Cited by 916Sepsis Diagnosis and TreatmentHemodynamic Monitoring and TherapyTrauma, Hemostasis, Coagulopathy, Resuscitation

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Angiotensin II for the Treatment of Vasodilatory Shock

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Khanna, Ashish, English, Shane W., Wang, Xueyuan S., Ham, Kealy, Tumlin, James, Szerlip, Harold, Busse, Laurence W., Altaweel, Laith, Albertson, Timothy E., Mackey, Caleb, McCurdy, Michael T., Boldt, David W., Chock, Stefan, Young, Paul J., Krell, Kenneth, Wunderink, Richard G., Ostermann, Marlies, Murugan, Raghavan, Gong, Michelle N., Panwar, Rakshit, Hästbacka, Johanna, Favory, Raphael, Venkatesh, Balasubramanian, Thompson, B. Taylor, Bellomo, Rinaldo, Jensen, Jeffrey, Kroll, Stew, Chawla, Lakhmir S., Tidmarsh, George F., Deane, Adam M.·2017·New England Journal of Medicine

DOI 10.1056/nejmoa1704154

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Abstract

BACKGROUND: Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS: We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS: A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P=0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P=0.12). CONCLUSIONS: Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843 .).

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Authors: Khanna, A., English, S. W., Wang, X. S., Ham, K., Tumlin, J., Szerlip, H., Busse, L. W., Altaweel, L., Albertson, T. E., Mackey, C., McCurdy, M. T., Boldt, D. W., Chock, S., Young, P. J., Krell, K., Wunderink, R. G., Ostermann, M., Murugan, R., Gong, M. N., Panwar, R., Hästbacka, J., Favory, R., Venkatesh, B., Thompson, B. T., Bellomo, R., Jensen, J., Kroll, S., Chawla, L. S., Tidmarsh, G. F., & Deane, A. M.
Affiliations: Cleveland Clinic (US)
Regions Hospital (US)
Inova Health System (US)
Albert Einstein College of Medicine (US)
University of Maryland, Baltimore (US)
Northwestern University (US)
ORCID: Khanna, Ashish
English, Shane W.
Ham, Kealy
Szerlip, Harold
Busse, Laurence W.
Albertson, Timothy E.
McCurdy, Michael T.
Young, Paul J.
Wunderink, Richard G.
Ostermann, Marlies
Murugan, Raghavan
Gong, Michelle N.
Panwar, Rakshit
Hästbacka, Johanna
Venkatesh, Balasubramanian
Thompson, B. Taylor
Bellomo, Rinaldo
Chawla, Lakhmir S.
Deane, Adam M.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2017-08-03
Volume: 377
Issue: 5
Pages: 419-430
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1704154
OpenAlex: W2614578436
Cited by: 916
References: 24
Citations by year: 2026: 100 · 2025: 103 · 2024: 121 · 2023: 103 · 2022: 90 · 2021: 95 · 2020: 123 · 2019: 80 · 2018: 75 · 2017: 25
FWCI: 64.87
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Figshare (submittedVersion)
Työväentutkimus Vuosikirja (submittedVersion)
Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
NOVA (University of Newcastle Australia) (submittedVersion)
Funders: Bristol-Myers Squibb
GlaxoSmithKline
La Jolla Pharmaceutical Company
Alexion Pharmaceuticals
Regeneron Pharmaceuticals
Genentech
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 › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
Keywords: angiotensin II, vasodilatory shock, septic shock, vasopressors, norepinephrine, mean arterial pressure, SOFA score, mortality, blood pressure response, adverse events, sepsis treatment, vasopressor-refractory shock, fluid resuscitation, vasopressor dose reduction, organ dysfunction, 28-day mortality
MeSH terms: Aged, Angiotensin II, Blood Pressure, Catecholamines, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hypotension, Male, Middle Aged, Shock, Vasoconstrictor Agents, Organ Dysfunction Scores

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Angiotensin II for the Treatment of Vasodilatory Shock

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