| OBJECTIVE1. To establish a sensitive method for the determination of sufentanil concentration in human plasma by HPLC/MS/MS2. To compute the clinical pharmacokinetic parameter of sufentanil in patients undergoing kidney transplantation.3. Comparison of sufentanil with propofol for normal renal function and renal failure recovery of general anesthesia.METHODS1. The concentrations of sufentanil in human plasma were detected by HPLC/MS/MS2. 10 patients scheduled for kidney transplantation were included in this study. After the patients entered the operating room, electrocardiogram(ECG), pulse oxygen saturation(SpO2), non-invasive blood pressure(NBP), end-tidal carbon dioxide partial pressure(PETCO2), were monitored by MP30. Real-time data is automatically collected by the Anesthesia Information Management System (AIMS). peripheral vein and radial artery were punctured under local anesthesia for invasive blood pressure (IBP) monitoring and collection of blood samples. 100% oxygen inhalation, 5min constant peripheral venous infusion of sufentanil 1.0μg/kg, intravenous propofol 1.5～2.5mg/kg, cis-atracurium 0.15～0.2 mg/kg induction of anesthesia, endotracheal intubation for mechanical ventilation. During surgery, isoflurane 1.5～2%, N2O: O2 = 50:50 to maintain anesthesia. Before the blood vessels of transplanted kidney were opened, Fluid volume was controlld less than or equal 500ml.Blood samples of sufentanil were obtained from the artery line at 1,3,5,7,10,15,20,30,60,90,120 minutes and hourly until the end of surgery. Heparinized vacuum blood collection vessel to take 3ml, plasma samples were separated in 30 minutes with 3000 r/min for 10min,divided into two separate plasma and -20℃to save. Sufentail plasma concentrations were measured by HPLC/MS/MS in 4 weeks. The sufentanil pharmacokinetic parameters of each patient were computed by DAS software, The data were analyzed by Microsoft Excel 2003 and SPSS13.03. 20 patients scheduled for kidney transplantation and their relative living specimen supplies kidney were included in this study. After the patients entered the operating room, ECG, SpO2, NBP, PETCO2, IBP was monitored by MP30. The plasma target controlled infusion of propofol(Cp4～5mg/L),sufentanil (Cp0.4ng/ml) and cis-atracurium 0.15～0.2 mg/kg IV. Anesthesia was maintained with the plasma target controlled infusion of propofol(Cp3～4mg/L),sufentanil(Cp0.2～0.4ng/ml) and cis-atracurium 0.05mg/kg Intermittent IV. When the blood vessels of transplanted kidney were opened, maintain systolic blood pressure 130～150mmHg, to ensure renal perfusion. 1h before the end of operation to disable cis-atracurium, 5min before completion of surgery to stop infusion of propofol, sufentanil target concentration of 0.1ng/ml maintained until extubation. The autonomous respiration restores time,awakening time,extubation time and conscious state were observed. Evaluation of the safety of Sufentanil for renal failure patients.RESULTS1. Sufentanil linear range 0.05～2ng/ml(r = 0.9964), good linear relationship. The recovery rate was 83.68%～88.06%. The intra and inter precision were RSD <10%.2. 131 plasma samples were measured, 10 patients plasma concentration of sufentanil decreased rapidly from 2.025 to 0.189ng/ml in 30 minutes. The concentration began to slow down from 0.189 to 0.053ng/ml after 30 minutes, sufentail concentration has dropped to near detection limited line after 120 minutes.3. The dosages of sufentanil were used in two group patients were 1.75±0.28 and 1.67±0.31μg/kg(P>0.05), autonomous respiration restores time were 10.6±2.5 and 12.7±3.1min(P>0.05), awakening time were 14.5±3.2 and 15.6±3.6min(P>0.05), extubation time were 16.3±3.5 and 18.8±4.0min(P>0.05). There are no differences in autonomous respiration restores time,awakening time,extubation time,conscious state,postoperative nausea,vomit and skin titillation. All patients does not appear respiratory depression and other adverse reactions of sufentanil during anesthesia and after surgery.CONCLUSION1. HPLC/MS/MS is an accurate, sensitive and rapid method that can be applied in the evaluation of sufentanil target, and suitable for clinical pharmacokinetic study of sufentanil.2. Sufetanil T1/2a phase was short, sufentail distribute quickly from the central compartment to peripheral compartment, sufentanil is rapidly inactivated and excreted in the body, plasma concentration decreased rapidly after the intravenous injection sufentanil has been. In this study the pharmacokinetics of a comprehensive income can be described using two-compartment model, weight factor was 1. T1/2a=2.29±1.93min , T1/2β=30.47±28.10min , Vc=0.54±0.54L/kg , CL =0.06±0.04L/min/kg , K10(min-1) =0.18±0.13, K12 (min-1) =0.38±0.26, K21(min-1)=0.10±0.07.3. There are no significant differences in the dosage of sufentanil and propofol target-controlled infusion, the speed and quality of anesthesia recovery. Commonly used dosage of sufentanil is safe anesthesia for kidney transplantation, results were satisfactory anesthesia, anesthesia recovery is smooth. This may be related with transplanted kidney's function to recovery, it would need further clinical validation.
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