The influence of hypoxia and hyperoxia on the kinetics of propofol emulsion.
OBJECTIVE
To study the effect of hypoxia and hyperoxia on the pharmacokinetics of propofol emulsion, hepatic blood flow and arterial ketone body ratio in the rabbit.


METHODS
Twenty four male rabbits were anesthetized with isoflurane (1.5-2%) in oxygen. After the surgical procedure, isoflurane administration was discontinued and intravenous propofol infusion (30 mg x kg(-1) x hr(-1)) was started. The infusion rate of propofol was maintained throughout the study. After an initial 90 min period of propofol infusion, rabbits were randomly allocated to one of three groups: hypoxia (F(I)O2 = 0.1), normoxia (F(I)O2 = 0.21), and hyperoxia (F(I)O2 = 1.0). Propofol infusion was continued under the allocated F(I)O2 for 60 min. Propofol concentrations in arterial blood, total body clearance of propofol, hepatic blood flow and arterial ketone body ratio were measured.


RESULTS
The mean arterial propofol concentration at the end of infusion was higher in the hypoxia group (15.2 +/- 2.8 microg x mL(-1), mean +/- SD) than in the normoxia (7.4 +/- 1.7) and hyperoxia (8.0 +/- 1.9) groups (P < 0.05). Total body clearance of propofol, hepatic blood flow and arterial ketone body ratio were all reduced in the hypoxia group (P < 0.05). Total ketone body concentration in arterial blood increased in the hyperoxia group (P < 0.01).


CONCLUSIONS
Hypoxia produced an accumulation of propofol in blood and reduced propofol clearance. These changes could result from decreased hepatic blood flow and low cellular energy charge in the liver. Hyperoxia, on the other hand, increased total ketone body in arterial blood.
Yamamoto
K
K
Department of Anesthesiology and Intensive Care Medicine, School of Medicine, Kanazawa University, Japan. kenyam@med.kanzawa-u.ac.jp
Tsubokawa
T
T
Yagi
T
T
Ishizuka
S
S
Ohmura
S
S
Kobayashi
T
T
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004655:Emulsions; D018496:Hyperoxia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000097:blood; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
D018686:Anesthetics, Intravenous; D004655:Emulsions; D007657:Ketone Bodies; D010100:Oxygen; D015742:Propofol