Opioid-Induced Respiratory Depression

What to do right now

If you suspect someone is not breathing properly after opioids:

1. Try to wake them: shout their name and rub hard on the breastbone with your knuckles.
2. Call 911 or your local emergency number.
3. Give naloxone: spray one dose into one nostril (nasal spray) or inject as directed. If there is no response in 2 to 3 minutes, give another dose.
4. Support breathing: if they are not breathing or are only gasping, start rescue breaths or CPR as instructed by the dispatcher.
5. Recovery position: if they are breathing, turn them on their side to keep the airway clear.
6. Stay with them: naloxone wears off in 30 to 90 minutes, sometimes before the opioid does, so breathing can slow again. They still need emergency care.

Naloxone is safe even if the person has not taken opioids. In the US it is available over the counter in pharmacies.

How opioids affect breathing

Opioids act on receptors in the brainstem that control breathing rhythm and the response to rising carbon dioxide. They:

• slow the breathing rate
• reduce the depth of each breath
• blunt the urge to breathe when carbon dioxide rises
• relax throat muscles, worsening airway blockage during sleep

Sedation usually comes before respiratory depression, so increasing sleepiness is a key early warning sign.

Risk factors

Medicine-related

• starting an opioid or increasing the dose, especially in the first days
• high daily doses
• long-acting or extended-release formulations, methadone and fentanyl patches
• combining opioids with benzodiazepines (see benzodiazepine overdose), gabapentinoids, sleep medicines, muscle relaxants or alcohol
• illicit fentanyl and other potent synthetic opioids, often in counterfeit pills
• loss of tolerance after a period of not using (after detox, hospital stays or prison)

Patient-related

• older age
• obstructive sleep apnea or obesity
• COPD and other lung diseases
• kidney or liver disease, which slow opioid clearance
• opioid-naive patients after surgery
• children, particularly after tonsillectomy in certain cases

Signs and symptoms

• excessive sleepiness that is hard to rouse
• slow breathing (fewer than about 10 breaths a minute in adults) or shallow breathing
• pauses in breathing, snoring or gurgling
• pinpoint pupils
• blue or gray lips and fingertips
• limp body, slow heart rate
• confusion or slurred speech

Pulse oximetry can miss early respiratory depression in people given oxygen, because carbon dioxide may build up before oxygen falls. Hospitals use sedation scores and sometimes capnography to monitor.

Diagnosis

In hospital, doctors assess consciousness, breathing rate, oxygen levels and sometimes carbon dioxide levels on a blood gas. Improvement after naloxone supports the diagnosis. They also look for other drugs and conditions causing drowsiness.

Treatment

• Naloxone: an opioid antagonist that reverses respiratory depression within minutes. In hospital, small doses are given and repeated or infused as needed. In people dependent on opioids, it can trigger withdrawal.
• Breathing support: oxygen, bag-mask ventilation and sometimes a breathing tube.
• Observation: for long-acting opioids, monitoring for many hours or a naloxone infusion.
• Review medicines: reduce doses, stop sedatives, switch formulations.
• Treatment for opioid use disorder when relevant, including buprenorphine or methadone, which lower overdose risk. See opioid use disorder.

Prevention

• use the lowest effective opioid dose for the shortest time
• avoid combining opioids with benzodiazepines, sleeping pills or alcohol
• never take more than prescribed or someone else's medicine
• keep naloxone at home if you or someone you live with uses opioids, and tell family where it is
• get screened for sleep apnea and use CPAP if prescribed
• store opioids securely and dispose of leftovers
• for people who use drugs: never use alone, use fentanyl test strips, start with a small amount

Frequently asked questions

What are the signs of opioid-induced respiratory depression?

Signs include extreme drowsiness or being hard to wake, slow or shallow breathing, long pauses between breaths, snoring or gurgling sounds, pinpoint pupils and blue or gray lips. Increasing sleepiness is often the first warning sign.

How does naloxone work?

Naloxone blocks opioid receptors, rapidly reversing the effect of opioids on breathing, usually within 2 to 3 minutes. It may need repeating, and its effect can wear off before the opioid's, so the person still needs emergency care.

Who is most at risk of opioid respiratory depression?

Risk is highest when starting or increasing opioids, at high doses, when combining opioids with benzodiazepines, alcohol or other sedatives, and in older adults and people with sleep apnea, lung disease, or kidney or liver problems. Illicit fentanyl greatly increases risk.

Can you die from opioid respiratory depression?

Yes. It is the main cause of death in opioid overdose. Hypoxic brain injury can occur within minutes of breathing stopping. Giving naloxone and calling 911 promptly saves lives.

Should I keep naloxone at home if I take prescription opioids?

Yes. Health authorities recommend naloxone for anyone taking higher-dose opioids, taking opioids with benzodiazepines, or with other risk factors, and for households where someone uses opioids. It is available over the counter in the US.