Hemodynamic and clinical effects of oral levodopa in children with congestive heart failure

[摘要] Objectives. This study was undertaken to evaluate the safety, efficacy and pharmacodynamic variables of oral levodopa in pediatric patients with congestive heart failure refractory to standard therapy. Background. Therapeutic options for children with congestive cardiomyopathies are limited to digoxin, diuretic agents and angiotensin-converting enzyme inhibitors. Previous work-in adults with congestive heart failure has shown a short-term effectiveness of levodopa and improvement of cardiac function. Methods. Baseline two-dimensional and M-mode echocardiography, surface electrocardiography, Holter monitoring and exercise testing, when applicable, were performed. Levodopa was administered in a dose escalation scale from 8 mg/kg body weight per dose to 20 mg/kg per dose over 3 days with concomitant metoclopramide and pyridoxine. Catecholamine levels at initiation of the trial and throughout dose escalation were measured, with echocardiographic and electrocardiographic correlation. After 24-h drug washout, cardiac catheterization was performed both before and after administration of levodopa. Results. Between February 1992 and December 1995, nine children (age 10 +/- 1.7 years, weight 27.8 +/- 4.3 kg) were enrolled in this study. At cardiac catheterization, serum dopamine levels rose from 108.5 +/- 59.2 pg/ml to 1,375.8 +/- 567.9 pg/ml (p = 0.03) at 100 +/- 14.8 min after levodopa administration without a significant change in serum norepinephrine dr epinephrine levels. Paralleling these increases, there were significant changes in the cardiac index (1.7 +/- 0.3 to 3.2 +/- 0.7 liters/min per m(2)),stroke volume index (16.1 +/- 3.2 to 31.2 +/- 7.0 ml/m(2) per min), oxygen consumption (138.6 +/- 24.4 to 188.3 +/- 30.8 ml/min per m(2)) and systemic vascular resistance (36.8 +/- 8 to 21.9 +/- 5.5 indexed Wood's units; all p < 0.01). There was a significant reversal of the daily fluid volume output/input ratio from 0.8 +/- 0.1 to 1.2 +/- 0.1 (p < 0.01). Levodopa administration was complicated by hypertension or tachycardia, or both, requiring a dose reduction in three patients, and by significant gastrointestinal distress in one. There was sustained symptomatic improvement a median of 19.5 months after drug initiation in seven of the patients. Conclusions. These preliminary data support the hemodynamic value of oral levodopa in the treatment of severe congestive heart failure in children. (C) 1997 by the American College of Cardiology.

[发布日期] 1997-07-01

[效力级别]  Proceedings Paper