Pharmacokinetics and haemodynamics of ketamine in intensive care patients with brain or spinal cord injury.
BACKGROUND
Ketamine is used as an anaesthetic agent for short surgical procedures, and as a sedative and analgesic in intensive care patients. Intensive care patients with brain or spinal cord injury may have physiological changes that could alter the pharmacokinetics of ketamine. The pharmacokinetics of ketamine have been studied in healthy volunteers and in patients undergoing different types of surgery, but no data are available in intensive care patients.


METHODS
We determined the pharmacokinetics of ketamine and its active metabolites, norketamine and dehydronorketamine, in 12 intensive care patients with brain or spinal cord injury. The effect of ketamine on haemodynamic variables was also investigated.


RESULTS
The total clearance of ketamine, mean (SD), was 36.0 (13.3) ml min(-1) kg(-1), the volume of distribution (Vbeta) was 16.0 (8.6) litre kg(-1), and the elimination half-life was 4.9 (1.6) h. Ketamine did not alter any haemodynamic variables in the patients studied.


CONCLUSIONS
Pharmacokinetic variables of ketamine in intensive care patients are greater than in healthy volunteers and in surgical patients. The increase in the volume of distribution is greater than the increase in clearance, resulting in a longer estimated half-life of ketamine in this patient group.
Hijazi
Y
Y
Université Claude Bernard Lyon 1, Faculté de Pharmacie, Département de Pharmacie, Clinique de Pharmacocinétique et d'Evaluation du Médicament, 8 Avenue Rockefeller, F-69373 Lyon, Cedex 08, France.
Bodonian
C
C
Bolon
M
M
Salord
F
F
Boulieu
R
R
D000328:Adult; D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000378:metabolism* / Q000628:therapy; D003422:Critical Care / Q000379:methods*; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007649:Ketamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000628:therapy
D000778:Anesthetics, Dissociative; D007649:Ketamine; C033419:norketamine