Background: We sought to determine if subdissociative dose ketamine (SDDK) is effective in relieving acute exacerbations of chronic pain.
Methods: Randomized double-blind placebo-controlled trial conducted May 2017 – June 2018 at a public teaching hospital (ClinicalTrials.gov: NCT02920528). Primary endpoint was a 20 mm decrease on a 100 mm Visual Analog Scale (VAS) at 60 minutes. Power analysis using three groups (ketamine 0.5 mg/kg, 0.25 mg/kg, or an equal volume of saline placebo infused over 20 minutes) estimated 96 subjects were needed for 90% power. Inclusion: age > 18 years, chronic pain > 3 months, acute exacerbation (VAS ≥ 70 mm). Exclusion: history of psychosis, seizures, uncontrolled hypertension, heart or thyroid disease. To maintain blinding, subjects wore sunglasses to conceal involuntary eye movements and pharmacists de-identified study medications. VAS was used to independently assess pain, agitation, and sedation at baseline and 20, 40, 60 min after initiation of study drug. Telephone follow-up at 24-48 hr used a 10-point Likert pain scale. Mann-Whitney U, RMANOVA or Fisher’s exact test were used for comparisons between groups.
Results: 106 subjects were recruited, 3 were excluded for baseline pain < 70 mm and 3 for incomplete data. 33 were randomized to 0.5 mg/kg, 35 to 0.25 mg/kg, and 32 to placebo. 3 subjects receiving 0.5 mg/kg withdrew during the infusion due to adverse effects, leaving 97 for analysis. Initial pain scores in mm (91.6±8.9, 92.1±8.9, 92.0±8.9), age in years (47.8±12, 44.3±11.2, 47.6±15), male gender (12/30, 14/35, 14/32) and types of pain reported were similar. Primary endpoint analysis found 25/30 (83%) improved with 0.5 mg/kg, 28/35 (80%) with 0.25 mg/kg, and 13/32 (41%) with placebo (p=0.001). More adverse effects occurred in the ketamine groups: 12/30 with 0.5 mg/kg, 14/35 with 0.25 mg/kg, vs 1/32 with placebo. Subjects receiving placebo required more rescue medications. The majority (89%) of subjects were contacted at 24-48 hr and no difference in pain level was detected between groups.
Conclusion: Ketamine infusions at both 0.5 mg/kg and 0.25 mg/kg over 20 minutes were effective in treating acute exacerbations of chronic pain but resulted in more adverse effects when compared to placebo. Ketamine did not result in longer term pain control over the next 24–48 hr.