The Effect of a Perioperative Ketamine Infusion on the Incidence of Chronic Postsurgical Pain—A Pilot Study

Abstract

Chronic postsurgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study at three hospitals to assess the feasibility of a proposed large multicentre placebo-controlled randomised trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine, 0.5 mg/kg pre-incision, 0.25 mg/kg/hour intraoperatively and 0.1 mg/kg/hour for 24 hours, or placebo, was administered to 80 patients, recruited over a 15-month period, undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at six-month telephone follow-up using a structured questionnaire. Fourteen patients (17.5%) reported CPSP (relative risk [95% confidence interval] if received ketamine 1.18 [0.70 to 1.98], P=0.56). Four patients in the treatment group and three in the control group reported ongoing analgesic use to treat CPSP and two patients in each group reported their worst pain in the previous 24 hours at ≥3/10 at six months. There were no significant differences in adverse event rates, quality of recovery scores, or cumulative morphine equivalents consumption in the first 72 hours. Numeric Rating Scale pain scores (median [interquartile range]) for average pain in the previous 24 hours among those patients reporting CPSP were 17.5 [0 to 40] /100 with no difference between treatment groups. A large (n=4,000 to 5,000) adequately powered multicentre trial is feasible using this population and methodology.

Rationale and design of influence of volatile anesthesia versus total intravenous anesthesia on chronic postsurgical pain after cardiac surgery using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials criteria assessment: study protocol for a prospective randomized controlled trial

“…CPSP is defined as persistent or recurrent pain lasting longer than 3 months, and without apparent cause [32]. Our results are clinically important because the incidence of CPSP has been considered to occur in up to 11-56% of patients undergoing cardiac or thoracic surgery with median sternotomy, with no established methods of prevention currently established [10][11][12]. As we know, general anesthesia is routinely used in cardiac surgery.…”

“…Besides standard postoperative analgesics, the use of corticosteroids, N-methyl-D-aspartate (NMDA) antagonists, alpha-2 agonists, local anesthetics and gabapentinoids are all suggested to reduce the risk for CPSP after cardiac surgery [5]. However, no specific therapy is vertified to protect against CPSP [10][11][12].…”

Rationale and design of influence of volatile anesthesia versus total intravenous anesthesia on chronic postsurgical pain after cardiac surgery using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials criteria assessment: study protocol for a prospective randomized controlled trial

“…Besides standard postoperative analgesics, the use of corticosteroids, N-methyl-D-aspartate (NMDA) antagonists, alpha-2 agonists, local anesthetics and gabapentinoids are all suggested to reduce the risk for CPSP after cardiac surgery [5]. However, no specific therapy is verified to protect against CPSP [10][11][12].…”

Does perioperative ketamine have a role in the prevention of chronic postsurgical pain: the ROCKet trial

“…To assess the feasibility of the trial and its design, a pilot study randomising 80 patients was performed successfully. 17 The final design of the ROCKet trial is a definitive, large, multicentre, double-blind, placebo-controlled and randomised Phase 3/4 trial of the effect of intravenous ketamine on the incidence and severity of CPSP. This design was submitted as a grant proposal for a 2016 Project Grant to the National Health and Medical Research Council (NHMRC) in Australia.…”

“…To assess the feasibility of the trial and its design, a pilot study randomising 80 patients was performed successfully. 17…”