Optimizing the Treatment of CRPS With Ketamine

Abstract

Objective: This study aimed to develop a method that objectively measures the clinical benefits of ketamine infusions to treat complex regional pain syndrome (CRPS), thus making it possible, for the first time, to determine the optimal dosing of ketamine and duration of treatment to treat CRPS. Materials and Methods: All patients were diagnosed with hyperalgesia associated with CRPS. Patients underwent an outpatient, 4-day, escalating dose ketamine infusion. Hyperalgesia was measured using pain thresholds. Clinical outcome was determined without knowledge of the patient’s pain thresholds throughout treatment. Results: We found a correlation between pain thresholds and the intensity of pain reported by the patient at various sites of the body. We found that clinical outcomes correlated with improvement in pain thresholds. There was a plateau in pain thresholds between days 3 and 4 for the lower extremities. There was no plateau in pain thresholds observed for the upper extremities. Discussion: Our findings suggest that 4 days of treatment are sufficient for the treatment of CRPS of the lower extremities. For the upper extremities, >4 days may be required. Our study is the first to utilize quantitative sensory testing to direct the treatment of a chronic pain disorder.

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

“…A distinction is made when treating extremity pain in patients with CRPS, with pain threshold plateaus being realized between 3 and 4 days, and greater than 4 days of ketamine treatment for patients with CRPS of the lower and upper extremities, respectively. 24 Similarly, long-term (100-h) escalating doses of ketamine infusion starting at 5mg/hr/70kg to 20mg/hr/70kg demonstrate effectiveness in pain relief for CRPS-1 patients, with analgesia outlasting the treatment period by 50 days. 35 This observation suggests that ketamine initiates a cascade of events, including desensitization of excitatory receptor systems in the CNS which persist but abate slowly, even when ketamine molecules are no longer detectable in the body.…”

“…Instead of a pain score, Kirkpatrick et al 24 measured pain threshold, which is defined as the amount of stimulation before the sensation of pain is experienced. In 13 of the studies, ketamine infusion resulted in a decrease in pain scores or threshold.…”

“…Most studies tailored ketamine dosages based on individual weight, with doses ranging from 0.15 to 7 mg/kg/hour. Kirkpatrick et al 24 , Kiefer et al 25 , and Goldberg et al 26 did not calculate dosages based on patient weight, and instead used dosages between 10 to 200 mg/hour.…”

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

“…Duration of analgesia ranged from five minutes to 10 days based on the dosage of ketamine All studies but one used some form of subjective pain scales, such as the visual analog scale (VAS) or verbal numeric rating scale (NRS), which range from 0 (no pain) to 10 (worst possible pain). Instead of a pain score, Kirkpatrick et al measured pain threshold, which is defined as the amount of stimulation before the pain is experienced [17]. In 13 of the studies, ketamine infusion resulted in a decrease in pain scores and threshold.…”

Possible Therapeutic Options for Complex Regional Pain Syndrome

“…However, most of these drugs, including gabapentin, exhibit withdrawal symptoms, such that administration of them is limited. Recently, clinical results have also reported reduced pain with injections of ketamine, a selective NMDA antagonist in CRPS1, although some patients with CRPS1 have reported no effect [ 16 , 17 ].…”