Opioid overdose results from the toxic effects of exogenous opioids. Deaths related to opioid overdose have been steadily increasing in the United States over the past two decades because of a sharp increase in the prescription of opioids for chronic pain and increasing amounts of illegally manufactured fentanyl. Common clinical features of opioid overdose include respiratory depression, CNS depression, and miosis. Treatment of suspected opioid overdose requires airway management and prompt assessment of the need for naloxone to counter opioid-induced respiratory depression, which can be fatal. Inpatient admission is indicated for patients with ongoing respiratory depression, overdose from long-acting opioids, or medical complications from an opioid overdose. All patients with a noniatrogenic opioid overdose should undergo an (SUD) and be discharged with take-home intranasal naloxone.
Iatrogenic overdose occurs when a prescribed dose exceeds an individual's tolerance for opioids. Noniatrogenic overdose (i.e., in the setting of ) may be intentional or unintentional (e.g., use of a higher dose than intended).
Risk factors for opioid overdose 
- Opioid-specific factors
- Any opioid use in patients with the following:
- Constipation and ↓ bowel sounds
- Nausea, vomiting
Acute management 
- Follow an ABCDE approach (see “ABCDE approach in poisoning” for details).
- Start SpO2 monitoring and initiate oxygen therapy and airway management as needed.
- Obtain IV access.
- Administer naloxone if indicated (e.g., in patients with ).
- Assess for comorbid conditions.
- If opioid use disorder is suspected: 
- Consult addiction medicine and perform .
- Offer .
Naloxone administration 
There is no consensus on the optimal naloxone dosage for in-hospital settings; follow local protocols when available.
- Goal: restore respiratory drive while avoiding precipitated withdrawal
- Indication: moderate to severe opioid-induced respiratory depression 
- Initial dose: Choose the lowest possible initial dose. 
- No improvement
- Initial improvement with recurrent respiratory depression: Consider continuous naloxone infusion.
- Precipitated opioid withdrawal: Do not administer additional naloxone.
Do not administer naloxone to patients with opioid intoxication who do not have respiratory depression (e.g., patients with a spontaneous respiratory rate ≥ 12 breaths/minute) or those who are already intubated and on a ventilator. 
Naloxone has a dose-dependent duration of action that is shorter than most opioids and does not shorten the duration of opioid toxicity. Monitor patients for 4–6 hours after administering naloxone for a resumption of opioid effects. 
Consider the following to identify comorbid conditions.
- Safety assessment: in patients with
- Physical examination to assess for:
- Laboratory studies
- ECG: Assess for . 
- Observation period: 4–6 hours after the last naloxone dose 
- Admit patients with:
- Discharge criteria
- Opioid withdrawal syndrome (OWS)
- Precipitated opioid withdrawal: the acute onset of opioid withdrawal syndrome triggered by opioid antagonists (e.g., naloxone) or partial agonists (e.g., buprenorphine)
- Concurrent toxidromes
- QRS widening, prolonged QTc interval
- Rhabdomyolysis, compartment syndrome, myoglobinuria
- Noncardiogenic pulmonary edema, acute lung injury
- Serotonin syndrome
- Biliary colic due to spasm of the sphincter of Oddi 
- Sensorineural hearing loss
- Infections (in )
We list the most important complications. The selection is not exhaustive.
- Harm reduction: Encourage safe-use strategies. 
- Prior to prescribing opioids for pain