Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

patients with signs of opioid overdose or toxicity: in cardiac arrest

1st line – CPR and advanced life support

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: in cardiac arrest
|
without retained drug packages
1st line – 

CPR and advanced life support

If the patient is in cardiac arrest, start CPR immediately according to local advanced life support protocols.[26][32]​​ 

Consider – naloxone

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: in cardiac arrest
|
without retained drug packages
Consider – 

naloxone

Additional treatment recommended for SOME patients in selected patient group

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.[25] However, if there is uncertainty as to whether there is a pulse, naloxone should be given.[25] 

The endpoint of therapy is the restoration of adequate spontaneous ventilation but not necessarily complete arousal.[31]

If intravenous 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.[31] Intranasal administration is often used in the pre-hospital setting. Intranasal naloxone has been shown to be safe and effective in the pre-hospital setting in a number of trials.[38][39][40] The intramuscular route provides a slower onset of action and a prolonged duration of effect, which may minimise rapid onset of withdrawal symptoms in patients with suspected opioid dependence. A hand-held auto-injector is available in some countries and can be used by lay people in a pre-hospital setting. The subcutaneous route can be used if intravenous access cannot be safely obtained.

Use in opioid-dependent/tolerant patients may precipitate acute opioid withdrawal, and naloxone should be used with caution in these patients. A lower dose of naloxone with slow titration to response is recommended. Consult a specialist for further guidance.

Most patients respond with 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 naloxone is 30 to 90 minutes, and patients should be observed after this time frame for re-sedation. Higher doses may be required before a response is seen in patients who have taken overdoses of buprenorphine or propoxyphene. Fentanyl and its analogues (e.g., 3-methylfentanyl, carfentanil) are potent opioids; patient response may require the administration of multiple doses of naloxone.[8] Counterfeit hydrocodone/paracetamol tablets containing fentanyl have been associated with delayed, recurrent toxicity.[41]

Some patients exposed to long-acting or very potent opioids may require further intravenous bolus doses or an infusion of naloxone.[41][42] The dose or infusion rate should be titrated to the smallest effective dose that maintains spontaneous normal respiratory drive.[43]

Patients should be monitored for recurrence of toxicity for at least 4 hours from the last naloxone dose or discontinuation of naloxone infusion. Patients exposed to long-acting or very potent opioids should have more prolonged monitoring.

Primary options

naloxone: (standard syringe) 0.4 to 2 mg intravenously/intramuscularly/subcutaneously initially, repeat dose every 2-3 minutes according to response, maximum 10 mg/total dose; (auto-injector 5 mg/0.5 mL) 5 mg intramuscularly/subcutaneously initially, may repeat every 2-3 minutes according to response

More

OR

naloxone nasal: (4 mg/0.1 mL) 4 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response; (8 mg/0.1 mL) 8 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response

More

1st line – CPR and advanced life support

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: in cardiac arrest
|
with retained drug packages
1st line – 

CPR and advanced life support

If the patient is in cardiac arrest, start CPR immediately according to local advanced life support protocols.[26][32]​​

Consider – naloxone

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: in cardiac arrest
|
with retained drug packages
Consider – 

naloxone

Additional treatment recommended for SOME patients in selected patient group

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.[25] However, if there is uncertainty as to whether there is a pulse, naloxone should be given.[25] 

The endpoint of therapy is the restoration of adequate spontaneous ventilation but not necessarily complete arousal.[31]

If intravenous 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.[31] Intranasal administration is often used in the pre-hospital setting. Intranasal naloxone has been shown to be safe and effective in the pre-hospital setting in a number of trials.[38][39][40] The intramuscular route provides a slower onset of action and a prolonged duration of effect, which may minimise rapid onset of withdrawal symptoms in patients with suspected opioid dependence. A hand-held auto-injector is available in some countries and can be used by lay people in a pre-hospital setting. The subcutaneous route can be used if intravenous access cannot be safely obtained.

Use in opioid-dependent/tolerant patients may precipitate acute opioid withdrawal, and naloxone should be used with caution in these patients. A lower dose of naloxone with slow titration to response is recommended. Consult a specialist for further guidance.

Most patients respond with 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 naloxone is 30 to 90 minutes, and patients should be observed after this time frame for re-sedation. Higher doses may be required before a response is seen in patients who have taken overdoses of buprenorphine or propoxyphene. Fentanyl and its analogues (e.g., 3-methylfentanyl, carfentanil) are potent opioids; patient response may require the administration of multiple doses of naloxone.[8] Counterfeit hydrocodone/paracetamol tablets containing fentanyl have been associated with delayed, recurrent toxicity.[41]

Some patients exposed to long-acting or very potent opioids may require further intravenous bolus doses or an infusion of naloxone.[41][42] The dose or infusion rate should be titrated to the smallest effective dose that maintains spontaneous normal respiratory drive.[43]

Patients should be monitored for recurrence of toxicity for at least 4 hours from the last naloxone dose or discontinuation of naloxone infusion. Patients exposed to long-acting or very potent opioids should have more prolonged monitoring.

Primary options

naloxone: (standard syringe) 0.4 to 2 mg intravenously/intramuscularly/subcutaneously initially, repeat dose every 2-3 minutes according to response, maximum 10 mg/total dose; (auto-injector 5 mg/0.5 mL) 5 mg intramuscularly/subcutaneously initially, may repeat every 2-3 minutes according to response

More

OR

naloxone nasal: (4 mg/0.1 mL) 4 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response; (8 mg/0.1 mL) 8 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response

More

Consider – whole bowel irrigation

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: in cardiac arrest
|
with retained drug packages
Consider – 

whole bowel irrigation

Additional treatment recommended for SOME patients in selected patient group

This should be considered in patients who have large numbers of carefully wrapped packets (body packers) and not in patients with small numbers of loosely wrapped packages (body pushers).

Whole bowel irrigation can speed up the passage of drug packages in body packers where there is radiological evidence of retained packages and no clinical features of opioid toxicity 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, haemodynamic instability, or clinical evidence of packet leakage.

patients with signs of opioid overdose or toxicity: not in cardiac arrest

1st line – initial ventilation

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: not in cardiac arrest
|
without retained drug packages
1st line – 

initial ventilation

Ventilatory support is the most important intervention and may be life-saving on its own.[32]​ 

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.[33] In these patients, maintain the airway through chin-lift, head-tilt, or jaw-thrust manoeuvres.[33] 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.[49] 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.[33][34][35] 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.[36][37]

Consider – naloxone

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: not in cardiac arrest
|
without retained drug packages
Consider – 

naloxone

Additional treatment recommended for SOME patients in selected patient group

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.[25] If the patient has reduced level of consciousness but is breathing normally, naloxone treatment should be considered.[25]  

The endpoint of therapy is the restoration of adequate spontaneous ventilation but not necessarily complete arousal.[31]

If intravenous 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.[31] Intranasal administration is often used in the pre-hospital setting. Intranasal naloxone has been shown to be safe and effective in the pre-hospital setting in a number of trials.[38][39][40] The intramuscular route provides a slower onset of action and a prolonged duration of effect, which may minimise rapid onset of withdrawal symptoms in patients with suspected opioid dependence. A hand-held auto-injector is available in some countries and can be used by lay people in a pre-hospital setting. The subcutaneous route can be used if intravenous access cannot be safely obtained.

Use in opioid-dependent/tolerant patients may precipitate acute opioid withdrawal, and naloxone should be used with caution in these patients. A lower dose of naloxone with slow titration to response is recommended. Consult a specialist for further guidance.

Most patients respond with 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 naloxone is 30 to 90 minutes, and patients should be observed after this time frame for re-sedation. Higher doses may be required before a response is seen in patients who have taken overdoses of buprenorphine or propoxyphene. Fentanyl and its analogues (e.g., 3-methylfentanyl, carfentanil) are potent opioids; patient response may require the administration of multiple doses of naloxone.[8] Counterfeit hydrocodone/paracetamol tablets containing fentanyl have been associated with delayed, recurrent toxicity.[41]

Some patients exposed to long-acting or very potent opioids may require further intravenous bolus doses or an infusion of naloxone.[41][42] The dose or infusion rate should be titrated to the smallest effective dose that maintains spontaneous normal respiratory drive.[43]

Patients should be monitored for recurrence of toxicity for at least 4 hours from the last naloxone dose or discontinuation of naloxone infusion. Patients exposed to long-acting or very potent opioids should have more prolonged monitoring.

Primary options

naloxone: (standard syringe) 0.4 to 2 mg intravenously/intramuscularly/subcutaneously initially, repeat dose every 2-3 minutes according to response, maximum 10 mg/total dose; (auto-injector 5 mg/0.5 mL) 5 mg intramuscularly/subcutaneously initially, may repeat every 2-3 minutes according to response

More

OR

naloxone nasal: (4 mg/0.1 mL) 4 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response; (8 mg/0.1 mL) 8 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response

More

1st line – initial ventilation

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: not in cardiac arrest
|
with retained drug packages
1st line – 

initial ventilation

Ventilatory support is the most important intervention and may be life-saving on its own.[32]​ 

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.[33] In these patients, maintain the airway through chin-lift, head-tilt, or jaw-thrust manoeuvres.[33] 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.[49] 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.[33][34][35] 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.[36][37]

Consider – naloxone

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: not in cardiac arrest
|
with retained drug packages
Consider – 

naloxone

Additional treatment recommended for SOME patients in selected patient group

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.[25] If the patient has reduced level of consciousness but is breathing normally, naloxone treatment should be considered.[25]  

The endpoint of therapy is the restoration of adequate spontaneous ventilation but not necessarily complete arousal.[31]

If intravenous 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.[31] Intranasal administration is often used in the pre-hospital setting. Intranasal naloxone has been shown to be safe and effective in the pre-hospital setting in a number of trials.[38][39][40] The intramuscular route provides a slower onset of action and a prolonged duration of effect, which may minimise rapid onset of withdrawal symptoms in patients with suspected opioid dependence. A hand-held auto-injector is available in some countries and can be used by lay people in a pre-hospital setting. The subcutaneous route can be used if intravenous access cannot be safely obtained.

Use in opioid-dependent/tolerant patients may precipitate acute opioid withdrawal, and naloxone should be used with caution in these patients. A lower dose of naloxone with slow titration to response is recommended. Consult a specialist for further guidance.

Most patients respond with 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 naloxone is 30 to 90 minutes, and patients should be observed after this time frame for re-sedation. Higher doses may be required before a response is seen in patients who have taken overdoses of buprenorphine or propoxyphene. Fentanyl and its analogues (e.g., 3-methylfentanyl, carfentanil) are potent opioids; patient response may require the administration of multiple doses of naloxone.[8] Counterfeit hydrocodone/paracetamol tablets containing fentanyl have been associated with delayed, recurrent toxicity.[41]

Some patients exposed to long-acting or very potent opioids may require further intravenous bolus doses or an infusion of naloxone.[41][42] The dose or infusion rate should be titrated to the smallest effective dose that maintains spontaneous normal respiratory drive.[43]

Patients should be monitored for recurrence of toxicity for at least 4 hours from the last naloxone dose or discontinuation of naloxone infusion. Patients exposed to long-acting or very potent opioids should have more prolonged monitoring.

Primary options

naloxone: (standard syringe) 0.4 to 2 mg intravenously/intramuscularly/subcutaneously initially, repeat dose every 2-3 minutes according to response, maximum 10 mg/total dose; (auto-injector 5 mg/0.5 mL) 5 mg intramuscularly/subcutaneously initially, may repeat every 2-3 minutes according to response

More

OR

naloxone nasal: (4 mg/0.1 mL) 4 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response; (8 mg/0.1 mL) 8 mg (1 spray) into one nostril initially, may repeat every 2-3 minutes in alternating nostrils according to response

More

Consider – whole bowel irrigation

Back
ACUTE
|
patients with signs of opioid overdose or toxicity: not in cardiac arrest
|
with retained drug packages
Consider – 

whole bowel irrigation

Additional treatment recommended for SOME patients in selected patient group

This should be considered in patients who have large numbers of carefully wrapped packets (body packers) and not in patients with small numbers of loosely wrapped packages (body pushers).

Whole bowel irrigation can speed up the passage of drug packages in body packers where there is radiological evidence of retained packages and no clinical features of opioid toxicity 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, haemodynamic instability, or clinical evidence of packet leakage.

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer