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*Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; Departments of Anesthesiology and Pediatrics, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Department of Anesthesiology, Harvard Medical School, and Boston Children’s Hospital, Boston, Massachusetts; and Glaxo Wellcome, Inc., Research Triangle Park, North Carolina
Address correspondence and reprint requests to Peter J. Davis, MD, Professor of Anesthesiology and Pediatrics, Department of Anesthesiology, Children’s Hospital of Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213-2583. Address e-mail to davis{at}smtp.anes.upmc.edu
Remifentanil hydrochloride is an ultra-short-acting opioid that undergoes rapid metabolism by tissue and plasma esterases. We aimed to characterize the pharmacokinetics and determine the hemodynamic profile of remifentanil after a single-bolus dose in children aged 0 to 18 yr. Forty-two children undergoing elective surgical procedures received remifentanil 5 µg/kg infused over 1 min. Patients were divided into age groups as follows: young infants (
2 mo), older infants (>2 mo to <2 yr), young children (2 to <7 yr), older children (7 to <13 yr), adolescents (13 to <16 yr), and young adults (16 to <18 yr). Arterial blood samples were collected and analyzed by mass spectroscopy to determine remifentanil pharmacokinetic profiles. Hemodynamic measurements for remifentanil’s effect were made after the infusion. Methods of statistical analysis included analysis of variance and linear regression, with significance at P 0.05. Complete remifentanil pharmacokinetic data were obtained from 34 patients. The volume of distribution was largest in the infants <2 mo (mean, 452 mL/kg) and decreased to means of 223 to 308 mL/kg in the older patients. There was a more rapid clearance in the infants <2 mo of age (90 mL · kg-1 · min-1) and infants 2 mo to 2 yr (92 mL · kg-1 · min-1) than in the other groups (means, 46 to 76 mL · kg-1 · min-1). The half-life was similar in all age groups, with means of 3.4 to 5.7 min. Seven subjects (17%) developed hypotension related to the remifentanil bolus. Remifentanil showed an extremely rapid elimination similar to that in adults. The fast clearance rates observed in neonates and infants, as well as the lack of age-related changes in half-life, are in sharp contrast to the pharmacokinetic profile of other opioids. Remifentanil in a bolus dose of 5 µg/kg may cause hypotension in anesthetized children.
IMPLICATIONS: The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.
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