Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study
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Introduction: Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown. Methods: In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg. Results: ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort ( P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00). Conclusion: Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min. Trial registration: Clinicaltrials.gov NCT01393782 . Registered 12 July 2011.
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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 [290]
The Methods (Treatment assignments; page unavailable) describe randomization to angiotensin II or placebo for high-output shock. Our copy does not address RCTs comparing short and long treatment courses for pneumonia, urinary tract infection, bacteremia, or intraabdominal infection; searches for those conditions and antibiotic treatment duration found no relevant passage. (LLM, conf=0.77)
Experimental — accuracy not yet measuredA small pilot in 20 patients with vasodilatory septic shock showed physiological efficacy without obvious safety issues for angiotensin II.
“After a small, short-term pilot of 20 patients with vasodilatory (septic) shock 10 patients in each group which showed physiological efficacy without obvious safety issues [365]”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [365]
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Bellomo, R., Zarbock, A., & Landoni, G. (2024) · Intensive Care Medicine · doi:10.1007/s00134-023-07290-7 · Cited by 21 · see citing works
New drugs for acute kidney injury
Hariri, G., & Legrand, M. M. (2024) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2024.08.001 · Cited by 20 · see citing works
Safe Use of Vasopressin and Angiotensin II for Patients with Circulatory Shock
Bauer, S. R., Sacha, G. L., & Lam, S. W. (2018) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2147 · Cited by 18 · see citing works
Impaired angiotensin II signaling in septic shock
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Vasodilatory shock in the ICU and the role of angiotensin II
Wakefield, B. J., Sacha, G. L., & Khanna, A. K. (2018) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000000517 · Cited by 18 · see citing works
Angiotensin II in Vasodilatory Shock
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Self-citationHaemodynamic management of septic shock
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Acute kidney injury in pediatrics: an overview focusing on pathophysiology
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Arterial blood pressure and heart rate regulation in shock state
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Vasoactive Agents for Adult Septic Shock: An Update and Review
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Angiotensin II Brings More Questions Than Answers.
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The Role of Angiotensin II in Poisoning-Induced Shock—a Review
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Intensive care medicine in 2050: vasopressors in sepsis
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A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock
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The use of angiotensin II for the management of distributive shock: expert consensus statements
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ANGIOTENSIN II IN THE TREATMENT OF DISTRIBUTIVE SHOCK: A SYSTEMATIC-REVIEW AND META-ANALYSIS
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Approach to Acute Kidney Injuries in the Emergency Department
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Angiotensin II for the Treatment of Vasodilatory Shock — Promise and Caution
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Roles of Angiotensin II as Vasopressor in Vasodilatory Shock
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Angiotensin II - A Brief Review and Role in Severe SARS-COV-2 Sepsis
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Major publications in the critical care pharmacotherapy literature: January–December 2017
Hammond, D. A., Baumgartner, L. J., Cooper, C. M., Donahey, E. E., Harris, S. A., Mercer, J. M., Morris, M., Patel, M. K., Plewa-Rusiecki, A. M., Poore, A., et al. (2018) · Journal of Critical Care · doi:10.1016/j.jcrc.2018.02.012 · Cited by 9 · see citing works
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An, H. M., Hu, Z., Chen, Y., Cheng, L., Shi, J., & Han, L. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-621 · Cited by 9 · see citing works
Circulatory shock in adults in emergency department
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- Authors
- Chawla, L. S., Busse, L., Brasha-Mitchell, E., Davison, D., Honiq, J., Alotaibi, Z., & Seneff, M. G.
- Affiliations
- United States Department of Veterans Affairs (US)
- Inova Fairfax Hospital (US)
- Riyadh Armed Forces Hospital (SA)
- Corresponding author
- Chawla, Lakhmir S
- Venue
- Critical Care
- Published
- 2014-10-06
- Volume
- 18
- Issue
- 5
- Pages
- 534-534
- ISSN
- 1364-8535 (ISSN-L)
- PMC
- PMC4212099
- OpenAlex
- W2031987490
- Cited by
- 197
- References
- 19
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 20 · 2023: 19 · 2022: 11 · 2021: 16 · 2020: 25 · 2019: 28 · 2018: 21 · 2017: 17 · 2016: 7 · 2015: 2 · 2014: 1
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Critical Care (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- George Washington University
- Topics
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- angiotensin II, distributive shock, 30-day mortality
- MeSH terms
- Aged, Angiotensin II, Blood Pressure, Cardiac Output, Catecholamines, Female, Humans, Male, Middle Aged, Norepinephrine, Pilot Projects, Shock, Septic, Vasoconstrictor Agents, Treatment Outcome, Administration, Intravenous
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