The effect of temperature management during cardiopulmonary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization.

Several studies suggest that normothermic ("warm") bypass techniques may improve myocardial outcomes for patients undergoing cardiac operations. Normothermic temperatures during cardiopulmonary bypass may, however, decrease the brain's tolerance to the ischemic insults that accompany all cardiac procedures. To assess the effect of bypass temperature management strategy on central nervous system outcomes in patients undergoing coronary revascularization, 138 patients were randomly assigned to two treatment groups: (1) hypothermia (n = 70), patients cooled to a temperature less than 28 degrees C during cardiopulmonary bypass, or (2) normothermia (n = 68), patients actively warmed to a temperature of at least 35 degrees C. Patients underwent detailed neurologic examination before the operation, on postoperative days 1 to 3 and 7 to 10, and at approximately 1 month after operation. In addition, a battery of five neuropsychologic tests was administered before operation, on postoperative days 7 to 10, and at the 4- to 6-week follow-up visit. Patients in the normothermic treatment group were older (65 +/- 10 vs 61 +/- 11 years in the hypothermic group), had statistically less likelihood of preexisting cerebrovascular disease, and had higher bypass blood glucose values (276 +/- 100 mg/% vs. 152 +/- 66 mg/% in the hypothermic group). All other patient characteristics and intraoperative variables were similar in the two treatment groups. Seven of 68 patients in the normothermic group were found to have a central neurologic deficit, compared with none of the patients cooled to 28 degrees C (p = 0.006). Performance on at least one neuropsychologic test deteriorated in the immediate postoperative period in more than one half of all patients in both treatment groups but returned to preoperative levels approximately 1 month after the operation in most (85%). This pattern was not related to bypass temperature management strategy. We conclude that active warming during cardiopulmonary bypass to maintain systemic temperatures > or = 35 degrees C increases the risk of perioperative neurologic deficit in patients undergoing elective coronary revascularization.

Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat.

From March 1991 through July 1992, 1,001 patients having elective coronary artery bypass grafting were randomized to receive either continuous warm (> or = 35 degrees C) blood cardioplegia with systemic normothermia (> or = 35 degrees C) or intermittent cold (< or = 8 degrees C) oxygenated crystalloid cardioplegia and moderate systemic hypothermia (< or = 28 degrees C). Preoperative variables including age, sex, prior coronary bypass grafting, hypertension, prior myocardial infarction, diabetes, angina class, and preoperative heart failure class were similar in both groups, as were the intraoperative variables of number of coronary grafts, mammary artery use, and cardiopulmonary bypass time. Aortic cross-clamp time was significantly longer in the warm group (46 +/- 23 minutes versus 40 +/- 21 minutes). Most postoperative variables including mortality (warm, 1.0%, and cold, 1.6%), Q wave infarction (warm, 1.4%, and cold, 0.8%), and need of an intraaortic balloon pump (warm, 1.4%, and cold, 2.0%) were similar between groups. Total neurologic events (warm, 4.5%, and cold, 1.4%; p < 0.005) and perioperative strokes (warm, 3.1%, and cold, 1.0%; p < or = 0.02) were significantly higher in the warm group. Neurologic events included perioperative stroke (warm, 15 patients, and cold, 5 patients; p < 0.02), perioperative encephalopathy (warm, 2 patients, and cold, 1 patient), and delayed (> or = 3 in-hospital days) stroke (warm, 5 patients, and cold, 1 patient). All patients experiencing a stroke had a persistent neurologic deficit at the time of discharge. Encephalopathy resolved completely in all instances.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of propofol in adult patients undergoing coronary revascularization. The Multicenter Study of Perioperative Ischemia Research Group.

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 drug's 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; Cl1 (elimination clearance) = 0.68 l/min; Cl2 (distribution clearance) = 1.97 l/min1; and Cl3 (distribution clearance) = 0.70 l/min. The effects of CPB were optimally modeled by step changes in V1 and Cl1 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 Cl1. Predictive accuracy of the derived pharmacokinetic parameters was excellent as measured by cross-validation and a prospective test.

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.

Sedative and ventilatory effects of midazolam infusion: effect of flumazenil reversal.

The purpose of this study was to evaluate the effects of flumazenil (1 mg i.v.) on the ventilatory response of premedicated patients receiving a continuous infusion of midazolam for sedation. After assessing baseline ventilatory function using a modified Read rebreathing method for determining hypercapnic ventilatory drive, 16 healthy outpatients were administered fentanyl, 50 micrograms i.v., and midazolam 2 mg i.v., followed by a variable-rate midazolam infusion, 0.3-0.5 mg.min-1. Upon termination of the midazolam infusion, serum midazolam concentrations were measured and ventilatory function was reassessed. Then, 10 ml either saline or flumazenil (1 mg) were administered according to a randomized, double-blind protocol. Ventilatory function was subsequently measured at 5 min, 30 min and 60 min intervals after study drug. Compared with the baseline value, midazolam infusion reduced tidal volume and increased respiratory rate and alveolar dead space. However, midazolam did not decrease the slope of the CO2-response curve. Flumazenil reduced the degree of midazolam-induced sedation and the decrease in tidal volume (P < 0.05), but not the change in resting respiratory rate. In some patients, the ventilatory response to hypercarbia actually decreased after flumazenil administration compared with the immediate prereversal (sedated) values. It is concluded that midazolam infusion, 0.43 mg.min-1, did not impair CO2-responsiveness. Flumazenil's effect on central ventilatory drive was more variable than its reversal of midazolam-induced sedation.

Effects of diazepam and flumazenil on sedation and hypoxic ventilatory response.

We evaluated the effects of a benzodiazepine antagonist, flumazenil (Ro 15-1788), 1 mg intravenous, on the hypoxic ventilatory response in 10 healthy patients who had received diazepam 0.97 +/- 0.34 mg/minute (mean +/- SD) for sedation during minor operative procedures. When assessed using a sedation analog scale, flumazenil significantly decreased diazepam-induced sedation. In only two of the five patients with evidence of diazepam-induced depression of the ventilatory response to hypoxia was there significant reversal of this depression after flumazenil administration. Finally, patients in whom the duration of sedation with diazepam was shorter (78 +/- 14 minutes) had a significantly greater decrease in the slope of their hypoxic ventilatory response curve (1.3 +/- 0.8 L.min-1.%sat-1 [-43% from baseline]) than did patients with longer sedation times (145 +/- 37 minutes duration; 2.0 +/- 0.8 L.min-1.%sat-1 [-5% from baseline]). These data suggest that flumazenil, 1 mg intravenous, is only partially effective in reversing diazepam-induced depression of hypoxic ventilatory drive and that tolerance may develop to the respiratory depressant effects of diazepam.

The effects of anesthetic technique on the hemodynamic response and recovery profile in coronary revascularization patients.

This study was undertaken to assess the effects of propofol (versus enflurane, fentanyl, and thiopental) on hemodynamic stability and recovery characteristics when used for maintenance of anesthesia during elective coronary artery bypass grafting (CABG) procedures. Ninety premedicated patients scheduled for elective coronary revascularization had anesthesia induced with fentanyl 25 micrograms/kg intravenously (i.v.). When the mean arterial blood pressure (MAP) increased 10% above preoperative baseline values, patients were randomized to receive one of four anesthetic treatments: enflurane, 0.25-2.0%; fentanyl, 10-20 micrograms/kg i.v. bolus doses; propofol, 50-250 micrograms.kg-1.min-1 i.v.; or thiopental, 100-750 micrograms.kg-1.min-1 i.v.. The maintenance anesthesia was titrated to achieve hemodynamic stability (i.e., maintain the MAP within 10% of the baseline values and heart rate [HR] within 20% of the baseline values). After bypass, anesthetic and cardiovascular drugs were titrated to maintain the MAP > 65 mm Hg and the cardiac index (CI) > 2.3 L.min-1.m-2. Recovery was assessed by noting the times at which patients first opened their eyes, responded to verbal communication, correctly responded to specific commands, underwent tracheal extubation, and were discharged from the intensive care unit (ICU). Although less intraoperative hypertension was noted in the propofol-treated patients (19 +/- 11 min vs 38 +/- 26 min, 30 +/- 24 min, and 30 +/- 23 min in the enflurane, fentanyl, and thiopental groups, respectively) (P = 0.04), the incidence of hypotension did not differ significantly among the groups. Vasopressor drugs were required more often during the prebypass period in fentanyl and propofol patients (4/22 and 5/23, respectively) compared to the thiopental group (0/21) (P < 0.05). During CPB, fentanyl-treated patients required vasoconstrictors more often than patients in the other three treatment groups (14/22 vs 6/24, 4/23, and 5/21 in the enflurane, propofol, and thiopental groups, respectively) (P < 0.01). Although fentanyl-treated patients had significantly greater requirements for inotropic support during weaning from CPB than propofol-treated patients (14/22 vs 7/23) (P < 0.038), there were no significant differences among the groups in the postbypass or ICU periods. Propofol-treated patients responded to verbal stimuli (2.1 +/- 1.3h vs 4.0 +/- 3.5h, 4.7 +/- 2.7h, and 5.6 +/- 3.6h in the enflurane, fentanyl, and thiopental groups, respectively) (P = 0.01) and followed commands earlier (propofol 7.3 +/- 5.2h vs enflurane 12.5 +/- 5.7h, fentanyl 13.1 +/- 6.6h, and thiopental 12.8 +/- 6.7 h) (P = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

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 patient's 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 CO2 response curve. We conclude that prolonged alfentanil administration may result in severe arterial O2 desaturation with significant depression of the hypercapnic 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.