PROSPECTIVE MULTICENTER EVALUATION OF TRAMADOL EXPOSURE

Background: Tramadol is a novel analgesic possessing both opiate and n oradrenergic effects. Its low potential for abuse suggests increasing use, but there are limited data on the toxicity in overdose. Methods: Multicenter prospective case series. All exposures from October 1995 t hrough August 1996 reported to seven Poison Centers were evaluated. Re sults: There were 126 cases of which 87 were tramadol alone. Of the tr amadol alone cases, 51 were female (59%). Age ranged from 1 to 86 y wi th a mean and median of 26.8 y (SD 17.2) and 25 y, respectively. There were 15 cases of children less than 6 years old. Symptoms reported wi th overdose were: lethargy 26 (30%), nausea 12 (14%), tachycardia 11 ( 13%), agitation 9 (10%), seizures 7 (8%), 4 each (5%) of coma and hype rtension, and respiratory depression 2 (2%). All seizures were brief. Naloxone reversed sedation and apnea in 4 of 8 patients. One patient e xperienced a seizure immediately after administration of naloxone. Oth er treatments were: diazepam (3 patients), and phenytoin, lorazepam an d nifedipine (1 patient each). Tramadol 500 mg was the lowest dose ass ociated with seizure, tachycardia, hypertension or agitation while 800 mg was the lowest dose associated with coma and respiratory depressio n. Urine drug screens performed on 19 patients were negative for opiat es. All symptomatic cases exhibited effects within 4 h of ingestion. M ean hospital stay was 15.2 h (range 2-96 h, SD 15.8). Nineteen patient s were admitted to an intensive care unit with a mean stay of 25 h (SD 20). Discussion: Much of the toxicity in tramadol overdose appears to be attributable to the monoamine uptake inhibition rather than its op ioid effects. Agitation, tachycardia, confusion and hypertension sugge st a possible mild serotonin syndrome. No arrhythmias beyond tachycard ia were seen. Conclusion: This study suggests significant neurologic t oxicity from tramadol overdose. Serious cardiovascular toxicity was no t seen.