepsis or septic shock, we suggest using pharmacological VTE prophylaxis alone over pharmacological VTE prophylaxis plus mechanical VTE prophylaxis.

Conditional recommendation, moderate certainty evidence

Change from 2021: Carryover.

Quick Reference: Adjunctive & Supportive Therapies Summary

ADJUNCTIVE & SUPPORTIVE THERAPIES — AT A GLANCE

A. ADJUNCTIVE THERAPIES FOR SEPSIS
   ✓  IV corticosteroids for septic shock                              [Conditional]
   ✗  Against antipyretic therapy to improve clinical outcomes         [Conditional against]
   ✗  Against IV vitamin C                                             [Conditional against]
   ✗  Against IV immunoglobulins                                       [Conditional against]
   ✗  Against blood purification (hemoperfusion/hemofiltration/PLEX)   [Conditional against]
   ✗  Against polymyxin B hemoperfusion                                [Conditional against]
   ✗  Against vitamin D for sepsis treatment                           [Conditional against]
   ✗  Against XueBiJing (outside approved jurisdictions)               [Conditional against]

B. SUPPORTIVE THERAPIES
   ✓  PPIs for stress ulcer prophylaxis (if GI bleeding risk factors)   [Conditional]
   ✗  Against probiotics                                                [Conditional against]
   ✓  Active fluid removal after acute resuscitation phase              [Conditional]
   ✓✓ Restrictive transfusion strategy                                  [Strong]
   ✓  Early enteral nutrition (within 72 hours)                         [Conditional]
   ✓✓ Insulin therapy at glucose ≥ 180 mg/dL (10 mmol/L)               [Strong]
   ✗  Against RRT without definitive indication                         [Conditional against]
   ✓  Either continuous or intermittent RRT when indicated               [Conditional]
   ✗  Against sodium bicarbonate for lactic acidosis                    [Conditional against]
   ✓  Sodium bicarbonate for severe acidemia (pH ≤ 7.2) + AKI          [Conditional]
   ✓✓ Pharmacologic VTE prophylaxis                                     [Strong]
   ✓✓ LMWH over unfractionated heparin                                  [Strong]
   ✓  Pharmacologic VTE prophylaxis alone (not combined with mechanical) [Conditional]

KEY: ✓✓ = Strong recommendation | ✓ = Conditional for | ✗ = Conditional against

References