After reports of severe and fatal respiratory depression in children following the use of codeine for pain relief, questions surround the safety of pain management therapy after ambulatory tonsillectomy in children. Tramadol is an opioid indicated for moderate to moderately severe pain in adults but is not recommended for use in children; however, it has been proposed as a codeine alternative due to its association with decreased postoperative sedation and respiratory depression. The first reported case of opioid intoxication association with severe respiratory depression in a child taking tramadol after day-case tonsillectomy has been reported in Pediatrics.

A boy aged 5 years underwent ambulatory adenotonsillectomy under general anesthesia for OSAS and was discharged after an uneventful six hour postoperative stay. Later that day, the patient complained of increasing pain and was administered one oral 20mg dose of tramadol. One day after discharge, he was lethargic and was brought back to the medical center where the surgery was performed; on arrival at the emergency department, he was comatose with pin-point pupils, minimal respiratory effort, frequent apnea episodes, and an oxygen saturation of 48% in room air. His condition improved dramatically with noninvasive ventilation and intravenous naloxone. He was fully recovered and was discharged the following day.

Genotyping of CYP2D6 showed the presence of three functional alleles corresponding to CYP2D6*2 X 2 / CYP2D6*2 genotype, which is associated with ultrarapid metabolism. This ultrarapid metabolism led to increased O-desmethyltramadol concentrations and then severe respiratory depression. The µ-opioid-derived hypoalgesic effect of tramadol is dependent on CYP2D6 activity, with reduced clinical efficacy in CYP2D6 poor metabolizers and life-threatening adverse effects in ultrarapid metabolizers.

The authors state that alternative pain management options such as steroidal or nonsteroidal anti-inflammatory drugs (NSAIDs) should be further evaluated, along with CYP2D6 genotyping or phenotyping to prevent adverse events and target an individualized analgesic therapy.