How Do Opioids Cause Respiratory Depression?

What Is Respiratory Depression?

Respiratory depression, also referred to as hypoventilation, is a critical medical condition characterized by abnormally slow or shallow breathing, as identified by the Cleveland Clinic. This condition impedes the expulsion of carbon dioxide from the bloodstream, resulting in its accumulation (hypercapnia).

Additionally, it can sometimes obstruct oxygen from reaching the lungs, leading to decreased oxygen levels in the blood (hypoxemia). The normal respiratory rate for adults ranges from approximately 12 to 20 breaths per minute; however, in cases of respiratory depression, this rate can decrease to 8 to 10 breaths per minute or even lower.

High carbon dioxide levels in your blood can lead to life-threatening complications, including:

• Respiratory acidosis, blood becoming too acidic
• Respiratory failure
• Cardiac arrest
• Brain damage
• Coma
• Death

Certain medications and substances can cause respiratory depression, including sedative medications, narcotic pain medications like opioids, and other substances that depress brain function, such as alcohol and certain illegal drugs. Underlying medical conditions affecting the brain, lungs, muscles, or chest wall, such as stroke, sleep apnea, COPD, and severe obesity, can also lead to respiratory depression.

Why Is Respiratory Depression the Leading Cause of Opioid Overdose Deaths?

According to the Centers for Disease Control and Prevention (CDC), opioids were responsible for an estimated 54,743 overdose deaths in 2024, despite a nearly 27% decrease in overall overdose deaths in the U.S. Opioid respiratory depression is the primary cause of death in opioid overdoses because these drugs affect the brain’s ability to regulate breathing.

Opioids bind to specific receptors in the brainstem, which controls automatic functions such as breathing, heart rate, and consciousness. This interaction causes the brain to be unable to send signals to the diaphragm and other respiratory muscles, resulting in slowed or shallow breathing. High doses of opioids or mixing alcohol with opioids severely slow or stop breathing completely.

Opioids reduce the body’s response to carbon dioxide, which typically triggers an automatic increase in breathing rate and depth to expel excess carbon dioxide when it accumulates in the blood. Consequently, even when carbon dioxide levels become high, the body’s protective response is diminished, leading to significant hypercapnia. This suppression of respiratory functions results in reduced oxygen levels in the brain and body, potentially causing unconsciousness, brain damage, heart attacks, or death if not addressed.

Reduced oxygen levels in the blood deprive vital organs, especially the brain, of the oxygen they need to function properly. Severe acidosis from too much carbon dioxide in the blood can impair heart function and other critical cellular processes, accelerating organ failure. Brain cells begin to die within minutes without enough oxygen, causing permanent damage within 3 to 5 minutes. After 5 to 10 minutes, widespread cell death occurs, potentially leading to death without intervention.

Which Opioids Are the Most Likely to Cause Respiratory Depression?

All opioids have the potential to lead to respiratory depression, especially in higher doses; however, those with high potency and/or rapid onset of action, as well as those with long half-lives, can accumulate in the body. Respiratory depression from opioids is more likely to occur in the following:

• Fentanyl and its analogs (e.g., carfentanil): These synthetic opioids are significantly more potent than morphine, and even a small amount can cause a fatal overdose. According to the British Journal of Pharmacology, fentanyl’s potency, rate of onset, lowered sensitivity to naloxone, and lowered cross tolerance to heroin combine to make it more likely to cause opioid respiratory depression and overdose death than other commonly abused opioids.
• Methadone: While not as acutely potent as fentanyl, methadone has a very long half-life, which means it stays in the body for a prolonged period. Repeated doses can lead to accumulation, causing delayed and severe respiratory depression.
• Heroin: As an illegal, unregulated opioid, heroin’s strength can vary and is often laced with fentanyl, increasing its overdose risk.
• Morphine and Oxycodone: While less potent than other opioids, these are still strong and can cause respiratory depression, especially in high doses or when combined with other central nervous system (CNS) depressants.

Factors that increase the risk of Opioid overdose respiratory failure include:

• Higher doses
• Rapid administration, such as intravenously
• Lack of opioid tolerance, including those who are detoxing
• Concurrent use of other CNS depressants like benzodiazepines and alcohol
• Underlying medical conditions, such as respiratory diseases, kidney and liver impairments, or in older adults

What Our Customers are Saying

 

What Are the Symptoms of Opioid-Induced Respiratory Depression?

Opioid-induced respiratory depression (OIRD) can occur very quickly, potentially within minutes of opioid administration, and especially with high-potency or rapidly acting opioids. While the onset can be rapid, the duration and severity can vary greatly, from subtle symptoms initially to complete cessation of respiration. OIRD is a life-threatening condition, and recognizing the symptoms quickly is crucial for administering life-saving aid.

Here are the key symptoms of opioid respiratory depression:

• Slow or irregular breathing, becoming noticeably shallow, or dropping below 10 breaths per minute.
• Gurgling or snoring sounds indicate the airway may be partially obstructed or there’s fluid in the lungs.
• Extreme drowsiness or unresponsiveness
• Pinpoint pupils
• Cold or clammy skin
• Bluish lips, fingernails, or skin
• Limp body
• Confusion or disorientation
• Vomiting
• Slowed or absent pulse/heartbeat
• In severe cases, breathing may stop altogether

If you suspect someone is experiencing OIRD or an opioid overdose, it is a medical emergency. Immediately call 911 or your local emergency number, administer naloxone (Narcan) if available, and begin CPR if they have stopped breathing.

Key Takeaways on Opioid Respiratory Depression

• Opioids induce respiratory depression by attaching to mu-opioid receptors in the brainstem. This lowers the brain’s responsiveness to increasing carbon dioxide levels, thereby reducing the urge to breathe.
• Insufficient oxygen in the body, coupled with elevated carbon dioxide levels, can lead to respiratory acidosis, cardiac arrest, brain injury, coma, and ultimately death.
• Opioid respiratory depression is the primary cause of death in opioid overdoses because it suppresses the brain’s ability to control breathing, leading to a lack of oxygen to vital organs, including the brain.
• Fentanyl and its analogs, methadone, heroin, morphine, and oxycodone, all have a higher likelihood of causing respiratory depression from opioids.
• Key signs include slow or irregular breathing, blue lips or skin, pinpoint pupils, unresponsiveness, and no breathing or pulse in severe cases.

If you or someone you care about is facing challenges with opioid dependence or addiction, it’s crucial to reach out for professional help before a crisis occurs. At Resurgence Behavioral Health, we offer personalized programs for prescription drug addiction treatment designed to provide the guidance and support necessary to overcome opioid use disorder and mitigate the risks associated with opioid respiratory depression.

Our medical detox programs ensure around-the-clock supervision, effective medications, and emotional support to help manage opioid withdrawals safely. This sets the stage for a smooth transition into one of our inpatient or outpatient treatment programs, which are focused on addressing the root causes of addiction. Whether you’re struggling to stop using opioids or have been dealing with years of illicit drug use, our experienced clinicians are here to create a customized treatment plan that fits your unique needs and paves the way to a healthier, brighter future.

Contact Resurgence Behavioral Health today at 855-458-0050 to take the first step toward recovery.

Resources

• • Cleveland Clinic – Respiratory Depression (Hypoventilation)
  • British Journal of Pharmacology – Fentanyl depression of respiration: Comparison with heroin and morphine