Opioid-related respiratory depression

Breathing is automatic, driven by a control centre in the brainstem that responds to rising carbon dioxide. Opioids dampen that response, so breathing becomes slower and shallower, and a person may not wake or respond to the usual signals to breathe. Oxygen levels fall and carbon dioxide rises, which causes more drowsiness and can progress to loss of consciousness.

The effect depends on the amount of opioid, how fast it was given, the person's tolerance and the other things in their system. Sleep itself lowers the breathing drive a little, so the risk is greater at night, when a person cannot notice that they are becoming over-sedated.

Risk is highest at the start of treatment, after a dose increase, when switching to a different opioid, or when a new medicine is added. It is also higher in older adults, in people with chronic lung disease or sleep apnoea, those with kidney or liver impairment, which slow clearance, and in people who are very frail or have low body weight. The NHS zopiclone page, for example, lists breathing problems, muscle weakness and sleep apnoea among reasons a sedating medicine may be unsuitable.

• Older age and frailty.

• COPD, asthma, sleep apnoea or other breathing problems.

• Reduced kidney or liver function.

• Recent dose change, switch of opioid or new medicine.

• Alcohol or other sedating substances taken at the same time.

• Opioids taken by someone not prescribed them, or used in ways not intended.

The most important practical message is that sedating medicines add up. The NHS morphine guidance advises against mixing it with sedatives used for insomnia and anxiety, such as diazepam, flags nerve-pain medicines such as gabapentin as a concern and says it is best not to drink alcohol while taking morphine because it can make you sleepy and increase the risk of serious side effects. For pregabalin, the NHS says to tell the doctor before starting if you take strong opioid painkillers such as morphine, codeine or oxycodone.

The MHRA's gabapentin warning notes that people taking opioids at the same time as gabapentin, older people, and those with respiratory disease, kidney impairment or neurological disease are among those at greater risk of severe breathing depression, and that the risk exists even without opioids. Our guide on gabapentinoid misuse covers that medicine group in more detail.

Early signs are marked drowsiness, difficulty staying awake in conversation, slurred speech, confusion and slow, noisy or shallow breathing. Later signs include snoring-like or gurgling sounds, pale, blue or grey lips and fingertips, and failure to respond to voice or a firm shake. Pinpoint pupils are a typical clue with opioids.

Because the person may not recognise their own deterioration, relatives and carers have a role. If someone on opioids is more difficult to rouse than usual, take it seriously, even if they usually sleep a lot.

Call 999 straight away if a person cannot be woken, is breathing very slowly or not at all, or has blue or grey lips. Try to rouse them, place them on their side if they are breathing, and be ready to start CPR if told to by the call handler or if breathing stops. Naloxone is a medicine that reverses opioid effects; where it has been prescribed or supplied by a drug service, it can be given as directed while waiting for the ambulance, and it does not replace the call to 999.

For a person who has simply taken more than prescribed but is alert, the NHS advises contacting NHS 111 or going to A&E, and bringing the medicine packaging. The NHS morphine page says to call 111 if you suspect serious side effects such as slowed or difficult breathing.

The MHRA advises that opioids should have a plan agreed at the start, including an end-of-treatment plan, regular monitoring and slow tapering rather than abrupt stopping. Following the prescribed schedule, keeping alcohol out of the picture, telling every prescriber and pharmacist about all sedating medicines and storing opioids safely away from children all reduce risk. Do not share opioids, and dispose of leftovers through a pharmacy. If you are a carer, ask the prescriber whether naloxone is appropriate for the household.