Abstract
Purpose: Little research has been reported to date on the usefulness of olprinone in pediatric cardiac surgery, and no standard pediatric infusion protocol is currently established. Our study sought to confirm that the regimen described herein rapidly achieves the requisite plasma olprinone concentrations. Methods: For the purposes of our study, we enrolled 13 patients: 7 biventricular repair candidates and 6 Fontan-type operation candidates. We administered a continuous infusion of olprinone to our study subjects at 0.3 μg/kg/min with no loading dose starting approximately 30 minutes (min) before weaning from cardiopulmonary bypass (CPB). We performed blood sampling at 15, 30, 45, 60, 90, and 120 min after the start of infusion and at the same elapsed intervals after separation from CPB. We measured plasma olprinone concentrations using ultra-fast liquid chromatography. Results: We observed effective plasma olpri-none concentrations (>20 ng/ml) at 30 min after weaning from CPB, or at 60 min after the start of infusion. Conclusion: We conclude that continuous olprinone infusion at 0.3 μg/kg/min without a loading dose initiated immediately after the release of aortic cross-clamping or immediately after the completion of all surgical procedures quickly and reliably achieves effective plasma concentrations.
Highlights
The effects of milrinone on hemodynamics and outcomes in pediatric cardiac surgery have been extensively investigated
After dividing the patients into three groups based on the time elapsed from initiation of infusion to separation from cardiopulmonary bypass (CPB), we found concentrations elevated above the effective concentration by 60 min after separation from CPB, even in patients with times of less than 30 min (Figure 1(b))
The study results showed that our infusion protocol achieved effective plasma concentrations quite rapidly, within 30 min after weaning from CPB
Summary
The effects of milrinone on hemodynamics and outcomes in pediatric cardiac surgery have been extensively investigated. A large multi-center study in North America (the PRIMACORP study) demonstrated high-dose milrinone significantly reduced mortality or the incidence of low cardiac output syndrome (LOS) after pediatric cardiac surgery and that even low-dose milrinone likewise tended to reduce mortality or LOS development, low-dose results failed to reach statistically significant levels [1]. Olprinone is a phosphodiesterase-3 (PDE-3) inhibitor developed and commercially available in Japan since 1996. Little data on olprinone is available at this time, data on use during pediatric cardiac surgery in particular. Even optimal regimens for achieving effective blood concentrations remain uncertain. Our study sought to confirm that our infusion method rapidly achieves effective blood concentrations on weaning from CPB during pediatric cardiac surgery
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