Epidural ketamine for postoperative analgesia

T WO factors have increased interest in ketamine for postoperative analgesia. The first was the discovery of the N-Methyl-D-asparrate (NMDA) receptor and its role in central pain processing and spinal cord neural plasticity. 1 Ketamine is one of two clinically useful NMDA receptor antagonists available (the other is dextromethorphan). Ketamine binds non-competitively to the PCI, (phencyclidine) recognition site in the NMDA receptor channel# In addition, interest in the concept of preemptive analgesia makes ketamine a natural candidate for investigation of postoperative pain relief since blockade of the NMDA receptor reduces noxious stimulusinduced allodynia and hyperalgesia. To avoid the well-known psychomimetic effects ofketamine, investigators have focused on the use of smaller doses than are required for general anaesthesia and alternative administration routes for postoperative analgesia. Spinal administration would seem to be especially interesting due to the proximity of the NMDA receptors and the potential for decrease in dose requirements. Reports on intraspinal administration of ketamine include caudal subarachnoid ketamine administration, with or without local anaesthetic agents, lumbar epidural ketamine alone or with local anaesthetic agents and/or opioids and thoracic epidural ketamine with opioids. There are several case reports, comments and uncontrolled studies related to epidural ketamine analgesia 3-s but only a few controlled clinical trials. 6~s Although two observational studies claimed epidural ketamine is effective as a postoperative analgesic s,4 other uncontrolled trials could find little or no postoperative analgesic effect, s Similarly, properly controlled trials using either small (4-8 mg)7or large (30 mg) s,s doses were unable to document effective postoperative epidural analgesia. Epidural ketamine may have an adjuvant effect when added to epidural morphine s or local anaesthetic agents. 9 Wong et al. s administered 10 mg ketamine and 0.5 mg morphine epidurally to patients scheduled for major joint replacement. The kelanainc/morphine combination produced the same degree of analgesia (with movement) as did 2 mg epidural morphine alone. In this study 10% of patients displayed psychomimetic effects requiting treatment. Yanli et aL, 9 in a controlled study, added 25 mg ketamine to a bupivacaine 0.5% with 1;200,000 adrenalin mixture and administered 20 ml epidurally to patients undergoing lower abdominal or orthopaedic surgery. There was a small but significant decrease in onset time to anaesthesia and a slightly higher segmental blockade in the ketamine group. There were no difference between the ketamine group and the non-ketamine group with regard to postoperative analgesic requirements and no adverse psychomimetic effects were seen. There are some claims that epidural ketamine and morphine combinations may have a preemptive analgesic effect. 1~ Choe et al. I1 in a controlled study added a large dose of ketamine (60 mg) to 2 mg epidural morphine and administered the combination before induction of general anaesthesia or 2-3 hr after the start of abdonfinal surgery. The only measure of analgesic efficacy was analgesic duration which was significantly prolonged in the preincisional group. No psychomimetic effects were noted. The comparative roles of the ketamine or the morphine in the possible preemptive effect are unclear. Wong et al. 1~ used a smaller dose of ketamine (20 mg) with 1.5 mg morphine given epidurally before or after incision to patients having knee joint replacement. Both groups received epidural anaesthesia with lidocaine intraoperatively. Postoperatively all patients received epidural ketamme (10 nag) mad morphine (1 mg) in lidocaine every 12 hr and also had additional PCA morphine available for rescue analgesia. Administration of the morphine/ketamine/fidocaine mixture before surgery resulted in less pain and lower PCA requirements than administration 30 rain after surgery had commenced. The preemptive effect of epidural ketamine alone is difficult to evaluate in this study as corn-