Why?

Although often used to manage chronic pain acutely, the longer-term benefits of ketamine infusions remain uncertain. Despite this there has been significant growth in using ketamine infusions to treat chronic pain, rationalised by ketamine’s expected effect to reduce central sensitisation.

What?

This meta-analysis identified a small benefit for up to two weeks after a ketamine infusion, although little evidence of longer-term benefit. There appears to be a dose-response effect, suggesting greater efficacy with high-dose ketamine infusions.

The underlying problem...

Most research on ketamine infusions focuses on perioperative analgesia. Trials invetsigating ketamine infusions for chronic pain are universally small, lack standardisation and are often low quality.

This meta-analysis unfortunately does not add clarity to the question of whether ketamine infusions have long-term benefit in chronic pain syndromes. Clinicians will continue to need to judge indication on a case-by-case basis...

summary

• Vwaire Orhurhu, Mariam Salisu Orhurhu, Anuj Bhatia, and Steven P Cohen.
• From the Department of Anesthesiology, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
• Anesth. Analg. 2019 Jul 1; 129 (1): 241-254.

BackgroundIV ketamine is widely used to treat patients with chronic pain, yet the long-term impact remains uncertain. We synthesized evidence from randomized control trials to investigate the effectiveness of IV ketamine infusions for pain relief in chronic conditions and to determine whether any pain classifications or treatment regimens are associated with greater benefit.MethodsWe searched Medline, Embase, and Google Scholar, as well as the clinicaltrials.gov website from inception through December 16, 2017 for randomized control trials comparing IV ketamine to placebo infusions for chronic pain that reported outcomes for ≥48 hours after the intervention. Three authors independently screened the studies, pooled the data, and appraised risk of bias. Random-effects model was used to calculate weighted mean differences for pain scores and secondary outcomes. Our primary outcome was the lowest recorded pain score ≥48 hours after cessation of treatment. Secondary outcomes included responder rate and adverse effects.ResultsAmong 696 studies assessed for eligibility, 7 met inclusion criteria. All studies except one were at high risk of bias. These studies randomly assigned 211 patients with neuropathic (n = 2), mixed (n = 2), and nonneuropathic (nociplastic or nociceptive) (n = 3) pain. Three studies reported significant analgesic benefit favoring ketamine, with the meta-analysis revealing a small effect up to 2 weeks after the infusion (mean difference in pain scores, -1.83 points on a 0-10 numerical rating scale; 95% CI, -2.35 to -1.31 points; P < .0001). In the 3 studies that reported responder rates, the proportion with a positive outcome was greater in the ketamine than in the placebo group (51.3% vs 19.4%; relative risk, 2.43; 95% CI, 1.10-5.40; P = .029; I = 0.0%). No differences were noted based on pain classification or condition. Compared to low-dose ketamine studies and investigations that evaluated non-complex regional pain syndrome conditions, a small but nonsignificant greater reduction in pain scores was found among studies that either utilized high-dose ketamine therapy (P = .213) or enrolled complex regional pain syndrome patients (P = .079).ConclusionsEvidence suggests that IV ketamine provides significant short-term analgesic benefit in patients with refractory chronic pain, with some evidence of a dose-response relationship. Larger, multicenter studies with longer follow-ups are needed to better select patients and determine the optimal treatment protocol.

This article appears in the collections: Ketamine infusions and Ketamine.

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