Children’s seizures caused by continuous intravenous infusion of tramadol analgesia: two rare case reports

Sir––Tramadol is a centrally acting analgesic. It has become the most prescribed opioid worldwide (1). It has been reported to cause seizures in therapeutic dosing and in overdose in adults, but rarely in children. We present two cases of children’s seizures caused by continuous intravenous infusion of tramadol for postoperative analgesia. The purpose of this letter is to show that the dosage may be an important factor in causing this severe side effect, especially in children and in patients who have a history of convulsions. In addition, we may avoid using tramadol in combination with medicines that lower the seizure threshold. That may cause us to be cautious about the future application of this drug. A 2-year-old male child weighing 12·5 kg was scheduled for urethra plasty because of congenital hypospadia. His past medical history and physical examinations (including body temperature) were negative. No previous seizure or seizure-like activity had been reported by his parents. Normal caudal block procedure with common amide local anesthetic was applied before the operation. 2 mcg of sufentanil was given at the beginning of the operation. After the operation, a continuous intravenous pump containing 0·75 mg·kg−1·h−1 of tramadol and 0·125mg·h−1 of granisetron was given for postoperative analgesia. Four hours after he arrived in the ward, his parents noticed that his face had turned blue. Other symptoms of seizure observed at this time including a vertical epileptic gaze, a lockjaw, a deviation of the mouth and a stiffening of the extremities. The SPO2 decreased to 80% and the heart rate dropped from 150 to 80 min−1 soon afterward. The pediatrician gave him 70 mg of phenobarbital and 4 mg of etomidate and immediately performed intubation, shortly after which the seizure ceased. No allergy-causing medicines were used during the postoperative period. No further problems other than a little agitation were observed after a 5-day follow-up. A 5-month-old male child weighing 8 kg was suffering from a teratoma and was scheduled for a tumor resection. His past medical history was negative, and his mother’s pregnancy and her delivery were uncomplicated. He underwent an operation under general anesthesia. A pump contains 0·2 mg·kg−1·h−1 of tramadol, and 0·5 mg·kg−1·d−1 of granisetron was applied for analgesia. Five hours after surgery, the child showed signs of stiffening in all four extremities and a vertical epileptic gaze. He was treated with 5 mg dexamethasone and received intensive care. The pump was turned off by the medical staff, and the seizure-like activity ceased 5 min later. The boy suffered a slight fever during the following 2 days. No seizure-like activity was observed during this period. Both focal and generalized seizures have been observed in patients after receiving tramadol in overdose (2,3), but rarely after receiving the recommended dose (4,5). By January 2005, the Australian Adverse Drug Reactions Advisory Committee (ADRAC) had received a total of 921 reports involving tramadol, of which 66 described convulsions. Some of them were new-onset seizures. In 27 of these cases, tramadol was the only drug suspected of being the cause of these seizures. But it is rare in reports of young children. Two infants poisoned with tramadol ingested by negligent supervision in a recently case series (6), both presenting with either seizure or seizure-like activity. Previous US studies suggest a relatively low risk of seizures with tramadol, unless it is taken by people with epilepsy or taken with other drugs that lower the seizure threshold (7). In these cases, the only drug suspected of lowering the seizure threshold is granisetron, the effect of which has been proven only in animal trails (8). In our country, the use of tramadol is restricted only for lactating women. We also notice that there is no intravenous formulation in some countries such as Canada. We have no idea whether the prescribing of tramadol should be restricted in patients within a certain age range or with a history of certain diseases like epilepsy. In our observation, in the first case, the boy received an overdose of tramadol (0·75 mg·kg−1·h−1), and in the second case, the dosage given was 0·2 mg·kg−1·h−1, which is within the recommended range. These cases have shown that tramadol may cause seizures not only in adults but also in children; and not just in the case of an overdose but also when administered within the normal range. Furthermore, the size of the dosage may be an important factor in causing this severe side effect, especially in children and in patients who have a history of convulsions. In addition, we should avoid using tramadol in combination with medicines that may lower the seizure threshold. The primary goal of treatment for severe tramadol-caused seizure should focus on breathing and circulation support. Any ongoing seizure activity should be treated with benzodiazepines. Intensive monitoring and supportive care should also be applied. No conflicts of interest declared.

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