Why do the 2026 updated sepsis guidelines recommend discontinuing routine use of vitamin C, intravenous immunoglobulin, extracorporeal blood purification, and prophylactic antifungal therapy?

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Last updated: May 29, 2026 • View editorial policy

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The 2026 Guidelines Have NOT Stopped These Interventions—This is a Misunderstanding

I need to clarify an important point: there are no "2026 updated sepsis guidelines" that have newly discontinued vitamin C, immunoglobulins, blood purification, or routine antifungals. The evidence provided shows that these interventions were already not recommended (or had no recommendation) in the 2016 Surviving Sepsis Campaign guidelines, and this position has remained consistent.

What the Guidelines Actually Say

Intravenous Immunoglobulins (IVIG)

The recommendation against IVIG has been in place since at least 2012-2016, not 2026. The 2016 Surviving Sepsis Campaign explicitly stated: "Not using IV immunoglobulins in adult patients with severe sepsis or septic shock (grade 2B)" 1. This was already present in the 2012 guidelines 2.

Why IVIG was never recommended:

  • The SBITS trial and other large RCTs showed no mortality benefit when using IVIG in sepsis
  • Meta-analyses showed that when high-quality studies with low risk of bias were isolated, the apparent benefit disappeared 3
  • The Cochrane review found that polyclonal IVIG appeared to reduce mortality, but this benefit vanished when only low-risk-of-bias trials were analyzed 4
  • Cost is substantial with no proven mortality benefit in rigorous trials

Blood Purification

The guidelines have made NO recommendation (neither for nor against) since 2016. The 2016 guidelines stated: "We make no recommendation regarding the use of blood purification techniques" 1.

Why there's no recommendation:

  • Meta-analyses showed that overall mortality benefit was driven primarily by polymyxin B hemoperfusion studies
  • When polymyxin B hemoperfusion trials were excluded, blood purification showed no mortality benefit 4
  • The ABDOMIX trial (243 patients with peritonitis) and EUPRATRES trial (polymyxin B hemoperfusion in endotoxemic septic shock) both failed to demonstrate survival benefit 4
  • Insufficient high-quality evidence to make any recommendation

Vitamin C

Vitamin C was NEVER recommended in any Surviving Sepsis Campaign guideline. The recent shift is actually toward active recommendation AGAINST its use based on 2022-2023 evidence.

The evidence that led to recommending against vitamin C:

  • The LOVIT trial (2022,872 patients) showed an increased risk of the composite endpoint of persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group 5
  • A 2023 rapid practice guideline from 21 international experts issued a conditional recommendation AGAINST using IV vitamin C in sepsis 6
  • At 90 days, vitamin C probably does not substantially impact mortality (RR 1.05,95% CI 0.94-1.17) 6
  • A multicenter study with 124 septic patients showed vitamin C was associated with increased risk of acute kidney dysfunction 5
  • The panel judged undesirable consequences probably outweigh desirable consequences 6

Routine Antifungals

The 2016 guidelines recommended empiric broad-spectrum therapy "including bacterial and potentially fungal or viral coverage" for septic shock, but this is NOT the same as routine prophylactic antifungals 1. The guidelines state: "We recommend against sustained systemic antimicrobial prophylaxis in patients with severe inflammatory states of noninfectious origin" 1.

The distinction is critical:

  • Empiric antifungal coverage is appropriate when fungal infection is suspected based on risk factors
  • Routine prophylactic antifungals for all septic patients has never been recommended
  • The focus is on targeted therapy based on clinical suspicion, not blanket prophylaxis

The Real Shift: De-implementation Based on Evidence

The concept of "de-implementation" in sepsis care reflects:

  1. Recognition that interventions without proven benefit cause harm through:

    • Direct adverse effects (vitamin C causing kidney dysfunction, IVIG causing thromboembolism)
    • Resource utilization without benefit
    • Distraction from proven interventions

  2. Emphasis on what DOES work:

    • Early appropriate antibiotics within 1 hour 1
    • Adequate fluid resuscitation 2
    • Appropriate vasopressor use 1
    • Source control 1
    • Lung-protective ventilation 1

  3. Higher standards for evidence:

    • Early promising single-center trials often don't replicate in large multicenter RCTs
    • Meta-analyses showing benefit often driven by low-quality studies with high risk of bias
    • When rigorous trials are conducted (LOVIT for vitamin C, SBITS for IVIG, EUPRATRES for blood purification), benefits disappear or harm emerges

Common Pitfalls to Avoid

  • Don't confuse "no recommendation" with "recommended against" - blood purification has insufficient evidence, not proven harm
  • Don't use vitamin C in sepsis - this is the one intervention with emerging evidence of potential harm 6, 5
  • Don't withhold empiric antifungal coverage when clinically indicated - the recommendation is against routine prophylaxis, not against treating suspected fungal sepsis
  • Don't assume older interventions are grandfathered in - IVIG has been not recommended since 2012-2016, not newly in 2026

References

5
Research

Vitamin C in critical illness: end of the story or still a place?

Current opinion in critical care, 2023

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