Acute Hemodynamic Response to Intravenous Enoximone

Abstract

In light of previous studies in adults, we considered that enoximone could be useful in treating children with therapy-resistant cardiovascular insufficiency. Prior to clinical administration, we investigated the cardiovascular properties of enoximone in anesthetized and ventilated piglets characterized by small stroke volume and high heart rate. Enoximone was administered intravenously in increasing doses (0.25, 0.5, and 1 mg/kg). The animals were monitored with heart rate, systemic and pulmonary arterial pressures, and continuous electromagnetic flow. Enoximone induced a dose-dependent flow increase, whereby heart rate and systemic arterial pressure changed only slightly. With regard to persistent pulmonary hypertension in newborns, enoximone was also used in piglets to investigate the effects on endotoxin-induced, dopamine-resistant pulmonary hypertension. Enoximone (1 mg/kg i.v.) was given immediately after E. coli endotoxin (1.5 micrograms/kg i.v.) and inhibited the endotoxin-induced, eicosanoid-mediated pulmonary hypertension, whereas during infusion of dopamine (2 mg/kg/h), no drop in systemic blood pressure could be observed. In the clinical study, six infants with post-cardiac surgery low output syndrome despite maximal catecholamine inotropic support were given enoximone (i.v. bolus of 0.2, 0.5, or 1 mg/kg followed by continuous infusion of 7.5-10 micrograms/kg/min). Continuously measured mixed-venous oxygen saturation increased in a dose-related manner. Cardiac output increased significantly by 28%, accompanied by a decrease of arteriovenous oxygen content difference and O2 utilization ratio. The preliminary results show that intravenous enoximone produces acute useful hemodynamic effects in infants, in particular allowing a weaning of vasoactive amines.