Sigtermans Marnix J, van Hilten Jacobus J, Bauer Martin C R, Arbous Sesmu M, Marinus Johan, Sarton Elise Y, Dahan Albert
Department of Anesthesiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands Department of Intensive Care, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Pain. 2009 Oct;145(3):304-311. doi: 10.1016/j.pain.2009.06.023. Epub 2009 Jul 14.
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.
1型复杂性区域疼痛综合征（CRPS-1）对标准疼痛治疗反应不佳。我们评估了N-甲基-D-天冬氨酸受体拮抗剂S(+)-氯胺酮是否能改善CRPS-1患者的疼痛。60例患有严重疼痛的CRPS-1患者（48名女性）参与了一项双盲随机安慰剂对照平行组试验。根据效果（疼痛缓解）和副作用（恶心/呕吐/拟精神病效应），采用个体化逐步调整剂量的方法，给予患者为期4.2天的低剂量氯胺酮静脉输注（n = 30）或安慰剂（n = 30）。该研究的主要结局是12周研究期间的疼痛评分（数字评分量表：0 - 10）。患者的中位（范围）病程为7.4（0.1 - 31.9）年。输注结束时，氯胺酮剂量为22.2±2.0 mg/h/70 kg。接受氯胺酮治疗的患者在12周研究期间的疼痛评分显著低于接受安慰剂的患者（P<0.001）。最低疼痛评分出现在第1周结束时：氯胺酮组为2.68±0.51，安慰剂组为5.45±0.48。在第12周时，两组之间的疼痛缓解差异不再显著（P = 0.07）。治疗未导致功能改善。接受氯胺酮治疗的患者在药物输注期间更常出现轻度至中度的拟精神病副作用（76% 对18%，P<0.001）。总之，在基线时大多为慢性严重疼痛的CRPS-1患者群体中，为期多天的氯胺酮输注可显著缓解疼痛，但未改善功能。氯胺酮治疗安全，其拟精神病副作用大多数患者可以接受。
