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 intramuscular (IM) or intraosseous (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, if WEAPONISED opioid suspected:
- Initial bolus 4 mg (4000 micrograms) naloxone IV / IO.
- If no response after 60 seconds, give another 4 mg bolus IV.
- High doses of naloxone may be required to reverse respiratory depression and maintain the respiratory rate. Titrate dosing to response.
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 to a maximum 10 mg.
Adults WITH suspected opioid dependence (if cardiac or respiratory arrest use without dependence doses above):
- Excessive administration of naloxone may precipitate opioid withdrawal (see below) in dependant patients. Therefore, small 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 the patient is not responsive to naloxone and remains respiratory depressed (including hypercapnia) ventilatory support should be provided either by mechanical ventilation or bag valve mask.
Consider alternative diagnoses including other causes of pinpoint pupils e.g. pontine stroke, organophosphate poisoning, antipsychotic overdose
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.