Lumanauw DD, Youn S, Horeczko T, et al. Subdissociative-dose Ketamine Is Effective for Treating Acute Exacerbations of Chronic Pain. Acad Emerg Med. 2019 Mar 22. doi: 10.1111/acem.13755. (Original study)

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.

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Comments from MORE raters

Physician rater

This study, which shows that ketamine is better than nothing in alleviating pain in patients presenting to the ED with exacerbations of a chronic condition, is itself probably 'better than nothing' as evidence, However, the occurrence of agitation requiring physical restraints in 1 out of 70 patients receiving active treatment (statistically consistent with a 4% incidence) is likely enough to dissuade many practitioners and patients from 'trying this at home'.

Physician rater

This very interesting article establishes that there is little benefit for increasing infusion beyond 0.25mg/kg. Over time, we'll have to establish the optimal dose and whether the benefits outweigh the risks.

Physician rater

As an emergency medicine physician and medical toxicologist, I find this article interesting but disappointing with regards to long-term pain control in patients suffering from chronic pain. In the emergency department setting, sub-dissociative ketamine dresses are quite useful based on this article, a finding that correlates with my clinical practice experience.

Physician rater

This may be useful for my practice in the ED.
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