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Pain. 2008 Mar;135(1-2):108-18. Epub 2007 Jun 20.

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

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  • 1Department of Anaesthesia Critical Care and Pain Medicine, Clinical and Surgical Sciences, The University of Edinburgh, Royal Infirmary, Little France, Edinburgh EH16 4SA, UK.


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.

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