Levosimendan versus milrinone in neonates and infants after corrective open-heart surgery: A pilot study

Objective: Low cardiac output syndrome commonly complicates the postoperative course after open-heart surgery in children. To prevent low cardiac output syndrome, prophylactic administration of milrinone after cardiopulmonary bypass is commonly used in small children. The aim of this study was to compare the effect of prophylactically administered levosimendan and milrinone on cardiac index in neonates and infants after corrective open-heart surgery. Design: Prospective, single-center, double-blind, randomized pilot study. Setting: Tertiary care center, postoperative pediatric cardiac intensive care unit. Patients: After written informed consent, 40 infants undergoing corrective open-heart surgery were included. Interventions: At weaning from cardiopulmonary bypass, either a 24-hr infusion of 0.1 mu g/kg/min levosimendan or of 0.5 mu g/kg/min milrinone were administered. Cardiac output was evaluated at 2, 6, 9, 12, 18, 24, and 48 hrs after cardiopulmonary bypass using a transesophageal Doppler technique (Cardio-QP, Deltex Medical, Chichester, UK). Cardiac index was calculated from cardiac output and the patients' respective body surface area. Results: Intention-to-treat data of 39 patients (19 in the levosimendan and 20 in the milrinone group) were analyzed using analysis of variance for repeated measurements for statistics. Analysis of variance revealed for both, cardiac index and cardiac output, similar results with no significant differences of the factors group and time. A significant interaction for cardiac output (p = .005) and cardiac index (p = .007) was found, which indicates different time courses of cardiac index in the two groups. Both drugs were well tolerated; no death or serious adverse event occurred. Conclusions: In our small study, postoperative cardiac index over time was similar in patients with prophylactically administered levosimendan and patients with prophylactically given milrinone. We observed an increase in cardiac output and cardiac index over time in the levosimendan group, whereas cardiac output and cardiac index remained stable in the milrinone group. This pilot study has primarily served to obtain experience using the new drug levosimendan in neonates and infants and to initiate further multicenter trials in pediatric patients. (Pediatr Crit Care Med 2012; 13:542-548)