"Angiotensin II for the Treatment of Vasodilatory Shock".The New England Journal of Medicine. 2017.

Clinical Question

Does intravenous angiotensin II improve blood pressure in patients with vasodilatory shock who are receiving high-dose vasopressors?

Bottom Line

Angiotensin II effectively increased blood pressure in patients with vasodilatory shock not responsive to high doses of conventional vasopressors.

Major Points

Patients with vasodilatory shock and hypotension despite high doses of vasopressors have poor prognosis, and treatment options are limited. This trial investigated the efficacy of angiotensin II as an additional therapy in these patients.

Guidelines

As of the last knowledge update, no guidelines have been published that reflect the results of this trial.

Design

Multi-center, double-blind, parallel-group, randomized, placebo-controlled trial.

Population

Inclusion Criteria:
- Age ≥18 years
- Vasodilatory shock despite intravenous volume resuscitation
- Receiving high-dose vasopressors (>0.2 μg/kg/min norepinephrine equivalent)
Exclusion Criteria:
- Burns covering >20% of the body
- Acute coronary syndrome
- Bronchospasm
- Liver failure
- Active bleeding
- Abdominal aortic aneurysm
- Neutropenia
- Venoarterial extracorporeal membrane oxygenation
- High-dose glucocorticoids

Interventions

- Angiotensin II (n=163)
- Placebo (n=158)

Outcomes

Primary Outcome:
- Increase in mean arterial pressure to ≥75 mm Hg or by at least 10 mm Hg without an increase in the dose of background vasopressors at hour 3
Secondary Outcomes:
- Change in cardiovascular SOFA score at hour 48
- Change in total SOFA score at hour 48
- Safety evaluated by adverse events, adverse event-related drug discontinuations, and all-cause mortality at 7 and 28 days

Criticisms

- Study may have allowed treating clinicians to correctly guess treatment assignment
- Relatively small sample size
- Not powered to detect mortality differences
- Follow-up limited to 28 days, restricting long-term outcome assessments
- Larger trials with longer duration needed for definitive conclusions

Funding

La Jolla Pharmaceutical Company

Further Reading

Additional references, including the full text of the article on NEJM.org.