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Anesth Analg 2006;102:1062-1069
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000198626.67391.34

PEDIATRIC ANESTHESIA

Population Pharmacokinetics of Milrinone in Neonates with Hypoplastic Left Heart Syndrome Undergoing Stage I Reconstruction

Athena F. Zuppa, MD MSCE, Susan C. Nicolson, MD, Peter C. Adamson, MD, Gil Wernovsky, MD, John T. Mondick, Nancy Burnham, RN, MSN, Timothy M. Hoffman, MD, J. William Gaynor, MD, Lauren A. Davis, BS, William J. Greeley, MD, MBA, Thomas L. Spray, MD, and Jeffrey S. Barrett, PhD

Division of Clinical Pharmacology and Therapeutics, Department of Pediatrics, Division of Critical Care, Department of Anesthesiology and Critical Care Medicine, Division of Cardiothoracic Anesthesia, Department of Anesthesiology and Critical Care Medicine, Division of Cardiology, Department of Pediatrics, Division of Cardiothoracic Surgery, Department of Surgery, Abramson Research Center, Philadelphia, Pennsylvania

Address correspondence and reprint requests to Athena F. Zuppa, MD, Abramson Research Center, Suite 916, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318. Address e-mail to zuppa{at}email.chop.edu.

We performed a blinded, randomized pharmacokinetic study of milrinone in 16 neonates with hypoplastic left heart undergoing stage I reconstruction to determine the impact of cardiopulmonary bypass and modified ultrafiltration on drug disposition and to define the drug exposure during a continuous IV infusion of drug postoperatively. Neonates received an initial dose of either a 100 or 250 µg/kg of milrinone into the cardiopulmonary bypass circuit at the start of rewarming. Postoperatively, milrinone was infused to clinical needs. A mixed-effect modeling approach was used to characterize milrinone pharmacokinetics during cardiopulmonary bypass, modified ultrafiltration, and postoperatively using the NONMEM algorithm. All patients in this study demonstrated a modified ultrafiltration concentrating effect that occurred despite a modified ultrafiltration drug clearance of 3.3 mL · kg–1 · min–1. The infants in this study demonstrated an impaired renal clearance during the immediate postoperative period. A constant infusion of 0.5 µg · kg–1 · min–1 resulted in drug accumulation during the initial 12 h of drug administration. Postoperatively, milrinone clearance was significantly impaired (0.4 mL · kg–1 · min–1), improved by the 12th postoperative hour, and approached steady-state clearance (2.6 mL · kg–1 · min–1) by postoperative day 4. In the postoperative setting of markedly impaired renal function, an infusion rate of 0.2 µg · kg–1 · min–1 should be considered.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.