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Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock
Open accessAbstract
BACKGROUND: Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors. METHODS: In this multicenter, randomized, double-blind trial, we assigned patients who had septic shock and were receiving a minimum of 5 microg of norepinephrine per minute to receive either low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine (5 to 15 microg per minute) in addition to open-label vasopressors. All vasopressor infusions were titrated and tapered according to protocols to maintain a target blood pressure. The primary end point was the mortality rate 28 days after the start of infusions. RESULTS: A total of 778 patients underwent randomization, were infused with the study drug (396 patients received vasopressin, and 382 norepinephrine), and were included in the analysis. There was no significant difference between the vasopressin and norepinephrine groups in the 28-day mortality rate (35.4% and 39.3%, respectively; P=0.26) or in 90-day mortality (43.9% and 49.6%, respectively; P=0.11). There were no significant differences in the overall rates of serious adverse events (10.3% and 10.5%, respectively; P=1.00). In the prospectively defined stratum of less severe septic shock, the mortality rate was lower in the vasopressin group than in the norepinephrine group at 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of more severe septic shock, there was no significant difference in 28-day mortality (44.0% and 42.5%, respectively; P=0.76). A test for heterogeneity between these two study strata was not significant (P=0.10). CONCLUSIONS: Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors. (Current Controlled Trials number, ISRCTN94845869 [controlled-trials.com].).
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In the citing paper
“Given the lack of definitive and generalizable data regarding the optimal duration of therapy for patients who are critically ill, it is not surprising that there is considerably practice variation (281,294).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [281]
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“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 [281]
Experimental — accuracy not yet measuredIn the citing paper
“in a subgroup analysis, patients with less severe shock receiving norepinephrine < 15 μg/min had improved survival with the addition of vasopressin (26.5% vs. 35.7%, p = 0.05).”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [356]
In the citing paper
“the main study (the VASST trial) comparing norepinephrine alone to norepinephrine plus vasopressin (0.01–0.03 U/min) showed no improvement in 28-day mortality (39.3% vs 35.4%, p = 0.26) [356].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [356]
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Metadata
- Authors
- Russell, J. A., Walley, K. R., Singer, J., Gordon, A. C., Hébert, P. C., Cooper, D. J., Holmes, C. L., Mehta, S., Granton, J. T., Storms, M. M., Cook, D. J., Presneill, J. J., & Ayers, D.
- Affiliations
- St. Paul's Hospital (CA)
- University of Ottawa (CA)
- The Alfred Hospital (AU)
- University of British Columbia (CA)
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- McMaster University (CA)
- The Royal Melbourne Hospital (AU)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-02-28
- Volume
- 358
- Issue
- 9
- Pages
- 877-887
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2108153775
- Cited by
- 1,924
- References
- 36
- Citations by year
- 2026: 106 · 2025: 119 · 2024: 101 · 2023: 91 · 2022: 88 · 2021: 85 · 2020: 104 · 2019: 205 · 2018: 114 · 2017: 104 · 2016: 100 · 2015: 83 · 2014: 91 · 2013: 84 · 2012: 89
- FWCI
- 88.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Surgery › Abdominal Surgery and Complications
- Keywords
- septic shock, vasopressin, norepinephrine, vasopressor therapy, catecholamines, mortality, 28-day mortality, 90-day mortality, sepsis treatment, blood pressure support, adverse events, subgroup analysis
- MeSH terms
- Adult, Aged, Blood Pressure, Catecholamines, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Norepinephrine, Severity of Illness Index, Shock, Septic, Vasoconstrictor Agents, Vasopressins, Treatment Failure, Kaplan-Meier Estimate
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