Intravenous angiotensin II for the treatment of high-output shock ATHOS trial: a pilot studyReport as inadecuate

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Critical Care

, 18:534

First Online: 06 October 2014Received: 08 April 2014Accepted: 05 September 2014


IntroductionPatients 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.

MethodsIn 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.

ResultsATII 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.

ConclusionAngiotensin 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 NCT01393782. Registered 12 July 2011.


ACEiangiotensin-converting-enzyme inhibitor

ACTHadrenocorticotropin hormone

ADHantidiuretic hormone

AKIacute kidney injury

APACHEacute physiology and chronic health evaluation II

ATIIangiotensin II

CHFcongestive heart failure

CKDchronic kidney disease

COPDchronic obstructive pulmonary disease

CVAcerebrovascular accident

CVPcentral venous pressure

DMdiabetes mellitus

DSMdata and safety monitor



IDSInvestigational Drug Services

IHDischemic heart disease

MAPmean arterial pressure

MOSFmultiple organ system failure

SOFAsequential organ function assessment

WBCwhite blood cell

Electronic supplementary materialThe online version of this article doi:10.1186-s13054-014-0534-9 contains supplementary material, which is available to authorized users.

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Author: Lakhmir S Chawla - Laurence Busse - Ermira Brasha-Mitchell - Danielle Davison - Jacqueline Honiq - Ziyad Alotaibi - Michael


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