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Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1

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

doi: 10.1016/j.pain.2009.06.023
Articles

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.

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

*Corresponding author. Tel.: +31 71 526 2301; fax: +31 71 526 4824.

E-mail: a.dahan@lumc.nl

1These authors contributed equally to this work.

Received April 1, 2009; Received in revised form May 20, 2009; Accepted June 18, 2009.

© 2009 Lippincott Williams & Wilkins, Inc.
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