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Amrinone in neonates and infants after cardiac surgery
S Lawless1, G Burckart, W Diven
1Department of Anesthesia, Children's Hospital of Pittsburgh, PA.
Insights
Current amrinone dosing is inadequate for neonates and infants. This study found age-dependent pharmacokinetic differences, necessitating adjusted dosages for these young patients to achieve therapeutic levels safely.
Area of Science:
- Pharmacology
- Pediatric Critical Care
- Cardiovascular Surgery
Background:
- Amrinone is used for critically ill postoperative infants with congenital heart defects.
- Understanding amrinone pharmacokinetics in young children is crucial for safe and effective treatment.
- Previous dosing guidelines may not be optimal for neonates and infants.
Purpose of the Study:
- To determine the pharmacokinetics and adverse effects of amrinone in critically ill postoperative patients under 1 year of age.
- To compare amrinone pharmacokinetics between neonates (less than 4 weeks) and infants (greater than 4 weeks).
- To establish appropriate amrinone dosage recommendations for different age groups in this population.
Main Methods:
- Studied 18 critically ill postoperative patients (<1 yr) undergoing cardiopulmonary bypass.
- Collected plasma samples to determine amrinone steady-state concentrations and elimination half-life (T1/2).
- Calculated clearance and volume of distribution; monitored platelet transfusion incidence.
Main Results:
- Significant differences in T1/2 (22.2 vs. 6.8 h) and clearance (1.1 vs. 2.6 ml/min.kg) between neonates and infants.
- A strong negative correlation between T1/2 and age (r = -.79) was observed.
- Platelet transfusion rates were similar to controls, suggesting amrinone did not increase bleeding risk.
Conclusions:
- Current amrinone dosage recommendations are insufficient for neonates and infants.
- Age-specific dosing is required: infants need higher infusion rates than neonates.
- Recommended dosages: Infants (3.0-4.5 mg/kg bolus, 10 mcg/kg/min infusion); Neonates (3.0-4.5 mg/kg bolus, 3-5 mcg/kg/min infusion).
Abstract:
Eighteen critically ill postoperative patients less than 1 yr of age were studied to determine the pharmacokinetics and adverse effects of amrinone. All patients had undergone cardiopulmonary bypass for repair of congenital heart lesions. Plasma samples were obtained every 12 h while patients were receiving amrinone to determine when steady state was achieved; samples were also obtained within 24 h after amrinone had been discontinued. Elimination half-life (T1/2), clearance, and volume of distribution were calculated from plasma amrinone concentrations, and the incidence of platelet transfusion was monitored. T1/2(22.2 vs. 6.8 h) and clearance (1.1 vs. 2.6 ml/min.kg), but not the volume of distribution (1.8 vs. 1.6 L/kg), differed significantly in patients less than 4 wk of age in comparison to patients greater than 4 wk of age. A negative correlation between T1/2 and age (r = -.79) was observed. Platelets were administered no more frequently in study patients than in a similar group that did not receive amrinone. To achieve the plasma concentration of amrinone that is therapeutic in adults, current dosage recommendations are inadequate in neonates and infants. Infants should receive an initial iv amrinone bolus of 3.0 to 4.5 mg/kg in divided doses followed by a continuous infusion of 10 micrograms/kg.min, while neonates should receive a similar bolus followed by a continuous infusion of 3 to 5 micrograms/kg.min.