methadone is a potentially lethal medication when taken in overdose, and its variable half-life and gradual onset, prolonged effects on respiratory depression which may persist for 48hrs or more can lead to delayed deaths even after 24hrs of naloxone infusion therapy
toxicity of methadone depends on the amount consumed and the tolerance of the individual
peak blood levels after oral ingestion occur at 2 to 6 hours, but because of significant protein binding (>90%), levels are constant over 24 hours, and there is a delayed release from the liver and tissues.
toxicity is particularly problematic in opiate naive patients in whom the half life can be much longer - up to 59hrs, and the potentially lethal dose much lower - 50mg in adults, 10mg in children
activated charcoal can be considered if the patient does not have respiratory depression yet but has taken a concerning amount
the antidote, naloxone (Narcan) has a half-life of only 60-90 minutes, and thus a prolonged infusion is required
whilst resp. depression is the primary concern, in some cases, pulmonary oedema, bradycardia, hypotension, prolonged QTc,partial or complete airway obstruction, atypical snoring can also occur.
marked mydriasis rather than the usual opiate miosis may be seen in hypoxia in overdose situations
deaths have occurred after cessation of 24 hrs naloxone (Narcan) infusion, in a seemingly resolved overdose, usually overnight without adequate monitoring at 36-44hrs post-overdose1)
Mx of methadone without respiratory depression
onset of toxicity is likely to take several hours post-ingestion, and should declare itself within 24hrs
consider activated charcoal
observe for at least 24hrs
Mx of methadone overdose with respiratory depression
ABC's as per usual
initial stat doses of naloxone (Narcan) until resp. depression reversed:
100 micrograms IV or 400 micrograms I/Nasal, IM or SC (children: 10 microgram/kg to a maximum of 400 micrograms)
rpt as needed every 30-60secs or so, until spontaneously breathing
some use significantly higher doses, but this can precipitate acute opiate withdrawal - severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered
consider intubation if not responding as may have hypoxic brain injury or other pathology causing coma warranting CT brain, etc
100 microgram/hour can be made up of a 2 mg naloxone vial diluted in 100 ml of 0.9% saline and running at 5 ml/hour
start hourly infusion at 2/3rd of the total initial doses of naloxone required in the first 1 hour
in addition, one-half of the initial hour bolus dose should be administered (as a bolus) 15-20 min. after the start of the infusion to prevent a drop in naloxone levels
best way to titrate the naloxone is breathing but still mainly unconscious to reduce probability of premature absconding patient who will then have a high chance of delayed onset death
in methadone overdoses causing resp. depression, infusion is likely to need to be continued for at least 24hrs and then the patient should be closely observed for at least 2 hours after cessation, with infusion re-commenced if signs of persisting overdosage
unused solution must be discarded after 24 hours
consider a longer acting antidote such as naltrexone
given the long duration of infusion required, patient should be considered for HDU admission if general wards are not able to manage a naloxone infusion
discharge home criteria
no evidence of methadone overdosage clinically at more than 2hrs post-cessation of naloxone infusion
If the patient is alert, breathing normally and ambulating without supplemental oxygen, it is unlikely that significant hypercapnia is present
mental health assessment completed as indicated if suspect suicidality component, and deemed safe for discharge
responsible family or friends to observe him for next 24 hours, and bring him back if concerns of increasing re-sedation
discharge instructions given:
no sedative type medications including alcohol, benzodiazepines, opiates (including methadone) until at least 72hrs post-overdose
observe for signs of increasing re-sedation which may occur even without addition medication or substance use due to slow delayed re-distribution of methadone from the liver and tissues