Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials
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.
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Restricting antimicrobial therapy to the shortest course associated with better outcomes is an important part of antimicrobial stewardship.
“Restricting antimicrobial therapy to the shortest course associated with better outcomes is an important part of antimicrobial stewardship (281-285).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [284]
The Trial identification and Conclusions sections address vasopressin versus norepinephrine in septic shock, not antimicrobial treatment duration. Searches for the shortest antimicrobial course and antimicrobial stewardship found no passage in our copy addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredAn individual patient data meta-analysis of 4 RCTs in septic shock found vasopressin alone or with norepinephrine led to higher risk of digital ischaemia but lower risk of arrhythmia compared with norepinephrine alone.
“a recent individual patient data meta-analysis of patients with septic shock from 4 RCTs showed that vasopressin alone or in combination with norepinephrine led to higher risk of digital ischaemia (risk difference [RD] 1.7%; 95% CI 0.3–3.2) but lower risk of arrhythmia (RD −2.8%; 95% CI −0.2 to −5.3) compared to norepinephrine alone [359].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [359]
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- Authors
- Nagendran, M., Russell, J. A., Walley, K. R., Brett, S. J., Perkins, G. D., Hajjar, L., Mason, A. J., Ashby, D., & Gordon, A. C.
- Affiliations
- Imperial College London (GB)
- University of British Columbia (CA)
- Imperial College Healthcare NHS Trust (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Gordon, Anthony C.
- ORCID
- Venue
- Intensive Care Medicine
- Published
- 2019-05-06
- Volume
- 45
- Issue
- 6
- Pages
- 844-855
- ISSN
- 0342-4642 (ISSN-L)
- 1432-1238
- OpenAlex
- W2944740795
- Cited by
- 161
- References
- 40
- Citations by year
- 2026: 21 · 2025: 25 · 2024: 28 · 2023: 23 · 2022: 20 · 2021: 17 · 2020: 20 · 2019: 7
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Intensive Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (ACF-2018-21-014, NIHR/CS/009/007, PB-PG-0610-22350, RP-2015-06-018)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- vasopressin, septic shock, vasoactive drugs, 28-day mortality, digital ischemia, cardiac arrhythmias, mesenteric ischemia, acute coronary syndrome, renal replacement therapy, norepinephrine, subgroup analysis
- MeSH terms
- Aged, Female, Humans, Length of Stay, Male, Middle Aged, Shock, Septic, Vasoconstrictor Agents, Vasopressins, Randomized Controlled Trials as Topic, Survivors, APACHE
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