Perioperative intravenous low‐dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo‐controlled study

Abstract

Background Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low‐dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, 6 and 12 months after major lower back surgery. Methods In this single‐centre randomized trial, 80 patients received intravenous ketamine 0.25 mg/kg preoperatively, followed by 0.25 mg kg−1 hr−1 intraoperatively, and 0.1 mg kg−1 hr−1 from 1 hr before the end of surgery until the end of recovery room stay; 80 controls received placebo. Results Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8 mg (IQR 67.4–106.7) and the median plasma level was 97 ng/ml (IQR 77.9–128.0). At 6 months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI −10.7 to 21.1; p = .607). At 12 months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI −6.7 to 23.6; p = .319). Conclusions In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low‐dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at 6 or 12 months postoperatively. Significance We were unable to show any analgesic benefit of a short‐term perioperative ketamine infusion as an adjuvant to multimodal analgesia in patients with a high prevalence of neuropathic lower back pain undergoing major back surgery. Based on these data, the widespread opinion that ketamine is universally analgesic across different pain conditions must be challenged. Prior presentations Abstract presentation at the annual congress of the Swiss Society of Anaesthesiology, 2016, Basel, Switzerland. Clinical trial number and registry URL Registered by Dr Christoph Czarnetzki as principal investigator on February 20, 2008 at clinicaltrials.gov (NCT00618423).

Pharmacotherapy for the Prevention of Chronic Pain after Surgery in Adults: An Updated Systematic Review and Meta-analysis

“…Thirteen new studies (n = 1,283 participants) 14–27 evaluated ketamine or (S)-ketamine (total, 27 studies; n = 2,757). 14–41 Nine of 27 studies reported prevalence of any pain at 3 months, 16,20,22,26,29,37,39–41 16 studies at 6 months, 14–17,22,24–26,30,33–37,40,41 and five studies at 12 months.…”

“…Thirteen new studies (n = 1,283 participants) 14–27 evaluated ketamine or (S)-ketamine (total, 27 studies; n = 2,757). 14–41 Nine of 27 studies reported prevalence of any pain at 3 months, 16,20,22,26,29,37,39–41 16 studies at 6 months, 14–17,22,24–26,30,33–37,40,41 and five studies at 12 months. 14–16,28,30 Prevalence of any pain at 3 months ranged from 5.6 to 72.2% (mean, 35.0%) in the placebo arm and 5.6 to 83.3% (mean, 31.5%) in the ketamine arm.…”

Ketamine Analgesia: Not All Patients or Surgeries Seem to Be Equal

“…The crosses represent the weighed means taking into account each study size. A total of 226 patients received ketamine in the 8 positive studies (De Kock et al, 3 Suzuki et al, 5 Perrin and Purcell, 6 Remérand et al, 7 Aveline et al, 8 Nielsen et al, 9 Liu et al, 10 Kang et al 11 ) and 694 in the 16 negative studies (Katz et al, 12 Hayes et al, 13 Dualé et al, 14 Ryu et al, 15 Joseph et al, 16 Mendola et al, 17 Wilson et al, 18 Crousier et al, 19 Sveticic et al, 20 Dullenkopf et al, 21 Sen et al, 22 Spreng et al, 23 Bilgen et al, 24 Peyton et al, 25 Shanthanna et al, 26 Czarnetzki et al 27 ). The concentrations provided in the positive studies (green) are significantly higher ( P < .001) than those provided in the negative studies (pink), but extreme values show that some studies escape the average behavior.…”

Perioperative Intravenous Low-Dose Ketamine Infusion to Minimize Pain for Septorhinoplasty: A Prospective, Randomized, Double-Blind Study

“…[5][6][7] In the last 2 decades, many studies have been conducted on the effects of ketamine on postoperative pain, chronic pain, depression, and postop delirium treatment. [8][9][10][11] Ketamine is a phencyclidine derivative synthesized in 1962. 12 It is the only anesthetic agent with analgesic, hypnotic, and amnesic effects.…”