Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety

• Authors: Laurence W. Busse, Emory University; Xueyuan Shelly Wang, Duke University; Divya M. Chalikonda, Thomas Jefferson University; Kevin W. Finkel, University of Texas; Ashish K. Khanna, Cleveland Clinic Foundation; Harold M. Szerlip, Baylor University; David Yoo, University of Maryland; Sharon L. Dana, La Jolla Pharmaceutical Company; Lakhmir S. Chawla, La Jolla Pharmaceutical Company
• Journal Title: Critical Care Medicine
• Volume: Volume 45, Number 8
• Publisher: Lippincott, Williams & Wilkins | 2017-08-01, Pages 1285-1294
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1097/CCM.0000000000002441
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Critical Care Medicine; General & Internal Medicine; aldosterone; angiotensin II; mean arterial pressure; renin-angiotensin system; safety; METABOLIC-CLEARANCE RATE; REFRACTORY SEPTIC SHOCK; BLOOD-PRESSURE; HEART-FAILURE; INDUCED BRONCHOCONSTRICTION; ENALAPRIL OVERDOSE; SPINAL-ANESTHESIA; ADRENAL-CORTEX; HUMAN AIRWAY; IN-VITRO

Abstract

Objective: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. Data Sources: PubMed, Medline, Scopus, and Cochrane. Study Selection: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. Data Extraction: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events. Data Synthesis: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis. Conclusion: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.