The Pharmacokinetics Of Sufentanil In Patients Undergoing Different Cardiac Surgery

Objective: To use liquid chromatography-mass spectrometry techniques, blood concentrations of sufentanil were measured, and pharmacokinetic parameters of sufentanil were calculated in order to analyse the pharmacokinetic characteristics of sufentanil.Methods: Sixteen ASAâ…¡orâ…¢patients age 34 to 61 yr undergoing open heart surgery were randomly divided into two groups(n=8 each). according to disease type:â… group (valvular heart disease group) in 8 cases (6 males and 2 females),â…¡group (CHD group) in 8 cases (4 males and 4 females). No spirit of the history of preoperative neuropathy, without uncontrolled hypertension (BP≧ 160/100mmHg), no long-term use of opioid or antipsychotic drugs, body mass index, heart, liver and kidney function was normal, no fever, all patients were injected 30min before surgery scopolamine 0.003～0.006mg·kg^-1, morphine 0.1～0.2mg·kg^-1. The operating room temperature is kept between 22²4℃. After the patient into the operating room, the patients'heart rate, electrocardiogram, and pulse oxygen saturation were monitored. To open upper intravenous infusion of sodium lactate Ringer's solution. The parallel left-invasive radial artery blood pressure monitoring, a control blood sample was obtained. At the same time intravenous midazolam 0.05⁰.1mg·kg^-1, etomidate 0.2⁰.3mg·kg^-1 , vecuronium 0.1～0.2mg·kg^-1, and then sufentanil 5μg·kg^-1 was injected as a bolus into an left arm vein. 3⁵ minutes after the administration, tracheal intubation, mechanical ventilation in parallel. Done to monitor the central venous pressure central venous puncture. Technique using propofol and vecuronium, anesthesia was maintained. Blood samples were taken at 1, 3, 5, 10, 20, 30, 60, 120, 180, 240 and 360min after injection. Plasma was separated from blood sample and stored at -80℃until assayed. Take samples of plasma 200μl, adding an internal standard 10μl, then add acetonitrile 400μl after mixing, the mixture was vortex mixed 1min, placed 5min, centrifuged 10min (15000r·min^-1), the supernatant 200μl placed in vials, injection volume of 50μl. Liquid chromatography mass spectrometry conditions: Column for Agilent XDB Eclipse C18 (150*4.6 mm, 5μm), a mobile phase of 10mM ammonium acetate (pH3.0) / acetonitrile = 15/85; flow 1ml/min. API3000 using APCI ion source, positive ion mode, ion source temperature of 500℃, discharge current 3μA. Ion acquisition mode for multiple reaction monitoring mode (MRM), sufentanil ion pairs for the m / z 387.2/238.1, fentanyl (internal standard) for m / z 337.2/188.5.Results:1,Valvular disease group: Sufentanil pharmacokinetics was most appropriately described by a three-compartment open model, plasma concentration-time curve with three exponential function can be used, said: Cp(t)=24.84e^-0.5260t+5.3774e^-0.0523t+0.1602e^-0.0017tPharmacokinetic parameters, see table 4.As a bolus intravenous injection of sufentanil 5μg·kg^-1, plasma sufentanil concentrations immediately reached 20.8ng?ml^-1 after 1min, 3 5min after the sufentanil administration, No. 1 and 5 patients had a small peak, and then continued to decline. 30min after, the plasma concentration of sufentanil decreased by 94.1%. 60min after,97.5% was removed from the plasma. After cardiopulmonary bypass compared with pre-CPB plasma concentration of sufentanil decreased by 70.6%. No. 1 patient, have a second peak after 4h,, and then continued to decline. 6h after administration of sufentanil in plasma concentrations decreased to 0.05ng?ml^-1. Sufentanil at this time does not produce inhibitory effect on respiration. This was followed by most of the patients resumed spontaneous breathing.2,Congenital heart disease Group: Sufentanil pharmacokinetics was most appropriately described by a three-compartment open model, plasma concentration-time curve with three exponential function can be used, said: Cp(t)=12.79e^-0.4571t+3.3295e^-0.0462t+0.3999e^-0.0048t Pharmacokinetic parameters, see table 4.As a bolus intravenous injection of sufentanil 5μg·kg^-1, plasma sufentanil concentrations immediately reached 11.8ng·ml^-1 after 1min. 5 10min After the sufentanil administration No.10 and 14patients had a small peak, and then continued to decline. After 30min of the administration, the plasma concentration of sufentanil decreased by 90.4%. 60min after,95.6% was removed from the plasma. After cardiopulmonary bypass the plasma concentration of sufentanil sharply declined, Decreased compared with pre-CPB by 52.0%. 6h after administration of sufentanil in plasma concentrations decreased to 0.07ng·ml^-1.There were significant differences in pharmacokinetic parameters between two groups. Vd value of patients with valvular heart disease group was larger than Vd value of the congenital heart disease group (P<0.05), t1/2βvalue was longer than the t1/2βvalue of congenital heart disease group(P<0.01), while Vc value of congenital heart disease group was larger than the value Vc of valvular heart disease group (P<0.05), CL value was larger than the CL values of valvular heart disease group (P<0.05) (See table 4) .Conclusion:1,Two groups of the pharmacokinetics of sufentanil were most appropriately described by a three-compartment open model, the best fit to the concentration-time date was by a tri-exponential equation.2,There were significant differences in pharmacokinetic parameters between the two groups. T1/2βvalue of valvular disease group was longer than the t1/2βvalue of congenital heart disease group, the patients after valve replacement surgery should be given adequate respiratory support treatment.3,After cardiopulmonary bypass, the sufentanil plasma concentration dramatically dropped, because of blood dilution.4,The pharmacokinetics of sufentanil in this study was significantly different from that report in foreign studies.5,Data analysis techniques can affect the pharmacokinetic parameters and relevant.