The effect of ephedrine and phenylephrine on BIS values during propofol anaesthesia.

BACKGROUND: The purpose of this study was to evaluate the effect of ephedrine and phenylephrine on propofol concentrations and bispectral index during propofol anesthesia. METHODS: General anaesthesia was induced with propofol and was maintained with propofol (4 mg kg-1 h-1) and fentanyl. Vecuronium was used to facilitate the artificial ventilation of the lungs. Patients with systolic blood pressure > 90 mmHg were defined as the control group (n = 16). Patients who had to be treated for larger decreases in arterial blood pressure (systolic blood pressure 60, whereas no patient in the control or phenylephrine groups had bispectral index >60. There were no significant differences in propofol concentrations or cardiac output relative to baseline at 3 or 10 min after the administration of ephedrine or phenylephrine. CONCLUSIONS: Ephedrine increases bispectral index values without decreasing propofol concentrations during general anesthesia.

Changes in the effect of propofol in response to altered plasma protein binding during normothermic cardiopulmonary bypass.

BACKGROUND: During normothermic cardiopulmonary bypass (CPB), the effect on propofol pharmacokinetics of changes in its binding to plasma proteins is consistent with the predictions of the well-stirred model of hepatic elimination for nonrestrictively cleared drug. However, whether changes in binding lead to clinically significant changes in the drug effect remains unclear. The purpose of this study was to assess changes in the drug effect of propofol in response to altered plasma binding using quantitative EEG measurements. METHODS: Thirty patients undergoing cardiac surgery were assigned randomly to receive propofol infusions at 4 (Group P-4) or 6 (Group P-6) mg kg(-1) h(-1) during surgery. The concentration of propofol in blood samples, collected from the radial artery at predetermined intervals, was determined by HPLC. The unbound fraction of drug in plasma was estimated using equilibrium dialysis. Bispectral index (BIS) and burst suppression ratio (BSR) were measured at the time blood samples were collected. RESULTS: The total concentration of propofol in blood was unchanged during CPB relative to the pre-CPB value in both groups. However, the fraction of unbound propofol in blood increased by 2-fold during CPB. While BIS values were unchanged during CPB in Group P-4, there was a slight, but significant, decrease in Group P-6. In both groups, BSR significantly increased during CPB. BIS values showed a weak correlation with the concentration of unbound propofol (r(2)=0.19, P<0.001). BSR showed a moderate correlation with the concentration of unbound propofol (r(2)=0.56, P<0.001). CONCLUSIONS: The anaesthetic effect of propofol significantly increased during CPB without any alteration in the total drug concentration. The enhanced efficacy may be caused by a reduction in plasma binding of the drug.

Preparative-scale Enzyme-catalyzed Synthesis of (R)-α-Fluorophenylacetic Acid.

A preparative-scale asymmetric synthesis of (R)-α-fluorophenylacetic acid, a useful chiral derivatizing reagent, is described. Starting from ethyl α-bromophenylacetate, α-fluorophenylmalonic acid dipotassium salt was prepared in three steps (54% yield), including nucleophilic substitution by the fluoride ion as the keystep. Both the purified form and crude preparation of arylmalonate decarboxylase in E. coli worked well on this substrate, and (R)-α-flurophenylacetic acid (>99% e.e.) was prepared in a quantitative yield.