A randomised double blind trial of the effect of pre-emptive epidural ketamine on persistent pain after lower limb amputation

John A Wilson, Alastair F Nimmo, Susan M Fleetwood-Walker, Lesley A Colvin

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)108-118
Number of pages11
Issue number1-2
Publication statusPublished - Mar 2008

Keywords / Materials (for Non-textual outputs)

  • phantom limb
  • epidural analgesia
  • ketamine
  • NMDA receptors
  • RCT


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