New class of drug for septic/ Vasodilatory shock

Ashish Khanna, M.D., Shane W. English, M.D., Xueyuan S. Wang, M.D et el Published in NEJM a new trial Of angiotensin II in vasodilatory shock [Treatment of High-Output Shock (ATHOS-3) trial].


Vasodilatory shock is the most common cause of shock in the critical care world. It is charecterized by peripheral vasodilatation and reduce blood pressure in spite preserved cardiac output in most patients. There are two classes of medications currently available, mainly catecholamines and vasopressin.

In patients with severe vasodilation, higher doses of catecholamines are used and  these patients have  poor mortality.  In a recent pilot study by Chawla LS, Busse L, Brasha-Mitchell E, et al angiotensin II was shown to consistently have vasopressor effect.


In this multinational, double-blind, randomized, controlled trial, 321 patients with the vasodilatory shock who were receiving more than 0.2 µg of norepinephrine per kilogram per minute were randomized to tthis CU angiotensin II or placebo.


Angiotensin II was started at 20 ng per kilogram per minute, and adjusted in the first three hours, keeping the standard of care vasopressors at constant dose. Maximum dose was 40 ng per kg per minute. This was tappered  off at 48 hours.


Angiotensin II effectively increase blood pressure in patients with vasodilatory shock who did not respond to high doses of conventionalism vvasopressors.

Tachyarrhythmias, digital ischemia were similar in both groups.

Patients who received angiotensin II had lower requirements for catecholamines and cardiovascular SOFA scores. Mortality was same in both groups.


Angiotensin II needs to be directly compared with other agents. This study was not powered to study mortality. Patients in the study were chosen who had normal cardiac output. We do not know the effect of angiotensin II in patients of vasodilatory shock also have low cardiac output. Hypoalbuminemia and higher doses of catecholamines was associated with poor response to angiotensin II. With a large study, we may find more subgroups which do not respond to angiotensin II.


It is good to have a third agent for treatment of vasodilatory shock. We need a large study before we can implement its use in clinical practice.

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