Effects of chronic use of tramadol on pregnant albino rats - Revista Brasileira de Ginecologia e Obstetrícia

Purpose: to examine the effects of tramadol hydrochloride on rat pregnancy. Methods: five groups of 10 pregnant albino rats each were treated from the 1st up to the 20th day of pregnancy as follows: GI = intact controls; GII = controls which received 0.5 ml of distilled water (drug vehicle) once a day by gavage; GIII, GIV and GV = groups treated respectively with 6.7, 20.1 or 45.6 mg/kg of tramadol hydrochloride once a day by gavage in a final volume of 0.5 mL. Body weight gain was monitored by weighing at the beginning and on the 7th, 14th and 20th day of pregnancy. At term the animals were killed under deep ether anesthesia and the following parameters were evaluated: number of implantations, of resorptions, of viable fetuses and of placentae; presence of major malformations; maternal and fetal mortality and weights of fetuses and placentae. Results: tramadol significantly affected maternal body weight gain, this effect being more apparent in groups IV and V (mean reductions of weight gain of 41 and 56%, respectively). In group III the weight gain was affected more at days 7 and 14 (33% mean gain reductions) than at day 20 (19%). Drug treatment affected significantly and in a dose-dependent fashion the following parameters: individual weight of fetuses (GV = -39.2%), offspring weight (GIV = -51.7%; GV = -44.2%), number of placentae (GIV = -28.4%; GV = -11.6%), individual weight of placentae (GV = -10%) and the total weight of placentae (GIV = -28.4%; GV = -16.8%). Though among the treated animals there was an increase in resorptions and deaths at birth, these events were not significantly different from those found in controls. Conclusions: Tramadol showed definite deleterious effects on albino rat pregnancy, and these effects were exerted not only on the maternal but also the on fetal organisms. Overall, the effects were more pronounced at the 14th than at the 20th day of pregnancy, thus suggesting that the organogenic phase of the fetus is more susceptible than its initial (embryogenic) or final (term) phases. The results call attention to the care which is to be taken when the use of this opioid is considered during pregnancy.