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BACKGROUND: IV 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. METHODS: We 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. RESULTS: Among 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 2 = 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). CONCLUSIONS: Evidence 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.

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Context: Carpal tunnel syndrome (CTS) is the most frequent peripheral compression-induced neuropathy observed in patients worldwide. Surgery is necessary when conservative treatments fail and severe symptoms persist. Traditional Open carpal tunnel release (OCTR) with visualization of carpal tunnel is considered the gold standard for decompression. However, Endoscopic carpal tunnel release (ECTR), a less invasive technique than OCTR is emerging as a standard of care in recent years. Evidence Acquisition: Criteria for this systematic review were derived from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two review authors searched PubMed, MEDLINE, and the Cochrane Database in May 2018 using the following MeSH terms from 1993-2016: ‘carpal tunnel syndrome,’ ‘median nerve neuropathy,’ ‘endoscopic carpal tunnel release,’ ‘endoscopic surgery,’ ‘open carpal tunnel release,’ ‘open surgery,’ and ‘carpal tunnel surgery.’ Additional sources, including Google Scholar, were added. Also, based on bibliographies and consultation with experts, appropriate publications were identified. The primary outcome measure was pain relief. Results: For this analysis, 27 studies met inclusion criteria. Results indicate that ECTR produced superior post-operative pain outcomes during short-term follow-up. Of the studies meeting inclusion criteria for this analysis, 17 studies evaluated pain as a primary or secondary outcome, and 15 studies evaluated pain, pillar tenderness, or incision tenderness at short-term follow-up. Most studies employed a VAS for assessment, and the majority reported superior short-term pain outcomes following ECTR at intervals ranging from one hour up to 12 weeks. Several additional studies reported equivalent pain outcomes at short-term follow-up as early as one week. No study reported inferior short-term pain outcomes following ECTR. Conclusions: ECTR and OCTR produce satisfactory results in pain relief, symptom resolution, patient satisfaction, time to return to work, and adverse events. There is a growing body of evidence favoring the endoscopic technique for pain relief, functional outcomes, and satisfaction, at least in the early post-operative period, even if this difference disappears over time. Several studies have demonstrated a quicker return to work and activities of daily living with the endoscopic technique.