Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates

Abstract

The intramuscular application of tramadol in birth-giving mothers almost freely reaches the neonate, confirming a high degree of placental permeability. The neonates already possess the complete hepatic capacity for the metabolism of tramadol into its active metabolite. However, the renal elimination of the active tramadol metabolite M1 is delayed, in line with the slow maturation process of renal function in neonates. Despite this difference in pharmacokinetics between neonates and adults, the intramuscular application of tramadol at the recommended dosage range during delivery appears to effective in the relief of labour pain.

Tramadol withdrawal in a neonate after long-term analgesic treatment of the mother

“…A study on the pharmacokinetics of tramadol in infants after treating the mother for labour pain measured a half-life of 420 min for tramadol. It led to a remarkably prolonged estimated half-life of 5097 min (sic) for M1 in neonates [2]. Delayed excretion of M1 seems to be due to the reduced glomerular filtration rate of the infant (about 30% of adult GFR) and to the higher amount of extracellular fluid causing a relatively larger distribution volume.…”

Probable association of neonatal death with the use of tramadol to treat labour pain

“…The respiratory status in this child immediately improved with naloxone treatment. (8) In our case naloxone was not used, since association of respiratory depression with tramadol use in the mother was not immediately recognized. Our hypothesis that neonatal death could be associated with the UM phenotype of the mother is further supported by a published case report of respiratory depression associated with elevated levels of M1 in an adult patient with renal impairment and CYP2D6 gene duplication who was treated with tramadol.…”

“…(8) Depending on the postmenstrual age, neonates possess almost complete hepatic capacity of tramadol metabolism to M1; however, compared to mothers, the renal elimination of M1 is notably prolonged. (8,9) Despite its use in the treatment of labour pain for over a decade, there is no report, to our knowledge, of a fatal event with such use. This case report suggests a probable association between fatal respiratory depression in a neonate and antenatal administration of tramadol in the mother for labour pain.…”

Comparison of Methods of Pain Relief during Labour: Epidural Analgesia, Intravenous Tramadol and TENS

“…Studies have shown that tramadol is an effective analgesic without the maternal and neonatal respiratory depression common to other opioids. [6] Tramadol can be used as labour with minimum cost and less training as compared to the proven epidural analgesia that requires trained staff and equipment Section: Anaesthesia and has higher cost. It also avoids the side effects associated with epidural analgesia like fetal heart rate changes, urinary retention, delayed pushing, and a prolonged second stage of labor.…”