Effect of enteral versus parenteral feeding on hepatic blood flow and steady state propofol pharmacokinetics in ICU patients.

OBJECTIVE: The main objective of this study was to evaluate the effect of switching from parenteral to enteral feeding on liver blood flow and propofol steady-state blood concentrations in patients in the intensive care unit (ICU). DESIGN AND PATIENTS: Steady-state blood concentrations of propofol were measured in eight ICU patients before (on days D -3, D -2, and D -1) and after (on days D + 1, D + 2, and D + 3) switching from parenteral to enteral feeding (on day DO). All patients received a continuous intravenous infusion of propofol (4.5 mg x kg(-1) x h(-1)) from several days before the start of the study, continuing throughout the experimental period. Hepatic blood flow was estimated by measuring steady-state D-sorbitol hepatic clearance. RESULTS: Hepatic blood flow was high and was not affected by switching from parenteral to enteral feeding: 33 +/- 8 ml x min(-1) x kg(-1) (mean +/- SD) and 33 +/- 10 ml min(-1) x kg(-1) on D -3 and D -1, respectively, as compared to 37 +/- 11 ml x min(-1) kg(-1) and 34 +/- 8 ml x min(-1) x kg(-1) on days D + 1 and D + 3, respectively. Systemic clearance of propofol was much higher than liver blood flow with average values on the six observation days ranging from 74.0 to 81.2 ml x min(-1) x kg(-1) and was not affected by switching from parenteral to enteral feeding. CONCLUSIONS: Liver blood flow and systemic clearance of propofol were not affected by switching from parenteral to enteral feeding in the eight ICU patients studied. Extrahepatic clearance accounted for at least two thirds of the overall systemic clearance of propofol.

A rapid high-performance liquid chromatographic method for the measurement of midazolam plasma concentrations during long-term infusion in ICU patients.

A new high-performance liquid chromatographic method was developed for quantification of midazolam in plasma samples from intensive care unit patients on long-term intravenous infusion of this benzodiazepine. Plasma samples (0.5 ml) were mixed with 1 microgram flurazepam (internal standard), alkalinized with 2.5 N NaOH, and extracted with toluene. The organic phase was evaporated to dryness, and the residue was dissolved in the mobile phase (acetonitrile/0.05 M phosphate buffer pH 4.5) and injected into the analytical column (C18 Nova-Pak 3.9 x 150 mm, 4 microns, maintained at room temperature; mobile phase flow rate: 1.2 ml/minute). The eluate was monitored at 207 nm, which reduced the risk of interferences from concurrent medications. Retention times of flurazepam, 1'-hydroxymidazolam (an active metabolite) and midazolam were approximately 4.5, 6.1 and 13.5 minutes, respectively. The assay was linear over the range 100 to 3000 ng/ml. The coefficients of variation of the within-day and between-day assay for the 100 to 3000 ng/ml range were < 5% and < 7%, respectively. The developed method is fast, reproducible, and well suited to monitor steady state midazolam plasma concentrations in clinical samples.