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Vasopressin in septic shock : an individual patient data meta-analysis of randomised controlled trials
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Nagendran, Myura, Russell, James A., Walley, Keith R., Brett, Stephen J., Perkins, Gavin D., Hajjar, Ludhmila, Mason, Alexina J., Ashby, Deborah and Gordon, Anthony C. (2019) Vasopressin in septic shock : an individual patient data meta-analysis of randomised controlled trials. Intensive Care Medicine, 45 . pp. 844-855. doi:10.1007/s00134-019-05620-2 ISSN 0342-4642.
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Official URL: http://dx.doi.org/10.1007/s00134-019-05620-2
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.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QP Physiology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Septic shock, Vasopressin | ||||||||
Journal or Publication Title: | Intensive Care Medicine | ||||||||
Publisher: | Springer | ||||||||
ISSN: | 0342-4642 | ||||||||
Official Date: | 1 June 2019 | ||||||||
Dates: |
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Volume: | 45 | ||||||||
Number of Pages: | 12 | ||||||||
Page Range: | pp. 844-855 | ||||||||
DOI: | 10.1007/s00134-019-05620-2 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Reuse Statement (publisher, data, author rights): | This is a post-peer-review, pre-copyedit version of an article published in Intensive Care Medicine. The final authenticated version is available online at: https://doi.org/10.1007/s00134-019-05620-2 | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 15 May 2019 | ||||||||
Date of first compliant Open Access: | 6 May 2020 | ||||||||
RIOXX Funder/Project Grant: |
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