CARDIORESPIRATORY EFFECTS OF CONTINUOUS IV ADMINISTRATION OF THE ACE-INHIBITOR ENALAPRILAT IN THE CRITICALLY ILL (Publication with Expression of Concern. See vol. 88, pg. 2475, 2022)

1 Cardiorespiratory effects of long-term, continuous i.v, administration of the ACE inhibitor enalaprilat were studied. 2 Forty-five consecutive critically patients suffering from trauma or postoperative complications were randomly separated into three groups (15 patients in each up) receiving either 0.25 mg h(-1) or 0.50 mg h(-1) enalaprilat, respectively, or saline solution as placebo (= control group). The infusion was continued for 5 days. 3 Haemodynamic and respiratory parameters were intensively monitored on admission to the intensive care unit (= 'baseline' values) and daily during the next 5 days. 4 Mean arterial blood pressure (MAP) decreased significantly only in the enalaprilat-treated patients, whereas heart rate (HR) remained unchanged in these patients. 5 Pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressure (PAP) were decreased by enalaprilat (0.50 mg h(-1): PAP (mean +/- s.d.) decreased from 28.0 +/- 4.1 to 24.0 +/- 3.0 mm Hg) and remained significantly lower than in the control group. In the untreated control group, cardiac index (CI), oxygen consumption (VO2I) and oxygen delivery (DO2I) significantly decreased, which was blunted by enalaprilat infusion. Oxygen extraction (O-2-extr) increased in both enalaprilat groups (0.25 mg h(-1): from 26.1 +/- 5.5 to 30.4 +/- 4.0%; 0.50 mg h(-1): 25.2 +/- 5.6 to 30.9 +/- 4.4%) and decreased in the control patients. 6 Right ventricular haemodynamics improved by enalaprilat infusion (0.50 mg h(-1): RVEF increased from 40.0 +/- 3.5 to 45.5 +/- 4.0%). Lactate plasma concentrations decreased in the group with 0.50 mg h(-1) enalaprilat (from 1.9 +/- 1.0 to 1.3 +/- 0.3 mg dl(-1)) and increased in the control patients. 7 Continuous infusion of the ACE inhibitor enalaprilat exerted beneficial cardiorespiratory effects in the critically ill. The widespread common risk of altered perfusion with decreased CI, DO2, VO2, O-2-extr and increased lactate concentration was blunted by enalaprilat infusion. 8 Although 0.5 mg h(-1) enalaprilat was most effective, a dose of 0.25 mg h(-1) also showed beneficial haemodynamic effects in the critically ill.