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Basic Information ⬇

AUTHORS: Tyler DeJong, MD and Manuel Shayne Weekley, MD

Definition

Excessive use of an opioid, either derived from the opium poppy or semi- or fully synthetic, resulting in respiratory depression, central nervous system depression, and/or death

Synonyms

Opiate overdose

Heroin overdose

Narcotic overdose

Opioid poisoning

ICD-10CM CODES
T40.0X1Poisoning by opium, accidental (unintentional)
T40.0X2Poisoning by opium, intentional self-harm
T40.0X3Poisoning by opium, assault
T40.0X4Poisoning by opium, undetermined
T40.0X5Adverse effect of opium
T40.1XPoisoning by heroin
T40.4Poisoning by other synthetic narcotics
T40.2X1Poisoning by other opioids, accidental (unintentional)
Epidemiology & Demographics
Incidence

Drug overdose deaths and opioid-involved deaths continue to increase in the U.S. Around 75% of drug overdose deaths involved opioids in 2020. Approximately 252 Americans died every day from an opioid overdose in 2020.

Prevalence

From 1999 to 2020 more than 900,000 U.S. residents died from drug overdoses. From 2013 to 2017, the number of opioid-involved overdose deaths (opioid deaths) in the U.S. increased 90% from 25,052 to 47,600. From 2017 to 2020 another 50% increase occurred with a total of 68,840 deaths in 2020. Between 2019 and 2020 opioid deaths increased in 40 states and stayed the same in the remaining 10 suggesting overall worsening of the opioid epidemic. This increase was primarily driven by substantial increases in deaths involving illicitly manufactured fentanyl (IMF) or fentanyl analogs mixed with heroin, sold as heroin, or pressed into counterfeit prescription pills. From 2018 to 2019, opioid-involved death rates increased by over 6%, prescription opioid-involved deaths decreased by nearly 7%, heroin-involved deaths decreased by over 6%, and synthetic-opioid-involved death rates (excluding methadone) increased by greater than 15%.1,2

Predominant Sex & Age

The “typical” heroin death involves experienced users in their 20s to 30s using coingestants, with a male predilection. Opioid overdose deaths occurs more commonly in men in their 20s and 30s who are not first-time users.1

Risk Factors

The majority of drug-overdose deaths are unintentional or accidental (78%). The following increase risk for opioid overdose:

  • Opioid dependence, in particular, following reduced tolerance (following detoxification, release from incarceration, cessation of treatment)
  • Injecting opioids
  • Using prescription opioids, in particular, taking higher doses
  • Using opioids in combination with other sedating substances
  • Using opioids and having comorbidities such as HIV, liver or lung disease, or suffering from depression
  • Household members of people in possession of opioids (including prescription opioids)
  • History of other substance use disorders

The highest drug-induced mortality is associated with the following factors: 40 to 49 yr of age, male gender, non-Hispanic whites, and living in the South, all of which account for approximately 38.2% of drug-induced deaths in the U.S.1,2

Physical Findings & Clinical Presentation

Patients with opioid overdose classically present with the triad of altered mental status, pinpoint pupils, and respiratory depression. Patients may be apneic or with low respiratory rate and tidal volumes. Respiratory depression becomes profound enough to cause anoxia, leading to death. Little to no response will be elicited from painful stimuli. Look for clinical clues, such as “track marks” or darkening along the length of veins from injection drug use that may suggest opioid overdose. The use of coingestants, which is exceedingly common in opioid overdose, can alter the classic exam findings one may expect. For example, use of sympathomimetics like cocaine can cause pupillary dilation. Respiratory rate <12 breaths/min is most sensitive for predicting response to naloxone. Once the patient is hemodynamically stable, examine for other sequelae of drug use, including pulmonary rales suggestive of aspiration pneumonia or murmurs and skin lesions associated with endocarditis in IV drug abusers.3

Diagnosis ⬆ ⬇

Differential Diagnosis

  • Hypoglycemia
  • Alcohol or sedative overdose
  • Postictal state
  • Infectious or metabolic encephalopathy
  • Clonidine overdose
  • Phenothiazine overdose
  • Organophosphate exposure
Workup

Opioid overdose requires little workup if the patient’s altered mental status can be completely attributed to the overdose (i.e., by full recovery with naloxone). However, if the patient remains altered or with significant respiratory compromise after adequate treatment, continue appropriate workup. Obtain an ECG in the following scenarios: Use of methadone, oxycodone, loperamide, or a coingestant tricyclic antidepressant to screen for QTc prolongation; coingestion of a sympathomimetic to rule out arrhythmias.3

Laboratory Tests

  • Serum glucose should be quickly obtained as with any resuscitation.
  • Urine drug screen is not routinely required unless the history or physical exam raises suspicion for coingestants that would alter management.
  • Tylenol, aspirin, and alcohol levels in intentional overdoses or when used in a combination formulation with an opioid.
Imaging Studies

Not required unless guided by your physical exam and/or response to therapy:

  • Computed tomography of the head and cervical spine for suspected trauma
  • Chest X-ray if signs of aspiration
  • Echocardiogram if concerned for endocarditis

Treatment ⬆ ⬇

The principal goals of treatment for opioid overdose are support of ventilation and reversal of the drug.

Nonpharmacologic Therapy

Support the airway and breathing. For apneic or bradypneic patients, use bag-valve-mask ventilation.

Acute General Rx

Administer naloxone, a short-acting opioid antagonist, as soon as possible. Intravenous is the preferred route; however, in November 2015, Narcan Nasal Spray became the first FDA-approved noninjectable naloxone product for the treatment of opioid overdose. Higher concentration intranasal naloxone 2 mg/ml seems to have efficacy similar to IM naloxone for reversal of opioid overdose. Via the IV route, onset of action is within 1 to 2 min. Dosing is as follows:

  • For most adult patients, 0.4 to 1.2 mg should yield recovery of consciousness.
  • For patients in cardiac arrest, 2 mg is the starting dose.
  • Younger than 5 yr or body weight 20 kg or less: 0.1 mg/kg administered by IV push, intraosseous (IO) push, or by endotracheal tube (ETT).
  • 5 yr and older or body weight more than 20 kg: 2 mg administered by IV push, IO, or ETT.
  • If, after the initial dose, toxicity returns, repeat dosing may be required, and a naloxone infusion may be prepared by using two thirds of the dose required for the initial reversal every hr. If patients develop withdrawal signs during an infusion it should be stopped, and if opioid toxicity returns the infusion may be restarted at half the initial rate. If respiratory depression occurs during naloxone infusion, half of the initial bolus may be given every few minutes until symptoms resolve, and the infusion may be increased by half the initial rate.3,4
  • The FDA has approved a higher dose injectable of naloxone for emergency treatment of opioid overdose to reverse opioid overdoses due to potent synthetic opioids such as fentanyl.

Prepare for adverse effects of acute withdrawal, including agitation, nausea, vomiting, mydriasis (especially in methadone maintained patients), piloerection, diarrhea, lacrimation, yawning, and rhinorrhea after naloxone administration to chronic opioid users, especially with higher doses. Naloxone continues to block binding of additional opioids to the receptor for 20 to 90 min. For this reason, patients on longer acting opioid formulations including methadone, morphine SR, oxycodone SR, and fentanyl patches must be monitored closely for recurrence of apnea and mental status deterioration.5

The FDA has recently approved a generic injectable formulation of the opioid antagonist, nalmefene, for known or suspected opioid overdose. Nalmefene has a longer half-life than naloxone, which could decrease the need for repeat drug administration but could also cause prolonged withdrawal symptoms in patients physically dependent on opioids.5a Dosage is 0.5 mg/70 Kg IV (preferred), IM, or SC; if needed, a 1 mg/70 Kg dose can be given 2 to 5 min later.

Chronic Rx

  • Naloxone autoinjectors and nasal sprays are available in some states and intended for buddy administration. Patients can buy these formulations over-the-counter in some states, whereas others require a prescription. Check your state’s legislature for continual updates on this matter. Some states require naloxone coprescription with any opioid prescription.
  • A 2016 nonrandomized study demonstrated that patients prescribed opioids plus naloxone had 47% fewer opioid-related emergency department visits within 6 mo than those not prescribed naloxone.6
Referral

Patients can be offered referral to drug rehabilitation services. Otherwise, follow up with the primary care physician is appropriate.

Related Content

Drug Use Disorder (Related Key Topic)

Opioid Use Disorder (Related Key Topic)

Pain Management in Chronic Pain (Related Key Topic)

Substance Use Disorder (Related Key Topic)

Related Content ⬆

  1. Centers for Disease Control and Prevention: Drug overdose. Available from www.cdc.gov/drugoverdose/index.html.
  2. World Health Organization: Opioid overdose. Available from www.who.int/substance_abuse/information-sheet/en/.
  3. U.S. Food and Drug Administration: Naloxone for treatment of opioid overdose, Insys Development Company, 2016.
  4. Chou R. : Management of suspected opioid overdose with naloxone in out-of-hospital settingsAnn Int Med. ;167:867-875, 2017.
  5. Wayne R. : Prescription of long-acting opioids and mortality in patients with chronic noncancer painJAMA. ;315(22):2415-2423, 2017.
  6. Britch S.C., Walsh S.L. : Treatment of opioid overdose: current approaches and recent advancesPsychopharmacology (Berl). ;239(7):2063-2081, 2022.
  7. O’Coffin P. : Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for painAnn Int Med. ;165(4):245-252, 2016.