title: Comparison of the pharmacokinetics of methohexital during cardiac surgery with cardiopulmonary bypass and vascular surgery.
abstract: The aim of this study was to assess the pharmacokinetics of methohexital (ME) in major vascular surgery (VASC) and to compare these data with the pharmacokinetics of ME during hypothermic cardiopulmonary bypass (HCPB) (temperature: 28 degrees C) and normothermic cardiopulmonary bypass (NCPB) (temperature: 37 degrees C). An ME bolus (2 mg/kg) was administered to 8 VASC patients at the start of surgery and to 11 HCPB patients and 11 NCPB patients at the start of cardiopulmonary bypass (CPB). Twenty-one arterial blood samples were withdrawn over the following 24 hours for ME assays. All of the patients were given similar anesthesia (fentanyl, diazepam) and muscle relaxation (pancuronium). In the VASC group, ME total body clearance (TBC) was 6 +/- 2 mL/kg/min (mean +/- SD), which is less than in previous studies. When comparing HCPB and NCPB groups, elimination half-life (T1/2), TBC, volume of distribution (VD), area under the curve (AUC), and mean residence time (MRT) were similar. When comparing VASC and CPB patients, TBC and VD were greater in CPB patients than in VASC patients; thus, T1/2 (equal to 0.693 x VD/TBC) was similar. AUC was smaller in CPB patients because of hemodilution, but MRT was similar. It is concluded that ME clearance is lower in patients undergoing major vascular surgery than in healthy patients. The temperature and the duration of CPB do not seem to substantially influence the pharmacokinetics of ME when a bolus is administered. Parameters such as AUC, TBC, and VD appear modified by hemodilution during CPB; however, T1/2 and MRT, which allow comparisons between CPB and non-CPB patients, were similar in these patients.
authors.affiliation: Hôpital Cardiovasculaire et Pneumologique Louis Pradel, Service d'Anesthésie-Réanimation, Lyon, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lehot
authors.forename: R
authors.initials: R
authors.lastname: Boulieu
authors.forename: A
authors.initials: A
authors.lastname: Foussadier
authors.forename: M
authors.initials: M
authors.lastname: George
authors.forename: J
authors.initials: J
authors.lastname: Clerc
authors.forename: J
authors.initials: J
authors.lastname: Villard
authors.forename: J
authors.initials: J
authors.lastname: Chassignolle
authors.forename: S
authors.initials: S
authors.lastname: Ferry
authors.forename: S
authors.initials: S
authors.lastname: Estanove
mesh_terms: D001798:Blood Proteins / Q000032:analysis; D002303:Cardiac Output, Low / Q000209:etiology; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D005260:Female; D006207:Half-Life; D006400:Hematocrit; D006801:Humans; D007022:Hypotension / Q000209:etiology; D007036:Hypothermia, Induced; D008297:Male; D008723:Methohexital / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D014656:Vascular Surgical Procedures; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D001798:Blood Proteins; D014665:Vasodilator Agents; D008723:Methohexital