Flamm E S, Young W, Collins W F, Piepmeier J, Clifton G L, Fischer B
J Neurosurg. 1985 Sep;63(3):390-7. doi: 10.3171/jns.1985.63.3.0390.
Results of a Phase I trial of the opiate antagonist naloxone for treatment of patients with acute spinal cord injury are reported. Naloxone was administered in doses ranging from 5 to 200 mg/sq m (0.14 to 5.4 mg/kg) for up to 48 hours. The patients ranged in age from 16 to 79 years (mean 37 years). Twenty patients received naloxone as a loading dose of 5 to 50 mg/sq m (0.14 to 1.43 mg/kg), followed by a maintenance dose of 20% of the loading dose given as a continuous infusion hourly for 47 hours (Group 1). Nine patients received a loading dose of 100 to 200 mg/sq m (2.7 to 5.4 mg/kg) and a maintenance dose of 75% of the initial dose hourly for 23 hours (Group 2). These higher doses (2.7 to 5.4 mg/kg) have been found to be effective in experimental spinal cord injury. Neurological examinations were performed and somatosensory evoked potentials (SEP's) were obtained as soon after admission as possible and again 1, 2, 3, and 7 days, 3 weeks, and 6 weeks to 6 months after admission. The 20 Group 1 patients who received 1.43 mg/kg or less of naloxone showed no improvement in neurological status or SEP's. All but three (15%) of these patients had a complete neurological deficit at the time of admission. Treatment was begun an average of 12.9 hours after injury. Among the nine Group 2 patients treated with 2.7 mg/kg or more, there were five patients (56%) with incomplete deficits. This group received naloxone an average of 6.6 hours after admission. Two of the five Group 2 patients with incomplete lesions showed improvement in their neurological condition and/or SEP's within 36 hours of receiving the drug. One of the four Group 2 patients with a complete lesion at the time of admission was able to localize pressure sensation in his legs 36 hours after completion of the drug infusion. Four Group 2 patients (two with complete and two with incomplete lesions) have shown improvement in their SEP's, suggesting recovery of SEP's in a dose-related fashion. Four patients experienced increased pain after administration of the loading dose and during the maintenance infusion; in only one patient was this severe enough to require discontinuation of the drug. Of the 29 patients treated with naloxone, four died within 6 weeks of admission, for a mortality rate of 13.8%.(ABSTRACT TRUNCATED AT 400 WORDS)
本文报告了阿片类拮抗剂纳洛酮治疗急性脊髓损伤患者的Ⅰ期试验结果。纳洛酮的给药剂量为5至200mg/平方米（0.14至5.4mg/kg），持续给药48小时。患者年龄在16至79岁之间（平均37岁）。20名患者接受了5至50mg/平方米（0.14至1.43mg/kg）的负荷剂量纳洛酮，随后以负荷剂量的20%作为维持剂量，每小时持续输注47小时（第1组）。9名患者接受了100至200mg/平方米（2.7至5.4mg/kg）的负荷剂量和初始剂量75%的维持剂量，每小时给药23小时（第2组）。已发现这些较高剂量（2.7至5.4mg/kg）在实验性脊髓损伤中有效。入院后尽快进行神经学检查并记录体感诱发电位（SEP），并在入院后1、2、3和7天、3周、6周以及6个月时再次进行检查。第1组中接受1.43mg/kg或更低剂量纳洛酮的20名患者，神经功能状态或SEP均无改善。这些患者中除3人（15%）外，入院时均有完全性神经功能缺损。治疗平均在受伤后12.9小时开始。在接受2.7mg/kg或更高剂量治疗的9名第2组患者中，有5名患者（56%）存在不完全性缺损。该组患者平均在入院后6.6小时接受纳洛酮治疗。第2组中5名不完全性损伤患者中有2名在接受药物治疗后36小时内神经状况和/或SEP有所改善。第2组中4名入院时为完全性损伤的患者中有1名在药物输注结束后36小时能够定位腿部的压觉。4名第2组患者（2名完全性损伤和2名不完全性损伤）的SEP有所改善，表明SEP以剂量相关的方式恢复。4名患者在给予负荷剂量和维持输注期间疼痛加剧；只有1名患者疼痛严重到需要停药。在接受纳洛酮治疗的29名患者中，有4名在入院后6周内死亡，死亡率为13.8%。（摘要截选至400字）
