✓ 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%.
This study demonstrates that, in spinal cord-injured patients, naloxone given as an intravenous loading dose of 200 mg/sq m, followed by a continuous infusion of up to 150 mg/sq m/hr for 23 hours, has minimal side effects. The observed improvement in the clinical examination and SEP's at the higher doses, while not statistically verified in this Phase I trial, is encouraging.