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

TLDR: The expanding role of intravenous nitroglycerin (GTN) in the management of critically ill hospitalized patients demands a clear knowledge of its pharmacodynamics and kinetics in both normal and diseased states, and this study established the relationship between blood levels of GTN and its physiologic effects during and after an i.v. infusion.

Abstract: SUMMARYThe expanding role of intravenous nitroglycerin (GTN) in the management of critically ill hospitalized patients demands a clear knowledge of its pharmacodynamics and kinetics in both normal and diseased states. Accordingly, we studied 16 patients with congestive cardiac failure 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 either a greater than 25% fall in pulmonary capillary wedge presure or more than a tenfold increment over the initial GTN infusion rate. Infusion rate of GTN and blood concentration correlated well (r = 0.75, p < 0.001). Patients were divided into two groups based on their blood GTN concentration. Group I patients (n = 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 μg/min. Group 2 patients (n = 8) had blood levels greater than 11.1 ng/ml and only three 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 < 0.0011). In addition, group 2 had lower total body clearance of GTN (3.6 ± 1.8 1/min) than group 1 (13.8 ± 5.8 1/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 five patients after cessation of the GTN infusion and revealed a short half-life of 1.9 minutes. Some patients failed to reach the hemodynamic end point with high infusion rates of GTN (220-4 μg/min), and blood levels of 42.2-481.3 ng/ml. There was no evidence of toxicity despite these high GTN blood levels.