When both RR <8 breaths/minute AND oxygen saturations <85% (or RR<10 breaths/minute AND oxygen saturations <90% if using individualised ranges):
- commence oxygen therapy, and
- consider naloxone administration
Naloxone should only be administered where there is a concern of life-threatening respiratory depression.
Use of naloxone for the management of life-threatening opioid-induced respiratory depression
Naloxone is an opioid antagonist.
The aim of naloxone use is to reverse life-threatening, opioid-induced respiratory depression without impacting symptom control or causing withdrawal.
Cautions
- Naloxone is not indicated for:
- opioid-induced drowsiness and/or delirium that are not life-threatening.
- people on opioids who are in the last short days of life, in which case seek specialist advice about further symptom management.
- Individuals on regular opioids for pain and symptom control are physically dependent; naloxone given in too large a dose or too quickly can cause an acute withdrawal reaction and an abrupt return of pain that is difficult to control.
- People with pre-existing cardiovascular disease are at more risk of side effects.
- Do not use ‘take home naloxone’ in pre-filled syringe or nasal spray formulations for people receiving palliative care. These preparations are intended for use in substance use disorder and the doses are usually too high for the palliative setting.
Side effects
In those on regular opioids, total antagonism will result in severe pain with hyperalgesia and, if physically dependent, severe physical withdrawal symptoms, including:
- anxiety
- irritability
- muscle aches
- nausea and vomiting
- diarrhoea
- dizziness
- headache
- tremor
- seizures
- hyperventilation, and
Important: Life-threatening tachycardia/cardiac arrhythmias, pulmonary oedema and cardiac arrest have also been reported as side effects.
Dose and administration
- Discontinue the background opioid.
- Discontinue any ‘take home naloxone’ in pre-filled syringe or nasal spray formulations for people receiving palliative care.
- Prescribe naloxone 100 micrograms bolus doses, using the 400 micrograms/ml injection (1 ml ampoule) preparation for those receiving palliative care. See table below.
- Naloxone injection is licensed for intravenous (IV) administration.
- Small doses of naloxone by slow IV injection improve respiratory status without completely blocking the opioid analgesia.
- Onset of action of IV naloxone is one to two minutes.
- If IV access is not readily available, it may also be administered subcutaneously (SC) or intramuscularly (IM) with no dose adjustment. However, an IV line should be sited as soon as possible.
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How to prepare
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Dose to give
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Notes
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IV administration (where IV access is immediately available)
Onset of action 1–2 mins (plasma half-life ~1 hour)
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Dilute 400 micrograms naloxone (1 ampoule) to 8 ml with sodium chloride 0.9% injection in a 10 ml syringe.
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100 micrograms (2 ml of diluted solution) as a slow IV bolus every 2 minutes until the patient’s respiratory status is satisfactory (≥8 respirations/minute).
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Flush the cannula with 1–2 ml sodium chloride 0.9% between the naloxone doses.
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IM/SC administration (where IV access is not immediately available)
Onset of action 2–5 mins (plasma half-life ~1 hour)
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Give undiluted.
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100 micrograms (0.25 ml) of naloxone IM/SC, repeat every 5 minutes until the patient’s respiratory status is satisfactory (≥8 respirations/minute).
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An IV line should be sited as soon as possible
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Initial management and response to treatment
- Individuals usually respond after 100 to 200 micrograms naloxone with deeper breathing and an improved conscious level. Note that IM or SC administration may have slower onset of action than intravenous administration.
- Naloxone should be titrated to respiratory rate, not conscious level.
- If there is little or no response, consider other causes (for example, other sedatives, an intracranial event, acute sepsis or acute renal failure causing opioid accumulation).
- In exceptional circumstances individuals may need 1 mg to 2 mg of naloxone (requiring 3 to 5 ampoules).
- Obtain specialist palliative care advice before restarting background opioid – see section Management of background opioid, within the opioid toxicity guideline.
Monitoring
- Closely monitor respiratory rate and oxygen saturation for a minimum of 4 hours after respiratory rate reaches ≥8/min or >10/min if using individualised range.
- Monitor for signs of opioid toxicity.
- Consider IV or SC fluids to promote renal excretion of opioid metabolites.
- Consider appropriateness of checking bloods for U&Es, calcium, LFTs, CRP and FBC.
- Ensure review of other medicines which may be contributing to clinical picture of CNS depression that may need withheld or stopped, including for example, gabapentinoids or benzodiazepines.
Important: further doses or IV infusion may be needed as the duration of action of naloxone (15 to 90 minutes) is much shorter than most opioids, and impaired liver or renal function will slow clearance of the opioid.
Naloxone infusion: prolonged, or recurrent, opioid-induced respiratory depression
If giving repeated doses of naloxone via the SC/IM route site an IV line as soon as possible. Refer to local guidance where available.
Seek specialist palliative care advice if an IV line is unavailable.
To start a continuous IV infusion of naloxone via an adjustable infusion pump:
- Add 1 mg of naloxone (= 2.5 ml of 400 micrograms/ml naloxone injection) to 100 ml of sodium chloride 0.9% to give a concentration of 10 micrograms/ml.
- Calculate the dose requirement per hour by totalling the naloxone bolus doses and dividing by the time period over which all the doses have been given.
- Start the IV infusion of naloxone at 60% of this calculated hourly rate.
- Adjust the naloxone infusion rate to keep the respiratory rate ≥ 8/min (do not titrate to the level of consciousness).
- Continue to monitor the individual closely.
- Continue the infusion until the individual’s condition has stabilised.
- If respiratory depression has arisen due to methadone administration, the infusion may be required for several days.
- Occasionally, additional IV boluses using naloxone diluted in sodium chloride 0.9% may still be necessary, despite IV infusion. Refer to dose and administration section above.
- If appropriate, use other resuscitative measures such as administration of oxygen.
- Dependent on stage of disease trajectory, care setting, individual future care plans (such as a Treatment Escalation Plan or ReSPECT plan), the views of anyone with power of attorney (POA) or other relevant information, it may be appropriate to consider mechanical ventilation or artificial respiration, alongside naloxone, following discussion with the responsible consultant or palliative care specialist.
If pain or features of opioid withdrawal occur whilst administering a naloxone infusion the infusion rate MUST be reduced or stopped. DO NOT administer opioids without first seeking urgent specialist palliative care advice.
Palliative care
