Tehran University Medical Journal

Background: Tramadol is a synthetics 4-phenyl-piperidine analogue of codeine used for treating moderate to severe pain. Tramadol is a FDA pregnancy category C medication which induces release of serotonin and inhibits the reuptake of norepinephrine. Chronic use of this drug during pregnancy may lead to physical dependency and withdrawal syndrome in the neonate.
Case presentation: We report the newborn of a woman admitted in the delivery ward of Mostafa Khomeini Hospital in Tehran, Iran in 2011. The mother suffered from chronic low back pain and headache and frequently took tramadol during pregnancy. The infant had a gestational age of 38.5 w, a birth weight of 2950 gr and an Apgar score of 9/10 at 1 and 5 minutes after birth.
The first signs of withdrawal syndrome occurred after 24 h with nausea, vomiting, poor feeding, and tremor. Later, agitation, tremor, hyprertonicity, and repeated multifocal myoclonus, and generalized tonic-clonic seizures developed. Clinical signs of withdrawal syndrome waned under phenobarbital therapy.
Conclusion: Drug withdrawal syndrome should be considered in the neonates of pregnant mothers who chronically take tramadol. Tramadol administration during pregnancy should be restricted to carefully selected cases.

Background: It is demonstrated that morphine and tramadol affects seizure but the mode of action of these drugs on seizure has not been compared yet with increasing of age. The aim of this study was to compare the impact of exposure to these drugs on Pentylenetetrazol-induced seizure in immature rat.
Methods: Male neonate rats were randomly chosen and divided into three groups namely Saline (n=21), Morphine (n=12) and Tramadol (n=13). On postnatal days 8-14, Saline group received normal saline and two other groups received morphine and tramadol with additive doses, respectively. On postnatal days 22-28, the saline treated rats divided into three subgroups and received saline (n=8), morphine (n=8) or tramadol (n=5). Morphine treated rats received saline or morphine (each n=6), and tramadol treated rats received saline (n=7) or tramadol (n=6). At postnatal day 29, they were evaluated for PTZ-induced seizure.
Results: Number of tonic-clonic seizure was increased in all groups compared with control and tramadol+saline groups (P<0.05). Duration of tonic-clonic seizure was decreased in tramadol+saline group compared with other tramadol groups (P<0.05). Latency of tonic-clonic seizurewas decreased in tramadol+saline group compared with control rats (P<0.05), But it was increased in saline+tramadol group compared with other groups except to saline group (P<0.05). Latency of myoclonic contractions in saline+morphine and saline+tramadol groups was lower than in control rats (P<0.05).
Conclusion: Similar age-related changes may occur inchronic exposure to morphine and tramadol in the neonatal period which leads to an increase in severity of seizures in rats on postnatal days 22-28. The effect of morphine and tramadol does not show any significant difference.

Background: Tramadol is a synthetic drug which is prescribed in moderate and severe pain. Tramadol overdose can induce severe complications such as consciousness impairment and convulsions. This study was done to determine the convulsions incidence after tramadol use until one week after hospital discharge. Methods: This prospective study was done in tramadol overdose patients without uncontrolled epilepsy and head injury history. All cases admitted in Loghman and Rasol Akram Hospitals, Tehran, Iran from 1, April 2011 to 1, April 2012 were included and observed for at least 12 hours. Time interval between tramadol intake and first seizure were record. Then, patients with second drug-induced seizure were recognized and log time between the first and second seizure was analyzed. The patients were transferred to the intensive care unit (ICU) if clinical worsening status observed. One week after hospital discharge, telephone follow-up was conducted. Results: A total of 150 patients with a history of tramadol induced seizures (141 men, 9 women, age: 23.23±5.94 years) were enrolled in this study. Convulsion was seen in 104 patients (69.3%). In 8 out of 104 patients (7.6%) two or more convulsion was seen. Time interval between tramadol use and the onset of the first and second seizure were 0.93±0.17 and 2.5±0.75 hours, respectively. Tramadol induced seizures are more likely to occur in males and patients with a history of drug abuse. Finally, one hundred forty nine patients (99.3%) were discharged with good condition and the only one patient died from tramadol overdose. Conclusion: The results of the study showed tramadol induced seizure most frequently occurred within the first 4 hours of tramadol intake. The chance of experiencing a second seizure exists in the susceptible population. Thus, 4 hours after drug intake is the best time for patients to be hospital discharged.