Approach

Opioid overdose causes central nervous system (CNS) depression and respiratory depression. Supportive ventilation is usually sufficient to prevent death but invasive ventilation may be avoided by cautious administration of naloxone.

Cardiac arrest

If cardiac arrest occurs, start CPR immediately according to local advanced life support protocols.[49]​​[58]​​ The opioid antagonist, naloxone, is unlikely to be beneficial if the patient is definitely pulseless and receiving CPR. For these patients, standard resuscitation alone is indicated due to the theoretical basis for harm.[48] However, if there is uncertainty as to whether there is a pulse, naloxone should be given.[48] See Initial naloxone administration below. 

Initial ventilation

Ventilatory support is the most important intervention and may be life-saving on its own.[58]​ The primary focus should be to support the airway and breathing, particularly for patients with stupor and a respiratory rate of 12 breaths/minute or less.[59] In these patients, maintain the airway through chin-lift, head-tilt, or jaw-thrust maneuvers.[59] Breathing may require additional ventilatory support through the use of a bag-valve mask with supplemental oxygen in order to maintain oxygen saturations within target range. It is important to adequately ventilate the patient prior to administration of naloxone, to decrease the likelihood of precipitating acute respiratory distress syndrome, which may be associated with reversal in the presence of hypercarbia.[59][60][61] Patients who present with acute respiratory distress syndrome may require higher concentrations of supplemental oxygen and should be managed with supportive care, low tidal volume ventilation, and positive end-expiratory pressure.[62][63]

Initial naloxone administration

If the patient has signs of opioid-induced respiratory depression but has a pulse, or if there is uncertainty as to whether there is a pulse, naloxone should be given.[48] In the US, intranasal naloxone is now approved for use without a prescription. Healthcare professionals should therefore be aware that naloxone may have initially been administered by a patients’ family or caregivers.

If the patient has reduced level of consciousness but is breathing normally, naloxone treatment should be considered.[48] 

The endpoint of naloxone therapy should be the restoration of adequate spontaneous ventilation but not necessarily complete arousal.[2][57]​​

Administer naloxone through one of the following routes:[2][57][64][65][66]​​​​

  • Intravenous: if access can be safely obtained, this administration route is likely to be the safest in terms of patient management due to the ability to titrate the dose.​

  • Intranasal: often used in the prehospital setting. Intranasal naloxone has been shown to be safe and effective in the prehospital setting in a number of trials, and is now approved for use without a prescription in the US.​​​​

  • Intramuscular: provides a slower onset of action and a prolonged duration of effect, which may minimize rapid onset of withdrawal symptoms in patients with suspected opioid dependence. A handheld autoinjector is available in some countries and can be used by lay people in a prehospital setting.

  • Subcutaneous: an alternative if intravenous access cannot be safely obtained.

Repeat doses of naloxone

Most patients respond with a return of spontaneous respirations and minimal withdrawal symptoms. Repeat doses of naloxone can be given every 2 to 3 minutes.

The duration of effect of most opioids is 4 hours or less, but some may last significantly longer. The effects of methadone, levomethadyl, and buprenorphine can last from 24 to 72 hours. Higher doses of naloxone may be required before a response is seen in patients who have taken overdoses of opioids such as buprenorphine or propoxyphene.

Fentanyl and its analogs (e.g., 3-methylfentanyl, carfentanil) are potent opioids; patient response may require the administration of multiple doses of naloxone.[11][51]​ Counterfeit hydrocodone/acetaminophen tablets containing fentanyl have been associated with delayed, recurrent toxicity.[67]

The duration of effect of naloxone is 30 to 90 minutes, and patients should be observed after this time frame for resedation. Some patients who have taken longer-acting or potent opioids may require further intravenous bolus doses or an infusion of naloxone.[67][68] The dose or infusion rate should be titrated to the smallest effective dose that maintains spontaneous normal respiratory drive.[69]​ All patients should be monitored for recurrence of signs and symptoms of opioid toxicity for at least 4 hours from the last dose of naloxone or discontinuation of the naloxone infusion. Patients who have overdosed on long-acting or very potent opioids should have more prolonged monitoring.

Naloxone-resistant patients

Patients who do not respond to naloxone should have an alternative diagnosis sought for their clinical symptoms. The exception to this is intoxication with buprenorphine, a long-acting opioid partial agonist. This drug has a higher affinity for the opioid receptors than other opioids, and naloxone may not be effective at reversing the effects of buprenorphine-induced opioid overdose.[70][71] Naloxone may be less effective in reversing an overdose among patients who have taken illicit opioid products containing xylazine (an alpha adrenergic agonist).[14] In all cases, support of ventilation, oxygenation, and blood pressure should be sufficient to prevent the complications of opioid overdose and should be given priority if the response to naloxone is not prompt.

Safety of naloxone

Naloxone given to nonopioid-intoxicated or nondependent patients, even in high doses, produces no clinical effects. The safety profile of naloxone is remarkably high, especially when used in low doses and titrated to effect.

Use naloxone with caution in opioid-dependent/tolerant patients. Withdrawal may be induced in opioid-tolerant patients with use of naloxone; the onset of withdrawal is faster with higher doses of naloxone. Although rarely life-threatening, the patient's behavior may be unpredictable and opioid withdrawal can be unpleasant for both the patient and healthcare staff. Vomiting often accompanies opioid withdrawal after antidote administration and can result in pulmonary aspiration if patients do not rapidly regain consciousness. Opioid-tolerant patients who receive larger doses of naloxone and experience withdrawal still have an excellent prognosis, with withdrawal symptoms subsiding in about an hour.

Naloxone can safely be used to manage opioid toxicity during pregnancy, particularly when used in combination with buprenorphine.[72]​ Both the American Society of Addiction Medicine and the American College of Obstetricians and Gynecologists note that combination products are likely to be safe and effective during pregnancy, if used as prescribed.[73][74]​​​ 

Naloxone unavailable

If naloxone is unavailable, ventilatory support is usually all that is needed in respiratory compromise or apnea, until the patient can maintain intrinsic ventilation or naloxone can be obtained. The duration of supportive treatment will depend on the specific opioid taken. Ventilatory support should continue to maintain oxygen saturations within target range until spontaneous normal respiratory drive returns.

Patients with retained opiate-filled drug packages

Patients who ingest opioids for transport may present in various ways and varying levels of toxicity, from asymptomatic or mild signs, to deep sedation and cardiac arrest.[55]

  • Body packers ingest large quantities of carefully wrapped packages. The packages generally are more resistant to leakage and breaking as they pass through the digestive tract, but if they do, the excessive amount of the drug may quickly lead to a fatal overdose.

  • Body stuffers usually ingest fewer, more loosely wrapped packages, but as the packets are more prone to breaking they may also induce significant toxicity.

  • Body pushers are patients who hide smaller quantities of the drug in various orifices.

If a suspected body packer presents with signs of opioid overdose, they should immediately be treated with naloxone and urgent surgical consult. Indications for surgical removal of packages include abdominal pain (possible obstruction or ileus), radiologic evidence of remaining package(s) which are too large to pass through the gastrointestinal tract, and/or evidence of significant or worsening toxicity. A computed tomography (CT) scan prior to surgery is helpful but only if the patient is stable enough to be safely maintained on naloxone. The patient should be monitored closely as there is a high risk of death. In the event of cardiac arrest, CPR should be continued for at least an hour. Prolonged resuscitation, even for several hours, may be appropriate following opioid overdose as recovery with good neurologic outcome may occur.[53] Once the patient is stabilized, immediately consult a surgeon for potential surgical removal of the drug packets.[55][75]

In clinically stable, asymptomatic patients (suspected packers who are asymptomatic or only showing very mild signs of opioid ingestion), low-dose abdominal CT is the initial imaging choice. This can help determine the location and estimated number of objects, along with potential complications. In the asymptomatic body packer, whole bowel irrigation can speed up the passage of drug packages where there is radiologic evidence of retained packages but no clinical features suggestive of package leakage. An osmotically balanced polyethylene glycol electrolyte solution may be given orally or via a nasogastric tube until the rectal effluent is clear and all packages have been passed. Contraindications to whole bowel irrigation include loss of protective airway reflexes, ileus, bowel obstruction, bowel perforation, hemodynamic instability, or clinical evidence of packet leakage.[53][76]​​​​ Some experts recommend giving a single dose of activated charcoal an hour before starting the bowel irrigation. Activated charcoal is more clearly recommended for the management of body stuffers or pushers, whose packets are at high risk of breaking, but remains controversial in the management of body packers.[53][55][77]​​​​ If whole bowel irrigation is not available or not feasible, activated charcoal in combination with oral laxatives can be considered.[78]​ The patients should then be observed for at least 24 hours and until all packets have been passed (2-3 normal stools or negative repeated radiologic study).[55]

Asymptomatic body stuffers and pushers presenting to the emergency department should be managed according to toxicology protocols. The risk of leakage for stuffers and subsequent opioid overdose is high. These patients should initially be managed with close observation in the ER (i.e., intravenous access, cardiac monitor, frequent physical exams, and appropriate laboratory tests). It is reasonable to give these patients an initial dose of activated charcoal if they are compliant. It may take several hours for symptoms to develop. Signs of impending complication and overdose include abdominal pain, vomiting, bradycardia, hypotension, CNS depression, respiratory compromise, pulmonary edema. Patients generally should be observed for at least 8-12 hours and until all packets have passed, although overnight monitoring may also be reasonable for patients stuffing opioid agonists. Surgical consult should be called if there is any suspicion of surgical complications (e.g., obstruction, perforation), in which case immediate surgical removal is required.[53][55]​​​ Whole bowel irrigation is not recommended for body pushers or body stuffers as it can cause package disruption and leakage.

Naltrexone

Naltrexone is an opioid antagonist used to prevent relapse in detoxified formerly opioid-dependent patients, but it has no place in the acute overdose setting.

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