Pharmacokinetic profile of the induction dose of propofol in chronic renal failure patients undergoing renal transplantation.

Study Objective: To define the pharmacokinetic profile of the induction dose of propofol in chronic renal failure patients.

Design And Setting: Determination of propofol blood concentrations after the bolus dose of 2 mg.kg-1 bw injected in 30 seconds in a peripheral vein in a group of chronic renal failure (CRF) patients and in a group of normal patients (controls).

Patients: 10 CRF patients (7 males, 3 females, mean age 47 +/- 8 years old, mean body weight 66 +/- 8 kg) candidates to cadaveric renal transplantation and free from major hepatic diseases (study group); 8 ASA I patients (5 males, 3 females), without major cardiorespiratory, hepatic, renal, hematologic or metabolic diseases undergoing minor elective surgical procedures lasting from 50 to 90 minutes (control group).

Measurements: a) propofol blood concentrations by means of HPLC; b) derived pharmacokinetic parameters (calculated by means of Siphar, version 4.0, Societé de informatique médicale, Simed, Paris, 1991); c) cardiovascular parameters (heart rate, central venous pressure, invasive arterial pressure).

Main Results: The decay of propofol whole blood concentrations, distribution, redistribution and elimination half lives were similar in CRF and in control patients. On the contrary, significantly different in CRF patients were propofol blood concentrations from two to ten minutes following the induction dose (lower), the area under concentration- time curve (AUC) (smaller), the mean resident time (longer), the total body clearance (greater), the volumes of distribution at steady state and during the elimination phase (larger). The larger volumes of distribution are closely correlated with the significantly lower albumin concentrations in the uremic patients. An accelerated hepatic biotransformation is one of the possible explanations for the greater total body clearance of propofol in the uraemic patients: in fact an increased glucuronyltrasferase activity and glucuronoconjugation induced by phenols has been demonstrated in uraemia. On the other hand, large volumes of distribution are often associated with elevated total body clearance. The only significant change in the cardiovascular profile was a reduction of 17 +/- 8% of the systolic blood pressure one minute after the administration of the induction dose of propofol, whereas heart rate, arterial and central venous pressures were rather stable after intubation and at skin incision: proper vascular filling before the induction of anaesthesia has probably played a crucial role in maintaining hemodynamic stability.

Conclusions: From the data gathered in this study, propofol can be considered a suitable anaesthetic agent for the induction of general anaesthesia in uraemic patients. In our opinion these data could constitute a basis for future protocols of total intravenous anaesthesia with propofol in uremic patients.