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Lookup NU author(s): Dr Tom Hellyer, Professor John SimpsonORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90–1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04–1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78–0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87–0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51–0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55–0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs.
Author(s): Robey RC, Logue C, Caird CA, Hansel J, Hellyer TP, Simpson J, Dark P, Mathioudakis AG, Felton T
Publication type: Review
Publication status: Published
Journal: Anaesthesia
Year: 2024
Volume: 79
Issue: 8
Pages: 869-879
Print publication date: 01/08/2024
Online publication date: 24/03/2024
Acceptance date: 05/02/2024
ISSN (print): 0003-2409
ISSN (electronic): 1365-2044
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1111/anae.16263
DOI: 10.1111/anae.16263
PubMed id: 38523060
Data Access Statement: Data are available upon reasonable request to the corresponding author and may be used on condition of acknowledgement of its source from the authors of this paper (data includes data on serious adverse events, all-cause mortality and adverse event extracted from published reports of randomised controlled trials included in this study). Statistical code is not available.
