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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
- Patients with
Opioid toxidrome 
The classic triad consists of:
- Altered mental status (e.g., CNS depression, euphoria)
- Bilateral (pinpoint pupils) 
- Opioid-induced respiratory depression
Opioid-induced respiratory depression (OIRD) 
- ↓ Respiratory rate and/or apnea
- ↓ Tidal volume
- Disordered control of breathing
- Signs of ↑ , e.g.,
- Can progress to respiratory arrest
Other clinical features 
- Opioid overdose is a based on suggestive clinical features (e.g., opioid toxidrome) and a compatible history of substance exposure.
- Begin empiric as soon as it is clinically suspected; do not wait for confirmatory diagnostic tests.
- Examine for signs of:
Typically performed to evaluate for comorbid conditions, complications, and differential diagnoses.
- Laboratory studies
- ECG: Assess for , e.g., QTc ≥ 500 ms, cardiac arrhythmias and ectopy, and/or ischemic ECG changes. 
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.
- Administer in patients with .
- Consider diagnostic tests to support the diagnosis, identify complications, and evaluate for comorbidities (see “Diagnostics”).
- Determine if the overdose was intentional, e.g., a .
- Assess for comorbid conditions.
Naloxone for opioid overdose 
- Goal: restore respiratory drive while avoiding precipitated withdrawal
- Indication: (OIRD) 
Dosage: There is no consensus on the optimal regimen for in-hospital settings; follow local protocols when available. 
- Choose the lowest possible starting dose to avoid then titrate as needed to reverse .
- Consider empiric dosage adjustment for:
- There is no direct correlation between OIRD severity and the naloxone dose required to reverse it. 
Starting dose 
The following dosages are suggested based on expert opinion and FDA guidance. 
- Preferred route: intravenous
- No IV access
Lower doses are typically sufficient for opioid-dependent patients. Higher doses are appropriate for opioid-naive patients and are typically required for any patients with synthetic opioid (e.g., fentanyl) overdose. 
- Repeat the dose every 2–3 minutes as needed.
- Consider increasing the dose on each repeat administration if there is no response.
- Repeat doses can range widely; follow local protocols and tailor to the individual clinical response. 
- After ≥ 10 mg of naloxone, reconsider the diagnosis and evaluate for other causes of respiratory depression e.g., xylazine intoxication.
- Initial improvement with recurrent OIRD: Consider continuous naloxone infusion.
- naloxone. : Do not administer additional
Naloxone is typically unnecessary in intubated and mechanically ventilated patients. 
Mental health disorder management 
- Patients with a confirmed psychiatry and consider . or multiple : Consult
- Stabilized patients with suspected or confirmed
- Consult addiction medicine and perform .
- Offer .
- Observation period: 4–6 hours after the last naloxone dose 
- Admit patients with:
- Discharge criteria
Xylazine intoxication 
- Etiology: consumption of (e.g., fentanyl) adulterated with xylazine 
- Mechanism of action: activity → inhibition of norepinephrine and dopamine release → peripheral vasoconstriction and CNS depression 
- Clinical features
- : using serum or urine specimens
- Blood glucose: possible hyperglycemia 
- Supportive care
- as needed
- Patient education on harm reduction strategies
Toxicity from other substances 
- Valproic acid
- Acute alcohol intoxication
- Sedative hypnotics
- Atypical antipsychotics
- See also “Approach to the poisoned patient.”
Cerebrovascular conditions 
The differential diagnoses listed here are not exhaustive.
- Opioid withdrawal syndrome (OWS)
- 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 cellulitis, abscess, endocarditis ), e.g.,
We list the most important complications. The selection is not exhaustive.
Harm reduction: Encourage safe-use strategies. 
- Provide take-home naloxone for patients who are prescribed long-term opioids and/or using illicit opioids.
- Advise patients about the availability of FDA-approved over-the-counter naloxone sprays.
- Only using opioids in the company of others
- Fentanyl test strips (if available) 
- Safe opioid storage
- Prior to prescribing opioids for pain