A pilot study for a multicentre double-blind placebo controlled randomized Phase 4 study of the effect of ketamine on the development of chronic post-surgical pain in patients undergoing elective abdominal or non-cardiac thoracic surgery under general anaesthesia.

Chronic post-surgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study for a proposed large multicentre placebo controlled randomized trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine at low doses or placebo was administered to 80 patients undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at 6 month telephone follow up using a structured questionnaire. Four patients in the treatment group and 3 in the control group reported ongoing analgesic use to treat CPSP and 2 patients in each group reported their worst pain in the previous 24 hours at more than 3/10 at 6 months. There were no significant differences in adverse event rates, quality of recovery scores, cumulative morphine equivalents consumption or total pain scores in the first 72 hours. Regardless of treatment allocation, CPSP incidence was associated with poorer psychological well being using Kessler K-10 score, and with greater disability on the World Health Organization Disability Assessment Scale. A large adequately powered trial is feasible using this population and methodology.