Continuous I.V. Administration of the Angiotensin-Converting Enzyme Inhibitor Enalaprilat in the Critically Ill

Abstract

Summary Several components are responsible for circulatory control at the central, regional, and microcirculatory level. Angiotensin-converting enzyme (ACE) inhibitors are known to act beneficially on circulation by various mechanisms. The influence of continuous i.v. administration of the ACE inhibitor enalaprilat on regulators of circulation was studied in 45 critically ill patients. According to a prospective randomized sequence, either 0.25 mg/h (group 1. n = 15) or 0.5 mg/h (group 2, n = 15) of enalaprilat or saline solution as placebo (control group, n = 15) were continuously given. Infusion was started on the day of admission to the intensive care unit (ICU) and continued for the next 5 days. From arterial blood samples, plasma levels of endothelin-1 (ET), atrial natriuretic peptide (ANP), renin, vasopressin, angiotensin-II, and catecholamines (epinephrine, norepinephrine) were measured. All measurements were carried out before infusion ( = baseline values) and during the next 5 days. In both enalaprilat groups, mean arterial blood pressure (MAP) decreased similarly; heart rate (HR) and central venous pressure (CVP) did not change, and were without differences in comparison to the untreated control. Except for ET, plasma levels of all vasoactive substances exceeded normal range at baseline. Angiotensin-II plasma concentrations significantly decreased during enalaprilat infusion (0.25 mg/h: from 53.1 ± 11.3 to 22.1 ± 9.3 pg/ml; 0.50 mg/h: 62.1 ± 14.4 to 17.9 ± 7.9 pg/ml). but they remained significantly elevated in the untreated control patients. Vasopressin plasma level increased only in the control group (p < 0.01) and decreased in the patients in whom 0.50 mg/h of enalaprilat was infused. ET plasma concentrations remained almost unchanged in group 2, whereas in the control patients, they increased significantly (from 4.9 ± 0.9 to 10.1 ± 1.9 pg/ml on the 5th day). Catecholamine plasma levels markedly increased in the control group (p < 0.01); in both enalaprilat groups, they did not change significantly throughout the study period. It is summarized that continuous i.v. administration of the ACE inhibitor enalaprilat beneficially influenced systemic and local vasoactive regulators of the circulation, which are normally increased in the critically ill. Thus patients at risk of circulatory abnormalities may profit from continuous enalaprilat infusion. However, large outcome studies are essential before widespread use can be recommended in this situation.