Subdissociative-dose Ketamine Is Effective for Treating Acute Exacerbations of Chronic Pain

Acad Emerg Med. 2019 Sep;26(9):1044-1051. doi: 10.1111/acem.13755. Epub 2019 Apr 29.


Background: Subdissociative-dose ketamine (SDDK) is used to treat acute pain. We sought to determine if SDDK is effective in relieving acute exacerbations of chronic pain.

Methods: This study was a randomized double-blind placebo-controlled trial conducted May 2017 to June 2018 at a public teaching hospital ( #NCT02920528). The primary endpoint was a 20-mm decrease on a 100-mm visual analog scale (VAS) at 60 minutes. Power analysis using three groups (0.5 mg/kg ketamine, 0.25 mg/kg ketamine, or placebo infused over 20 minutes) estimated that 96 subjects were needed for 90% power. Inclusion criteria included age > 18 years, chronic pain > 3 months, and acute exacerbation (VAS ≥ 70 mm). Pain, agitation, and sedation were assessed by VAS at baseline and 20, 40, and 60 minutes after initiation of study drug. Telephone follow-up at 24 to 48 hours used a 10-point numeric rating scale for pain.

Results: A total of 106 subjects were recruited, with three excluded for baseline pain < 70 mm. After randomization, 35 received 0.5 mg/kg ketamine, 36 received 0.25 mg/kg ketamine, and 35 received placebo. Three subjects receiving 0.5 mg/kg withdrew during the infusion due to adverse effects, and one subject in each group had incomplete data, leaving 97 for analysis. Initial pain scores (91.9 ± 8.9 mm), age (46.5 ± 12.6 years), sex distribution, and types of pain reported were similar. Primary endpoint analysis found that 25 of 30 (83%) improved with 0.5 mg/kg ketamine, 28 of 35 (80%) with 0.25 mg/kg ketamine, and 13 of 32 (41%) with placebo (p = 0.001). More adverse effects occurred in the ketamine groups with one subject in the 0.25 mg/kg group requiring a restraint code for agitation. A total of 89% of subjects were contacted at 24 to 48 hours, and no difference in pain level was detected between groups.

Conclusion: Ketamine infusions at both 0.5 and 0.25 mg/kg over 20 minutes were effective in treating acute exacerbations of chronic pain but resulted in more adverse effects compared to placebo. Ketamine did not demonstrate longer-term pain control over the next 24 to 48 hours.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Analgesics / administration & dosage*
  • Chronic Pain / drug therapy*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Ketamine / administration & dosage*
  • Male
  • Middle Aged
  • Pain Management / methods*
  • Pain Measurement / methods


  • Analgesics
  • Ketamine

Associated data