The Pharmacokinetics of Milrinone in Pediatric Patients after Cardiac Surgery

Bailey, James M.; Miller, Bruce E.; Lü, Wei; Tosone, Steven R.; Kanter, Kirk R.; Tam, Vincent K.H

doi:10.1097/00000542-199904000-00014

Cited by 98 publications

(71 citation statements)

References 16 publications

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“…MR improves mesenteric perfusion and attenuates myocardial oxydative stress following hypoxia-reoxygenation in piglets (5). Studies in pediatric populations appear to support the clinical usefulness of MR, which is similar to that observed in adults (6)(7)(8)(9)(10)(11).…”

supporting

confidence: 60%

“…However, the infusion of IND in this study began earlier than in other trials (7,23). It is noteworthy that early in the postoperative course, MR-treated infants showed MR plasma concentrations within the therapeutic range (8). In the case of LEVO-treated infants, the median plasma concentrations of the parent drug and OR1896 were, 10 h after infusion of IND started, within the range that showed positive hemodynamic effects in adults with heart failure (14) and in healthy male volunteers (15), respectively.…”

Section: Discussionmentioning

confidence: 74%

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Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery

et al. 2012

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Background: Inodilators are routinely used in cardiovascular surgery with cardiopulmonary bypass (cPB). Information regarding safety and tolerability of the novel molecule, levosimendan (LeVO), in newborns is anecdotal; no pharmacokinetic data in this population are available. Methods: This was a phase I, randomized, and blinded study. Neonates undergoing surgical repair for congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1 μg/kg/min, n = 9) or LeVO (0.1-0.2 μg/kg/min, n = 11) as an i.v. continuous infusion, starting before cPB. Infants had continuous, time-locked, physiological, and near-infrared spectroscopy (NIRs) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery. serial biochemistry and pharmacokinetic studies were performed. results: During the first 24 h postsurgery, patients showed time-related, group-independent increased cerebral tissue oxygenation and decreased diastolic blood pressure; in addition, group-dependent differences in heart rate and peripheral perfusion were found. early postsurgery, MR-treated infants showed lower ph, higher glycemia, and higher inotrope score. The groups differed in cerebral NIRs-derived variables from 24 to 96 h. study drug withdrawal at 96 h was more frequent with LeVO. LeVO intermediate metabolites were detected in plasma at day 14 after surgery. conclusion: LeVO is well tolerated in critically ill neonates. LeVO may have advantages over MR in terms of the dosing regimen.

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supporting

confidence: 60%

Section: Discussionmentioning

confidence: 74%

Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery

et al. 2012

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“…8 These effects of milrinone were evident after the bolus and were maintained during the infusion. Similarly, Bailey et al 9 reported an 18% mean increase in the cardiac index in 20 patients with an age range of 3 to 22 months who received milrinone after cardiac surgery. Similar hemodynamic effects of milrinone have been observed in adults.…”

Section: Discussionmentioning

confidence: 85%

“…12 In studies performed with patients having low cardiac index, phosphodiesterase inhibitors increased cardiac output, reduced systemic and pulmonary vascular resistance, and decreased filling pressures. 8,9 Because LCOS occurs frequently in pediatric patients after congenital heart surgery, the prophylactic use of a positive inotropic and vasodilatory agent, such as milrinone, may improve cardiac function and lower the risk of morbidity and mortality. The purpose of the PRIMACORP trial (PRophylactic Intravenous use of Milrinone After Cardiac OpeRation in Pediatrics) was to evaluate the efficacy and safety of the prophylactic use of milrinone in pediatric patients at high risk of developing LCOS after cardiac surgery.…”

mentioning

confidence: 99%

Efficacy and Safety of Milrinone in Preventing Low Cardiac Output Syndrome in Infants and Children After Corrective Surgery for Congenital Heart Disease

et al. 2003

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Background-Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. Methods and Results-The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25-g/kg bolus over 60 minutes followed by a 0.25-g/kg per min infusion for 35 hours; high dose, 75-g/kg bolus followed by a 0.75-g/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (Pϭ0.023) in 238 treated patients and 64% (Pϭ0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (Pϭ0.049). Conclusions-The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.

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“…It is reasonable to use an inodilator in a highly monitored setting for treatment of myocardial dysfunction with increased systemic or pulmonary vascular resistance (Class IIa, LOE B 352,[442][443][444] ). Administration of fluids may be required secondary to vasodilatory effects.…”

Section: Inodilatorsmentioning

confidence: 99%