title: A randomised double blind trial of the effect of pre-emptive epidural ketamine on persistent pain after lower limb amputation.
abstract: Persistent pain has been reported in up to 80% of patients after limb amputation. The mechanisms are not fully understood, but nerve injury during amputation is important, with evidence for the crucial involvement of the spinal N-methyl d-aspartate (NMDA) receptor in central changes. The study objective was to assess the effect of pre-emptively modulating sensory input with epidural ketamine (an NMDA antagonist) on post-amputation pain and sensory processing. The study recruited 53 patients undergoing lower limb amputation who received a combined intrathecal/epidural anaesthetic for surgery followed by a randomised epidural infusion (Group K received racemic ketamine and bupivacaine; Group S received saline and bupivacaine). Neither general anaesthesia nor opioids were used during the peri-operative period. Pain characteristics were assessed for 12 months. The primary endpoint was incidence and severity of post-amputation pain. Persistent pain at one year was much less in both groups than in comparable studies, with no significant difference between groups (Group K=21% (3/14) and 50% (7/14); and Group S=33% (5/15) and 40% (6/15) for stump and phantom pain, respectively). Post-operative analgesia was significantly better in Group K, with reduced stump sensitivity. The intrathecal/epidural technique used, with peri-operative sensory attenuation, may have reduced ongoing sensitisation, reducing the overall incidence of persistent pain. The improved short-term analgesia and reduced mechanical sensitivity in Group K may reflect acute effects of ketamine on central sensitisation. Longer term effects on mood were detected in Group K that requires further study.
authors.affiliation: Department of Anaesthesia Critical Care and Pain Medicine, Clinical and Surgical Sciences, The University of Edinburgh, Royal Infirmary, Little France, Edinburgh EH16 4SA, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Wilson
authors.forename: Alastair F
authors.initials: AF
authors.lastname: Nimmo
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fleetwood-Walker
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Colvin
mesh_terms: D000368:Aged; D000671:Amputation, Surgical; D015360:Analgesia, Epidural / Q000379:methods; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D010591:Phantom Limb / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D000700:Analgesics; D007649:Ketamine