Abstract
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 registrationClinicaltrials.gov NCT01393782. Registered 12 July 2011.
Highlights
Patients with distributive shock who require high dose vasopressors have a high mortality
Study patients Patients were eligible for randomization if they were older than 21 years and were deemed to have highoutput shock, which was defined as a cardiovascular sequential organ function assessment (SOFA) score of 4 as well as a cardiac index >2.4 L/min/BSA 1.73 m2 [10]
Newby et al describe the successful treatment of a patient with an angiotensin-convertingenzyme inhibitor (ACEi) overdose and profound shock, using an Angiotensin II (ATII) infusion [11]
Summary
Patients with distributive shock who require high dose vasopressors have a high mortality. Patients treated with catecholamines for shock often develop tachyphylaxis, thereby limiting the utility of these agents, and high doses of catecholamines can cause direct cardiotoxicity [3]. The toxic potential of catecholamines has been recently demonstrated in a randomized clinical trial of septic shock patients treated with norepinephrine [4]. Vasopressors that are not inotropes or chronotropes may be useful in patients with shock One such vasopressor is vasopressin, which is most commonly used as an adjuvant with catecholamines. Vasopressin has been shown to improve outcomes in patients with less severe septic shock, but has toxicity (that is, cardiac and mesenteric ischemia) at high doses and interacts with hydrocortisone [5]. The addition of a rescue vasopressor in this setting could be useful
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