Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis

Shannon M. Fernando, MD; Alexandre Tran, MD; Karim Soliman, MD; Barbara Flynn, BScRN; Thomas Oommen, PharmD; Li Wenzhe, MD; Neill K.J. Adhikari, MDCM; Salmaan Kanji, PharmD; Andrew J.E. Seely, MD, PhD; Alison E. Fox-Robichaud, MD; Randy S. Wax, MD, FCCM; Deborah J. Cook, MD; François Lamontagne, MD; Bram Rochwerg, MD, FCCM

doi:10.1097/CCE.0000000000001110

Critical Care Explorations (Jul 2024)

Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis

Shannon M. Fernando, MD,
Alexandre Tran, MD,
Karim Soliman, MD,
Barbara Flynn, BScRN,
Thomas Oommen, PharmD,
Li Wenzhe, MD,
Neill K.J. Adhikari, MDCM,
Salmaan Kanji, PharmD,
Andrew J.E. Seely, MD, PhD,
Alison E. Fox-Robichaud, MD,
Randy S. Wax, MD, FCCM,
Deborah J. Cook, MD,
François Lamontagne, MD,
Bram Rochwerg, MD, FCCM

Affiliations

Shannon M. Fernando, MD: 1 Department of Critical Care, Lakeridge Health Corporation, Oshawa, ON, Canada.
Alexandre Tran, MD: 2 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Karim Soliman, MD: 1 Department of Critical Care, Lakeridge Health Corporation, Oshawa, ON, Canada.
Barbara Flynn, BScRN: 1 Department of Critical Care, Lakeridge Health Corporation, Oshawa, ON, Canada.
Thomas Oommen, PharmD: 1 Department of Critical Care, Lakeridge Health Corporation, Oshawa, ON, Canada.
Li Wenzhe, MD: 6 Department of Critical Care Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Neill K.J. Adhikari, MDCM: 7 Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
Salmaan Kanji, PharmD: 2 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Andrew J.E. Seely, MD, PhD: 2 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Alison E. Fox-Robichaud, MD: 10 Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada.
Randy S. Wax, MD, FCCM: 1 Department of Critical Care, Lakeridge Health Corporation, Oshawa, ON, Canada.
Deborah J. Cook, MD: 10 Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada.
François Lamontagne, MD: 12 Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
Bram Rochwerg, MD, FCCM: 10 Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada.

DOI: https://doi.org/10.1097/CCE.0000000000001110
Journal volume & issue: Vol. 6, no. 7
p. e1110

Abstract

Read online

OBJECTIVES:. Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock. DATA SOURCES:. We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024. STUDY SELECTION:. We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration. DATA EXTRACTION:. Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates. DATA SYNTHESIS:. We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47–0.94], low certainty) and hospital length of stay (mean difference [MD] –2.1 d [95% CI, –1.4 to –2.8], low certainty). MB may also reduce duration of vasopressors (MD –31.1 hr [95% CI, –16.5 to –45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1–14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, –0.2% to 2.0%], very low certainty). We did not find any differences in adverse events. CONCLUSIONS:. Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed. REGISTRATION:. Center for Open Science (https://osf.io/hpy4j).

Published in Critical Care Explorations

ISSN: 2639-8028 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://journals.lww.com/ccejournal/pages/default.aspx

About the journal