Sleep-Disordered Breathing and Chronic Opioid Therapy

Lifetree Clinical Research and Pain Clinic, Salt Lake City, Utah, USA.
Pain Medicine (Impact Factor: 2.3). 07/2007; 9(4):425-32. DOI: 10.1111/j.1526-4637.2007.00343.x
Source: PubMed


To assess the relation between medications prescribed for chronic pain and sleep apnea.
An observational study of chronic pain patients on opioid therapy who received overnight polysomnographies. Generalized linear models determined whether a dose relation exists between methadone, nonmethadone opioids, and benzodiazepines and the indices measuring sleep apnea.
A private clinic specializing in the treatment of chronic pain.
Polysomnography was sought for all consecutive (392) patients on around-the-clock opioid therapy for at least 6 months with a stable dose for at least 4 weeks. Of these, 147 polysomnographies were completed (189 patients declined, 56 were directed to other sleep laboratories by insurance companies, and data were incomplete for seven patients). Available data were analyzed on 140 patients.
The apnea-hypopnea index to assess overall severity of sleep apnea and the central apnea index to assess central sleep apnea.
The apnea-hypopnea index was abnormal (> or =5 per hour) in 75% of patients (39% had obstructive sleep apnea, 4% had sleep apnea of indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea); 25% had no sleep apnea. We found a direct relation between the apnea-hypopnea index and the daily dosage of methadone (P = 0.002) but not to other around-the-clock opioids. We found a direct relation between the central apnea index and the daily dosage of methadone (P = 0.008) and also with benzodiazepines (P = 0.004).
Sleep-disordered breathing was common in chronic pain patients on opioids. The dose-response relation of sleep apnea to methadone and benzodiazepines calls for increased vigilance.

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    • "Sleep-disordered breathing, including obstructive sleep apnea (OSA) and central sleep apnea (CSA), is another potential factor leading to disrupted sleep in MMT patients. Some studies showed that CSA has been reported to occur in 30–60% of MMT patients [19] [20] and associated with methadone dose and concomitant benzodiazepine use [21]. "
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    • "The literature on the effect of opioids on sleep yields contradictory results, with one study demonstrating improvement in sleep quality and efficiency70 and several other studies reporting that opioids can cause inhibition of rapid eye movement and nonrapid eye movement phases of sleep.71,72 Patients receiving chronic opioid therapy also have a high prevalence of sleep apnea73,74 and hypoxemia.75 If sleep apnea is suspected, it is important to refer the patient to a sleep specialist for testing, especially if considering opioid therapy. "
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    • "Thus, pain management in patients with a long history of opiate use is considered to be a medical complication because the strategy of using a higher dose of opiates in such individuals is not only ineffective in alleviating their pain but could also increase their tolerance, hyperalgesia, and dependence (7, 9-11). Opioid-related side effects such as respiratory depression are also more likely to occur in these patients (12). Therefore, the use of non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) (13) and antidepressants, which have multiple analgesic mechanisms, is a logical treatment for such cases. "
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