Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published August 2, 2017

Is angiotensin II effective for the treatment of catecholamine-resistant vasodilatory shock?

Patients with severe vasodilation who have hypotension despite the use of high doses of vasopressors have a poor prognosis, with 30-day all-cause mortality exceeding 50%. Khanna et al. conducted the randomized, double-blind, placebo-controlled phase 3 Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial to determine whether the addition of angiotensin II to background vasopressors would improve blood pressure in patients with catecholamine-resistant vasodilatory shock. Read the Original Article on the subject.

Clinical Pearls

Q. What is vasodilatory shock and how is it treated?

A. Vasodilatory shock is the most common type of shock and is characterized by peripheral vasodilation and reduced blood pressure despite preserved cardiac output. Vasodilatory shock requires immediate treatment to ensure organ perfusion through the reestablishment of adequate blood pressure while the underlying cause of shock is identified and treated. Vasopressors are used when intravenous fluid resuscitation alone fails to restore blood pressure. Currently, only two classes of vasopressors are available: catecholamines (and other sympathomimetic amines) and vasopressin. Both classes have narrow therapeutic windows owing to substantial toxic effects at high doses.

Q. What are the treatment options for catecholamine-resistant vasodilatory shock?

A. Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects. Specific options include glucocorticoids, vasopressin, methylene blue, and high-volume hemofiltration, all of which are used as adjunct therapies to maintain blood pressure in patients with vasodilatory shock. Previously, new therapies proved to be disappointing. Notably, the nitric oxide synthase inhibitor 546C88 increased blood pressure in patients with septic shock but was associated with more frequent cardiovascular side effects and increased 28-day mortality.

Morning Report Questions

Q: Is angiotensin II effective for the treatment of catecholamine-resistant vasodilatory shock?

A: In the ATHOS-3 trial, the primary end point was the response with respect to mean arterial pressure at hour 3, with response defined as a mean arterial pressure of 75 mm Hg or higher or an increase in mean arterial pressure from baseline of at least 10 mm Hg, without an increase in the dose of background vasopressors. The authors found that significantly more patients in the angiotensin II group than in the placebo group met the criteria for the primary end point of response with respect to mean arterial pressure at hour 3 (69.9% vs. 23.4%, P<0.001; odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3). In the angiotensin II group, the mean arterial pressure increased rapidly, allowing the angiotensin II dose to be decreased from the original 20 ng per kilogram per minute in 67% of the patients within 30 minutes and permitting decreases in doses of concomitant vasopressors. In a finding consistent with this result, cardiovascular Sequential Organ Failure Assessment (SOFA) scores, which quantify catecholamine use, were significantly lower in the angiotensin group than in the placebo group at 48 hours.

Q: What are some of the limitations of the ATHOS-3 trial?

A: The study had a relatively small sample size, so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be excluded. Because follow-up was limited to 28 days, the possibility of either beneficial or harmful long-term effects of angiotensin II therapy cannot be excluded. Larger trials with longer duration of follow-up are warranted to address these questions, as are direct comparisons of angiotensin II with other vasopressors.

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