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Dopamine clearance in critically ill infants and children: effect of age and organ system dysfunction
D A Notterman1, B M Greenwald, F Moran
1Department of Pediatrics, New York Hospital-Cornell Medical Center 10021.
Insights
Dopamine clearance is significantly affected by age in infants and children, with younger children exhibiting nearly double the clearance rate compared to older children. This age-related difference impacts dopamine dosage requirements in pediatric patients.
Area of Science:
- Pharmacokinetics
- Pediatric Pharmacology
Background:
- Dopamine is a critical vasoactive agent used in managing critically ill infants and children.
- Understanding dopamine's pharmacokinetic behavior is essential for optimizing therapeutic efficacy and safety in pediatric populations.
Purpose of the Study:
- To investigate age-related differences in plasma dopamine clearance in acutely ill infants and children.
- To identify factors influencing dopamine clearance, including age, conjugated bilirubin levels, and hepatic/renal function.
Main Methods:
- Plasma dopamine clearance was determined in 27 acutely ill infants and children receiving continuous intravenous dopamine infusions.
- Steady-state clearance was calculated using arterial blood dopamine concentrations.
- Statistical analysis was performed to assess the impact of age and other clinical parameters on dopamine clearance.
Main Results:
- Overall mean dopamine clearance was 60.7 +/- 28.1 ml/kg/min.
- Age significantly influenced dopamine clearance (r = -0.63; p < 0.05), with clearance rates nearly twice as high in children younger than 2 years (82.3 ml/kg/min) compared to older children (45.9 ml/kg/min).
- Elevated conjugated bilirubin and combined hepatic and renal dysfunction were associated with reduced dopamine clearance.
Conclusions:
- Age is a critical determinant of dopamine clearance in pediatric patients.
- Infants and young children generally require higher dopamine infusion rates due to faster clearance.
- Conjugated bilirubin levels and organ dysfunction can further modify dopamine clearance, necessitating careful dose adjustments.
Abstract:
To learn if there are age-related differences in the pharmacokinetic behavior of dopamine, plasma dopamine clearance was determined in 27 acutely ill infants and children who were receiving a continuous intravenous infusion of the drug. Steady-state clearance was calculated from dopamine concentration in arterial blood. Dopamine clearance was 60.7 +/- 28.1 ml/kg/min. The age of the patient exerted an effect on clearance of dopamine (r = -0.63; p less than 0.05), and dopamine clearance was nearly twice as rapid in children younger than 2 years as it was in older children (82.3 +/- 27.7 ml/kg/min versus 45.9 +/- 17.0 mg/kg/min). Conjugated bilirubin exerted an age-independent effect on clearance of dopamine; clearance was 44.8 +/- 28.6 ml/kg/min in children with abnormal conjugated bilirubin (greater than or equal to 0.9 mg/dl) and 70.1 +/- 2.56 ml/kg/min in children with normal conjugated bilirubin (less than 0.9 mg/dl). Clearance was lowest (29.8 +/- 5.7 ml/kg/min) in the four children who had both hepatic and renal dysfunction. Age is an important determinant of dopamine clearance, explaining in part the clinical observation that infants and young children require higher infusion rates.