Cited by 1,924Sepsis Diagnosis and TreatmentHemodynamic Monitoring and TherapyAbdominal Surgery and Complications

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Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

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Russell, James A., Walley, Keith R., Singer, Joel, Gordon, Anthony C., Hébert, Paul C., Cooper, D. James, Holmes, Cheryl L., Mehta, Sangeeta, Granton, John T., Storms, Michelle M., Cook, Deborah J., Presneill, Jeffrey J., Ayers, Dieter·2008·New England Journal of Medicine

DOI 10.1056/nejmoa067373

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Abstract

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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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: Russell, James A.
Walley, Keith R.
Singer, Joel
Gordon, Anthony C.
Hébert, Paul C.
Cooper, D. James
Holmes, Cheryl L.
Mehta, Sangeeta
Granton, John T.
Presneill, Jeffrey J.
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
DOI: 10.1056/nejmoa067373
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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Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

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