heroin or other opiate overdose

introduction

opiate overdose is an extremely common presentation to ED's - usually due to iv heroin OD or the newer more potent opiates such as fentanyl or nitazene but can also be iatrogenic in patients at risk of respiratory depression such as in the elderly, or those with COPD or obstructive sleep apnoea
methadone overdose with respiratory depression is a special case, and requires prolonged iv naloxone (Narcan) infusion of at least 20hrs

xylazine is a non-opioid sedative, analgesic, and muscle relaxant used in veterinary medicine which is increasingly being found as an additive in heroin and other substances.
it is a potent α2-adrenergic agonist that mediates via central α2-receptors, which decreases perception of painful stimuli
in humans, xylazine may cause hypotension, central nervous system depression, respiratory depression and bradycardia and associations have been made between the use of xylazine and painful open skin ulcers and abscesses among individuals who inject it which may lead to necrosis and even need for amputation ¹⁾ (and the pain relief from xylazine often results in repeated injections into that site) ²⁾
evidence suggests that combined use of xylazine and an opioid such as fentanyl may increase the risk of overdose fatality
- naloxone is not effective for xylazine but will reduce fatalities when there are other opiates taken as well
- additional treatment for xylazine poisoning may involve supportive care using intubation, ventilation and administration of intravenous fluid
aka 'tranq'
heroin and fentanyl cut with xylazine is referred to as 'tranq dope'
in 2023, xylazine became a major issue in the USA resulting in users behaving like zombies in the street: https://www.youtube.com/watch?v=xmfrvs24NmY

most will be dropped outside a clinic or hospital but may be in respiratory arrest and blue in a car
call a code as you will need a few people to assist and transport the patient
take a mini-resus box to the patient and commence:
- bag-valve mask ventilation with jaw thrust, and, preferably with an appropriate sized Guedel airway to help ensure adequate ventilation
- administer a dose of intra-nasal naloxone as soon as possible
- transport to a resus area on a trolley whilst continuing bag-valve-mask ventilation
high flow oxygen
continue bag and valve mask ventilation as needed
i/nasal or im naloxone doses
warn of risk of recurrence of toxicity if patient wakes and insists on self-discharge at their own risk - assuming they are cognitively able to make this decision.
offer prescription for naloxone and advice on how it is used for either:
- Nyxoid nasal spray
- Prenoxad for IM use
- https://www.health.gov.au/initiatives-and-programs/take-home-naloxone-pilot
patients who do not respond well to naloxone should be considered for possible hypoxic brain injury, concomitant overdose of other substances, or very large dosing (see below) and managed accordingly

they are unlikely to thank you for ruining their hit and naloxone may precipitate an aggressive behavior and premature self-discharge
as long as they are breathing and supporting their airway, a patient with heroin OD may be more safely managed in ED sleeping than if they are wakened sufficiently that they become aggressive and insist on premature self discharge

substantial overdoses of opiates can saturate the hepatic elimination mechanisms converting 1st-order pharmokinetics to zero order and resultant excessively prolonged duration of actions (this may be more than 72hrs for methadone or morphine instead of the usual 6-12 hours for morphine)
see methadone overdose
such patients are at risk of:
- respiratory depression
- stupor
- aspiration
- rhabdomyolysis with possible compartment syndrome and myoglobinuric renal failure
- hypothermia
- hypoxic brain injury
treatment is supportive with escalating dose naloxone as needed:
- move to a resus area
- oxygen
- support ventilation
- initial dose naloxone 0.04mg (paeds: 0.1mg/kg)
- if no response 2-3 minutes post-dose, one can consider escalating doses of naloxone as follows:
  - 0.5mg, 2mg, 4mg, 10mg, 15mg ³⁾
- if CK is high (>5x normal level), institute Rx as per rhabdomyolysis to prevent acute kidney injury (AKI) / acute renal failure (ARF) - iv fluids to maintain high urine output

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NEJM 367:2 p146-155 July 12 2013