Open Access Open Access  Restricted Access Subscription or Fee Access

Looking both ways before crossing the street: Assessing the benefits and risk of opioids in treating patients at risk of sleep disordered breathing for pain and dyspnea

Mellar P. Davis, MD, FCCP, FAAHPM, Bertrand Behm, MD, Diwakar Balachandran, MD


Opioids adversely influence respiration in five distinct ways. Opioids reduce the respiratory rate, tidal volume, amplitude, reflex responses to hypercapnia and hypoxia, and arousability related necessary for respiratory adaptive responses. Opioids cause impairment of upper pharyngeal dilator muscles leading to obstructive apnea. Opioids cause complex sleep disordered breathing (SDB) consisting of central sleep apnea and obstructive sleep apnea. Clinically opioids worsen preexisting SDB. Recent studies have shown increased morbidity and mortality in patients receiving opioids for chronic noncancer pain and chronic obstructive pulmonary disease, which appear to be related to cardiovascular events, not overdose. Both patient populations are at risk for sleep disordered breathing and increased risk for adverse cardiovascular events on opioids for dyspnea or pain. This review discusses the influence of opioids on respiration and SDB and will review the adverse respiratory and cardiovascular effects of opioid use in at risk populations. Recommendations regarding management will follow as a summary.


sleep, apnea, sleep disordered breathing, obstructive sleep apnea, central sleep apnea, opioid

Full Text:



Neuman A, Gunnbjornsdottir M, Tunsater A, et al.: Dyspnea in relation to symptoms of anxiety and depression: A prospective population study. Respir Med. 2006; 100(10): 1843-1849.

Dyspnea. Mechanisms, assessment, and management: A consensus statement. American Thoracic Society. Am J Respir Crit Care Med. 1999; 159(1): 321-340.

Parshall MB, Schwartzstein RM, Adams L, et al.: An official American Thoracic Society statement: Update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012; 185(4): 435-452.

Ekstrom M, Nilsson F, Abernethy AA, et al.: Effects of opioids on breathlessness and exercise capacity in chronic obstructive pulmonary disease. A systematic review. Ann Am Thorac Soc. 2015; 12(7): 1079-1092.

Barnes H, McDonald J, Smallwood N, et al.: Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst Rev. 2016; 3: CD011008.

Ray WA, Chung CP, Murray KT, et al.: Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016; 315(22): 2415-2423.

Vozoris NT, Wang X, Fischer HD, et al.: Incident opioid drug use and adverse respiratory outcomes among older adults with COPD. Eur Respir J. 2016; 48(3): 683-693.

Pattinson KT: Opioids and the control of respiration. Br J Anaesth. 2008; 100(6): 747-758.

Ferguson LM, Drummond GB: Acute effects of fentanyl on breathing pattern in anaesthetized subjects. Br J Anaesth. 2006; 96(3): 384-390.

Smith JC, Ellenberger HH, Ballanyi K, et al.: Pre-Botzinger complex: A brainstem region that may generate respiratory rhythm in mammals. Science. 1991; 254(5032): 726-729.

Mellen NM, Janczewski WA, Bocchiaro CM, et al.: Opioid-induced quantal slowing reveals dual networks for respiratory rhythm generation. Neuron. 2003; 37(5): 821-826.

Feldman JL, Smith JC, Ellenberger HH, et al.: Neurogenesis of respiratory rhythm and pattern: Emerging concepts. Am J Physiol. 1990; 259(5 Pt 2): R879-R886.

Emery MJ, Groves CC, Kruse TN, et al.: Ventilation and the response to hypercapnia after morphine in opioid-naive and opioid-tolerant rats. Anesthesiology. 2016; 124(4): 945-957.

Santiago TV, Edelman NH: Opioids and breathing. J Appl Physiol. 1985; 59(6): 1675-1685.

Lalley PM: Opioidergic and dopaminergic modulation of respiration. Respir Physiol Neurobiol. 2008; 164(1-2): 160-167.

Magosso E, Ursino M, van Oostrom JH: Opioid-induced respiratory depression: A mathematical model for fentanyl. IEEE Trans Bio-Med Eng. 2004; 51(7): 1115-1128.

Mitsis GD, Governo RJ, Rogers R, et al.: The effect of remifentanil on respiratory variability, evaluated with dynamic modeling. J Appl Physiol. 2009; 106(4): 1038-1049.

Barbour SJ, Vandebeek CA, Ansermino JM: Increased tidal volume variability in children is a better marker of opioidinduced respiratory depression than decreased respiratory rate. J Clin Monit Comput. 2004; 18(3): 171-178.

Pattinson KT, Governo RJ, MacIntosh BJ, et al.: Opioids depress cortical centers responsible for the volitional control of respiration. J Neurosci. 2009; 29(25): 8177-8186.

Takakura AC, Moreira TS, Colombari E, et al.: Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2-sensitive neurons in rats. J Physiol. 2006; 572(Pt 2): 503-523.

Finley JC, Katz DM: The central organization of carotid body afferent projections to the brainstem of the rat. Brain Res. 1992; 572(1-2): 108-116.

Poole SL, Deuchars J, Lewis DI, et al.: Subdivision-specific responses of neurons in the nucleus of the tractus solitaries to activation of mu-opioid receptors in the rat. J Neurophysiol. 2007; 98(5): 3060-3071.

Walker JM, Farney RJ: Are opioids associated with sleep apnea? A review of the evidence. Curr Pain Headache Rep. 2009; 13(2): 120-126.

Sherrey JH, Pollard MJ, Megirian D: Proprioceptive, chemoreceptive and sleep state modulation of expiratory muscle activity in the rat. Exp Neurol. 1988; 101(1): 50-62.

Ramachandran SK, Haider N, Saran KA, et al.: Life-threatening critical respiratory events: A retrospective study of postoperative patients found unresponsive during analgesic therapy. J Clin Anesth. 2011; 23(3): 207-213.

Gilmartin GS, Thomas RJ: Mechanisms of arousal from sleep and their consequences. Curr Opin Pulmonary Med. 2004; 10(6): 468-474.

Younes M: Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol. 2008; 105(5): 1389-1405.

White DP, Younes MK: Obstructive sleep apnea. Comprehensive Physiol. 2012; 2(4): 2541-2594.

Ehsan Z, Mahmoud M, Shott SR, et al.: The effects of anesthesia and opioids on the upper airway: A systematic review. Laryngoscope. 2016; 126(1): 270-284.

Burns G, DeRienz RT, Baker DD, et al.: Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse? Clin Toxicol. 2016; 54(5): 420-423.

Schwartzstein RM, Manning HL, Weiss JW, et al.: Dyspnea: A sensory experience. Lung. 1990; 168(4): 185-199.

De Peuter S, Van Diest I, Lemaigre V, et al.: Dyspnea: The role of psychological processes. Clin Psychol Rev. 2004; 24(5): 557-581.

Ekstrom MP, Abernethy AP, Currow DC: The management of chronic breathlessness in patients with advanced and terminal illness. BMJ. 2015; 349: g7617.

Currow DC, Ekstrom M, Abernethy AP: Opioids for chronic refractory breathlessness: Right patient, right route? Drugs. 2014; 74(1): 1-6.

Currow D, Johnson M, White P, et al.: Evidence-based intervention for chronic refractory breathlessness: Practical therapies that make a difference. Br J Gen Pract. 2013; 63(616): 609-610.

Martins RT, Currow DC, Abernethy AP, et al.: Effects of low-dose morphine on perceived sleep quality in patients with refractory breathlessness: A hypothesis generating study. Respirology. 2016; 21(2): 386-391.

Baumgartner U, Buchholz HG, Bellosevich A, et al.: High opiate receptor binding potential in the human lateral pain system. NeuroImage. 2006; 30(3): 692-699.

Banzett RB, Mulnier HE, Murphy K, et al.: Breathlessness in humans activates insular cortex. Neuroreport. 2000; 11(10): 2117-2120.

Peiffer C, Poline JB, Thivard L, et al.: Neural substrates for the perception of acutely induced dyspnea. Am J Respir Crit Care Med. 2001; 163(4): 951-957.

Herigstad M, Hayen A, Wiech K, et al.: Dyspnoea and the brain. Respir Med. 2011; 105(6): 809-817.

Peiffer C, Costes N, Herve P, et al.: Relief of dyspnea involves a characteristic brain activation and a specific quality of sensation. Am J Respir Crit Care Med. 2008; 177(4): 440-449.

Mahler DA: Opioids for refractory dyspnea. Expert Rev Respir Med. 2013; 7(2): 123-134.

Mahler DA: Understanding mechanisms and documenting plausibility of palliative interventions for dyspnea. Curr Opin Support Palliat Care. 2011; 5(2): 71-76.

Kotrach HG, Bourbeau J, Jensen D: Does nebulized fentanyl relieve dyspnea during exercise in healthy man? J Appl Physiol. 2015; 118(11): 1406-1414.

Chiang AA: Obstructive sleep apnea and chronic intermittent hypoxia: A review. Chin J Physiol. 2006; 49(5): 234-243.

Ciftci TU, Kokturk O, Ozkan S: Apnea-hypopnea indexes calculated using different hypopnea definitions and their relation to major symptoms. Sleep Breath. 2004; 8(3): 141-146.

De Backer W: Obstructive sleep apnea/hypopnea syndrome. Panminerva Med. 2013; 55(2): 191-195.

Young T, Peppard PE, Gottlieb DJ: Epidemiology of obstructive sleep apnea: A population health perspective. Am J Respir Crit Care Med. 2002; 165(9): 1217-1239.

Young T, Shahar E, Nieto FJ, et al.: Predictors of sleep-disordered breathing in community-dwelling adults: The Sleep Heart Health Study. Archiv Internal Med. 2002; 162(8): 893-900.

Kutty K: Sleep and chronic obstructive pulmonary disease. Curr Opin Pulmonary Med. 2004; 10(2): 104-112.

Lin CC, Huang WC: [Sleep quality and nocturnal hypoxemia in patients with chronic obstructive pulmonary disease]. J Formosan Med Assoc. 1992; 91(suppl 3): S232-S238.

Reuveni H, Tarasiuk A, Wainstock T, et al.: Awareness level of obstructive sleep apnea syndrome during routine unstructured interviews of a standardized patient by primary care physicians. Sleep. 2004; 27(8): 1518-1525.

Lu B, Budhiraja R, Parthasarathy S: Sedating medications and undiagnosed obstructive sleep apnea: Physician determinants and patient consequences. J Clin Sleep Med. 2005; 1(4): 367-371.

Vozoris NT: Do benzodiazepines contribute to respiratory problems? Expert Rev Respir Med. 2014; 8(6): 661-663.

Vozoris NT, Fischer HD, Wang X, et al.: Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD. Eur Respir J. 2014; 44(2): 332-340.

Tarasiuk A, Greenberg-Dotan S, Simon-Tuval T, et al.: The effect of obstructive sleep apnea on morbidity and health care utilization of middle-aged and older adults. J Am Geriatr Soc. 2008; 56(2): 247-254.

Reuveni H, Greenberg-Dotan S, Simon-Tuval T, et al.: Elevated healthcare utilisation in young adult males with obstructive sleep apnoea. Eur Respir J. 2008; 31(2): 273-279.

Davis MJ, Livingston M, Scharf SM: Reversal of central sleep apnea following discontinuation of opioids. J Clin Sleep Med. 2012; 8(5): 579-580.

Selim BJ, Koo BB, Qin L, et al.: The association between nocturnal cardiac arrhythmias and sleep-disordered breathing: The DREAM study. J Clin Sleep Med. 2016; 12(6): 829-837.

Namtvedt SK, Randby A, Einvik G, et al.: Cardiac arrhythmias in obstructive sleep apnea (from the Akershus Sleep Apnea Project). Am J Cardiol. 2011; 108(8): 1141-1146.

Olmetti F, La Rovere MT, Robbi E, et al.: Nocturnal cardiac arrhythmia in patients with obstructive sleep apnea. Sleep Med. 2008; 9(5): 475-480.

Mehra R, Benjamin EJ, Shahar E, et al.: Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. Am J Respir Crit Care Med. 2006; 173(8): 910-916.

Gami AS, Howard DE, Olson EJ, et al.: Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005; 352(12): 1206-1214.

Monahan K, Storfer-Isser A, Mehra R, et al.: Triggering of nocturnal arrhythmias by sleep-disordered breathing events. J Am Coll Cardiol. 2009; 54(19): 1797-1804.

Dursunoglu D, Dursunoglu N: Effect of CPAP on QT interval dispersion in obstructive sleep apnea patients without hypertension. Sleep Med. 2007; 8(5): 478-483.

Guilleminault C, Connolly SJ, Winkle RA: Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome. Am J Cardiol. 1983; 52(5): 490-494.

Lopez-Padilla D, Alonso-Moralejo R, Martinez-Garcia MA, et al.: Continuous positive airway pressure and survival of very elderly persons with moderate to severe obstructive sleep apnea. Sleep Med. 2016; 19: 23-29.

Gami AS, Olson EJ, Shen WK, et al.: Obstructive sleep apnea and the risk of sudden cardiac death: A longitudinal study of 10,701 adults. J Am Coll Cardiol. 2013; 62(7): 610-616.

Marin JM, Agusti A, Villar I, et al.: Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012; 307(20): 2169-2176.

Abe H, Takahashi M, Yaegashi H, et al.: Efficacy of continuous positive airway pressure on arrhythmias in obstructive sleep apnea patients. Heart Vessels. 2010; 25(1): 63-69.

Pepperell JC, Davies RJ, Stradling JR: Systemic hypertension and obstructive sleep apnoea. Sleep Med Rev. 2002; 6(3): 157-173.

Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, et al.: Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: A randomised parallel trial. Lancet. 2002; 359(9302): 204-210.

Rossi VA, Stradling JR, Kohler M: Effects of obstructive sleep apnoea on heart rhythm. Eur Respir J. 2013; 41(6): 1439-1451.

Mieczkowski B, Ezzie ME: Update on obstructive sleep apnea and its relation to COPD. Int J Chron Obstruct Pulmon Dis. 2014; 9: 349-362.

Douglas NJ, White DP, Pickett CK, et al.: Respiration during sleep in normal man. Thorax. 1982; 37(11): 840-844.

Shepard JW Jr: Gas exchange and hemodynamics during sleep. Med Clin N Am. 1985; 69(6): 1243-1264.

Owens RL, Malhotra A: Sleep-disordered breathing and COPD: The overlap syndrome. Respir Care. 2010; 55(10): 1333-1344.

Gothe B, Goldman MD, Cherniack NS, et al.: Effect of progressive hypoxia on breathing during sleep. Am Rev Respir Dis. 1982; 126(1): 97-102.

Sanders MH, Newman AB, Haggerty CL, et al.: Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. Am J Respir Crit Care Med. 2003; 167(1): 7-14.

Sanders MH: The upper airway and sleep-disordered breathing: Getting the big picture. Am J Respir Crit Care Med. 2003; 168(5): 509-510.

Fleetham J, West P, Mezon B, et al.: Sleep, arousals, and oxygen desaturation in chronic obstructive pulmonary disease. The effect of oxygen therapy. Am Rev Respir Dis. 1982; 126(3): 429-433.

Gay PC: Chronic obstructive pulmonary disease and sleep. Respir Care. 2004; 49(1): 39-51.

Ali Zohal M, Yazdi Z, Kazemifar AM: Daytime sleepiness and quality of sleep in patients with COPD compared to control group. Global J Health Sci. 2013; 5(3): 150-155.

Budhiraja R, Siddiqi TA, Quan SF: Sleep disorders in chronic obstructive pulmonary disease: Etiology, impact, and management. J Clin Sleep Med. 2015; 11(3): 259-270.

Yue W, Hao W, Liu P, et al.: A case-control study on psychological symptoms in sleep apnea-hypopnea syndrome. Can J Psychiat Rev. 2003; 48(5): 318-323.

Di Marco F, Verga M, Reggente M, et al.: Anxiety and depression in COPD patients: The roles of gender and disease severity. Res Med. 2006; 100(10): 1767-1774.

Douglas NJ, Engleman HM: Effects of CPAP on vigilance and related functions in patients with the sleep apnea/hypopnea syndrome. Sleep. 2000; 23(suppl 4): S147-S149.

Engleman HM, Kingshott RN, Martin SE, et al.: Cognitive function in the sleep apnea/hypopnea syndrome (SAHS). Sleep. 2000; 23(suppl 4): S102-S108.

Kingshott RN, Vennelle M, Hoy CJ, et al.: Predictors of improvements in daytime function outcomes with CPAP therapy. Am J Respir Crit Care Med. 2000; 161(3 Pt 1): 866-871.

Park B, Palomares JA, Woo MA, et al.: Aberrant insular functional network integrity in patients with obstructive sleep apnea. Sleep. 2016; 39(5): 989-1000.

Kumar R, Macey PM, Cross RL, et al.: Neural alterations associated with anxiety symptoms in obstructive sleep apnea syndrome. Depress Anxiety. 2009; 26(5): 480-491.

Cross RL, Kumar R, Macey PM, et al.: Neural alterations and depressive symptoms in obstructive sleep apnea patients. Sleep. 2008; 31(8): 1103-1109.

Naegele B, Thouvard V, Pepin JL, et al.: Deficits of cognitive executive functions in patients with sleep apnea syndrome. Sleep. 1995; 18(1): 43-52.

Bedard MA, Montplaisir J, Richer F, et al.: Obstructive sleep apnea syndrome: Pathogenesis of neuropsychological deficits. J Clin Exp Neuropsychol. 1991; 13(6): 950-964.

Marin JM, Soriano JB, Carrizo SJ, et al.: Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010; 182(3): 325-331.

Ganga HV, Nair SU, Puppala VK, et al.: Risk of new-onset atrial fibrillation in elderly patients with the overlap syndrome: a retrospective cohort study. J Geriatr Cardiol. 2013; 10(2): 129-134.

Taranto-Montemurro L, Messineo L, Perger E, et al.: Cardiac sympathetic hyperactivity in patients with chronic obstructive pulmonary disease and obstructive sleep apnea. COPD. 2016; 3(6): 1-6.

Mansukhani MP, Kara T, Caples SM, et al.: Chemoreflexes, sleep apnea, and sympathetic dysregulation. Curr Hypertens Rep. 2014; 16(9): 476.

Rose AR, Catcheside PG, McEvoy RD, et al.: Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy. J Clin Sleep Med. 2014; 10(8): 847-852.

Lee LA, Caplan RA, Stephens LS, et al.: Postoperative opioid-induced respiratory depression: A closed claims analysis. Anesthesiology. 2015; 122(3): 659-665.

Chung F, Liao P, Elsaid H, et al.: Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology. 2014; 120(2): 299-311.

Lam KK, Kunder S, Wong J, et al.: Obstructive sleep apnea, pain, and opioids: Is the riddle solved? Curr Opin Anaesthesiol. 2016; 29(1): 134-140.

Hudgel DW, Hendricks C: Palate and hypopharynx—Sites of inspiratory narrowing of the upper airway during sleep. Am Rev Respir Dis. 1988; 138(6): 1542-1547.

Hudgel DW, Hendricks C, Dadley A: Alteration in obstructive apnea pattern induced by changes in oxygen- and carbon-dioxide-inspired concentrations. Am Rev Respir Dis. 1988; 138(1): 16-19.

Hanly P, Powles P: Hypnotics should never be used in patients with sleep apnea. J Psychosomat Res. 1993; 37(suppl 1): 59-65.

Stuth EA, Stucke AG, Zuperku EJ: Effects of anesthetics, sedatives, and opioids on ventilatory control. Compr Physiol. 2012; 2(4): 2281-2367.

Pampati S, Manchikanti L: What is the prevalence of symptomatic obstructive sleep apnea syndrome in chronic spinal pain patients? An assessment of the correlation of OSAS with chronic opioid therapy, obesity, and smoking. Pain Physician. 2016; 19(4): E569-E579.

Olmos SR, Garcia-Godoy F, Hottel TL, et al.: Headache and jaw locking comorbidity with daytime sleepiness. Am J Dentistry. 2016; 29(3): 161-165.

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

Mogri M, Khan MI, Grant BJ, et al.: Central sleep apnea induced by acute ingestion of opioids. Chest. 2008; 133(6): 1484-1488.

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

Sharkey KM, Kurth ME, Anderson BJ, et al.: Assessing sleep in opioid dependence: A comparison of subjective ratings, sleep diaries, and home polysomnography in methadone maintenance patients. Drug Alcohol Depend. 2011; 113(2-3): 245-248.

Farney RJ, McDonald AM, Boyle KM, et al.: Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone. Eur Respir J. 2013; 42(2): 394-403.

Mogri M, Desai H, Webster L, et al.: Hypoxemia in patients on chronic opiate therapy with and without sleep apnea. Sleep Breath. 2009; 13(1): 49-57.

Webster LR, Choi Y, Desai H, et al.: Sleep-disordered breathing and chronic opioid therapy. Pain Med. 2008; 9(4): 425-432.

Schwarzer A, Aichinger-Hinterhofer M, Maier C, et al.: Sleep-disordered breathing decreases after opioid withdrawal: Results of a prospective controlled trial. Pain. 2015; 156(11): 2167-2174.

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.

Correa D, Farney RJ, Chung F, et al.: Chronic opioid use and central sleep apnea: A review of the prevalence, mechanisms, and perioperative considerations. Anesth Analg. 2015; 120(6): 1273-1285.

Filiatrault ML, Chauny JM, Daoust R, et al.: Medium increased risk for central sleep apnea but not obstructive sleep apnea in long-term opioid users: A systematic review and metaanalysis. J Clin Sleep Med. 2016; 12(4): 617-625.

Hassamal S, Miotto K, Wang T, et al.: A narrative review: The effects of opioids on sleep disordered breathing in chronic pain patients and methadone maintained patients. Am J Addict. 2016; 25(6): 452-465.

Ekstrom M, Bornefalk-Hermansson A, Abernethy A, et al.: Low-dose opioids should be considered for symptom relief also in advanced chronic obstructive pulmonary disease (COPD). Evid Based Med. 2015; 20(1): 39.

Vozoris NT, Gill SS, O'Donnell DE: Opioids in COPD: The ‘whole picture’ includes results from real-world, population-based observational studies. Br J Clin Pharmacol. 2016; 81(4): 797-798.

Vozoris NT, O'Donnell DE, Bell CM, et al.: Opioids in COPD: A cause of death or a marker of illness severity? Eur Respir J. 2016; 48(5): 1521-1522.

Smallwood N, Le B, Currow D, et al.: Management of refractory breathlessness with morphine in patients with chronic obstructive pulmonary disease. Internal Med J. 2015; 45(9): 898-904.

Lanken PN, Terry PB, Delisser HM, et al.: An official American Thoracic Society clinical policy statement: Palliative care for patients with respiratory diseases and critical illnesses. Am J Respir Crit Care Med. 2008; 177(8): 912-927.

Mahler DA, Selecky PA, Harrod CG, et al.: American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease. Chest. 2010; 137(3): 674-691.

Sanders MH: Sleep-disordered breathing. Sleep Med. 2003; 4(5): 469-471.

Chaouat A, Weitzenblum E, Krieger J, et al.: Association of chronic obstructive pulmonary disease and sleep apnea syndrome. Am J Respir Crit Care Med. 1995; 151(1): 82-86.

Douglas NJ, White DP, Weil JV, et al.: Hypoxic ventilator response decreases during sleep in normal men. Am Rev Respir Dis. 1982; 125(3): 286-289.

Elkington H, White P, Addington-Hall J, et al.: The healthcare needs of chronic obstructive pulmonary disease patients in the last year of life. Palliat Med. 2005; 19(6): 485-491.

Vozoris NT: Response to Ekstrom et al regarding low-dose opioids in advanced chronic obstructive pulmonary disease. Evid Based Med. 2015; 20(1): 40.

Chung F, Abdullah HR, Liao P: STOP-bang questionnaire: A practical approach to screen for obstructive sleep apnea. Chest. 2016; 149(3): 631-638.

Wang TY, Lo YL, Lee KY, et al.: Nocturnal CPAP improves walking capacity in COPD patients with obstructive sleep apnoea. Respir Res. 2013; 14: 66.

Epstein LJ, Kristo D, Strollo PJ Jr, et al.: Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009; 5(3): 263-276.

Loredo JS, Ancoli-Israel S, Kim EJ, et al.: Effect of continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: A placebo-CPAP-controlled study. Sleep. 2006; 29(4): 564-571.

Jaoude P, Lal A, Vermont L, et al.: Pain intensity and opioid utilization in response to CPAP therapy in veterans with obstructive sleep apnea on chronic opioid treatment. J Clin Sleep Med. 2016; 12(8): 1105-1111.

Vozoris NT, Wang X, Fischer HD, et al.: Incident opioid drug use among older adults with chronic obstructive pulmonary disease: A population-based cohort study. Br J Clin Pharmacol. 2016; 81(1): 161-170.

Vozoris NT, O'Donnell DE, Bell C, et al.: Incident opioid use is associated with risk of respiratory harm in non-palliative COPD. Eur Respir J. 2017; 49(3): 1602529.

Borge CR, Wahl AK, Moum T: Pain and quality of life with chronic obstructive pulmonary disease. Heart Lung. 2011; 40(3): e90-e101.

Chaparro LE, Furlan AD, Deshpande A, et al.: Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013; (8): CD004959.

Ballantyne JC: Avoiding opioid analgesics for treatment of chronic low back pain. JAMA. 2016; 315(22): 2459-2460.

Lee-Iannotti J, Parish JM: The epidemic of opioid use: Implications for the sleep physician. J Clin Sleep Med. 2014; 10(6): 645-646.

Shinde S, Gordon P, Sharma P, et al.: Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: Does this improve pain control and reduce opioid requirements? Support Care Cancer. 2015; 23(3): 695-703.

Colella J, Scrofine S, Galli B, et al.: Prostate HDR radiation therapy: A comparative study evaluating the effectiveness of pain management with peripheral PCA vs. PCEA. Urolog Nurs. 2006; 26(1): 57-61.

Nightengale B, Brune M, Blizzard SP, et al.: Strontium chloride Sr 89 for treating pain from metastatic bone disease. Am J Health Syst Pharmacy. 1995; 52(20): 2189-2195.

Joishy SK, Walsh D: The opioid-sparing effects of intravenous ketorolac as an adjuvant analgesic in cancer pain: Application in bone metastases and the opioid bowel syndrome. J Pain Sympt Manage. 1998; 16(5): 334-339.

Lauretti GR, Lima IC, Reis MP, et al.: Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management. Anesthesiology. 1999; 90(6): 1528-1533.

Lema MJ: Emerging options with coxib therapy. Cleveland Clin J Med. 2002; 69(suppl 1): SI76-S184.

Sun WZ, Chang MC, Hsiao PN, et al.: Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine. Int J Immunopathol Pharmacol. 2010; 23(1): 91-104.

Raptis E, Vadalouca A, Stavropoulou E, et al.: Pregabalin vs. opioids for the treatment of neuropathic cancer pain: A prospective, head-to-head, randomized, open-label study. Pain Pract. 2014; 14(1): 32-42.

Webster LR, Smith MD, Mackin S, et al.: Comparative effects of morning vs. evening dosing of extended-release hydromorphone on sleep physiology in patients with low back pain: A pilot study. Pain Med. 2015; 16(3): 460-471.

Vozoris NT: Benzodiazepines and opioids need to be prescribed with caution in advanced COPD. Evid Based Med. 2014; 19(5): 170.

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.

Troitino A, Labedi N, Kufel T, et al.: Positive airway pressure therapy in patients with opioid-related central sleep apnea. Sleep Breath. 2014; 18(2): 367-373.

Wang D, Rowsell L, Yee BJ: Positive airway pressure treatment for opioid-related central sleep apnea, where are we now? Sleep Breath. 2014; 18(2): 229-231.

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.

Javaheri S, Harris N, Howard J, et al.: Adaptive servoventilation for treatment of opioid-associated central sleep apnea. J Clin Sleep Med. 2014; 10(6): 637-643.

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.

Van Ryswyk E, Antic NA: Opioids and sleep-disordered breathing. Chest. 2016; 150(4): 934-944.



  • There are currently no refbacks.