title: Pharmacodynamics and pharmacokinetics of high-dose oxycodone infusion during and after coronary artery bypass grafting.
abstract: OBJECTIVE
  In small to moderate doses, oxycodone has similar analgesic efficacy to morphine with fewer side effects. The present study evaluated the pharmacokinetics and dynamics of high doses of oxycodone during anesthesia for primary coronary artery bypass grafting.
  
  
  METHODS
  A randomized, prospective clinical evaluation.
  
  
  METHODS
  A major Scandinavian university clinic.
  
  
  METHODS
  Two groups with 10 patients each were studied.
  
  
  METHODS
  Invasive hemodynamics, echocardiograms, and electrocardiograms were monitored. Oxycodone kinetics, histamine liberation, and plasma cortisol levels were measured. Anesthesia was induced with 1.0 mg/kg of oxycodone and, thereafter, in a random order, maintained with a continuous infusion of oxycodone at a rate of either 0.5 mg/kg/h (group OX 0.5, 10 patients) or 1.0 mg/kg/h (group OX 1.0, 10 patients). An additional bolus dose of 0.5 mg/kg (OX 0.5) or 1.0 mg/kg (OX 1.0) of oxycodone was given before the incision. Enflurane was administered according to hemodynamic criteria.
  
  
  RESULTS
  The induction of and the course of anesthesia were hemodynamically stable in all patients. Enflurane was given to every patient. The mean total doses of oxycodone were 3.5 mg/kg (OX 0.5) and 6.2 mg/kg (OX 1.0). The median t(1/2) of oxycodone varied from 5.1 to 5.9 hours. No hemodynamic differences were found between the groups. No histamine liberation was detected. During anesthesia, the predominant waves in the EEG were theta;- and delta-waves. The mean times to awakening were 3.8 hours and 7.0 hours in the groups OX 0.5 and 1.0, respectively. All patients were intubated until the first postoperative morning. No recall of awareness was reported.
  
  
  CONCLUSIONS
  A combination of oxycodone and enflurane provides hemodynamically stable anesthesia. No advantages were gained with the higher dose. Elimination of oxycodone was slower than reported previously.
authors.affiliation: Department of Anasthesia and Intensive Care, Helsinki University Central Hospital, Helsinki, Finland. reino.poyhia@hus.fi
authors.forename: Reino
authors.initials: R
authors.lastname: Pöyhiä
authors.forename: Markku
authors.initials: M
authors.lastname: Hynynen
authors.forename: Timo
authors.initials: T
authors.lastname: Seppälä
authors.forename: Risto O
authors.initials: RO
authors.lastname: Roine
authors.forename: Kalervo
authors.initials: K
authors.lastname: Verkkala
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Olkkola
mesh_terms: D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019162:Anesthetics, Combined / Q000627:therapeutic use; D018685:Anesthetics, Inhalation / Q000627:therapeutic use; D001026:Coronary Artery Bypass / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D004737:Enflurane / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous / Q000379:methods; D007430:Intraoperative Care / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011182:Postoperative Care / Q000379:methods*; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D019162:Anesthetics, Combined; D018685:Anesthetics, Inhalation; D006632:Histamine; D004737:Enflurane; D010098:Oxycodone; D006854:Hydrocortisone