• If respiratory rate > 8 breaths/min with normal oxygen saturations, and the patient is easily rousable and not cyanosed, adopt a policy of ‘wait and see’; consider reducing or omitting the next regular dose of opioid or reducing rate of/discontinuing continuous parenteral administration.
  
  Pupil size is an unreliable indicator of opioid overdose in patients taking regular opioids.
  
  Consider “is the patient more drowsy than usual” as this will also help evaluate the clinical situation and assess if naloxone is indicated.
  
  
• Administer high flow oxygen via face mask if the patient is hypoxic. Administer oxygen to maintain SpO₂ >95% (88–92% if pre-existing hypercapnic respiratory failure)
• Naloxone is best given IV but, if not practical, may be given IM or SC.
• If respiratory rate < 8 breaths/min, and the patient is comatose/unconscious and/or cyanosed:
  • Stop opioid administration
  • Follow the authorisation chart to prepare the naloxone injection concentration and administration of stepwise doses according to patient response.
  • The aim is for slow, paced administration of the drug to avoid a surge of pain from complete antagonism of opioid
  • After the last dose of naloxone, monitor consciousness and respiratory rate every 15 mins for 2 hours then hourly for 6 hours after immediate release opioid, 12 hours after sustained release opioid, and 24 hours after methadone or transdermal opioid.
  • Wait until there has been a sustained improvement in consciousness before restarting a lower dose of opioid, it may be preferable to switch the type of opioid
  • If there is little or no response, consider other causes (e.g. other sedatives)
• If repeated naloxone doses (more than 3 repeat bolus doses) are required, consider starting a continuous intravenous infusion of naloxone.
  • An infusion of naloxone is a specialist intervention – clinicians need to consider the intensive monitoring requirements which is suggested to be every 15 minutes including blood pressure, pulse, respiratory rate, oxygen saturation and level of consciousness.
  • Patients should be observed for a minimum of six hours after the last dose of naloxone.
  • In this circumstance, transfer to the acute hospital setting should be considered and discussed with the patient or their advocate, and the consultant in charge of the patient’s care or the on-call consultant.
  • Nursing and medical staff should be competent at IV administration and monitoring of opioid toxicity and withdrawal prior to a decision to utilise a continuous intravenous infusion in the hospice setting.

Dilute Naloxone 400micrograms/1ml in 100 ml 0.5% glucose or 0.9% sodium chloride to produce a 4microgram/ml solution. If 100ml bags are not available, this can be multiplied accordingly to achieve the same concentration i.e. 1mg Naloxone in 250ml, or 2mg Naloxone in 500ml)

Due to very strong receptor affinity (reflected in its high relative potency with morphine), naloxone in standard doses does not reverse the effects of buprenorphine and higher doses must be used, see below:

Reversal of buprenorphine induced respiratory depression

1. Discontinue buprenorphine (remove transdermal patch)
2. Give Oxygen by mask
3. Give IV naloxone 2mg stat over 90 seconds
4. Commence naloxone 4mg/hour by CIVI
5. Continue CIVI until the patient’s condition is satisfactory (probably <90min)
6. Monitor the patient frequently for the next 24h, and restart CIVI if
respiratory depression recurs
7. If the patient’s condition remains satisfactory, restart buprenorphine at a
reduced dose, e.g. half of the previous dose

• Intra-venous is the preferred route of administration for naloxone, but can be given intra-muscularly or subcutaneously if venous cannulation is not possible.
• If using IM/SC route, be aware that onset of action will be slower (approximately 2–5 minutes) compared to IV (1–2 minutes), though duration of action may be more prolonged.
• Nasal naloxone is also available (Nyxoid: 1.8 mg naloxone per spray, or Naloxone: 1.26 mg per spray).
• Administer high flow oxygen via face mask if the patient is hypoxic.
• Delayed-onset pulmonary oedema (48 h after overdose treated with naloxone) due to acute cardiomyopathy has also been reported, possibly the result of cardiac muscle damage caused by hypoxaemia.
• Complete an incident form for your organisation that naloxone has been administered.

• Naloxone has a much shorter half-life than morphine. There is a risk that opioid toxicity will recur as the naloxone wears off and the opioid is still active. Respiratory rate and oxygen saturation should be monitored closely until stable. The length of this period of monitoring will be dependent on the half-life of the opioid causing toxicity. The half-life of morphine and some other opioids is prolonged in renal failure and other metabolic disturbance.
• After the last dose of naloxone, monitor level of consciousness and respiratory rate every 15 min for 2 h, then hourly for 6 h after immediate-release opioid; monitor for longer after a modified-release opioid or an opioid with a long half-life, e.g. 12 h after a 12-hourly modified-release opioid, 24 h after methadone.
• It may be appropriate to transfer the patient to a facility where naloxone infusion and monitoring can be initiated. This course of action should be considered if respiratory depression continues to recur despite repeated administration of naloxone (as above).

As per the NICE Guidance for use of opioids in palliative care, all patients, should be offered access to appropriate written information during their investigation and treatment, including information about opioid side effects and signs of toxicity

Adherence to the Network guidelines may from time to time be formally monitored.

Any use of naloxone should be reported as an incident within your organisation and to the CDAO who will need to add to their CDLIN quarterly report. The aim of incident reporting is to review and reflect on the time preceding the intervention and identify any changes in practice as a result