Reversal of Opioid-induced Respiratory Depression

This guideline relates to the use of naloxone in the urgent reversal of opioids and opiates in non-palliative adult patients. For naloxone guidance in palliative care patients see the Scottish Palliative Care Guideline and for further information regarding the management of opioid overdose, contact the National Poisons Information Service (telephone 0344 892 0111) or consult TOXBASE – www.toxbase.org (password required).

Management

Naloxone should be considered when there is an immediate threat to life, impaired consciousness or a diagnosis of respiratory depression. The primary aim of treatment is to reverse the toxic effects of opiates so that patients are no longer at risk of respiratory arrest, airways loss or other complications. Give:

1. Oxygen therapy (see guidelines on Blood Gas Analysis and Oxygen and Oximetry).
2. Naloxone - read the caution notes and dosing regimens below before prescribing.
3. Observe patients for at least 6 hours after the last dose of naloxone. Monitor BP, pulse, respiratory rate, oxygen saturation and conscious level at least every 15 minutes initially. 
4. If no response to naloxone, do not delay establishing a clear airway, adequate ventilation and oxygenation. 
5. Assistance from Intensive Care, Anaesthesia or Acute Pain Team may be required. 

Caution with naloxone

• Patients who have received longer term opioids / opiates treatment for pain control may have possible physical dependence.
• The use of inappropriate doses of naloxone may cause rapid reversal of the physiological effects of long-term opioids / opiates used to control pain leading to intense pain, distress and possibly acute withdrawal syndrome. 
• Too much naloxone may lead to hypertension, cardiac arrhythmia, pulmonary oedema and cardiac arrest.

Naloxone regimens

Two dosing regimens exist for naloxone:

• Higher initial dose regimen (severe opioid-induced respiratory depression / arrest following acute toxicity / overdose).  Associated with drug misuse and dependence. See below for dosing information. 
• Lower initial dose regimen (for acute toxicity with respiratory depression, in patients at risk of severe pain or acute withdrawal). For e.g. post-operative patients or patients on long-term opioid therapy requiring tailored reversal of accidental opioid induced respiratory depression. See below for dosing information. 

If response remains inadequate despite dosing guidance below, then review diagnosis and seek senior advice.

Higher initial dose regimen (for severe opioid-induced respiratory depression / arrest following acute toxicity / overdose)

• IV injection:
  • 400micrograms IV
  • No response after 1 minute give 800micrograms
  • Still no response after 1 minute give a further 800micrograms
  • If still no response, give 2mg then review diagnosis and seek senior advice.
• IM injection (if there is no IV access or if the patient is threatening to self-discharge):
  • 400micrograms IM
  • Give a further 400micrograms IM incrementally every 3 minutes until effect is noted. 

In both IV and IM injection regimes, aim for reversal of respiratory depression and maintenance of airway protective reflexes, not full reversal of unconsciousness. 

Lower initial dose regimen (for acute toxicity with respiratory depression, in patients at risk of severe pain or acute withdrawal)

• Dose 100-200micrograms IV. If response inadequate after 60 seconds, give increments of 100micrograms every 1 minute until respiratory function is adequate (up to 2mg). Lower doses may be appropriate in certain circumstances, but should be supervised by a clinician skilled in airway management (e.g. an anaesthetist). If unsure, seek senior input. 

Once an adequate response has been achieved, monitor blood gases, oxygen saturations and respiratory rate. The duration of action of naloxone is shorter than that of all opioid analgesics. Repeat doses of naloxone may be needed.

Naloxone IV infusion - administration information

A continuous infusion of naloxone may be required:

• Especially in cases of opiates with a long half-life or if particularly large doses have been given or where repeated doses are required.
• To prevent lapse back into sedation and respiratory depression following the initial treatment. Naloxone has a shorter plasma half-life than that of all opioid analgesics. 

The following administration advice is from TOXBASE www.toxbase.org (password required) and RCEM /NPIS 2024 guidance. The RCEM / NPIS guidance - Acute Opioid Toxicity - Best Practice Guidance - can be found under the Clinical Guidance section here.  

Dose: An infusion of 60% of the total dose administered over 1 hour is a useful starting point.

Preparation: Make up a solution of naloxone 100micrograms/1ml as follows:

• Draw up 4mg of naloxone from 10 ampoules, each containing 400micrograms/ml (total volume: 10ml).
• Dilute the 4mg concentrate with 30ml of normal saline 0.9% or glucose 5% to give a final volume of 40ml and a concentration of 100micrograms/ml.
• Infuse solution using an IV pump, adjust dose to clinical response. Infusions are not a substitute for frequent review of the patient's clinical state.

Administration: Table 1 gives indicative starting infusion rates in microgram/h and ml/h of prepared solution.  

Table 1: Recommended starting infusion rates for naloxone infusions

Guideline reviewed: November 2024

Page last updated: November 2024