Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial.

BACKGROUND: In this prospective, randomized, double-blind, placebo-controlled study, we investigated the effect of pregabalin on oxycodone consumption, postoperative confusion, and pain in elderly cardiac surgery patients. METHODS: Seventy patients, aged ≥75 yr, were randomized to receive either 150 mg of pregabalin before operation and 75 mg of pregabalin twice daily for 5 postoperative days or placebo. Pain intensity was measured with the Verbal Rating Scale (VRS). When pain intensity was ≥2 on the VRS, patients received oxycodone either i.v. (0.05 mg kg(-1)) or orally (0.10-0.15 mg kg(-1)). Postoperative confusion was measured with the Confusion Assessment Method for the intensive care unit (CAM-ICU). Postoperative pain was assessed by a telephone interview 1 and 3 months after operation. RESULTS: Cumulative consumption of parenteral oxycodone during 16 h after extubation was reduced by 44% and total oxycodone consumption from extubation to the end of the fifth postoperative day was reduced by 48% in the pregabalin group. Time to extubation was 138 min shorter and CAM-ICU scores were significantly lower on the first postoperative day in the placebo group, although there was no significant difference with respect to the Mini-Mental State Examination or the Richmond Agitation Sedation Score. The incidence of pain during movement was significantly lower in the pregabalin group at 3 months postoperative. CONCLUSIONS: The administration of pregabalin reduced postoperative opioid consumption after cardiac surgery reduced the incidence of confusion on the first postoperative day and increased time to extubation when compared with placebo. Three months after operation, patients in the pregabalin group experienced less pain during movement.

Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgery.

BACKGROUND: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients. METHODS: Thirty (>or=75 years, gender M9/F21) and 20 (

Coating of extracorporeal circuit with heparin does not prevent sequestration of propofol in vitro.

Propofol is sequestered in extracorporeal circuits, but the factors responsible for the phenomenon are mostly unknown. We have compared two extracorporeal circuits (oxygenators, reservoirs and tubings) coated with heparin with two corresponding uncoated circuits for their capacity to sequester propofol in vitro. Three experiments were conducted with each circuit. The circuit was primed with a mixture of Ringer's acetate solution and whole blood, and the study conditions (pump flow, temperature, pH) were standardized. Propofol was added to the solution to achieve a concentration of 2 micrograms ml-1. These studies were followed with concentrations of 10- and 100-fold to assess possible saturation of propofol binding. Serial samples were obtained from the circulating solution for measurement of propofol concentration. Propofol concentrations decreased to 22-32% of the initial predicted concentration of 2 micrograms ml-1 in the circuits (no significant difference between circuits). With greater concentrations, the circuits did not become saturated with propofol, even with the highest predicted concentration of 200 micrograms ml-1. We conclude that propofol was sequestered in extracorporeal circuits in vitro, irrespective of coating the circuit with heparin.

Effect of low-dose propofol infusion on total-body oxygen consumption after coronary artery surgery.

OBJECTIVE: To investigate the effect of low-dose propofol infusion on total-body oxygen consumption (VO2) after coronary artery bypass grafting (CABG) surgery. DESIGN: A prospective, randomized, placebo-controlled, double-blind study. SETTING: Cardiovascular intensive care unit in a university hospital. PARTICIPANTS: Thirty patients after elective, uncomplicated CABG surgery. INTERVENTION: Patients were administered a continuous infusion of propofol with a fixed rate of 1 mg/kg/h (n = 15) or placebo (n = 15) during the spontaneous rewarming period of approximately 5 hours after surgery. A light level of sedation (Ramsay sedation score > or =2) was maintained by administering small doses of diazepam, 0.1 mg/kg, as required. Morphine, 0.05 mg/kg, was administered for analgesia as required. MEASUREMENTS AND MAIN RESULTS: Total-body VO2 was measured by indirect calorimetry. In addition, shivering (on a five-grade scale), hemodynamics, and plasma catecholamine and serum cortisol concentrations were measured. Diazepam, 5.6+/-7.4 mg (mean +/- standard deviation), was administered to the patients receiving propofol, and 16.1+/-12.2 mg was administered to the patients receiving placebo (p < 0.05). There was no difference in the dose of morphine between the groups (3.2+/-3.9 v 4.2+/-5.5 mg in the propofol and placebo groups, respectively). At any time during the study, VO2 was not different between the groups. VO2 increased from 130+/-29 to 172+/-29 mL/min/m2 in the propofol group and from 118+/-24 to 167+/-27 mL/min/m2 in the placebo group. Mean arterial pressure and heart rate were lower in the propofol group (p < 0.05). Stress hormone levels did not differ between the groups. CONCLUSION: Low-dose propofol infusion and additional diazepam as required does not decrease total-body VO2 compared with a pure diazepam bolus-dose technique when administered for light sedation during the immediate recovery period after CABG surgery.

Cardiopulmonary bypass-induced changes in plasma concentrations of propofol and in auditory evoked potentials.

Unbound, rather than total, plasma concentrations may be related to the anaesthetic action of propofol. Therefore, we measured plasma concentrations of propofol and recorded Nb wave latencies of auditory evoked potentials (AEP) during continuous infusion of propofol in 15 patients undergoing coronary artery bypass grafting (CABG) surgery. After induction of anaesthesia with fentanyl, propofol was infused continuously at a rate of 10 mg kg-1 h-1 for 20 min, and then the rate was reduced to 3 mg kg-1 h-1. Administration of heparin before cardiopulmonary bypass (CPB) did not affect total or unbound propofol concentration. Initiation of CPB decreased mean total propofol concentration from 2.6 to 1.7 micrograms ml-1 (P < 0.01). Simultaneously, mean unbound propofol concentration remained at 0.06 micrograms ml-1 because of a slight increase in the mean free fraction of plasma propofol (from 2.3 to 3.5%; P > 0.05). During hypothermic CPB, mean total propofol concentration increased to concentrations measured before bypass (to 2.1 micrograms ml-1; P > 0.05 vs value before CPB) and the mean unbound propofol concentration was at its highest (0.07 microgram ml-1; P < 0.05 vs value before heparin). After CPB and administration of protamine, the mean total propofol concentration remained lowered (1.7 micrograms ml-1; P < 0.05 vs value before heparin) and the mean unbound propofol concentration returned to the level measured before heparin (P < 0.001 vs value during hypothermia). The latency of the Nb wave from recordings of AEP increased after induction of anaesthesia, reached its maximum during hypothermia and was prolonged during the subsequent phases of the study. The latency of the Nb wave did not correlate with total or unbound propofol concentration. We conclude that the changes in total and unbound concentrations of plasma propofol were not parallel in patients undergoing CABG. During CPB or at any other time during the CABG procedure, the unbound propofol concentration did not decrease and Nb wave latency was prolonged compared with baseline values measured after induction of anaesthesia before the start of CPB.

Haemodynamic effects of propofol infusion for sedation after coronary artery surgery.

We have compared the haemodynamic effects of a sedative dose of propofol with placebo (vehicle of propofol) in a randomized, double-blind study in 20 patients immediately after coronary artery bypass grafting (CABG). During a continuous infusion of a mixture of fentanyl and pancuronium, each patient was given in a crossover design, a loading dose of propofol 0.5 mg kg-1 and vehicle over 5 min followed by a continuous infusion of propofol 20 micrograms kg-1 min-1 and vehicle, respectively, for 55 min. Administration of propofol caused a significant decrease in mean arterial pressure (mean change from pre-drug values to those during drug infusion: -15.4% vs +1.3% with placebo; P < 0.001), mean pulmonary artery pressure (-6.5% vs +5.8%; P < 0.001), systemic vascular resistance (-13.8% vs -0.6%; P < 0.05), pulmonary vascular resistance (-2.0% vs +9.0%; P < 0.05), cardiac output (-2.4% vs +2.6%; P < 0.05) and pulmonary artery occlusion pressure (-8.0% vs +1.4%; P < 0.05). Propofol did not affect heart rate, but it tended to decrease stroke volume (P = 0.102). These data suggest that, during the recovery phase from CABG surgery, a short-term infusion of a sedative dose of propofol decreases systemic and pulmonary arterial pressure by decreasing systemic and pulmonary vascular resistance, respectively, and cardiac output. The decrease in cardiac output appeared to be caused mainly by a decrease in stroke volume.

Propofol sequestration within the extracorporeal circuit.

Various drugs administered during cardiac anaesthesia are sequestered in the extracorporeal circuit in vitro, but it is uncertain whether this sequestration phenomenon affects plasma drug concentration in vivo. The present study was undertaken to evaluate (1) in vitro sequestration of propofol in the extracorporeal circuit and (2) whether the change in plasma propofol concentration induced by initiation of cardiopulmonary bypass in vivo can be explained by haemodilution. For the in vitro evaluation, three separate experiments with a closed circuit (membrane oxygenator, reservoir, and tubings) were performed. The pH and PCO2 of the circulating solution (a mixture of Ringer's acetate and whole blood) were maintained within the normal physiological range, and the temperature of the solution was 28 degrees C. The solution was circulated at a flow of 4 L.min-1 and propofol was added to the solution to achieve a concentration of 2 micrograms.ml-1. Serial samples were taken from the circulating solution for measurement of propofol concentration by high performance liquid chromatography. In the in vivo part of the study, 14 patients received a continuous infusion of propofol, and samples for the determination of plasma propofol concentration and blood haematocrit were taken before and five and ten minutes after initiation of cardiopulmonary bypass. In vitro, at 5 and 120 min after addition of propofol into the circulating solution, approximately 65% and 25%, respectively, of the predicted propofol level was measurable in the solution.(ABSTRACT TRUNCATED AT 250 WORDS)