No abstract

Propofol (2,6-diisopropylphenol) is administered intravenously for induction and maintenance of anesthesia; however, cases of progressive myocardial failure (propofol syndrome) related to the use of propofol have been reported. In the present study, the individual differences in pharmacokinetics and/or pharmacodynamics of propofol were investigated in patients who were genotyped for CYP2B6 and UGT1A9. Fifty-one patients treated with propofol in St. Marianna University Hospital were recruited for this study and provided written informed consent. The following parameters were analyzed: awakening time as a pharmacodynamic parameter, duration of propofol infusion, drug concentration in plasma after treatment, genotypes of CYP2B6 and UGT1A9, and age (42-84 years, mean of 65 years). Propofol was rapidly cleared from the blood of the subjects as a result of distribution and elimination. The awakening time after stopping propofol infusion was significantly correlated with the duration of infusion and the maximum concentration of propofol in these subjects. The maximum plasma concentration of propofol after normalizing with the duration of infusion was affected by the CYP2B6 G516T variant (related to impaired function) and was significantly affected by a propofol risk index score that incorporated CYP2B6 G516T and UGT1A9 I399C>T (high expression) genotypes and advanced age. These results provide important information indicating that the genotypes of the two enzymes studied and advanced age are combinative determinant factors of the pharmacokinetics and/or pharmacodynamics of propofol.

PurposeAcute kidney injury (AKI) is common after cardiovascular surgery and is usually diagnosed on the basis of the serum creatinine (SCr) level and urinary output. However, SCr is of low sensitivity in patients with poor renal function. Because urinary liver-type fatty-acid-binding protein (L-FABP) reflects renal tubular injury, we evaluated whether perioperative changes in urinary L-FABP predict AKI in the context of abdominal aortic repair.MethodsStudy participants were 95 patients who underwent endovascular abdominal aortic aneurysm repair (EVAR) and 42 who underwent open repair. We obtained urine samples before surgery, after anesthesia induction, upon stent placement, before aortic cross-clamping (AXC), 1 and 2 h after AXC, at the end of surgery, 4 h after surgery, and on postoperative days (PODs) 1, 2, and 3, for measurement of L-FABP. We obtained serum samples before surgery, immediately after surgery, and on PODs 1, 2, and 3, for measurement of SCr. We also plotted receiver-operating characteristic (ROC) curves to identify cutoff laboratory values for predicting the onset of AKI.ResultsWith EVAR, urinary L-FABP was significantly increased 4 h after the procedure (P = 0.014). With open repair, urinary L-FABP increased significantly to its maximum by 2 h after AXC (P = 0.007). With AKI, SCr significantly increased (P < 0.001, P = 0.001) by POD 2. ROC analysis showed urinary L-FABP to be more sensitive than SCr for early detection of AKI.ConclusionUrinary L-FABP appears to be a sensitive biomarker of AKI in patients undergoing abdominal aortic repair.

The severe reductions in the UPBF and the placental oxygenation imply that regional hypoperfusion occurs in association with systemic mean arterial pressure. r-TM may be a candidate medical treatment for PE complications.

Background: Genetic polymorphisms of metabolic enzymes, as well as a patient's sex, age, and individual susceptibility, affect the pharmacokinetics of propofol. Several reports show that polymorphisms of metabolic enzymes of propofol affect loss of consciousness during propofol anesthesia. We investigated whether genetic polymorphisms of the liver cytochrome P450 2B6 (CYP2B6), the main metabolic enzyme for propofol, and UDP-glucuronosyltransferase 1A9 (UGT1A9), as well as sex differences, affect the pharmacokinetics of propofol.Methods: Between June 2009 and May 2011, 94 patients (51 males, 43 females) who underwent respiratory surgery with total intravenous anesthesia were examined. Arterial blood samples were collected immediately or 5, 10, 20, 30 and 60 min after the termination of propofol infusion for the determination of the propofol blood concentrations and genetic polymorphisms of CYP2B6 and UGT1A9. We analyzed blood pharmacokinetics of propofol and assessed the association between genetic polymorphisms, sex differences, and blood pharmacokinetics. Stepwise multiple linear regression analysis was used to detect important factors of pharmacokinetics of propofol.Results: Although C 0 (the blood concentrations of propofol immediately after the termination of propofol infusion) rose for the T/T mutation in CYP2B6, there were no significant differences in changes of blood propofol concentrations after the termination of drug infusion and in waking times for both genetic polymorphisms. C 0 was significantly higher in females than in males (1.7: 1.4 μg/mL, female: male, P=0.015) and the rate of decline in the blood propofol concentration from C 0 to C 5 was faster in females than in males (67: 60%, P=0.015). Stepwise multiple regression analysis revealed that sex (B = 0.32, P = 0.01) was a contributor to C 0 (R = 0.27, P = 0.01).Conclusions: We suggest that differences between females and males for C 0 and the rate of decline in the blood propofol concentration may cause individual differences in both sensitivity and recovery of consciousness from propofol anesthesia. We conclude that polymorphisms of CYP2B6, but not UGT1A, and sex differences affect the pharmacokinetics of propofol.