Pain 2012; International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Marnix J. Sigtermans a,1, Jacobus J. van Hilten b,1, Martin C.R. Bauer a, M. Sesmu Arbous c, Johan Marinus b, Elise Y. Sarton a, Albert Dahan a,*

a Department of Anesthesiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

b Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

c Department of Intensive Care, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands

Abstract

Complex Regional Pain Syndrome Type 1 (CRPS-1) responds poorly to standard pain treatment. We evaluated if the N-methyl-D-aspartate receptor antagonist S(+)-ketamine improves pain in CRPS-1 patients. Sixty CRPS-1 patients (48 females) with severe pain participated in a double-blind randomized placebo-controlled parallel-group trial. Patients were given a 4.2-day intravenous infusion of low-dose ketamine (n = 30) or placebo (n = 30) using an individualized stepwise tailoring of dosage based on effect (pain relief) and side effects (nausea/vomiting/psychomimetic effects). The primary outcome of the study was the pain score (numerical rating score: 0–10) during the 12-week study period. The median (range) disease duration of the patients was 7.4 (0.1–31.9) years. At the end of infusion, the ketamine dose was 22.2 ± 2.0 mg/h/70 kg. Pain scores over the 12-week study period in patients receiving ketamine were significantly lower than those in patients receiving placebo (P < 0.001). The lowest pain score was at the end of week 1: ketamine 2.68 ± 0.51, placebo 5.45 ± 0.48. In week 12, significance in pain relief between groups was lost (P = 0.07). Treatment did not cause functional improvement. Patients receiving ketamine more often experienced mild to moderate psychomimetic side effects during drug infusion (76% versus 18%, P < 0.001). In conclusion, in a population of mostly chronic CRPS-1 patients with severe pain at baseline, a multiple day ketamine infusion resulted in significant pain relief without functional improvement. Treatment with ketamine was safe with psychomimetic side effects that were acceptable to most patients.

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