Christina T. Mora

Pharmacokinetics of Propofol in Adult Patients Undergoing Coronary Revascularization

Background Propofol is increasingly used for cardiac anesthesia and for perioperative sedation. Because pharmacokinetic parameters vary among distinct patient populations, rational drug dosing in the cardiac surgery patient is dependent on characterization of the drugs pharmacokinetic parameters in patients actually undergoing cardiac procedures and cardiopulmonary bypass (CPB). In this study, the pharmacokinetics of propofol was characterized in adult patients undergoing coronary revascularization. Methods Anesthesia was induced and maintained by computer‐controlled infusions of propofol and alfentanil, or sufentanil, in 41 adult patients undergoing coronary artery bypass graft surgery. Blood samples for determination of plasma propofol concentrations were collected during the predefined study periods and assayed by high‐pressure liquid chromatography. Three‐compartment model pharmacokinetic parameters were determined by nonlinear extended least‐squares regression of pooled data from patients receiving propofol throughout the perioperative period. The effect of CPB on propofol pharmacokinetics was modeled by allowing the parameters to change with the institution and completion of extracorporeal circulation and selecting the optimal model on the basis of the logarithm of the likelihood. Predicted propofol concentrations were calculated by convolving the infusion rates with unit disposition functions using the estimated parameters. The predictive accuracy of the parameters was evaluated by cross‐validation and by a prospective comparison of predicted and measured levels in a subset of patients. Results Optimal pharmacokinetic parameters were: central compartment volume = 6.0 l; second compartment volume = 49.5 l; third compartment volume = 429.3 l; Chlorine1 (elimination clearance) = 0.68 l/min; Chlorine2 (distribution clearance) = 1.97 l/min1; and Chlorine sup 3 (distribution clearance) = 0.70 l/min. The effects of CPB were optimally modeled by step changes in V1 and Chlorine1 to values of 15.9 and 1.95, respectively, with the institution of CPB. Median absolute prediction error was 18% in the cross‐validation assessment and 19% in the prospective evaluation. There was no evidence for nonlinear kinetics. Previously published propofol pharmacokinetic parameter sets poorly predicted the observed concentrations in cardiac surgical patients. Conclusions The pharmacokinetics of propofol in adult patients undergoing cardiac surgery with CPB are dissimilar from those reported for other adult patient populations. The effect of CPB was best modeled by an increase in V1 and Chlorine1. Predictive accuracy of the derived pharmacokinetic parameters was excellent as measured by cross‐validation and a prospective test.

Time-course of respiratory depression after an alfentanil infusion-based anesthetic

Postoperative respiratory depression after alfentanil administration has been described in several case reports. The effects of a prolonged alfentanil infusion on the CO2 response curve or cognitive function have not been studied. Twenty-one ASA physical status I or II patients were studied after a prolonged alfentanil infusion (>90 min) to determine the incidence of postoperative respiratory depression, arterial O2 desaturation, and impairment of cognitive function. Each patients recovery was observed at 30-min intervals for evidence of respiratory depression (utilizing the Read CO2 rebreathing method), desaturation by pulse oximetry (severe desaturation defined as arterial O2 saturation <90%), and cognitive function (utilizing Trieger dot and digit substitution tests). Plasma samples were also examined for secondary elevations in alfentanil plasma concentrations. Significant depression of the CO2 response curve and cognitive function was found up to 1 h postoperatively. Arterial O2 desaturation was seen in 11 of 21 patients (52%). No correlation was found between arterial O2 desaturation and cognitive function scores or CO2 rebreathing results. Increased depression of the CO2 response curve was not necessarily associated with severe desaturation episodes. A secondary increase in plasma alfentanil concentration was detected in 5 of the 21 patients (24%), but these patients did not experience further depression of the CO2response curve. We conclude that prolonged alfentanil administration may result in severe arterial O2desaturation with significant depression of the hyper-capnic respiratory drive during the first hour in the postanesthesia care unit, even though the majority of our patients were easily aroused in response to verbal stimuli.

Evaluation of a new design pulmonary artery catheter for intraoperative ventricular pacing.

A new design pulmonary artery catheter and pacing probe were evaluated in 30 patients undergoing cardiac surgery. Ventricular pacing was attempted before, during, and after cardiopulmonary bypass. Ventricular current threshold, output, resistance, and R wave sensitivity were measured during all three periods. Successful pacing was achieved in 69 of 72 attempts, the vast majority completed in less than four minutes. Pacing thresholds and R wave sensitivities were within acceptable ranges and compatible with commercial pulse generators. Ventricular pacing can be quickly and reliably established with this type of pacing pulmonary artery catheter. The results suggest this system can be used to effect cardiac pacing in the patient requiring emergency extrinsic pacemaker support.