Use of Ketamine Infusions for Treatment of Complex Regional Pain Syndrome: A Systematic Review

Abstract

This systematic review aims to review clinical studies on the use of ketamine infusion for patients with treatment-resistant complex regional pain syndrome (CRPS).The following systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021228470). Studies for the systematic review were identified through three databases: PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Reviews. Inclusion criteria for studies consisted of randomized clinical trials or cohort studies that conducted trials on the use of ketamine infusion for pain relief in patients with CRPS. Exclusion criteria for studies included any studies that were systematic reviews, meta-analyses, case reports, literature reviews, or animal studies. In the included studies, the primary outcome of interest was the post-drug administration pain score.In this systematic review, 14 studies met the inclusion criteria and were reviewed. In these studies, the dosage of ketamine infusion used ranged from 0.15 mg/kg to 7 mg/kg with the primary indication being the treatment of CRPS. In 13 of the studies, ketamine infusion resulted in a decrease in pain scores and relief of symptoms.Patients who received ketamine infusion for treatment-resistant CRPS self-reported adequate pain relief with treatment. This suggests that ketamine infusion may be a useful form of treatment for patients with no significant pain relief with other conservative measures. Future large-scale studies, including randomized double-blind placebo-controlled trials on the use of ketamine infusion for CRPS, must be conducted in a large-scale population to further assess the effectiveness of ketamine infusion in these populations.

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2)

“…There is evidence that esketamine infusions can provide clinically effective pain relief in a subgroup of CRPS patients with refractory pain [ 10 , 11 ]. To our best knowledge, intermittent and continuous esketamine treatments have never been compared in RCTs.…”

“…Regarding the esketamine dose, there is significant heterogeneity between published studies on CRPS [ 10 , 11 ]. Most of the studies reported esketamine dose based on body weight, with doses ranging from 0.15 to 7.0 mg/kg/hour [ 11 ].…”

“…The investigators concluded that intravenous esketamine therapy for CRPS can provide effective pain reduction for up to 3 months post infusion in a subgroup of CRPS patients [ 10 ]. Unfortunately, CRPS literature contains a wide range of esketamine dosing regimens with the result that clinical protocols on dosage and administration are very heterogeneous [ 5 , 10 , 11 ].…”

Continuous Ketamine Infusion as a Treatment for Refractory Facial Pain

“…Ketamine infusion has shown promise in treating neuropathic pain. Being an analgesic and sedative agent that acts primarily as a non-competitive antagonist of N-methyl-Daspartate (NMDA) receptors and with endogenous opioid receptors at high thresholds, ketamine is thought to limit central sensitization through plasticity and the descending antinociceptive pathway [8][9][10][11]. Continuous infusion may impact central sensitization more than intermittent infusion [9].…”

“…Despite its efficacy as a general analgesic, the literature on ketamine infusions for refractory facial pain is limited. Intramuscular or parenteral infusion of ketamine has been associated with neuropathic pain relief in chronic orofacial pain, migraines, acute pain after oral surgery, chronic regional pain syndrome (CRPS), and refractory TN [8,[12][13][14][15]. This current retrospective case series aimed to explore the clinical efficacy of continuous ketamine infusions in patients with refractory orofacial pain, particularly those with AFP or TN, and identify key clinical characteristics that were associated with treatment responders and non-responders.…”