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Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials

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Vasopressin IPDMA (online supp) - v2.4 - 5 Apr 2019 - CLEAN.docxFile embargoed until 06 May 2020277.34 kBMicrosoft Word    Request a copy
Accepted version with Figs.docxFile embargoed until 06 May 20201.41 MBMicrosoft Word    Request a copy
Title: Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials
Authors: Nagendran, M
Russell, JA
Brett, S
Perkins, GD
Hajjar, L
Mason, AJ
Ashby, D
Gordon, A
Item Type: Journal Article
Abstract: Purpose We performed an individual patient data meta-analysis to investigate the possible benefits and harms of vasopressin therapy in adults with septic shock both overall and in pre-defined subgroups. Methods Our pre-specified study protocol is published on PROSPERO, CRD42017071698. We identified randomised clinical trials up to January 2019 investigating vasopressin therapy versus any other vasoactive comparator in adults with septic shock. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed as well as one-stage regression models with single treatment covariate interactions for subgroup analyses. Results Four trials were included with a total of 1453 patients. For the primary outcomes, there was no effect of vasopressin on 28-day mortality [relative risk (RR) 0.98, 95% CI 0.86–1.12] or serious adverse events (RR 1.02, 95% CI 0.82–1.26). Vasopressin led to more digital ischaemia [absolute risk difference (ARD) 1.7%, 95% CI 0.3%–3.2%] but fewer arrhythmias (ARD − 2.8%, 95% CI − 0.2% to − 5.3%). Mesenteric ischaemia and acute coronary syndrome events were similar between groups. Vasopressin reduced the requirement for renal replacement therapy (RRT) (RR 0.86, 95% CI 0.74–0.99), but this finding was not robust to sensitivity analyses. There were no statistically significant interactions in the pre-defined subgroups (baseline kidney injury severity, baseline lactate, baseline norepinephrine requirement and time to study inclusion). Conclusions Vasopressin therapy in septic shock had no effect on 28-day mortality although the confidence intervals are wide. It appears safe but with a different side effect profile from norepinephrine. The finding on reduced RRT should be interpreted cautiously. Future trials should focus on long-term outcomes in select patient groups as well as incorporating cost effectiveness analyses regarding possible reduced RRT use.
Issue Date: 1-Jun-2019
Date of Acceptance: 11-Apr-2019
URI: http://hdl.handle.net/10044/1/70208
DOI: https://dx.doi.org/10.1007/s00134-019-05620-2
ISSN: 0342-4642
Publisher: Springer (part of Springer Nature)
Start Page: 844
End Page: 855
Journal / Book Title: Intensive Care Medicine
Volume: 45
Issue: 6
Copyright Statement: © Springer-Verlag GmbH Germany, part of Springer Nature 2019. The final publication is available at Springer via https://link.springer.com/article/10.1007%2Fs00134-019-05620-2
Sponsor/Funder: National Institute for Health Research
National Institute for Health Research
Imperial College Healthcare NHS Trust
NIHR -RfPB
Funder's Grant Number: NIHR/CS/009/007
NIHR Fellowship
RDB17 79560
RD305
Keywords: Individual patient data
Meta-analysis
Septic shock
Vasopressin
Emergency & Critical Care Medicine
1103 Clinical Sciences
1117 Public Health and Health Services
Publication Status: Published
Embargo Date: 2020-05-06
Online Publication Date: 2019-05-06
Appears in Collections:Division of Surgery
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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