Can a patient with obstructive sleep apnea (OSA) take opioid medication?

From the Guidelines

Patients with obstructive sleep apnea (OSA) should avoid opioid medications whenever possible due to significant risks of worsening sleep apnea and increasing the risk of severe adverse outcomes, as evidenced by the 2020 study published in the Annals of Internal Medicine 1. The use of opioids in patients with OSA can lead to a combination of obstructive apnoeas and central sleep-disordered breathing, with 75-85% of patients treated with opioids having at least mild sleep apnoea, and 36-41% having severe sleep apnoea, as reported in the 2017 study published in the British Journal of Pharmacology 1. Key points to consider when managing pain in patients with OSA include:

• Avoiding opioids whenever possible due to their potential to worsen sleep apnea and increase the risk of respiratory depression
• Using alternative pain management strategies, such as acetaminophen, NSAIDs, certain antidepressants, anticonvulsants for neuropathic pain, and non-pharmacological approaches like physical therapy
• Prescribing opioids at the lowest effective dose for the shortest duration possible if they must be used, and closely monitoring patients for respiratory depression
• Ensuring proper use of CPAP therapy during sleep and informing all healthcare providers about the sleep apnea diagnosis for patients with OSA who require opioids, as recommended in the 2020 study published in the Annals of Internal Medicine 1. The combination of OSA and opioids is particularly dangerous, as OSA already causes intermittent hypoxia, and adding a respiratory depressant significantly increases the risk of severe adverse outcomes, highlighting the need for caution and careful management when using opioids in patients with OSA, as supported by the evidence from the 2017 study published in the British Journal of Pharmacology 1.

From the FDA Drug Label

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion Patients with Chronic Pulmonary Disease: Morphine sulfate tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of morphine sulfate tablets

The use of opioid medicine, such as morphine, may increase the risk of sleep-related breathing disorders, including central sleep apnea, in a dose-dependent fashion. Additionally, patients with chronic pulmonary disease, including those with obstructive sleep apnea, are at increased risk of decreased respiratory drive, including apnea, when taking morphine sulfate tablets. Caution should be exercised when prescribing opioid medicine to patients with obstructive sleep apnea. It is essential to monitor these patients closely, particularly when initiating and titrating opioid medicine, and consider alternative treatment options, such as non-opioid analgesics 2.

From the Research

Obstructive Sleep Apnea and Opioid Use

• The relationship between obstructive sleep apnea (OSA) and opioid use is complex, with some studies suggesting that opioids may worsen OSA, while others have found no significant effect 3, 4, 5.
• A randomized controlled trial found that 40 mg of morphine did not change upper airway collapsibility, pharyngeal muscle responsiveness, or arousal threshold in moderately severe OSA patients, but did reduce loop gain and hypercapnic ventilatory responses 3.
• Another study found that 40 mg oral controlled-release morphine did not worsen OSA in men, and that individual opioid response in patients with OSA may relate to baseline CO2 response threshold and OPRM1 genotype 4.

Effects of Opioids on Sleep and Respiratory Parameters

• A systematic review and meta-analysis found that a single dose of 30 or 40 mg morphine does not have a significant effect on sleep or respiratory outcomes compared to placebo in patients with OSA 5.
• A study found that opioids affect control of breathing and impair upper airway function, causing central apneas, upper airway obstruction, and hypoxemia during sleep, but the question of whether opioids can aggravate OSA remains unanswered 6.
• Another study found that nonobese OSA patients with opioid intake have obstructive breathing with a different pattern, and that bilevel positive-pressure therapy with a back-up rate was the most effective treatment 7.

Clinical Implications

• The use of opioids in patients with OSA requires careful consideration, as the relationship between opioids and OSA is complex and not fully understood 3, 4, 6, 5.
• Clinicians should be aware of the potential risks and benefits of opioid use in patients with OSA, and consider alternative treatments or closer monitoring of patients with OSA who are prescribed opioids 4, 6.