Target controlled infusion of propofol: A comparison of two pharmacokinetic models in patients with end stage kidney disease undergoing kidney transplant surgery

This study will be conducted after obtaining ethics committee approval and signed informed consent.  We will enroll 60 patients with end stage kidney disease scheduled for              kidney transplantation under general anesthesia. Exclusion criteria will be age less than 20 years and more than 60 years, obesity (BMI >30 kg/m2), severe cardiac or respiratory disease, allergy to any components of propofol. Patients will be divided into two groups of 30 patients each and will be randomized in any group based on computer generated table of random numbers. Patients in group M will receive propofol infusion by modified Marsh model and in group S will receive by Schinder model of target-controlled infusion (TCI). Propofol will be infused with Mindray TCI pump in both the groups. On arrival in the operating room, an intravenous cannula will be secured into a peripheral vein of non-fistula arm. Routine monitoring including ECG, non-invasive blood pressure, pulse oximetry and BIS monitor will be attached, and baseline hemodynamic parameters will be recorded. Intravenous midazolam 1 mg and fentanyl 3 µg/kg will be given to all patients 2 minutes before the start of propofol infusion. Propofol TCI pump will be connected to the intravenous canula with running IV fluid. The effect site target of propofol will be set at 4 µg/ml and will be increased by 0.5 µg/ml every 30 seconds until there is loss of responsiveness to verbal command in both the groups. Loss of responsiveness will be checked by other anaesthesiologist who will be blinded to the research protocol. The anaesthesiologist will check for loss of responsiveness every 10 s after starting the propofol infusion. Loss of responsiveness will be defined as lack of response to the verbal command to open the eyes without touching the patient. Calculated effect-site concentration of propofol and BIS will be recorded when there is loss of responsiveness. In both groups, after loss of responsiveness trachea will be intubated on achievement of train of four response 0 after intubating dose of cisatracurium (2 mg/kg). After tracheal intubation effect site concentration of propofol will be set at 2.5 µg/ml to maintain BIS between 40-60 throughout the surgery. Infusion rate of propofol will be adjusted if BIS value is > 60 or < 40 for 1 minute by increasing or decreasing the target effect site concentration by 0.5 µg/ml in both group. Propofol infusion will be stopped on start of closure of surgical wound.  Effect site concentration of propofol on start of wound closure, BIS and time to return of responsiveness, duration of BIS < 40 and > 60, and total propofol consumption will be recorded. Mean arterial pressure and heart rate will be recorded at baseline, at loss of responsiveness, just after intubation and at return of responsiveness. Hypotension will be defined if MAP is less than 70 mmHg before reperfusion and less than 90 mmHg after reperfusion and bradycardia will be defined if HR goes below 60/minutes.