CONTINUOUS IV ADMINISTRATION OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR ENALAPRILAT IN THE CRITICALLY ILL - EFFECTS ON REGULATORS OF CIRCULATORY HOMEOSTASIS

Several components are responsible for circulatory control at the cent ral, regional, and microcirculatory level. Angiotensin-converting enzy me (ACE) inhibitors are known to act beneficially on circulation by va rious mechanisms. The influence of continuous i.v. administration of t he ACE inhibitor enalaprilat on regulators of circulation was studied in 45 critically ill patients. According to a prospective randomized s equence, 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 = 1 5) were continuously given. Infusion was started on the day of admissi on to the intensive care unit (ICU) and continued for the next 5 days. From arterial blood samples, plasma levels of endothelin-1 (ET), atri al natriuretic peptide (ANP), renin, vasopressin, angiotensin-II, and catecholamines (epinephrine, norepinephrine) were measured. All measur ements were carried out before infusion (= baseline values) and during the next 5 days. In both enalaprilat groups, mean arterial blood pres sure (MAP) decreased similarly; heart rate (HR) and central venous pre ssure (CVP) did not change, and were without differences in comparison to the untreated control. Except for ET, plasma levels of all vasoact ive substances exceeded normal range at baseline. Angiotensin-II plasm a 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 elevat ed in the untreated control patients. Vasopressin plasma level increas ed 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 th e control group (p < 0.01); in both enalaprilat groups, they did not c hange significantly throughout the study period. It is summarized that continuous i.v. administration of the ACE inhibitor enalaprilat benef icially influenced systemic and local vasoactive regulators of the cir culation, which are normally increased in the critically ill. Thus pat ients at risk of circulatory abnormalities may profit from continuous enalaprilat infusion. However, large outcome studies are essential bef ore widespread use can be recommended in this situation.