0
Contemporary Reviews in Sleep Medicine |

Opioids and Sleep-Disordered Breathing FREE TO VIEW

Emer Van Ryswyk, PhD; Nick A. Antic, PhD
Author and Funding Information

Adelaide Institute for Sleep Health, A Flinders Centre of Research Excellence, Faculty of Medicine, Nursing and Health Sciences, The Flinders University of South Australia, Adelaide, Australia

CORRESPONDENCE TO: Nick A. Antic, PhD, Adelaide Sleep Health, SALHN, Repatriation General Hospital, C-Block, Daws Rd, Daw Park, SA, 5041, Australia


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(4):934-944. doi:10.1016/j.chest.2016.05.022
Text Size: A A A
Published online

Opioid use for chronic pain analgesia, particularly chronic noncancer pain, has increased greatly since the late 1990s, resulting in an increase in opioid-associated morbidity and mortality. A clear link between opioid use and sleep-disordered breathing (SDB) has been established, with the majority of chronic opioid users being affected by the condition, and dose-dependent severity apparent for some opioids. More evidence is currently needed on how to effectively manage opioid-induced SDB. This review summarizes the current state of knowledge relating to management of patients undergoing chronic opioid therapy who have SDB. Initial management of these patients requires a thorough biopsychosocial assessment of their need for opioid therapy, consideration of reduction or cessation of the opioid if possible, and analysis of alternative therapies for treatment of their pain. If opioid therapy must be continued, then management of the associated SDB may be important. Several small- to medium-scale studies have examined the efficacy of noninvasive ventilation, particularly adaptive servo-ventilation (ASV) for the treatment of opioid-associated SDB. This research is particularly important because opioids predispose predominantly to central sleep apnea and also, to a lesser extent, OSA. Generally, these studies have found positive results in treating opioid-associated SDB with ASV in terms of improving outcome measures such as central apnea index and the apnea-hypopnea index. Larger studies that measure longer term health outcomes, patient sleepiness, and compliance are needed, however. Registries of health outcomes of ASV-treated patients may assist with future treatment planning.

Figures in this Article

In recent years, developed countries have reported a large increase in the use of opioid analgesia, particularly for the management of chronic pain, with a doubling of use in the United States and a quadrupling of use in Australia (2011-2013 compared with 2001-2003 use). The United States in combination with Western and Central Europe currently account for 94% of analgesic opioid use worldwide. This finding is likely the result of many factors, including the release of a joint statement on treatment of chronic pain by the American Academy of Pain Medicine and the American Pain Society in 1997., This statement indicated that “pain is often managed inadequately, despite the ready availability of safe and effective treatments.”

The main indications for prescribing opioids are management of opioid dependency, acute pain, terminal pain, and chronic noncancer pain (CNCP). Escalations in the prescribing of opioids for CNCP have been associated with harms, including opioid hyperalgesia, misuse and abuse, and a marked increase in overdose deaths (> 100% increase between 1999 and 2009).,, There is a clear link between opioid use and sleep-disordered breathing (SDB), with dose-dependent severity for certain opioids. Recent research shows that 70% to 85% of patients taking opioids have SDB, and a high proportion of those cases are moderate to severe.,, Although there is a clear link between opioid use and SDB, how to effectively manage this SDB is much less clear. The present review summarizes the current state of knowledge relating to management of patients undergoing chronic opioid therapy who have SDB.

Opioids act on receptors that are members of the G protein-coupled receptor family. Pain, respiratory control, stress responses, appetite, and thermoregulation are all mediated by the endogenous opioid system. The brainstem generates respiratory drive, and this drive is influenced by conscious inputs from the cortex as well as central and peripheral chemoreceptors that sense changes in the chemical constituents of blood. Opioid-induced impairment of breathing encompasses central depression of the respiratory rate, amplitude and reflex responses, and reduced brain arousability, as well as upper airway dysfunction.,, Opioid medications that act on μ-opioid receptors present the potentially lethal side effect of respiratory depression, and the development of therapies to reduce this side effect is limited because the critical neural sites and mechanisms of action of opioids in causing respiratory depression remain unclear., One particular opioid-sensitive neural site, known as the pre-Bötzinger complex, has been studied closely in recent years because it is believed to have the inherent capacity to generate breathing rhythm. Although the exact role of this complex is still being elucidated, the isolated complex in vitro is being used to develop and test new therapies aiming to prevent respiratory depression.,,,,,

Management and assessment of opioid-associated breathing requires knowledge of the various abnormal breathing patterns that may result from opioid treatment (Fig 1). These patterns include ataxic breathing, Biot respiration, Cheyne-Stokes respiration, OSA, and central sleep apnea (CSA).,,, Ataxic breathing and Biot respiration are sometimes referred to interchangeably, although generally ataxic breathing is characterized by irregular frequency and tidal volume interspersed with unpredictable pauses in breathing or periods of apnea, whereas Biot respiration refers to a high frequency and regular tidal volume breathing interspersed with periods of apnea. Cheyne-Stokes respiration is characterized by a cyclical crescendo-decrescendo pattern of breathing, followed by periods of central apnea.

Figure 1
Figure Jump LinkFigure 1 Abnormal patterns of breathing associated with opioid use.Grahic Jump Location

A systematic review published in 2015, which examined the prevalence of SDB associated with chronic opioid therapy, found that, in general, the prevalence of OSA has been reported to be lower than the prevalence of CSA with opioid use (10% vs 60% and 8% vs 30%, respectively), although the exact distribution of CSA compared with OSA was difficult to determine.,, CSA is a term that describes a group of conditions characterized by the occurrence of cessations in airflow in the absence of the usual corresponding respiratory effort; this contrasts with OSA, in which there is ongoing respiratory effort during obstructive respiratory events. The systematic review found that hypoxemia is frequently associated with opioid use (in 62.5% of studies), although estimating the prevalence of hypoxemia during sleep was not possible due to heterogeneity among the studies.

The mechanisms are not fully understood, but it is believed that OSA occurs in some people using opioids because of opioid-induced reductions in airway muscle activation. CSA is postulated to arise from depression of hypoxic and hypercapnic ventilatory drives. There is evidence that with chronic opioid use, the balance between hypoxic and hypercapnic ventilatory drive changes, such that while the hypoxic ventilatory drive may recover or be augmented, depression of hypercapnic ventilation remains. This scenario may explain the characteristic episodes of under-breathing followed by augmentation of ventilation in response to hypoxemia that are observed with opioid use. Depression of hypercapnic drive would explain increases in Pco2 measured in a study of patients using opioid therapy for chronic pain analgesia; in this prospective study, mean (awake) Pco2 was 44.8 ± 4.1 mg, with a median Pco2 of 44.9 mg in the 24 included patients. Although the mean Pco2 was at the high end of the normal range, nine of the participants were reported to have hypercapnia (defined as Pco2 ≥ 45 mg) on daytime arterial blood gas (ABG) measurement, whereas two had even more pronounced hypercapnia., These findings are concerning given that the participants had normal lung function (measured by using spirometry) and were previously unaware of their hypercapnia. Furthermore, there is no current way of predicting who is at risk of this kind of borderline respiratory failure and at what dose of opioids. Screening all patients on opioid therapy by using ABG measurement is likely to be impractical, and more research is needed in this area.

Given the limitations of ABG measurement such as pain and cost, two noninvasive measures of CO2 measurement have been increasingly adopted into sleep studies. These measures are capnography, otherwise known as end-tidal CO2 (PETCO2) monitoring, and transcutaneous CO2 (PtCO2) monitoring. PETCO2 monitoring has been validated as an accurate indicator of arterial CO2 levels in patients who have undergone endotracheal intubation, and it has been used previously for patients with OSA. However, when supplemental oxygen or positive airway pressure are used, PETCO2 monitoring is less accurate. Difficulties with interpretation of PtCO2 monitoring may be encountered with patients with perfusion problems, skin diseases, edema, or hypovolemia. Recent studies assessing the efficacy of ASV or bi-level ventilation for treatment of opioid-induced SDB (described in the following text and in Table 1) did not measure either PETCO2 or PtCO2; it is therefore important that future studies take these measurements.

Table Graphic Jump Location
Table 1 Studies Examining Use of Positive Pressure Ventilation for Treatment of Opioid-Induced SDB
a ASVAuto in this study refers to enhanced minute ventilation-targeted ASV with auto titrating expiratory positive airway pressure (ResMed Ltd).

AHI = apnea-hypopnea index; AASM = American Academy of Sleep Medicine; ASV = adaptive servo-ventilation; CAI = central apnea index; CHF = congestive heart failure; CSA = central sleep apnea; CSR = Cheyne-Stokes respiration; ESS = Epworth Sleepiness Scale; HI = hypopnea index; OAI = obstructive apnea index; ODI = oxygen desaturation index; O2 = oxygen; PAP = positive airway pressure; PSG = polysomnogram; SaO2 = arterial oxygen saturation; SpO2 = oxygen saturation using pulse oximetry; SDB = sleep-disordered breathing; ST = spontaneous timed.

Another area of continued uncertainty is the ability to drive safely while taking opioids. A systematic review published in 2003 concluded that opioids do not impair driving-related skills in opioid-dependent or opioid-tolerant patients, in contrast to those who are opioid naive who do have dose-related impairment in their psychomotor skills related to driving. A more recent systematic review found that only a subset of patients on opioid therapy, who meet certain criteria, may be safe to drive. The review suggested that driving may be safe only for those who are taking pharmacologically stable doses of opioids; who are not concurrently taking other psychoactive drugs, alcohol, or illicit drugs; and who do not experience high levels of pain during therapy nor have a substantial sleep disorder, psychiatric condition, or excessive daytime sleepiness. It is, however, common that patients taking opioid medications are concurrently taking other psychoactive medications. The review findings concur with more recent findings from Rose et al, who discovered that the study patients, recruited from a chronic pain clinic, consistently performed poorly on the 10-min psychomotor vigilance task they were administered. Compared with healthy control subjects, who were similar in mean age and sex distribution but had lower mean BMI, the opioid-using participants in the study by Rose et al had significantly higher mean reaction times and more frequent minor lapses. More research is needed to explore and clarify effects of chronic opioid therapy on driving ability. Development of a broadly acceptable driving screening test may prove clinically useful.

Recommendations relating to management of opioid-induced SDB are hampered by a lack of research on the topic. Details on each care option and their evidence base are described in this section.

Reduction or Cessation of Opioid Therapy: Options and Considerations

Assessment of the need for opioids, in conjunction with the individual patient and the opioid-prescribing practitioner, is an essential part of initial management. Cochrane reviews on the use of opioids for treating rheumatoid arthritis, osteoarthritis (knee and hip), low back pain, and neuropathic pain have all found that there is insufficient evidence for long-term opioid use.,,, Common findings include that limited evidence (of low to moderate quality) exists of short-term analgesic efficacy and that adverse effects are so frequent that they may outweigh any analgesic benefit. Evidence for longer term efficacy was lacking.

The poor-quality evidence for long-term efficacy of opioids should be particularly concerning when considering the loss of analgesic efficacy due to pharmacologic tolerance or opioid-induced hyperalgesia (worsening pain sensitivity in patients chronically exposed to opioids) and the litany of associated morbidities and increased risk of mortality with chronic opioid use. In addition to SDB, adverse effects of opioid use can include addiction, hypogonadism, infertility, immunosuppression, falls and fractures in older adults, neonatal abstinence syndrome, cardiac problems such as QT prolongation, hyperalgesia, increased ED visits, constipation, nausea, vomiting, dizziness, drowsiness, respiratory depression, and death., There is evidence that SDB can be reversed with cessation of opioids, although more research is needed into the relationship between appropriate dose reduction and improvements in SDB.

The Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain was published in March 2016. This guideline provides recommendations for clinicians prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care, and it addresses opioid initiation, selection, prescribing, and risks. The CDC guidelines recommend that if opioid use is indicated, treatment should be initiated with immediate-release (IR) preparations rather than extended-release/long-acting (ER/LA) preparations. This recommendation is for a variety of reasons, including a lower risk of overdose and a lack of evidence that ER/LA preparations are more effective or safer. The benefits of using IR opioid medications rather than ER/LA preparations may include reductions in both respiratory depression and SDB frequency; this area warrants further research. However, the guidelines also state that ER/LA opioids may be considered for patients with severe, continuous pain who have received IR opioids daily for at least 1 week, and thus it is possible that those patients who have previously been prescribed ER/LA agents for chronic pain will continue to have ER/LA opioids prescribed, and those with more recent onset chronic pain may only be prescribed IR opioids for a short time before moving to ER/LA opioids. Thus, clinicians should pay careful attention when prescribing or taking a history of opioid use (eg, duration of action, dose and frequency) in their patients to make an assessment of how such factors may influence their breathing.

With regard to opioid use in subjects with SDB, the 2016 CDC guidelines recommend careful monitoring and cautious dose titration in mild SDB and avoidance of opioids in patients with moderate or severe SDB wherever possible due to the risk of overdose. Several other sources of information are available on opioid prescribing.,,,, A key common recommendation is use of nonpharmacologic therapies and nonopioid therapies wherever possible for chronic pain, rather than routine use of opioids. Such recommendations are highly prudent, although currently available alternative therapies (eg, antidepressant agents, anticonvulsant medications, nonsteroidal antiinflammatory agents, acetaminophen [paracetamol]) are also somewhat limited by side effects and/or lack of evidence for efficacy, and thus further research is necessary.,,,,,,,,,,,

Use of Positive Pressure Ventilation Modes for Treatment of SDB in Chronic Opioid Use

When long-term treatment with opioid therapy is continued, treatment of associated SDB is important. Small- to medium-scale studies have been conducted on the topic of treatment of opioid-induced SDB, although more research is needed in this area.,,,,,,,Table 1 provides details on studies that have examined the use of noninvasive positive pressure ventilation modes, including CPAP, adaptive servo-ventilation (ASV), and bi-level spontaneous timed (ST) therapy.

ASV was initially designed for patients with congestive heart failure, although more recent indications have been extended to cover other causes of CSA, including opioid-induced CSA. ASV allows variable inspiratory support, in addition to a fixed or automatic expiratory pressure. To minimize the risk of chronic hyperventilation, the support in inspiration varies between cycles based on the ventilation level measured in the patient. In the studies described in Table 1, ASV is compared with either CPAP or bi-level ST. In contrast to ASV, in which variable inspiratory support is provided, CPAP splints the airway open by providing a constant stream of positive pressure by blowing air through the nose/mouth and into the upper airways. Bi-level therapy uses two levels of pressure, an inspiratory pressure and an expiratory pressure; such devices are beneficial to people who have difficulty exhaling against standard CPAP pressure. Bi-level with ST machines determine the timing of when the user breathes in and out, whereas standard bi-level machines react to the users’ breathing.

The currently available literature points to use of ASV for controlling CSA associated with chronic opioid use, although further, larger and well-designed studies are needed on this topic. Sample sizes of existing studies (Table 1) ranged from six (of which only four received treatment) to 47 subjects., Studies have generally focused on AHI and CAI measurement rather than on patient symptoms. Only two studies measured patient symptoms., Alattar and Scharf reported scores on the Epworth Sleepiness Scale from just four participants, with improvements ranging from 4 to 9 points with bi-level titration. Cao et al found that participants were more likely to report feeling more awake and alert on ASVAuto than on bi-level ST, according to scores on their Morning After Patient Satisfaction Questionnaire (which contained questions relating to the patient’s sleep quality on the preceding night).

Of six recent studies, five indicated that ASV reduced AHI and CAI significantly, although AHI was not consistently reduced to < 10 per hour. The most recent study found that the benefits of ASV extended beyond the initial titration night into 3 months of home use. One of the six studies had less positive results. In this study, default settings were used (ie, end-positive airway pressure of 5 cm H2O, minimum pressure support of 3 cm H2O, maximum pressure support of 10 cm H2O). As previously reported by Cao et al, expiratory positive airway pressure set at 5 cm H2O was likely below the pressure required to maintain upper airway patency, and residual respiratory events therefore remained.

Recent results from the Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure (SERVE-HF) study are likely to make physicians more reluctant to use ASV devices. This trial (N = 1325) investigated the effects of ASV in patients with heart failure and reduced ejection fraction. Preliminary results of the study were reported in May 2015, with an increased risk of cardiovascular death in symptomatic patients with chronic heart failure and impaired left ventricular ejection fraction who were treated with ASV., This risk of death occurred despite normalization of AHI on ASV, was constant over time, and was independent of the clinical benefit perceived by the patient., Further analyses are in progress to investigate the cause of the increased cardiovascular mortality as well as to identify the most and least susceptible subgroups of patients. A safety warning was issued by ResMed as a result of the SERVE-HF findings; this warning was quickly communicated by several medical organizations, such as the American Academy of Sleep Medicine., It is now contraindicated to implement ASV in patients with chronic symptomatic systolic heart failure (New York Heart Association functional classes II-IV) with left ventricular ejection fraction ≤ 45% and mainly central AHI (≥ 50% central events).

It is important to note that the SERVE-HF results are not recommended to be extrapolated to patient groups other than those defined by the inclusion criteria of the study. SERVE-HF participants were likely to have significantly more cardiac dysfunction than patients with SDB who were taking opiates. Although, given the SERVE-HF findings, if patients have predominantly CSA, an echocardiogram to assess left ventricular function seems prudent before using ASV devices in this group.

French experts have recommended creating comprehensive registries of patients treated with ASV for CSA syndromes to study health outcomes. Beneficial items to include on such a register may be medical history, indication for use of ASV, implementation details (eg, CPAP failure, first-line prescription), therapeutic benefit (eg, reductions in abnormal respiratory events, daytime sleepiness, improvements in quality of life), compliance with ASV, and health outcomes such as hospitalizations, cardiovascular events, and mortality.

Several unanswered questions remain regarding the management of patients taking opioid therapy for chronic pain. Research into novel therapies and more robust research into existing alternatives to opioid medications are needed. The ultimate goal should be optimal patient analgesia with minimum side effects. Recently, research into the pharmacology of opiods has moved from the study of steroselective neuronal actions, to nonneuronal actions, particularly nonclassic and nonstereoselective sites of action. It has become apparent that opioids act on the innate immune pattern recognition receptors (the Toll-like receptors [TLRs]), and these signaling events modify the pharmacodynamics of opioids by stimulating proinflammatory reactivity from glia (immunocompetent cells of the CNS). Elevated neuronal excitability is a result of central immune signaling events, leading to heightened pain states and decreases in opioid analgesic efficacy. Therefore, it may be possible to improve analgesic effects of opiods through co-administration of: (1) general glial attenuators, including ibudilast, minocycline, propentofylline, or pentoxifylline; (2) glutamate transport enhancers, such as ceftriaxone; (3) drugs that block proinflammatory activity, such as IL-1 receptor antagonists; (4) drugs that encourage antiinflammatory conditions (eg, amitriptyline, ultra-low-dose naltrexone/naloxone); (5) a drug that blocks TLRs known to trigger the cascade; or (6) a molecule that combines general glial attenuator and/or TLR inhibitoin with opioid agonist activity. Further research into coadministration of these therapies is needed, particularly with respect to the long-term systemic immunologic consequences.

More research is also needed regarding risk factors for hypercapnia in opioid users and specifically which target groups should be screened clinically for this pathology. It may be useful to develop screening tools to aid clinicians with identifying patients undergoing opioid therapy who are at increased risk of SDB, such that they can be referred for formal screening. Further research into opioid dose and CSA, including effects of tapering opioid doses, is required. Development of widely acceptable driving assessments would likely be beneficial for clinicians managing patients on opioid therapy., For preexisting opioid alternatives, high-quality, randomized controlled trials with long-term follow-up are needed.

Thus, to summarize unanswered questions:

  • What opioid doses put patients at risk of SDB?

  • Which patients are at risk of hypercapnia and how can that risk best be predicted?

  • Can effective screening tools be developed to aid clinical identification of those at increased risk of SDB?

  • What novel therapies could be used to reduce opioid dose and SDB risk?

  • Do positive airway pressure therapies lead to favorable long-term health outcomes in opioid-related SDB?

  • How can we better predict driving safety in patients on opioid therapy?

Opioid use increases the likelihood of CSA and, to a lesser extent, OSA. Management of patients undergoing chronic opioid therapy with SDB is hampered by a lack of high-quality evidence. Based on currently available evidence, initial management requires biopsychosocial assessment of patients and their need for opioid therapy, consideration of tapering, or cessation if possible and offering alternative therapies for treatment of their pain. Novel alternatives require investigation, and currently available alternatives require more thorough investigation in high-quality, randomized controlled trials. Management of SDB is important when opioid therapy is continued. Several small- to medium-scale studies have examined the efficacy of noninvasive ventilation, particularly ASV, for the treatment of opioid-associated SDB. Generally, these studies have reported positive results in terms of AHI and CAI reduction with the use of ASV, but they often failed to investigate the impact on patient symptoms, quality of life, and health outcomes with long-term use. Larger, randomized controlled studies with longer term outcomes are needed for more thorough assessment of the efficacy of ASV for the treatment of opioid-associated SDB, and registries of health outcomes of ASV-treated patients may assist with future treatment planning.

Author contributions: E. V. R. and N. A. A. discussed potential review content. E. V. R. drafted and revised the manuscript; and advice on manuscript content as well as editing was provided by N. A. A. Both authors approved the final version of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. A. A. has received research funding from the National Health and Medical Research Council of Australia, Philips Respironics, and Fisher and Paykel; equipment donations from ResMed, Philips Respironics, and SomnoMed Limited; and lecture fees and payment for development of educational presentations from ResMed, AstraZeneca, and GlaxoSmithKline. None declared (E.V.R.).

Manchikanti L. .Helm S. .Fellows B. . Opioid epidemic in the United States. Pain Physician. 2012;15:- [PubMed]journal
 
Berterame S. .Erthal J. .Thomas J. .et al Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet. 2016;387:1644-1656 [PubMed]journal. [CrossRef] [PubMed]
 
Lee-Iannotti J. .Parish J.M. . The epidemic of opioid use: implications for the sleep physician. J Clin Sleep Med. 2014;10:645-646 [PubMed]journal. [PubMed]
 
American Academy of Pain Medicine and the American Pain Society The use of opioids for the treatment of chronic pain. A consensus statement from the American Academy of Pain Medicine and the American Pain Society. Clin J Pain. 1997;13:6-8 [PubMed]journal. [CrossRef] [PubMed]
 
Holiday S. .Hayes C. .Dunlop A. . Opioid use in chronic non-cancer pain. Part 1: known knowns and known unknowns. Australian Family Physician. 2013;42:98-102 [PubMed]journal. [PubMed]
 
Jungquist C.R. .Flannery M. .Perlis M.L. .et al Relationship of chronic pain and opioid use with respiratory disturbance during sleep. Pain Manag Nurs. 2012;13:70-79 [PubMed]journal. [CrossRef] [PubMed]
 
Webster L.R. .Choi Y. .Desai H. .et al Sleep-disordered breathing and chronic opioid therapy. Pain Med. 2008;9:425-432 [PubMed]journal. [CrossRef] [PubMed]
 
Mogri M. .Khan M.I. .Grant B.J. .et al Central sleep apnea induced by acute ingestion of opioids. Chest. 2008;133:1484-1488 [PubMed]journal. [CrossRef] [PubMed]
 
Correa D. .Farney R.J. .Chung F. .et al Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations. Anesth Analg. 2015;120:1273-1285 [PubMed]journal. [CrossRef] [PubMed]
 
Pattinson K.T. . Opioids and the control of respiration. Br J Anaesth. 2008;100:747-758 [PubMed]journal. [CrossRef] [PubMed]
 
Lalley P.M. .Pilowsky P.M. .Forster H.V. .Zuperku E.J. . CrossTalk opposing view: the pre-Botzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics. J Physiol. 2014;592:1163-1166 [PubMed]journal. [CrossRef] [PubMed]
 
Montandon G. .Horner R. . CrossTalk proposal: the preBotzinger complex is essential for the respiratory depression following systemic administration of opioid analgesics. J Physiol. 2014;592:1159-1162 [PubMed]journal. [CrossRef] [PubMed]
 
Smith J.C. .Ellenberger H.H. .Ballanyi K. .et al Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science. 1991;254:726-729 [PubMed]journal. [CrossRef] [PubMed]
 
Manzke T. .Guenther U. .Ponimaskin E.G. .et al 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science. 2003;301:226-229 [PubMed]journal. [CrossRef] [PubMed]
 
Ren J. .Poon B.Y. .Tang Y. .et al Ampakines alleviate respiratory depression in rats. Am J Respir Crit Care Med. 2006;174:1384-1391 [PubMed]journal. [CrossRef] [PubMed]
 
Farney R.J. .Walker J.M. .Cloward T.V. .et al Sleep-disordered breathing associated with long-term opioid therapy. Chest. 2003;123:632-639 [PubMed]journal. [CrossRef] [PubMed]
 
Wang D. .Teichtahl H. . Opioids, sleep architecture and sleep-disordered breathing. Sleep Med Rev. 2007;11:35-46 [PubMed]journal. [CrossRef] [PubMed]
 
Mogri M. .Desai H. .Webster L. .et al Hypoxemia in patients on chronic opiate therapy with and without sleep apnea. Sleep Breath. 2009;13:49-57 [PubMed]journal. [CrossRef] [PubMed]
 
Yuan G. .Drost N. .McIvor A. . Clinical review: respiratory rate and breathing pattern. MUMJ. 2013;10:23-25 [PubMed]journal
 
Teichtahl H. .Prodromidis A. .Miller B. .et al Sleep-disordered breathing in stable methadone programme patients: a pilot study. Addiction. 2001;96:395-403 [PubMed]journal. [CrossRef] [PubMed]
 
Farney R.J. .McDonald A.M. .Boyle K.M. .et al Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone. Eur Respir J. 2013;42:394-403 [PubMed]journal. [CrossRef] [PubMed]
 
Malhotra A. .Owens R.L. . What is central sleep apnea? Respir Care. 2010;55:1168-1178 [PubMed]journal. [PubMed]
 
Hajiha M. .DuBord M.A. .Liu H. .et al Opioid receptor mechanisms at the hypoglossal motor pool and effects on tongue muscle activity in vivo. J Physiol. 2009;587:2677-2692 [PubMed]journal. [CrossRef] [PubMed]
 
Dahan A. .Aarts L. .Smith T.W. . Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology. 2010;112:226-238 [PubMed]journal. [CrossRef] [PubMed]
 
Teichtahl H. .Wang D. .Cunnington D. .et al Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients. Chest. 2005;128:1339-1347 [PubMed]journal. [CrossRef] [PubMed]
 
Rose A.R. .Catcheside P.G. .McEvoy R.D. .et al Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy. J Clin Sleep Med. 2014;10:847-852 [PubMed]journal. [PubMed]
 
Mador M.J. .Henderson J. . Effect of opioids on sleep and breathing in chronic pain patients. J Clin Sleep Med. 2014;10:853-854 [PubMed]journal. [PubMed]
 
Kirk V.G. .Batuyong E.D. .Bohn S.G. . Transcutaneous carbon dioxide monitoring and capnography during pediatric polysomnography. Sleep. 2006;29:1601-1608 [PubMed]journal. [PubMed]
 
Morielli A. .Desjardins D. .Brouillette R.T. . Transcutaneous and end-tidal carbon dioxide pressures should be measured during pediatric polysomnography. Am Rev Respir Dis. 1993;148:1599-1604 [PubMed]journal. [CrossRef] [PubMed]
 
Fishbain D.A. .Cutler R.B. .Rosomoff H.L. .et al Are opioid-dependent/tolerant patients impaired in driving-related skills? A structured evidence-based review. J Pain Symptom Manage. 2003;25:559-577 [PubMed]journal. [CrossRef] [PubMed]
 
Mailis-Gagnon A. .Lakha S.F. .Furlan A. .et al Systematic review of the quality and generalizability of studies on the effects of opioids on driving and cognitive/psychomotor performance. Clin J Pain. 2012;28:542-555 [PubMed]journal. [CrossRef] [PubMed]
 
Whittle S.L. .Richards B.L. .Husni E. .et al Opioid therapy for treating rheumatoid arthritis pain. Cochrane Database Syst Rev. 2011;:CD003113- [PubMed]journal
 
Chaparro L.E. .Furlan A.D. .Deshpande A. .et al Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013;:CD004959- [PubMed]journal
 
da Costa B.R. .Nuesch E. .Kasteler R. .et al Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014;:CD003115- [PubMed]journal
 
McNicol E.D. .Midbari A. .Eisenberg E. . Opioids for neuropathic pain. Cochrane Database Syst Rev. 2013;:CD006146- [PubMed]journal
 
Franklin G.M. . Opioids for chronic noncancer pain. Neurology. 2014;83:1277-1284 [PubMed]journal. [CrossRef] [PubMed]
 
Davis M.J. .Livingston M. .Scharf S.M. . Reversal of central sleep apnea following discontinuation of opioids. J Clin Sleep Med. 2012;8:579-580 [PubMed]journal. [PubMed]
 
Dowell D. .Haegerich T. .Chou R. . CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65:1-49 [PubMed]journal
 
Holiday S. .Hayes C. .Dunlop A. . Opioid use in chronic non-cancer pain. Part 2: prescribing issues and alternatives. Aust Fam Physician. 2013;42:104-111 [PubMed]journal. [PubMed]
 
Freynhagen R. .Geisslinger G. .Schug S.A. . Opioids for chronic non-cancer pain. BMJ. 2013;346:f2937- [PubMed]journal. [CrossRef] [PubMed]
 
Cohen M.L. . Principles of prescribing for persistent non-cancer pain. Aust Prescr. 2013;36:113-115 [PubMed]journal. [CrossRef]
 
Towheed T.E. .Maxwell L. .Judd M.G. .et al Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006;:CD004257- [PubMed]journal
 
Moore R.A. .Derry S. .Aldington D. .et al Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;:CD008242- [PubMed]journal
 
Urquhart D.M. .Hoving J.L. .Assendelft W.W. .et al Antidepressants for non-specific low back pain. Cochrane Database Syst Rev. 2008;:CD001703- [PubMed]journal
 
Hearn L. .Moore R.A. .Derry S. .et al Desipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;:CD011003- [PubMed]journal
 
Lunn M.P. .Hughes R.A. .Wiffen P.J. . Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;:CD007115- [PubMed]journal
 
Hearn L. .Derry S. .Phillips T. .et al Imipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;:CD010769- [PubMed]journal
 
Wiffen P.J. .Derry S. .Moore R.A. . Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2013;:CD006044- [PubMed]journal
 
Enthoven W.T. .Roelofs P.D. .Deyo R.A. .et al Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016;:CD012087- [PubMed]journal
 
Derry S. .Wiffen P.J. .Aldington D. .et al Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;:CD011209- [PubMed]journal
 
Wienecke T. .Gotzsche P.C. . Paracetamol versus nonsteroidal anti-inflammatory drugs for rheumatoid arthritis. Cochrane Database Syst Rev. 2004;26:CD003789- [PubMed]journal
 
Derry S. .Moore R.A. .Rabbie R. . Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2012;:CD007400- [PubMed]journal
 
Gallagher H.C. .Gallagher R.M. .Butler M. .et al Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;:CD011091- [PubMed]journal
 
Shapiro C.M. .Chung S.A. .Wylie P.E. .et al Home-use servo-ventilation therapy in chronic pain patients with central sleep apnea: initial and 3-month follow-up. Sleep Breath. 2015;19:1285-1292 [PubMed]journal. [CrossRef] [PubMed]
 
Javaheri S. .Harris N. .Howard J. .et al Adaptive servoventilation for treatment of opioid-associated central sleep apnea. J Clin Sleep Med. 2014;10:637-643 [PubMed]journal. [PubMed]
 
Cao M. .Cardell C.Y. .Willes L. .et al A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids. J Clin Sleep Med. 2014;10:855-861 [PubMed]journal. [PubMed]
 
Ramar K. .Ramar P. .Morgenthaler T.I. . Adaptive servoventilation in patients with central or complex sleep apnea related to chronic opioid use and congestive heart failure. J Clin Sleep Med. 2012;8:569-576 [PubMed]journal. [PubMed]
 
Alattar M.A. .Scharf S.M. . Opioid-associated central sleep apnea: a case series. Sleep Breath. 2009;13:201-206 [PubMed]journal. [CrossRef] [PubMed]
 
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;4:305-310 [PubMed]journal. [PubMed]
 
Farney R.J. .Walker J.M. .Boyle K.M. .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;4:311-319 [PubMed]journal. [PubMed]
 
Priou P. .d'Ortho M.P. .Damy T. .et al Adaptive servo-ventilation: how does it fit into the treatment of central sleep apnoea syndrome? Expert opinions. Rev Mal Respir. 2015;32:1072-1081 [PubMed]journal. [CrossRef] [PubMed]
 
Cowie M.R. .Woehrle H. .Wegscheider K. .et al Adaptive servo-ventilation for central sleep apnea in systolic heart failure. N Engl J Med. 2015;373:1095-1105 [PubMed]journal. [CrossRef] [PubMed]
 
Johns M.W. . Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep. 1992;15:376-381 [PubMed]journal. [PubMed]
 
American Academy of Sleep Medicine. Special safety notice: ASV therapy for central sleep apnea patients with heart failure. AASA News Archive, 2015.http://www.aasmnet.org/articles.aspx?id=5562. Accessed June 25, 2016.
 

Figures

Figure Jump LinkFigure 1 Abnormal patterns of breathing associated with opioid use.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Studies Examining Use of Positive Pressure Ventilation for Treatment of Opioid-Induced SDB
a ASVAuto in this study refers to enhanced minute ventilation-targeted ASV with auto titrating expiratory positive airway pressure (ResMed Ltd).

AHI = apnea-hypopnea index; AASM = American Academy of Sleep Medicine; ASV = adaptive servo-ventilation; CAI = central apnea index; CHF = congestive heart failure; CSA = central sleep apnea; CSR = Cheyne-Stokes respiration; ESS = Epworth Sleepiness Scale; HI = hypopnea index; OAI = obstructive apnea index; ODI = oxygen desaturation index; O2 = oxygen; PAP = positive airway pressure; PSG = polysomnogram; SaO2 = arterial oxygen saturation; SpO2 = oxygen saturation using pulse oximetry; SDB = sleep-disordered breathing; ST = spontaneous timed.

References

Manchikanti L. .Helm S. .Fellows B. . Opioid epidemic in the United States. Pain Physician. 2012;15:- [PubMed]journal
 
Berterame S. .Erthal J. .Thomas J. .et al Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet. 2016;387:1644-1656 [PubMed]journal. [CrossRef] [PubMed]
 
Lee-Iannotti J. .Parish J.M. . The epidemic of opioid use: implications for the sleep physician. J Clin Sleep Med. 2014;10:645-646 [PubMed]journal. [PubMed]
 
American Academy of Pain Medicine and the American Pain Society The use of opioids for the treatment of chronic pain. A consensus statement from the American Academy of Pain Medicine and the American Pain Society. Clin J Pain. 1997;13:6-8 [PubMed]journal. [CrossRef] [PubMed]
 
Holiday S. .Hayes C. .Dunlop A. . Opioid use in chronic non-cancer pain. Part 1: known knowns and known unknowns. Australian Family Physician. 2013;42:98-102 [PubMed]journal. [PubMed]
 
Jungquist C.R. .Flannery M. .Perlis M.L. .et al Relationship of chronic pain and opioid use with respiratory disturbance during sleep. Pain Manag Nurs. 2012;13:70-79 [PubMed]journal. [CrossRef] [PubMed]
 
Webster L.R. .Choi Y. .Desai H. .et al Sleep-disordered breathing and chronic opioid therapy. Pain Med. 2008;9:425-432 [PubMed]journal. [CrossRef] [PubMed]
 
Mogri M. .Khan M.I. .Grant B.J. .et al Central sleep apnea induced by acute ingestion of opioids. Chest. 2008;133:1484-1488 [PubMed]journal. [CrossRef] [PubMed]
 
Correa D. .Farney R.J. .Chung F. .et al Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations. Anesth Analg. 2015;120:1273-1285 [PubMed]journal. [CrossRef] [PubMed]
 
Pattinson K.T. . Opioids and the control of respiration. Br J Anaesth. 2008;100:747-758 [PubMed]journal. [CrossRef] [PubMed]
 
Lalley P.M. .Pilowsky P.M. .Forster H.V. .Zuperku E.J. . CrossTalk opposing view: the pre-Botzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics. J Physiol. 2014;592:1163-1166 [PubMed]journal. [CrossRef] [PubMed]
 
Montandon G. .Horner R. . CrossTalk proposal: the preBotzinger complex is essential for the respiratory depression following systemic administration of opioid analgesics. J Physiol. 2014;592:1159-1162 [PubMed]journal. [CrossRef] [PubMed]
 
Smith J.C. .Ellenberger H.H. .Ballanyi K. .et al Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science. 1991;254:726-729 [PubMed]journal. [CrossRef] [PubMed]
 
Manzke T. .Guenther U. .Ponimaskin E.G. .et al 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science. 2003;301:226-229 [PubMed]journal. [CrossRef] [PubMed]
 
Ren J. .Poon B.Y. .Tang Y. .et al Ampakines alleviate respiratory depression in rats. Am J Respir Crit Care Med. 2006;174:1384-1391 [PubMed]journal. [CrossRef] [PubMed]
 
Farney R.J. .Walker J.M. .Cloward T.V. .et al Sleep-disordered breathing associated with long-term opioid therapy. Chest. 2003;123:632-639 [PubMed]journal. [CrossRef] [PubMed]
 
Wang D. .Teichtahl H. . Opioids, sleep architecture and sleep-disordered breathing. Sleep Med Rev. 2007;11:35-46 [PubMed]journal. [CrossRef] [PubMed]
 
Mogri M. .Desai H. .Webster L. .et al Hypoxemia in patients on chronic opiate therapy with and without sleep apnea. Sleep Breath. 2009;13:49-57 [PubMed]journal. [CrossRef] [PubMed]
 
Yuan G. .Drost N. .McIvor A. . Clinical review: respiratory rate and breathing pattern. MUMJ. 2013;10:23-25 [PubMed]journal
 
Teichtahl H. .Prodromidis A. .Miller B. .et al Sleep-disordered breathing in stable methadone programme patients: a pilot study. Addiction. 2001;96:395-403 [PubMed]journal. [CrossRef] [PubMed]
 
Farney R.J. .McDonald A.M. .Boyle K.M. .et al Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone. Eur Respir J. 2013;42:394-403 [PubMed]journal. [CrossRef] [PubMed]
 
Malhotra A. .Owens R.L. . What is central sleep apnea? Respir Care. 2010;55:1168-1178 [PubMed]journal. [PubMed]
 
Hajiha M. .DuBord M.A. .Liu H. .et al Opioid receptor mechanisms at the hypoglossal motor pool and effects on tongue muscle activity in vivo. J Physiol. 2009;587:2677-2692 [PubMed]journal. [CrossRef] [PubMed]
 
Dahan A. .Aarts L. .Smith T.W. . Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology. 2010;112:226-238 [PubMed]journal. [CrossRef] [PubMed]
 
Teichtahl H. .Wang D. .Cunnington D. .et al Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients. Chest. 2005;128:1339-1347 [PubMed]journal. [CrossRef] [PubMed]
 
Rose A.R. .Catcheside P.G. .McEvoy R.D. .et al Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy. J Clin Sleep Med. 2014;10:847-852 [PubMed]journal. [PubMed]
 
Mador M.J. .Henderson J. . Effect of opioids on sleep and breathing in chronic pain patients. J Clin Sleep Med. 2014;10:853-854 [PubMed]journal. [PubMed]
 
Kirk V.G. .Batuyong E.D. .Bohn S.G. . Transcutaneous carbon dioxide monitoring and capnography during pediatric polysomnography. Sleep. 2006;29:1601-1608 [PubMed]journal. [PubMed]
 
Morielli A. .Desjardins D. .Brouillette R.T. . Transcutaneous and end-tidal carbon dioxide pressures should be measured during pediatric polysomnography. Am Rev Respir Dis. 1993;148:1599-1604 [PubMed]journal. [CrossRef] [PubMed]
 
Fishbain D.A. .Cutler R.B. .Rosomoff H.L. .et al Are opioid-dependent/tolerant patients impaired in driving-related skills? A structured evidence-based review. J Pain Symptom Manage. 2003;25:559-577 [PubMed]journal. [CrossRef] [PubMed]
 
Mailis-Gagnon A. .Lakha S.F. .Furlan A. .et al Systematic review of the quality and generalizability of studies on the effects of opioids on driving and cognitive/psychomotor performance. Clin J Pain. 2012;28:542-555 [PubMed]journal. [CrossRef] [PubMed]
 
Whittle S.L. .Richards B.L. .Husni E. .et al Opioid therapy for treating rheumatoid arthritis pain. Cochrane Database Syst Rev. 2011;:CD003113- [PubMed]journal
 
Chaparro L.E. .Furlan A.D. .Deshpande A. .et al Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013;:CD004959- [PubMed]journal
 
da Costa B.R. .Nuesch E. .Kasteler R. .et al Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014;:CD003115- [PubMed]journal
 
McNicol E.D. .Midbari A. .Eisenberg E. . Opioids for neuropathic pain. Cochrane Database Syst Rev. 2013;:CD006146- [PubMed]journal
 
Franklin G.M. . Opioids for chronic noncancer pain. Neurology. 2014;83:1277-1284 [PubMed]journal. [CrossRef] [PubMed]
 
Davis M.J. .Livingston M. .Scharf S.M. . Reversal of central sleep apnea following discontinuation of opioids. J Clin Sleep Med. 2012;8:579-580 [PubMed]journal. [PubMed]
 
Dowell D. .Haegerich T. .Chou R. . CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65:1-49 [PubMed]journal
 
Holiday S. .Hayes C. .Dunlop A. . Opioid use in chronic non-cancer pain. Part 2: prescribing issues and alternatives. Aust Fam Physician. 2013;42:104-111 [PubMed]journal. [PubMed]
 
Freynhagen R. .Geisslinger G. .Schug S.A. . Opioids for chronic non-cancer pain. BMJ. 2013;346:f2937- [PubMed]journal. [CrossRef] [PubMed]
 
Cohen M.L. . Principles of prescribing for persistent non-cancer pain. Aust Prescr. 2013;36:113-115 [PubMed]journal. [CrossRef]
 
Towheed T.E. .Maxwell L. .Judd M.G. .et al Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006;:CD004257- [PubMed]journal
 
Moore R.A. .Derry S. .Aldington D. .et al Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;:CD008242- [PubMed]journal
 
Urquhart D.M. .Hoving J.L. .Assendelft W.W. .et al Antidepressants for non-specific low back pain. Cochrane Database Syst Rev. 2008;:CD001703- [PubMed]journal
 
Hearn L. .Moore R.A. .Derry S. .et al Desipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;:CD011003- [PubMed]journal
 
Lunn M.P. .Hughes R.A. .Wiffen P.J. . Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;:CD007115- [PubMed]journal
 
Hearn L. .Derry S. .Phillips T. .et al Imipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;:CD010769- [PubMed]journal
 
Wiffen P.J. .Derry S. .Moore R.A. . Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2013;:CD006044- [PubMed]journal
 
Enthoven W.T. .Roelofs P.D. .Deyo R.A. .et al Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016;:CD012087- [PubMed]journal
 
Derry S. .Wiffen P.J. .Aldington D. .et al Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;:CD011209- [PubMed]journal
 
Wienecke T. .Gotzsche P.C. . Paracetamol versus nonsteroidal anti-inflammatory drugs for rheumatoid arthritis. Cochrane Database Syst Rev. 2004;26:CD003789- [PubMed]journal
 
Derry S. .Moore R.A. .Rabbie R. . Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2012;:CD007400- [PubMed]journal
 
Gallagher H.C. .Gallagher R.M. .Butler M. .et al Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;:CD011091- [PubMed]journal
 
Shapiro C.M. .Chung S.A. .Wylie P.E. .et al Home-use servo-ventilation therapy in chronic pain patients with central sleep apnea: initial and 3-month follow-up. Sleep Breath. 2015;19:1285-1292 [PubMed]journal. [CrossRef] [PubMed]
 
Javaheri S. .Harris N. .Howard J. .et al Adaptive servoventilation for treatment of opioid-associated central sleep apnea. J Clin Sleep Med. 2014;10:637-643 [PubMed]journal. [PubMed]
 
Cao M. .Cardell C.Y. .Willes L. .et al A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids. J Clin Sleep Med. 2014;10:855-861 [PubMed]journal. [PubMed]
 
Ramar K. .Ramar P. .Morgenthaler T.I. . Adaptive servoventilation in patients with central or complex sleep apnea related to chronic opioid use and congestive heart failure. J Clin Sleep Med. 2012;8:569-576 [PubMed]journal. [PubMed]
 
Alattar M.A. .Scharf S.M. . Opioid-associated central sleep apnea: a case series. Sleep Breath. 2009;13:201-206 [PubMed]journal. [CrossRef] [PubMed]
 
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;4:305-310 [PubMed]journal. [PubMed]
 
Farney R.J. .Walker J.M. .Boyle K.M. .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;4:311-319 [PubMed]journal. [PubMed]
 
Priou P. .d'Ortho M.P. .Damy T. .et al Adaptive servo-ventilation: how does it fit into the treatment of central sleep apnoea syndrome? Expert opinions. Rev Mal Respir. 2015;32:1072-1081 [PubMed]journal. [CrossRef] [PubMed]
 
Cowie M.R. .Woehrle H. .Wegscheider K. .et al Adaptive servo-ventilation for central sleep apnea in systolic heart failure. N Engl J Med. 2015;373:1095-1105 [PubMed]journal. [CrossRef] [PubMed]
 
Johns M.W. . Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep. 1992;15:376-381 [PubMed]journal. [PubMed]
 
American Academy of Sleep Medicine. Special safety notice: ASV therapy for central sleep apnea patients with heart failure. AASA News Archive, 2015.http://www.aasmnet.org/articles.aspx?id=5562. Accessed June 25, 2016.
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543