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OPIOID PHARMACOKINETICS DURING & AFTER CARDIOPULMONARY BYPASS

Department of Anesthesia, University of Manitoba, St. Boniface General Hospital, 409 Taché Avenue, Winnipeg, Manitoba, R2H 2A6

INTRODUCTION

The pharmacokinetics of fentanyl and sufentanil in adults, during and after cardiopulmonary bypass (CPB), are unknown.

METHODS

Institutional ethical approval and informed consent were obtained from patients undergoing elective coronary artery surgery. They were randomized to receive either fentanyl (n=22) or sufentanil (n=21). Premedication was lorazepam 40 mg/kg PO. Target-controlled opioid infusions were administered using the program STANPUMP. The initial target effect-site fentanyl concentration was 7 ng/ml. It was decreased to 5 ng/ml (after sternotomy), and then to 1.5 ng/ml (30 minutes after initiation of CPB).Sufentanil target concentrations were 10-fold lower. Thiopental and succinylcholine were administered with either opioid during induction. Isoflurane, vecuronium, and vasoactive drugs were used as needed. Opioid arterial blood concentrations were measured perioperatively until 24 hours after induction (fentanyl 478; sufentanil 438 samples). Population modelling (naïve pooled data method) was used to derive pharmacokinetic parameters. First, a simple 3-compartment model, not adjusted for CPB, was determined. Then, additional models were developed, in which compartmental volumes & clearances were allowed to change at the start, and at the end, of CPB. Criteria for accepting a CPB-adjusted model were: an increase in log-likelihood (LL) of >2 per added parameter, and a significant (P>0.05) improvement in prediction error (PE, calculated as: ([Measured]![Predicted]) /[Predicted] ) or its absolute value (APE).

RESULTS

Demographic data, the parameters of the simple unadjusted 3-compartment models, and the median PE and APE are shown in the Table. Although several of the more complex, CPB-adjusted models increased LL by >2, none improved PE or APE, compared to the simple models (P=0.83 - 1.0 by ANOVA). Therefore, we chose the simple, unadjusted 3--compartment models as our final models for both opioids.

We have determined the first complete pharmacokinetic models for fentanyl and sufentanil in adults undergoing cardiopulmonary bypass. The predictive abilities of these models are excellent, with median PE near zero, and median APE <30%.¹ In combination with pharmacodynamic information,² these models can be used to design dose regimens that promote intraoperative hemodynamic stability, facilitate early tracheal extubation, and provide good postoperative analgesia.

REFERENCES

1 Anesthesiology 1990; 73:1082–90.[Medline]

2 Anesthesiology 1998; 89: 852–61.[Medline]

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