心内直视手术中大剂量芬太尼的药代动力学研究

Pharmacokinetics of High-dose Fentanyl in Patients Undergoing Cardiac Surgery

目的：研究心内直视手术中大剂量芬太尼的药代动力学。方法：随机选择１１例心内直视手术患者，芬太尼６０μｇ／ｋｇ静脉注射后，采集２４小时桡动脉血标本，应用气相色谱—质谱法检测血浆芬太尼浓度，ＮＯＮＬＩＮ软件计算药代动力学参数。结果：芬太尼药代动力学符合开放性三室模型。静脉注射芬太尼后血药浓度立刻达１２６．９～２５９．０ｎｇ／ｍｌ，在静脉注射后６０分钟血药浓度下降为１２．９ｎｇ／ｍｌ，有９３．１％的芬太尼从血浆中被清除。有７例患者在不同时间血药浓度出现第２次和第３次高峰。手术后８小时血药浓度仍可再次增高达３．９８±１．７６ｎｇ／ｍｌ。结论：在大剂量芬太尼麻醉时，手术后呼吸支持应超过８小时，尤其在患者清醒、体温恢复及有随意活动时，血浆芬太尼浓度增高。

? Objective:To study the pharmacokinetics of highdose fentanyl in patients undergoing cardiac surgery Methods:Eleven patients undergoing cardiac surgery,blood samples were collected following a bolus injection of highdose(60 μg/kg)fentanyl as the sole anestheticPlasma fentanyl concentration was determined by gas chromatography/mass spectrometry(GC/MS)methodPharmacokinetic parameter were calculated with NONLIN computer program Results:The kinetics can be described by triexponential decay curvePlasma fentanyl concentration reached a peak(1269_2590 ng/ml) immediately after a bolus injection of fentanylIt decreased to 129 ng/ml in 60 min,931% of fentanyl was removed in plasma.Seven patients had a second and third peak in plasma fentanyl concentration,which reincreased to 398±176 ng/ml even at 8 h after operation Conclusion:Respiratory therapy should be continued to eight hours following the end of operation under highdoes fentanyl anesthesia,because the increased plasam fentanyl level may lead to recurrence of respiratory depression, especially when the patients consciouseness is regained and the muscle tone,body temperature and voluntary movement are recovered