Propofol—fentanyl anaesthesia for coronary artery surgery and cardiopulmonary bypass

Abstract

SummaryA two-stage propofol infusion combined with fentanyl was w e d to maintain anaesthesia during coronary artery surgery in patients with good ventricular function. Whole blood propojol concentrations were measured at frequent intervals; plasma protein binding was measured before, during and after cardiopulmonary bypass. An initial infusion rate of 10 mg/kg/hour provided good protection from the pressor response to sternotomy. A predictable steady state concentration was achieved in the prebypass period with a maintenance infusion rate of 3 mglkglhour. The onset of bypass resulted in a small decrease in propofol concentration as a result of haemodilution. Induced hypothermia resulted in an increase in propofol concentration which returned rapidly to the prebypass steady state value during rewarming. The free propofol fraction increased during cardiopulmonary bypass. No patient had any recall of operative events or required inotropic support during weaning from bypass. Key wordsAnaesthesia; cardiovascular. Anaesthetics, intravenous; propofol.Propofol, a new intravenous anaesthetic agent, is suitable for maintenance of anaesthesia by infusion. It has been used recently for coronary artery surgery performed during cardiopulmonary bypass (CPB).1*2 Hypothermic CPB causes many physiological changes which have clinically significant effects on the disposition and elimination of drugs.3 This study was designed to assess the suitability of a two-stage propofol infusion for cardiac surgery and in particular to study the effect of hypothermic CPB on the kinetics of the drug. MethodsThe study received institutional ethics approval and each patient gave written informed consent. Ten male patients were studied; all were scheduled for coronary artery surgery with internal mammary artery anastomosis to the left anterior descending coronary artery. All had good or only moderately impaired ventricular function as defined by an ejection fraction of approximately 50%. All were receiving maintenance doses of a beta-adrenoceptor antagonist (metoprolol or atenolol), a calcium antagonist (nifedipine) and a nitrate (isosorbide dinitrate or glyceryl trinitrate). These drugs were continued up to and including the morning of operation.Premedication consisted of sodium amylobarbitone 300 mg on the evening before operation and diazepam 1 6 1 5 mg one hour before operation. Radial artery pressure monitoring was established under local anaesthesia. Electrocardiographic (ECG) monitoring was applied and lead 11 displayed continuously. Anaesthesia was induced with fentanyl 25 pg/kg, diazepam 0.1 mg/kg -and pancuronium 0.15 mg/kg, and the lungs were ventilated with oxygen-enriched air to normocapnia. An infusion of propofol at the rate of 10 mg/kg/hour was established through a dedicated peripheral arm vein 10 minutes before skin incision and continued for 15-20 minutes during which time sternotomy and sternal spread were performed. The infusion was then reduced to a maintenance rate of 3 mg/kg/hour until the final skin suture had been inserte...

Effects of Hypothermia on the Disposition of Morphine, Midazolam, Fentanyl, and Propofol in Intensive Care Unit Patients

“…This is in accordance with a previous study during deep hypothermia (25-27°C) for cardiopulmonary bypass in heart surgery (Russell et al, 1989). However, a study in healthy volunteers (34 6 0°C) showed reduced intercompartmental clearances, but not reduced CL tot , during TH (Leslie et al, 1995).…”

“…No significant differences in the activity of CYP2C were seen in a study on rats, but the clearance of phenytoin (CYP2C9 and CYP2C19) was reduced by 67% (Iida et al, 2001;. Propofol blood concentrations were increased by approximately 20% both in healthy volunteers at 34°C and during hypothermic cardiopulmonary bypass, likely due to reduced intercompartmental clearances in the former (Russell et al, 1989;Leslie et al, 1995). In summary, reduced elimination during hypothermia has been shown for morphine, midazolam, and fentanyl in both animals and man (Koren et al, 1987;Bansinath et al, 1988;Fukuoka et al, 2004;Fritz et al, 2005).…”

Propofol in patients with cardiac disease

“…ml -~ was achieved within 15 min of starting the infusion (4 mg. kg-t-hr-l) and remained constant throughout surgery. Russell et al 23 though reported a decreased plasma propofol concentration at the onset of CPB with a gradual rise in propofol level during the hypothermic period. Rewarming during CPB caused a gradual decline to prebypass plasma propofol concentration.…”

Effects of cardiopulmonary bypass and hypothermia on electroencephalographic variables

“…However, hypothermic CPB increases the distribution volume of propofol [29,30] and may lead to sequestration of propofol by the CPB circuit [31]. In addition, metabolism of propofol may be decreased, and haemodilution and heparin administration increase the protein unbound fraction of propofol [29]. Therefore, it is difficult to predict the changes of free propofol concentration during CPB.…”

“…The target control infusion system normally produces small discrepancies between the calculated and actual blood concentrations with a bias (the mean prediction error) of ¹2%, and precision (the mean of the individual absolute prediction errors) of 15.1% [28]. However, hypothermic CPB increases the distribution volume of propofol [29,30] and may lead to sequestration of propofol by the CPB circuit [31]. In addition, metabolism of propofol may be decreased, and haemodilution and heparin administration increase the protein unbound fraction of propofol [29].…”