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CARDIOVASCULAR ANESTHESIA

The Pharmacokinetics of Remifentanil in Patients Undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass

Luis G. Michelsen, MD^*, Nicholas H. G. Holford, MB ChB, Wei Lu, PhD^*, John F. Hoke, PhD, Carl C. Hug, MD PhD^*, and James M. Bailey, MD PhD^*

*Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia; Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand; and Department of Clinical Pharmacology, Glaxo, Inc., Research Triangle Park, North Carolina

Address correspondence to James M. Bailey, MD, PhD, Department of Anesthesiology, Emory University School of Medicine, 1364 Clifton Rd. NE, Atlanta, GA 30322. Address e-mail to james_bailey{at}emory.org

Remifentanil is a potent opioid with a short duration of action. It has the potential for large-dose opioid anesthesia without an obligatory prolonged period of mechanical ventilation. However, because of high clearance and rapid tissue distribution, cardiopulmonary bypass (CPB) may influence its pharmacokinetics and alter drug requirements. We administered remifentanil by continuous infusion to 68 patients having coronary artery bypass graft surgery during CPB with hypothermia to describe the effects of these interventions on its pharmacokinetics. Remifentanil concentrations were measured before, during, and after CPB. Disposition was best described by a two-compartment model. The volume of distribution increased by 86% with institution of CPB and remained increased after CPB. Elimination clearance decreased by 6.37% for each degree Celsius decrease from 37°C.

IMPLICATIONS: Remifentanil concentrations decrease with the institution of cardiopulmonary bypass because of an increase in the volume of distribution. The decrease in elimination clearance with hypothermia results in increased total remifentanil concentrations during cardiopulmonary bypass if the infusion rate is not altered. More constant blood remifentanil levels may be obtained by reducing remifentanil infusion rate by 30% for each 5°C decrease in temperature.

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