[Plasma concentration of fentanyl administered at a constant flow rate during prolonged anesthesia]

By radio-immunological estimation using fentanyl H-3, a study was undertaken in ten adults under anaesthesia of long duration obtained by infusion at a constant rate of alfadione and fentanyl of the plasma concentration of fentanyl during and after anaesthesia. Anaesthesia was induced by the administration of 4.3 ml of alfadione and 0.084 mg of fentanyl. The maintenance dose was on average 0.15 ml/kg-/h-1 +/- 0.03 of alfadione and 2.96 micrograms/kg-1/h-1 +/- 0.58 of fentanyl. The mean duration of anaesthesics was 388 minutes +/- 104. The results of this study showed that from the third hour onwards a plateau of serum concentration was established around a mean value of the order of 4.8 micrograms/l-1. The study of excretion curves demonstrated the existence of a three compartment system with respective half lives of 12.75 and 510 minutes. Maintenance of a stable plasma concentration may be explained by an increase in tissue diffusion (increase in mid and long term half life in comparison with single injections) and by increased metabolism. This study provided pharmacokinetic evidence to justify the administration of fentanyl at a constant flow rate preceded by a loading dose.