Pharmacokinetic-hemodynamic studies of intravenous nitroglycerin in congestive cardiac failure.

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Abstract
The expanding role of i.v. nitroglycerin (GTN) in the management of critically ill hospitalized patients demands a clear knowledge of its pharmacodynamics and kinetics in normal and diseased states. Patients (16) with congestive cardiac failure were studied to establish the relationship between blood levels of GTN and its physiologic effects during and after an i.v. infusion. The end point of this study was .apprx. 25% fall in pulmonary capillary wedge pressure or more than a 10-fold increment over the initial GTN infusion rate. Infusion rate of GTN and blood concentration correlated well (r [correlation coefficient] = 0.75, P < 0.001). Patients were divided into 2 groups based on their blood GTN concentration. Group 1 patients (no. = 8) achieved blood GTN concentrations of 1.2-11.1 ng/ml and all reached the hemodynamic end point. The minimum effective blood GTN concentration was 1.2 ng/ml at an infusion rate of 15 .mu.g/min. Group 2 patients (no. = 8) had blood levels > 11.1 ng/ml and only 3 achieved the hemodynamic end point. Group 2 had greater systemic venous congestion than group 1 (right atrial pressure 19 .+-. 4 mm Hg (SD) vs. 10 .+-. 4 mm Hg [P < 0.001]). Group 2 had lower total body clearance of GTN (3.6 .+-. 1.8 l/min) than group 1 (13.8 .+-. 5.8 l/min) (P < 0.005). The low clearance of GTN in group 2 patients may be explained in part by impaired hepatic metabolism secondary to severe systemic venous congestion. Complete blood GTN data were available on 5 patients after cessation of the GTN infusion and revealed a short half-life of 1.9 min. Some patients failed to reach the hemodynamic end point with high infusion rates of GTN (220-440 .mu.g/min) and blood levels of 42.2-481.3 ng/ml. There was no evidence of toxicity despite these high GTN blood levels.