Interaction Between Epidurally Administered Ketamine and Pethidine in Dogs

The present study was designed to test the hypothesis that a synergistic interaction could be recorded after epidural administration of ketamine-an N-methyl-D-aspartate (NMDA) antagonist and pethidine--an opioid agonist. Twelve adult mongrel dogs of either sex were randomly divided in three groups A, B and C of four animals each. Ketamine (5%) at 2.5 mg/kg and pethidine (3%) 2 mg/kg were injected at lumbosacral epidural space in animals of groups A and B, respectively. In animals of group C ketamine (2.5 mg/kg) and pethidine (2 mg/kg) were injected. Heart rate increased significantly up to 15 min in group A, whereas in groups B and C, the increase was non-significant for a period of 10 and 45 min, respectively. Respiration increased gradually up to 45-60 min in group A and for 15-20 min in group B. However, in animals of group C respiration fell below the baseline during the first 10-15 min and then returned near the baseline. Rectal temperature decreased only marginally in all the groups. Ketamine alone produced complete analgesia at tail and perineal region for a period of 5-10 min and then moderate analgesia for the next 20-30 min. Analgesia at the flank was moderate to complete between 5 and 15 min. In group B complete analgesia was only moderate at the tail and perineal region up to 30 min. In animals of group C, complete analgesia was observed only at perineal region for a very short period (5 min). Analgesia was not associated with sedation in any of the groups but animals of groups A and C showed signs of motor incoordination. Results of the study suggest rather antagonistic than synergistic interaction between epidurally administered ketamine and pethidine. Further studies are needed to confirm the antagonistic interaction between the two drugs.