Angiotensin II for the Treatment of Vasodilatory Shock
Open accessAbstract
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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There are data from RCTs on short versus long courses in specific conditions such as pneumonia, urinary tract infections, bacteremia, and intraabdominal infections.
“There are data from RCTs in specific conditions such as pneumonia (286-289), urinary tract infections (290), bacteremia (291, 292), and intraabdominal infections (293).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [291]
The Patients section describes a randomized trial of angiotensin II versus placebo for vasodilatory shock. The Discussion lists pneumonia as an adverse event, but neither that passage nor searches for antibiotic-course duration and the named infections found evidence about short versus long treatment courses. (LLM, conf=0.76)
Experimental — accuracy not yet measuredA larger RCT of 344 patients with vasodilatory shock found the primary endpoint of increased MAP was achieved in 69.9% with angiotensin II versus 23.4% with placebo.
“The primary endpoint, an increase of MAP of at least 10 mmHg or to at least 75 mmHg, was achieved in 114 of 163 patients in the angiotensin II group and in 37 of 158 patients in the placebo group (69.9% vs 23.4%, p < 0.001).”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [366]
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Self-citationVasopressor and Inotrope Therapy in Cardiac Critical Care
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Angiotensin II Infusion for Shock
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Self-citationThe initial resuscitation of septic shock
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Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury
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Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use
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Hypotension within one-hour from starting CRRT is associated with in-hospital mortality
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Hyperdynamic Left Ventricular Ejection Fraction in ICU Patients With Sepsis
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Self-citation
- 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
- 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 › Epidemiology › 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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