title: Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs.
abstract: This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg(-1) bolus and at a dose rate of 10 microg kg(-1) min(-1)) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography. Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog.
authors.affiliation: Department of Clinical Veterinary Medicine, Anaesthesiology division, Vetsuisse-Faculty, University of Berne, Berne, Switzerland. bergadano@bluewin.ch
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bergadano
authors.forename: Ole K
authors.initials: OK
authors.lastname: Andersen
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: Regula
authors.initials: R
authors.lastname: Theurillat
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
authors.forename: Claudia
authors.initials: C
authors.lastname: Spadavecchia
mesh_terms: D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000097:blood*; D000818:Animals; D004285:Dogs / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000662:veterinary; D007262:Infusions, Intravenous / Q000662:veterinary; D007649:Ketamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D011446:Prospective Studies; D013237:Stereoisomerism; D004561:Transcutaneous Electric Nerve Stimulation / Q000662:veterinary
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine; C033419:norketamine