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

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 +5 more·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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  • There is considerable practice variation in duration of antimicrobial therapy for critically ill patients.

    “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]

    The End Points section describes mortality and organ-support outcomes in a trial of vasopressin versus norepinephrine; it does not address antimicrobial-treatment duration. Searches for antimicrobial or antibiotic duration and practice variation found no passage in our copy that speaks to the claim. Page numbers were not available in the indexed passages. (LLM, conf=0.76)

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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 [281]

    The End Points and Drug Infusion sections describe a trial comparing vasopressin with norepinephrine in septic shock. Searches for antimicrobial stewardship and antibiotic treatment duration found no passage addressing how long antimicrobial therapy should be given or its relationship to outcomes. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • In a VASST subgroup with less severe shock receiving norepinephrine less than 15 μg/min, addition of vasopressin improved survival.

    “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]

  • The VASST trial found no improvement in 28-day mortality with norepinephrine plus vasopressin compared with norepinephrine alone.

    “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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Research works printed but not linked: 2

  1. Bomzon L, Rosendorff C. Renovascu- lar resistance and noradrenaline. Am J Physiol 1975;229:1649-53.
  2. Hayes MA, Yau EH, Hinds CJ, Watson JD. Symmetrical peripheral gangrene: as- sociation with noradrenaline administra- tion. Intensive Care Med 1992;18:433-6.

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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
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
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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