Pharmacodynamics and pharmacokinetics of high-dose oxycodone infusion during and after coronary artery bypass grafting.
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.
Pöyhiä
Reino
R
Department of Anasthesia and Intensive Care, Helsinki University Central Hospital, Helsinki, Finland. reino.poyhia@hus.fi
Hynynen
Markku
M
Seppälä
Timo
T
Roine
Risto O
RO
Verkkala
Kalervo
K
Olkkola
Klaus T
KT
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
D000701:Analgesics, Opioid; D019162:Anesthetics, Combined; D018685:Anesthetics, Inhalation; D006632:Histamine; D004737:Enflurane; D010098:Oxycodone; D006854:Hydrocortisone