Perioperative Intravenous Ketamine Infusion for the Prevention of Persistent Post-amputation Pain: A Randomized, Controlled Trial

Abstract

We hypothesized that perioperative ketamine administration would modify acute central sensitization following amputation and hence reduce the incidence and severity of persistent post-amputation pain (both phantom limb and stump pain). In a randomized, controlled trial, 45 patients undergoing above- or below-knee amputation received ketamine 0.5 mg x kg(-1) or placebo as a pre-induction bolus followed by an intravenous infusion of ketamine 0.5 mg x kg(-1) x h(-1) or normal saline for 72 hours postoperatively. Both groups received standardized general anaesthesia followed by patient-controlled intravenous morphine. The surface area of allodynia over the stump was mapped at days 3 and 6. Postamputation pain was assessed at days 3 and 6 and at 6 months postoperatively. We found no significant difference between groups in the surface area of stump allodynia or in morphine consumption. There was an unexplained, but significant, increase in the incidence of stump pain in the ketamine group at day 3. At six-month review, the incidence of phantom pain was 47% in the ketamine group and 71% in the control group. This did not reach statistical significance (P=0.28) as the power of the study was based on the search for a large treatment effect. The incidence of stump pain at six months was 47% in the ketamine group and 35% in the control group (P=0.72). There were no significant between-group differences in pain severity throughout the study period. Ketamine at the dose administered did not significantly reduce acute central sensitization or the incidence and severity of post-amputation pain.