Opiate Toxicity

Warning

Objectives

To guide the management of patients with opioid overdose and / or opioid withdrawal in the deployed environment.

Scope

This guideline describes the management of patients with suspected opioid toxicity in a forward medical context or deployed Emergency Department. It should not be used in the Firm Base or when access is available to TOXBASE® is available.

This guideline does not cover the management of patients exposed to weaponised opioids although the principles are similar. See separate CBRN guidance (link to follow).

Audience

This guideline is intended for the use of registered healthcare professionals fulfilling a general role in a forward medical location or in an Emergency Department on deployed operations.

Initial Assessment & Management

Toxicity (overdose) from opioids may result from administration of opioids for analgesia, use of illicit opioids or exposure to a weaponised opioid. Opioid receptor agonists can be classified as naturally occurring e.g. morphine derived from opium; semi-synthetic e.g. heroin, codeine, oxycodone; synthetic e.g. fentanyl, carfentanil, methadone, nitazenes. Regardless of the origin of their chemical structure the primary therapeutic and toxic effects of opioids result from agonism of opioid receptors in the central nervous system. 

If weaponised use is suspected follow guidance in CBRN CGOs. 

 

Symptoms and signs

Key features are reduced consciousness, respiratory depression and pinpoint pupils.

Airway

  • Progressive loss of protective reflexes
  • Airway obstruction

Breathing

  • Reduced respiratory rate
  • Hypercapnia
  • Hypoxia

Circulation

  • Hypotension
  • Bradycardia

Disability

  • Reduced consciousness
  • Coma
  • Euphoria in milder intoxication 
  • Miosis (Pinpoint pupils) not always present

Exposure

  • Nausea
  • Vomiting
  • Urticaria
  • Pruritis
  • Hypothermia
  • Seizures
     
Pinpoint pupils are not a universal finding - normal pupils do not exclude opiate toxicity. 
Co-ingestion with alcohol or other respiratory depressant drugs such as benzodiazepines may exacerbate features and reduce the effectiveness of treatment with naloxone. 
Mixed toxicity may be present if there has been exposure to other classes drugs such as sympathomimetics - for example cocaine which may mask the typical opioid features. 

 

Initial management 

Follow a systematic but rapid approach:

Use airway adjuncts and ventilatory support with bag valve mask as required. Give supplemental oxygen to maintain saturations >92%. Apply continuous oxygen saturations and cardiac monitoring plus end tidal CO2 if available.

Check respiratory rate - if there is respiratory depression, administer naloxone:

Initial bolus 400 micrograms naloxone IV. 

If no response after 60 seconds, give 800 micrograms IV. 

If still no response after another 60 seconds, given another 800 micrograms IV.

If still no response (after a total 2 mg), give a 2 milligram (mg) bolus IV. 

If still no response a further 2 mg boluses may be required if there is a high suspicious of exposure to a highly potent opioid. Aiming for reversal of respiratory depression. 

After 4 mg consider alternative diagnoses or, if opioid toxicity likely.

If IV access cannot be readily established, naloxone may also be administered intraosseous (IO), intramuscular (IM) or intranasal (IN). Be aware that IM and IN administration are associated with a slower and less predictable response.

For intranasal use, give half of the intended dose to each nostril - for example for the initial bolus, give 200 micrograms (0.5 mL) to each nostril, for a total of 400 micrograms. 

Reduced level of consciousness without respiratory depression is unlikely to be due to opiate toxicity, so treatment with naloxone is not indicated (unless a mixed overdose is suspected).
Historically patients with opiate toxicity could generally be expected to respond to one or two doses of naloxone, but the increased availability of potent opioids in the pharmaceutical and recreational context, as well as the potential for weaponised opioids, means that much higher doses of naloxone may now be required. If exposure to weaponised opioid is suspected, review CBRN CGO.

Hypotension and bradycardia found during circulatory assessment are not themselves an indication for naloxone, which should be administered based on respiratory depression, but a positive cardiovascular response may be seen with treatment. In addition intravenous fluids can be administered if hypotension persists. 

If symptoms of opioid withdrawal develop (see below) after naloxone provide reassurance. The duration of effect of naloxone is relatively short and withdrawal symptoms will likely resolve and opioid toxicity possibly re-occur. DO NOT administer additional opioids or give benzodiazepines. 

All patients requiring naloxone should be observed for a minimum 4 hours after the last administration and at least 6 hours from exposure to the likely opioid. The period of observation must be extended to 12 hours after the last administration if long-acting opioids such as methadone or novel synthetic agents are suspected. 

 Respiratory or Cardiac Arrest

Patients with respiratory or cardiac arrest thought to be secondary to opiate toxicity should be managed using standard BLS/ALS principles, noting that hypoxia is the most likely reversible cause in this situation.

Only when effective life support is established naloxone should be administered as per the dose regime shown above. Do not allow naloxone administration to distract from usual priorities in cardiac arrest.

Advanced Assessment & Management

Advanced assessment and management will follow the same principles outlined above.

If blood gas analysis is available then check for respiratory acidosis - if found then administer naloxone regardless of respiratory rate and repeat blood gases at regular intervals. 

Consider a naloxone infusion (see below) if repeat boluses of naloxone are required.

 

Prolonged Casualty Care

If evacuation is not possible then continue repeated boluses of naloxone as needed to maintain adequate respiration, recognising that delivering an infusion is unlikely to be possible in the forward environment.

Intramuscular naloxone should generally be avoided due to unpredictable distribution but may be used if IV access is difficult or circumstances require.

Paediatric Considerations

The principles of paediatric management are the same as adults.

Remember that normal respiratory rate is higher in children - compare to the normal range as shown in page-for-age when assessing for respiratory depression.

Naloxone in children under 12:

Give an initial dose of 100 micrograms/kg (0.1 mg/kg, maximum dose 2 mg) IV, if no response, repeat at intervals of 60 seconds to a total maximum 2 mg IV.

If no response then review diagnosis - but as per the guidance above, be aware that very high doses may be required if the patient may have been exposed to novel synthetic opioid or weaponised agents.

Naloxone (including infusions)

The aim of naloxone treatment is to reverse respiratory depression and improve oxygenation and ventilation. Reduced consciousness alone is not an indication for naloxone and full consciousness should not be used as a target endpoint for treatment. 

The duration of action of naloxone is shorter than most opioids resulting in re-occurrence of opioid toxicity as naloxone concentrations fall. In these cases a naloxone infusion will be required. 

All patients requiring naloxone should be observed for a minimum 4 hours after the last administration and at least 6 hours from exposure to the likely opioid. 

Naloxone should ideally be administered intravenously (IV) to allow for predictable titration of the required dose. However, it can be administered intramuscularly (IM) or intraosseously (IO) if required. The IM route has longer times to peak blood concentrations and more variable responses should be anticipated. 

 

Adults and children aged 12 or over, WITHOUT suspected opioid dependence: 

  • Initial bolus 400 micrograms naloxone IV. 
  • If no response after 60 seconds, give 800 micrograms IV. 
  • If still no response after another 60 seconds, given another 800 micrograms IV.
  • If still no response (after a total 2 mg), give a 2 milligram (mg) bolus IV. 
  • If still no response a further 2 mg boluses may be required if there is a high suspicious of exposure to a highly potent opioid. Aiming for reversal of respiratory depression. 
  • After 4 mg consider alternative diagnoses or, if opioid toxicity likely, continue 2 mg boluses. 

Adults WITH suspected opioid dependence (if cardiac or respiratory arrest use without dependence doses above): 

Although this situation is relatively unlikely to be encountered in the deployed environment, excessive administration of naloxone may precipitate opioid withdrawal in dependant patients, so in such circumstances smaller doses are recommended, titrated to response:

  • Given 100-200 micrograms naloxone IV every 60 seconds until RR > 10. 
  • If no response after 2 mg give further doses as for adults without dependence and reconsider diagnosis. 

Children under 12 years of age:

  • Give an initial dose of 100 micrograms/kg (0.1 mg/kg, maximum dose 2 mg) IV, if no response, repeat at intervals of 60 seconds to a total maximum 2 mg IV. Then review diagnosis.
If a patient is not responsive to naloxone and respiratory depression persists (including hypercapnia) ventilatory support should be provided either by mechanical ventilation or bag valve mask. Consider alternative diagnoses including other causes of pinpoint pupils such as pontine stroke, organophosphate or nerve agent poisoning.

Monitoring after naloxone response. 

Once an adequate response has occurred, monitor oxygen saturations, respiratory rate and conscious level every 15 minutes for the first hour, and then every 30 minutes for the subsequent three hours after naloxone. If the respiratory rates falls administer further doses of naloxone until adequate ventilation restored. A naloxone intravenous infusion should be considered at this stage. 

Naloxone infusion

If repeated doses of naloxone are likely to be required an infusion should be considered. 

The initial infusion hourly rate should be 60% of the total naloxone doses required to adequately reverse respiratory depression. The infusion rate can then to titrated to achieve an adequate effect. 

Infusion preparation: Add 4 mg (10 x 400 microgram vials) of naloxone in 30 mL of 0.9% sodium chloride solution (final volume 40 mL; dextrose can be used as an alternative), to provide a final concentration of 100 microgram/mL, for infusion using an IV pump.

Example:       400 mcg + 800 mcg boluses initially = 1.2 mg total dose. 

60% of 1.2 mg = initial rate of 720 mcg / h = 7.2 mL / h

Adjusting the naloxone infusion rate:

If respiratory depression recurs, further IV boluses of 100-200 micrograms naloxone should be given every 60 seconds until respiratory function is adequate. The infusion rate per hour can then be increased by 60% of the total bolus dose of naloxone that was required.

If the patient shows mild signs of opioid withdrawal, the infusion rate should be decreased, by 50%. If the patient is significantly agitated the naloxone infusion can be stopped temporarily; the infusion can be restarted after 30-60 minutes, at 50% of the previous infusion rate per hour, once the withdrawal has settled. 

For patients with stable respiratory function, continue the infusion at the same rate for at least 4 hours before titrating it down by 25% of the maximum infusion rate every 1-2 hours until it is stopped. A naloxone infusion should not generally be stopped at night (midnight to 0600) unless the patient is experiencing features of acute opioid withdrawal syndrome because recurrence of acute toxicity may be more difficult to routinely detect overnight if the patient is sleeping.

If the naloxone infusion dose/rate is changed, more frequent monitoring should recommence with observations every 15 minutes for the first hour and every 30 minutes thereafter.

Management of Opiate Withdrawal

Opioid withdrawal occurs when an individual is habituated to regular opioid exposure and has not received a sufficient opioid dose to meet their physiological need. Opioid withdrawal is not a life-threatening condition but it very unpleasant for the individual. Symptomatic therapeutic interventions are usually sufficient to manage symptoms of opioid withdrawal.

Symptoms and signs include flu-like symptoms: muscle aches, sweating, chills; GI upset: nausea, vomiting, diarrhoea; agitation or irritability; restlessness; tremor; yawing, gooseflesh skin (piloeretion); dilated pupils; running nose or tearing; tachycardia. 

In the deployed environment, opioids should not be given manage opioid withdrawal. Symptoms of withdrawal can be mitigated with: 

  • Psychological reassurance.
  • Loperamide for diarrhoea.
  • Hyoscine butylbromide or Mebeverine for abdominal cramps.
  • Paracetamol for aches and pains. 
  • Antiemetics for nausea and vomiting. 
  • A low dose benzodiazepine such as diazepam 2 mg orally as required (max 6 hourly) can be used on a short-term basis for severe anxiety, increased up to 5mg if needed.

Last reviewed: 21/05/2026

Next review date: 21/05/2027