Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy.

STUDY OBJECTIVES The use of opioid medication for chronic pain has been increasing. The main aim of this study was to assess how many patients on opioids for chronic pain had sleep disordered breathing (SDB) and the type of SDB. The impact of these medications on daytime arterial blood gas (ABG) measurements and psychomotor vigilance was also studied. METHODS Twenty-four patients (aged 18-75 years) on long-term opioids were prospectively recruited. Patients underwent home polysomnogram (PSG), psychomotor vigilance testing (PVT), and awake daytime ABG. Overnight PSG findings were compared to those of patients matched for age, sex, and BMI referred to our sleep service for evaluation of SDB. PVT results in the patient cohort were compared to PVT in healthy controls. RESULTS Forty-six percent of opioid patients had severe SDB as defined by an apnea hypopnea index (AHI) > 30/h. The severity of SDB was similar in opioid-treated pain clinic patients and sleep clinic patients (mean ± SD AHI: Opioid-treated patients 32.7 ± 25.6; Sleep Study comparator group 28.9 ± 24.6, p = 0.6). Opioid patients had a higher frequency of central apneas and a lower arousal index (CAI: 3.9 ± 8.3 vs. 0.3 ± 0.5 events/h; p = 0.004, AI 8.0 ± 4.1 vs. 20.1 ± 13.8, p < 0.001). Pain clinic patients had impaired gas exchange during sleep and wakefulness. Nine of 20 (45%) had daytime hypercapnia, indicating a surprising number were in chronic respiratory failure. Morphine equivalent doses correlated with the severity of SDB. PVT was impaired when compared to a healthy PVT comparator group (RT: Opioid-treated patients 0.43 ± 0.27: Healthy PVT comparator group 0.28 ± 0.03 sec; p < 0.001). CONCLUSIONS Patients on long-term opioids frequently have severe SDB, which in part is central in origin. PVT was markedly impaired. Half of the patients studied have evidence of chronic ventilatory failure. COMMENTARY A commentary on this article appears in this issue on page 853

[1]  P. Schofield,et al.  Guidance on the management of pain in older people. , 2013, Age and ageing.

[2]  S. Scharf,et al.  Reversal of central sleep apnea following discontinuation of opioids. , 2012, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[3]  R. Heinzer.  [Opioids and sleep disordered breathing]. , 2009, Revue medicale suisse.

[4]  J. Dorrian,et al.  Effects of Alcohol and Sleep Restriction on Simulated Driving Performance in Untreated Patients With Obstructive Sleep Apnea , 2009, Annals of Internal Medicine.

[5]  P. Haber,et al.  Examination of opioid prescribing in Australia from 1992 to 2007 , 2009, Internal medicine journal.

[6]  A. Caño,et al.  Comorbid chronic pain and depression: who is at risk? , 2009, The journal of pain : official journal of the American Pain Society.

[7]  S. Scharf,et al.  Opioid-associated central sleep apnea: a case series , 2009, Sleep and Breathing.

[8]  B. Erstad,et al.  Pain management principles in the critically ill. , 2009, Chest.

[9]  B. Grant,et al.  Hypoxemia in patients on chronic opiate therapy with and without sleep apnea , 2009, Sleep and Breathing.

[10]  R. Grunstein,et al.  Subjective daytime sleepiness and daytime function in patients on stable methadone maintenance treatment: possible mechanisms. , 2008, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[11]  A. Dahan,et al.  Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone) , 2008, Pain practice : the official journal of World Institute of Pain.

[12]  B. Grant,et al.  Sleep-disordered breathing and chronic opioid therapy. , 2008, Pain medicine.

[13]  S. Shea,et al.  Polysomnographic respiratory abnormalities in asymptomatic individuals. , 2008, Sleep.

[14]  R. Farney,et al.  Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. , 2007, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[15]  S. Raja,et al.  Opioid effectiveness, addiction, and depression in chronic pain. , 2006, Advances in psychosomatic medicine.

[16]  O. Drummer,et al.  Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients. , 2005, Chest.

[17]  O. Drummer,et al.  Central sleep apnea in stable methadone maintenance treatment patients. , 2005, Chest.

[18]  E. Bixler,et al.  Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. , 2005, The Journal of clinical endocrinology and metabolism.

[19]  E. Eisenberg,et al.  Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: systematic review and meta-analysis of randomized controlled trials. , 2005, JAMA.

[20]  Drew Dawson,et al.  Fatigue assessment in the field: validation of a hand-held electronic psychomotor vigilance task. , 2005, Aviation, space, and environmental medicine.

[21]  Gregory Belenky,et al.  The Walter Reed palm-held psychomotor vigilance test , 2005, Behavior research methods.

[22]  D. Fishbain,et al.  Are opioid-dependent/tolerant patients impaired in driving-related skills? A structured evidence-based review. , 2003, Journal of pain and symptom management.

[23]  R. Farney,et al.  Sleep-disordered breathing associated with long-term opioid therapy. , 2003, Chest.

[24]  T. Finkbeiner,et al.  Cognitive-Motor Performance of Methadone-Maintained Patients , 2000, European Addiction Research.

[25]  Daniel J Buysse,et al.  Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. , 1999, Sleep.

[26]  J R Bell,et al.  Australian trends in opioid prescribing for chronic non‐cancer pain, 1986‐1996 , 1997, The Medical journal of Australia.

[27]  P. Lovibond,et al.  The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. , 1995, Behaviour research and therapy.

[28]  M. Weinger,et al.  Elucidation of dose-effect relationships for different opiate effects using alfentanil in the spontaneously ventilating rat. , 1992, Anesthesiology.

[29]  M. Johns,et al.  A new method for measuring daytime sleepiness: the Epworth sleepiness scale. , 1991, Sleep.

[30]  T. V. Santiago,et al.  Control of breathing during methadone addiction. , 1977, The American journal of medicine.

[31]  C. Guilleminault,et al.  EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. , 1992, Sleep.