Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome

Pain Physician. 2005 Apr;8(2):175-9.


Background: Complex regional pain syndrome (CRPS) is characterized by pain that is out of proportion to the injury and is regional in distribution. A large body of literature supports a dynamic change in the physiology and structure of central pain projecting neurons mediated through the N-methyl-D-aspartate (NMDA) receptor. A critical factor in central sensitization seems to be the release of the magnesium block on the NMDA receptor with influx of calcium and initiation of intracellular cascades. Current literature supports the effectiveness of ketamine in blocking central sensitization through its effects on the NMDA receptor. Recent treatment with anesthetic doses of ketamine in severely ill patients with generalized CRPS prompted our interest in a lower dose therapy.

Objective: To report on the efficacy of low dose outpatient ketamine infusion for the treatment of CRPS diagnosed by International Association for the Study of Pain (IASP) criteria in patients who have failed conservative treatment.

Design: Open label, prospective, pain journal evaluation of a 10-day infusion of intravenous ketamine in the CRPS patient.

Methods: Patients diagnosed with CRPS by a single neurologist were assigned to receive a 10-day outpatient infusion of ketamine supervised by an Anesthesiologist/Pain Management Specialist. The infusion was administered in a short procedure unit after each patient had been instructed on how to complete a pain questionnaire. Monitoring consisted of continuous ECG, pulse oximetry, and non-invasive blood pressure every 15 minutes. Patients made journal entries each day prior to the infusion of 40-80 mg of ketamine. The subjects were also asked to rate their pain intensity using a verbal analog pain scale of 0-10 and the affective component using a verbal scale of 0-4.

Results: There was a significant reduction in pain intensity from initiation of infusion (Day 1) to the 10th day, with a significant reduction in the percentage of patients experiencing pain by Day 10 as well as a reduction in the level of their "worst" pain. The nadirs of pain were lower by Day 10 with a significant reduction in the incidence of "punishing pain." Moreover, there was a significant improvement in the ability to initiate movement by the 10th day.

Conclusion: A four-hour ketamine infusion escalated from 40-80 mg over a 10-day period can result in a significant reduction of pain with increased mobility and a tendency to decreased autonomic dysregulation.