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Meta-Analysis
. 2021 Dec 1;49(12):2112-2120.
doi: 10.1097/CCM.0000000000005262.

Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis

Benjamin Assouline  1 , Anna Faivre  2   3 , Thomas Verissimo  2 , Frédéric Sangla  1 , Lena Berchtold  3 , Raphaël Giraud  1   4 , Karim Bendjelid  1   4 , Sebastian Sgardello  5 , Nadia Elia  4   6 , Jérôme Pugin  1   4 , Sophie de Seigneux  1   2   3   4   5   6 , David Legouis  1   2
Affiliations
Meta-Analysis

Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis

Benjamin Assouline et al. Crit Care Med. .

Abstract

Objectives: Sepsis is a common condition in the ICU. Despite much research, its prognosis remains poor. In 2017, a retrospective before/after study reported promising results using a combination of thiamine, ascorbic acid, and hydrocortisone called "metabolic resuscitation cocktail" and several randomized controlled trials assessing its effectiveness were performed.

Design: We conducted a systematic review and meta-analysis of randomized controlled trials in septic ICU patients to assess the effects of this combination therapy.

Setting: PubMed, Embase, and the Cochrane library databases were searched from inception to March of 2021. Data were extracted independently by two authors. The main outcome was the change in Sequential Organ Failure Assessment score within 72 hours. Secondary outcomes included renal composite endpoints (acute kidney injury) Kidney Disease - Improving Global Outcome organization stage 3 or need for renal replacement therapy, vasopressor duration, and 28-day mortality.

Subjects: We included randomized controlled trials with patients admitted to the ICU with sepsis or septic shock.

Intervention: The trials compared a combination of thiamine, ascorbic acid, and hydrocortisone to standard care or placebo in patients admitted to ICU with sepsis or septic shock.

Measurements and main results: We included eight randomized controlled trials (n = 1,335 patients). Within 72 hours, the median of mean improvement was -1.8 and -3.2 in the control and intervention groups, respectively (eight randomized controlled trials, n = 1,253 patients); weighted mean difference -0.82 (95% CI, -1.15 to -0.48). Data were homogeneous and the funnel plot did not suggest any publication bias. Duration of vasopressor requirement was significantly reduced in the intervention group (six randomized controlled trials). There was no evidence of a difference regarding the ICU mortality and the renal composite outcome (acute kidney injury KDIGO 3 or need for renal replacement therapy, seven randomized controlled trials).

Conclusions: Metabolic resuscitation cocktail administrated in ICU septic patients improves change in Sequential Organ Failure Assessment score within 72 hours. However, this improvement is modest and its clinical relevance is questionable. The impact on renal failure and mortality remains unclear.

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Conflict of interest statement

Dr. Legouis was supported by a young researcher grant from University Hospital of Geneva (PRD 20-2017-I). Drs. de Seigneux and Legouis were supported by a STARTER grant (RS03-25) from the HUG private foundation (the foundation of the Geneva University Hospitals and the University of Geneva’s Faculty of Medicine). Dr. de Seigneux was supported by a SNF grant SNSF PP00P3-187186/1. Dr. Faivre is the recipient of a grant from the Swiss National Science Foundation (323530_191224). Dr. Elia disclosed that she is employed by the University Hospital of Geneva, Switzerland and that she is on the editorial board of the European Journal of Anesthesiology. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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