Management overview for tramadol poisoning

Tramadol is an opioid analgesic with centrally acting, weak mu-opioid receptor agonism; it is also an inhibitor of serotonin and noradrenaline reuptake, which contributes to its analgesic effect. At high doses, tramadol is also a GABA_A antagonistHara, 2005. Tramadol is available as both immediate-release and sustained-release preparations.

Tramadol is metabolised by the cytochrome P450 enzyme, CYP2D6, to an active metabolite that has a higher affinity for mu-opioid receptors than the parent compound and provides most of tramadol’s analgesic effectGillen, 2000. The extent of CYP2D6 metabolism is genetically determined, so there is considerable individual variation in the timing and extent of tramadol’s opioid effectsXu, 2014—in poisoning, rapid metabolisers have an increased risk of opioid toxicity, including sedation and respiratory depression.

Tramadol poisoning most commonly causes seizures and sedation, particularly after large ingestions. Seizures tend to be brief and respond to benzodiazepines. Respiratory depression is less common, but can occur with co-ingestion of other sedative drugs. Serotonergic toxidrome is uncommon unless tramadol is co-ingested with another serotonergic drug, in particular a monoamine oxidase inhibitorHabibollahi, 2019Ryan, 2015.

Management of tramadol poisoning is primarily supportive care of the airway, ventilation, control of seizures, and management of serotonergic toxidrome and cardiovascular effects. The opioid antagonist, naloxone, is used to reverse opioid effects in patients with hypoventilation. Support of airway and breathing to prevent hypoxia is the clinical priority while waiting for naloxone to take effect.