Open Access Open Access  Restricted Access Subscription or Fee Access

Treatment of opioid-related central sleep apnea with positive airway pressure: A systematic review

Roopika Reddy, MD, David Adamo, RPSGT, Thomas Kufel, MD, Jahan Porhomayon, MD, Ali A. El-Solh, MD, MPH


Objective: To systematically review the various modalities of positive airway pressure (PAP) in the treatment of opioid-related central sleep apnea (CSA).

Design: Systematic review.

Interventions: MEDLINE, the Cochrane Library, and EMBASE were screened through March 2013 to identify articles which investigated treatment of opioid-related CSA with PAP. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of eligible articles was assessed using a set of questions addressing both general and statistical methodologies.

Results: Five articles met the inclusion criteria for a total of 127 patients. All patients had been on opioids for at least 6 months. The dose ranged from 10 mg to 450 mg daily of morphine equivalent dose. Continuous positive airway pressure (CPAP) was proven mostly ineffective in reducing central apneic events. Bilevel positive airway pressure (BiPAP) with and without supplemental oxygen achieved elimination of central apneas in 62 percent of patients. Adaptive servo ventilation (ASV) yielded conflicting results with 58 percent of participants attaining a central apnea index <10 per hour. The presence of ataxic breathing predicted poor response to PAP.

Conclusions: The available evidence on the efficacy of PAP in opioid-related CSA is inconclusive. With the increasing use of opioids, further studies are needed to assess optimal PAP therapy and predictors of success in this group of patients.


central sleep apnea, opioids, ataxic breathing, positive airway pressure

Full Text:



Novak S, Nemeth WC, Lawson KA: Trends in medical use and abuse of sustained-release opioid analgesics: A revisit. Pain Med. 2004; 5(1): 59-65.

US Department of Justice DEA: Automation of Reports and Consolidated Orders System (ARCOS) 2—Report 7. 2005.

Farney RJ, Walker JM, Cloward TV, et al.: Sleep-disordered breathing associated with long-term opioid therapy. Chest. 2003; 123(2): 632-639.

Wang D, Teichtahl H, Drummer O, et al.: Central sleep apnea in stable methadone maintenance treatment patients. Chest. 2005; 128(3): 1348-1356.

Teichtahl H, Prodromidis A, Miller B, et al.: Sleep-disordered breathing in stable methadone programme patients: A pilot study. Addiction. 2001; 96(3): 395-403.

Sunjic S, Zador D: Methadone-related deaths in New South Wales. Med J Aust. 1997; 166(1): 54-55.

Piercefield E, Archer P, Kemp P, et al.: Increase in unintentional medication overdose deaths: Oklahoma, 1994-2006. Am J Prev Med. 2010; 39(4): 357-363.

Hall AJ, Logan JE, Toblin RL, et al.: Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA. 2008; 300(22): 2613-2620.

Webster LR, Cochella S, Dasgupta N, et al.: An analysis of the root causes for opioid-related overdose deaths in the United States. Pain Med. 2011; 12(Suppl 2): S26-S35.

Glidewell RN, Orr WC, Imes N: Acetazolamide as an adjunct to CPAP treatment: A case of complex sleep apnea in a patient on long-acting opioid therapy. J Clin Sleep Med. 2009; 5(1): 63-64.

Aurora RN, Chowdhuri S, Ramar K, et al.: The treatment of central sleep apnea syndromes in adults: Practice parameters with an evidence-based literature review and meta-analyses. Sleep. 2012; 35(1): 17-40.

Downs SH, Black N: The feasibility of creating a checklist for the assessment of the methodological quality both of randomized and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998; 52(6): 377-384.

Ramar K, Ramar P, Morgenthaler TI: Adaptive servoventilation in patients with central or complex sleep apnea related to chronic opioid use and congestive heart failure. J Clin Sleep Med. 2012; 8(5): 569-576.

Javaheri S, Malik A, Smith J, et al.: Adaptive pressure support servoventilation: A novel treatment for sleep apnea associated with use of opioids. J Clin Sleep Med. 2008; 4(4): 305-310.

Farney RJ, Walker JM, Boyle KM, et al.: Adaptive servoventilation (ASV) in patients with sleep disordered breathing associated with chronic opioid medications for non-malignant pain. J Clin Sleep Med. 2008; 4(4): 311-319.

Chowdhuri S, Ghabsha A, Sinha P, et al.: Treatment of central sleep apnea in U.S. veterans. J Clin Sleep Med. 2012; 8(5): 555-563.

Alattar MA, Scharf SM: Opioid-associated central sleep apnea: A case series. Sleep Breath. 2009; 13(2): 201-206.

Walker JM, Farney RJ, Rhondeau SM, et al.: Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. J Clin Sleep Med. 2007; 3(5): 455-461.

Teichtahl H, Wang D, Cunnington D, et al.: Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients. Chest. 2005; 128(3): 1339-1347.

Santiago TV, Goldblatt K, Winters K, et al.: Respiratory consequences of methadone: The response to added resistance to breathing. Am Rev Respir Dis. 1980; 122(4): 623-628.

Santiago TV, Pugliese AC, Edelman NH: Control of breathing during methadone addiction. Am J Med. 1977; 62(3): 347-354.

Leevers AM, Simon PM, Xi L, et al.: Apnoea following normocapnic mechanical ventilation in awake mammals: A demonstration of control system inertia. J Physiol. 1993; 472: 749-768.

Mulkey DK, Henderson RA III, Putnam RW, et al.: Hyperbaric oxygen and chemical oxidants stimulate CO2/H+-sensitive neurons in rat brain stem slices. J Appl Physiol. 2003; 95(3): 910-921.

Teschler H, Dohring J, Wang YM, et al.: Adaptive pressure support servo-ventilation: A novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med. 2001; 164(4): 614-619.



  • There are currently no refbacks.