Sleep among opioid users

Use of opioids in the treatment of both acute and chronic pain has increased significantly in the past 2 decades. Recent literature suggests that chronic opioid use is related to sleep-related breathing disorders, particularly central sleep apnea of both the periodic and nonperiodic breathing pattern. The clinical significance, pathogenesis, and treatment options of these sleep-related breathing disorders are not well understood. This article summarizes the current literature on the effects of both acute and chronic opioid use on sleep, sleep-disordered breathing, and the current evidence on various treatment options for breathing disorders related to chronic opioid use.     

Are opioids associated with sleep apnea? A review of the evidence

Chronic opioid use for nonmalignant pain has increased dramatically; nonillicit unintentional deaths have also increased. This article reviews the physiology of breathing, effects of sleep on respiration, effects of opioids on respiration, potential interactions between sleep and opioids on respiration, and current evidence that chronic opioid use is associated with sleep-disordered breathing.     

Sleep and medical disorders

Extensive evidence links cardiovascular disease and sleep disordered breathing. OSA has adverse effects on blood pressure, cardiovascular status,and mortality. Effective CPAP therapy can improve blood pressure and cardiac function in patients who have OSA. Patients who have congestive heart failure have a high prevalence of sleep-disordered breathing, with OSA occurring in 30% of such patients and Cheyne-Stokes respiration in 40%.CPAP is the preferred mode of therapy for both types of sleep-disordered breathing in patients who have coexistent congestive heart failure. Nocturnal worsening of asthma is a common manifestation of this disease that indicates increased disease severity. Therapy focuses on judicious use of long-acting bronchodilators, and the presence of OSA should also be considered. COPD is frequently associated with impaired sleep, likely because of chronic dyspnea and sleep-associated hypoxemia. Appropriate therapy again includes long-acting bronchodilators and possibly nocturnal supplemental oxygen.Gastroesophageal reflux during sleep may lead to prolonged episodes of esophageal acid exposure and may be a common sequela of OSA, perhaps triggering nocturnal worsening of asthma. Endstage renal disease and chronic dialysis are commonly associated with a host of troublesome sleep problems,including OSA, RLS, PLMD, and daytime sleepiness.     

Diagnosis and management of sleep apnea syndrome

Sleep apnea is the cessation of breathing during sleep. These episodes result in hypoxemia and sleep disruption; thus the consequences are both cardiorespiratory and neural. Sleep apnea syndrome is defined by a constellation of signs and symptoms, with the main presenting symptom being excessive daytime sleepiness. A diagnosis requires documentation of episodes of abnormal breathing during sleep. This disorder, once thought to be very rare, is so common that it is unlikely that any busy clinician has not encountered a case. Facilities for the evaluation of sleep breathing disorders are now available in most communities. With the introduction of continuous positive airway pressure and other treatments, most patients have complete resolution of their disabling symptoms.     

Sleep-disordered breathing in patients with heart failure: pathophysiology, assessment, and management

PURPOSE: To provide clinicians in primary care settings information on the effects of sleep-disordered breathing in patients with heart failure (HF). Assessment and screening tools, as well as management considerations, are presented. DATA SOURCES: Review of the scientific literature of the past 10 years, along with classic studies and Internet sources. CONCLUSIONS: HF is an increasingly prevalent problem with a high degree of associated sleep-disordered breathing. There are two broad categories of sleep-disordered breathing: obstructive sleep apnea and central sleep apnea/Cheyne-Stokes breathing. Both of these occur on a continuum of mild hypopnea to severe apnea with hypoxia. Sleep apneas are particularly harmful to patients with HF and, if left untreated, may adversely affect their prognosis. Yet sleep apnea is not routinely screened for in this population. IMPLICATIONS FOR PRACTICE: Given the serious consequences of untreated sleep-disordered breathing, there is sound justification to screen for sleep apnea in all patients with HF. Subsequent treatment of those patients with sleep apnea can significantly improve their quality of life and can decrease their mortality.     

Sleep apnea syndrome in chronic spinal cord injury: associated factors and treatment

OBJECTIVE: To determine the prevalence of sleep apnea in a sample of persons with chronic spinal cord injury (SCI) of varying injury levels and degrees of impairment. DESIGN: Cross-sectional study. SETTING: Inpatient SCI rehabilitation unit. PARTICIPANTS: Twenty men with SCI (motor complete and incomplete; American Spinal Injury Association classes A-D) of at least 1 year's duration, randomly selected from patients with SCI undergoing elective hospitalization. MAIN OUTCOME MEASURES: Apnea index, determined by sleep study (including chest wall movement, airflow, oxygen saturation), and daytime sleepiness, determined by Epworth sleepiness score. RESULTS: Eight subjects (40%) had sleep apnea, manifested by elevated apnea index (mean +/- SD, 17.1 +/- 6.9) and excessive daytime sleepiness. Sleep apnea was commonly diagnosed in motor-incomplete injuries. A trend (p = .07) existed toward a greater prevalence of sleep apnea with tetraplegia. Age and body mass index were not associated with sleep apnea. CONCLUSION: The prevalence of sleep apnea in men with chronic SCI admitted for nonrespiratory elective hospitalization is high relative to the general population.     

Long-term follow-up of obstructive sleep apnea syndrome following surgery in children and adults

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent apneas during sleep, resulting in repetitive hypoxemia. The present study retrospectively analyzed subjective and objective assessments of the patients with OSAS in a relatively long-term follow-up. From February 1986 to August 1996, 53 patients received surgical treatment for OSAS and snoring. Thirty-seven (27 males and 10 females) out of 53 patients completed the questionnaire and postoperative sleep study was obtained in 6 patients. In 20 children (<15 years), snoring, sleep apnea, and daytime sleepiness completely disappeared in 12, 19, and 16, and improved in 8, 1, and 4, respectively. These findings confirm that tonsillectomy and/or adenoidectomy in children may be the first selection for treatment. In 17 adults, snoring, sleep apnea, and daytime sleepiness completely disappeared in 2, 5, and 8, improved in 11, 8, and 7, and was unchanged in 4, 4, and 1, respectively. The apnea index in adults was significantly decreased in both early and late postoperative periods. These results suggest that surgery is a satisfactory alternative for adult patients if performed accurate preoperative diagnosis of the localization of the airway collapse and careful long-term follow-up.     

Central sleep apnea syndrome and Cheyne-Stokes respiration

This overview discusses pathogenesis, clinical presentation, prognostic implications and therapy of central sleep apnea with special reference to Cheyne-Stokes-Respiration or periodic breathing. In contrast to obstructive sleep apnea due to upper airway collapse during sleep, central sleep apnea (CSA) is mainly due to an instability of the breathing control system. Causes of central sleep apnea include alveolar hypoventilation disorders, heart failure, neurologic and autonomic disorders and idiopathic forms of CSA. Patients with idiopathic CSA often complain of insomnia and awakening during sleep but may also suffer from daytime sleepiness. Cheyne-Stokes-Respiration or peridic breathing is often associated with heart failure and neurological disorders especially those involving the brainstem. In heart failure periodic breathing has enormous prognostic implications. Treatment options for central sleep apnea are oxygen supplementation, medical therapy (i.e. acetazolamide) and CPAP. For patients with central sleep apnoea associated with alveolar hypoventilation nasal ventilation is treatment of choice. Newer nasal ventilation techniques (BiPAP, AutoSetCS) are under investigation for heart failure patients with Cheyne-Stokes-Respiration.     

Sleep-Disordered Breathing in Recipients of Implantable Defibrillators

Study Objectives: To examine the prevalence and clinical significance of sleep-disordered breathing in patients with implantable cardioverter defibrillators (ICD).
Methods and Results: Overnight sleep studies were performed in 129 ICD recipients who had no history of sleep apnea. The mean left ventricular ejection fraction (LVEF) was 29 ± 11%. Mild, moderate, and severe sleep apnea was diagnosed in the presence of an apnea/hypopnea index (AHI) of 5–15/h, 15.1–30/h, and >30/h, respectively. No sleep apnea was present in 49 patients (38%), 57 (44%) had central sleep apnea (CSA), and 23 patients (18%) had obstructive sleep apnea (OSA). Mild, moderate, and severe sleep apnea were present in 25%, 31%, and 44% of patients with CSA, compared with 52%, 22%, and 26% of patients with OSA (P < 0.05). LVEF was similar in patients with versus without OSA or CSA. Patients with CSA were significantly older and had a higher prevalence of ischemic cardiomyopathy than patients without sleep apnea.
Conclusions: Previously undiagnosed CSA is common in ICD recipients. Severely disordered breathing during sleep was more prevalent among patients with CSA than patients with OSA. This prospective, observational study will examine the long-term clinical significance of sleep-disordered breathing in ICD recipients.     

Sleep and breathing in patients with the Prader-Willi syndrome

The Prader-Willi syndrome is characterized by infantile hypotonia, early childhood obesity, mental deficiency, short stature, small hands and feet, and hypogonadism. Many patients also have hypersomnolence, experience daytime hypoventilation, and subsequently die prematurely of cardiorespiratory failure. Hypersomnolence and daytime hypoventilation are also common occurrences in the sleep apnea syndrome. For a better understanding of the relationship of sleep to the features of the Prader-Willi syndrome, we retrospectively reviewed five patients (two adults, one adolescent, and two children) with this syndrome who underwent polysomnography. All patients were obese; they had hypersomnolence and daytime hypoxemia, and they nored. In all patients, the apnea plus hypopnea index was less than 10 episodes per hour of sleep. During rapid eye movement sleep, nonapneic reductions in oxyhemoglobin saturation were detected in one adult and in one child. Despite the presence of morbid obesity and a history of snoring, patients with Prader-Willi syndrome seem to have only mild sleep-disordered breathing.     

Continuous opioid therapy (COT) is rarely advisable for refractory chronic daily headache: limited efficacy, risks, and proposed guidelines

Intractable pain, headache or otherwise, is a devastating and life-controlling experience. The need to effectively and aggressively control pain is a fundamental tenet of clinical care. In the past several years, increasing advocacy for continuous opioid therapy has become an important, if not controversial, theme in the development of treatment guidelines and teaching programs. Ironically, the increasing willingness of physicians to prescribe scheduled opioids for their headache and pain patients has occurred in the absence of compelling data demonstrating efficacy or long-term safety. To the contrary, two meta-analyses on chronic noncancer pain (CNCP) and one long-term uncontrolled study on headache patients demonstrate a relatively small number of patients benefiting from the treatment. Recent neuroscience data on the effects of opioids on the brain raise serious concern for long-term safety and also provide the basis for the mechanism by which chronic opioid use might induce progression of headache frequency and severity. Significant adverse effects, including influence on sexual hormonal balances, physical and psychological dependence, the development of opioid-induced hyperalgesia, and cardiac arrhythmia and sudden death that can be seen with standard dosages of methadone, make a strong argument against widespread use of continuous opioid therapy (COT) in otherwise healthy young and middle-aged headache patients.
We believe that COT should be used in rare circumstances for chronic headache patients, and propose initial guidelines for selecting patients and monitoring treatment. The physician should be well versed in the details of opioid prescribing, administration, and monitoring, and should be prepared to discontinue opioids when clinical justification, patient behavior, or failure to achieve therapeutic goals make discontinuance necessary.     

Treatment of obstructive sleep apnea in primary care

Obstructive sleep apnea should be suspected in patients who are overweight snore loudly, and have chronic daytime sleepiness. The diagnosis of sleep apnea may be confirmed by sleep laboratory studies. Patients' symptoms and the frequency of respiratory events on laboratory testing are important factors in determining the severity of disease. In patients with mild sleep apnea, conservative treatment measures include getting sufficient sleep, abstaining from the use of alcohol and sedatives, losing weight, and avoiding the supine position during sleep. Continuous positive airway pressure (CPAP) is the most consistently effective treatment for clinically significant obstructive sleep apnea. In general, heavier patients with thicker necks require higher pressure settings. As patients age or gain weight, additional pressure may be necessary. Bilevel pressure machines or machines that slowly ramp up the pressure may increase patient acceptance of CPAP therapy. Complications of CPAP use include nasal dryness and congestion, claustrophobia, facial skin abrasions, air leaks, and conjunctivitis. Strategies to improve patient compliance include allowing patients to try a number of masks to find the most comfortable fit, adding humidification, treating nasal disease and, most importantly, providing close follow-up and encouragement. Oral appliances are inconsistently effective in the management of obstructive sleep apnea but may be an option in patients with mild disease who cannot tolerate CPAP. Palatal surgery often decreases snoring but may not reduce the occurrence of sleep apnea. Patients with severe disease and intolerance of CPAP may be candidates for more invasive surgical procedures. Supplemental oxygen and drug therapy may have limited, adjunctive roles in the treatment of obstructive sleep apnea.     

Effects of long-term nocturnal oxygen treatment in patients with severe heart failure

Sleep-disordered breathing (SDB) is common in patients with heart failure (HF) and leads to disturbed sleep. The objective of this study was to determine the persistent effects of long-term nocturnal oxygen treatment in patients with severe HF regarding (1) objective outcomes, such as sleep, SDB, cardiac function, and functional capacity; (2) subjective outcomes, such as self-assessed sleep difficulties, daytime sleepiness, and health-related quality of life (HRQOL); and (3) the relationship between objective and subjective outcomes. In this open nonrandomized experimental study, 22 patients, median age 71 years, with severe HF were studied before and after 3 months of receiving nocturnal oxygen. The measures used were overnight polysomnography, echocardiography, 6-minute walk test, self-assessed sleep difficulties (Uppsala Sleep Inventory-HF), daytime sleepiness (Epworth Sleepiness Scale), and HRQOL (36-Item Short Form Health Survey and Minnesota Living with Heart Failure Questionnaire). SDB, with a 90% dominance of central sleep apnea, occurred in 41% of the patients with severe HF before intervention. After intervention, functional capacity improved for both the whole group of patients with HF (P < .01) and HF patients with SDB (P < .05). No improvements regarding cardiac function, objective sleep, subjective sleep, or SDB were seen, except for a decrease of > or = 4% desaturations (P < .05). HRQOL did not differ significantly between HF patients with and without SDB before or after intervention with nocturnal oxygen. Long-term nocturnal oxygen treatment improved functional capacity in patients with severe HF, with or without SDB. No improvements were seen regarding sleep, daytime sleepiness, SDB, cardiac function, or HRQOL.     

Excessive daytime sleepiness: etiology, differential diagnosis and diagnostic procedures

This article gives an overview on frequent causes of excessive daytime sleepiness in clinical practice. Specifically, the insufficient sleep syndrome, sleep disordered breathing, narcolepsy, restless legs syndrome/periodic limb movements in sleep, and circadian disorders causing daytime sleepiness are discussed. Other possible causes including symptomatic daytime sleepiness associated with various medical conditions are mentioned. Different methods to determine daytime sleepiness are discussed in the final section.     

Multiple sleep latency test

Daytime sleepiness is such a familiar thing for most Japanese, dozing off in a commuting train is regarded as completely normal. Sleepiness, however, can yield a lot of problems. Not only deteriorating efficiency of the work, it sometimes leads to traffic accidents, and also serves as a cause for disastrous accidents. Although excessive daytime sleepiness has been gradually known to Japanese health workers as one of the symptoms of sleep apnea syndrome, some patients cannot recognize sleepiness, and even neglect it, feeling others are sleepy as well. In this respect multiple sleep latency test is a valuable tool as an objective measures of daytime sleepiness, and commonly used procedures of this testing was described in details.     

Management of chronic neuropathic pain with methadone: a review of 13 cases

The synthetic opioid methadone has generated much interest in recent years among clinicians involved in the management of intractable chronic cancer pain. Its use as an analgesic is starting to extend to the treatment of noncancer pain, particularly neuropathic pain. Unfortunately, the evidence for its use in the management of neuropathic pain is limited to a few case studies. We examined retrospectively during a 12-month study period the clinical response of all 13 patients at our pain clinic who were prescribed methadone in an attempt to control neuropathic pain resistant to conventional analgesics. A questionnaire was also administered to the 9 patients who continued to take methadone at 12 months posttreatment. A total of 4 patients (31%) discontinued it by the end of the 12-month study period. Patients discontinued methadone due to the absence of pain relief and due to various intractable, undesirable side effects. Somnolence was the most common adverse effect reported, followed by nausea, constipation, and vomiting. All patients took coanalgesics (eg, amitriptyline, gabapentin) or other analgesics (eg, morphine, nonsteroidal anti-inflammatory drugs) during methadone treatment to control pain. The 9 patients who continued to take methadone at 12 months reported experiencing on average 43% pain relief (range 0-80%), 47% improvement in quality of life (range 0-100%), and 30% improvement in quality of sleep (range 0-60%). Methadone was effective at relieving pain and ameliorating quality of life and sleep in 62% of patients. These findings suggest that methadone can offer an acceptable success rate for the treatment of neuropathic pain. Prospective randomized, placebo-controlled studies are now needed to examine more rigorously the benefits of methadone for this type of pain.     

Intentional Intrathecal Opioid Detoxification in 3 Patients: Characterization of the Intrathecal Opioid Withdrawal Syndrome

Objective: Intrathecal (IT) drug delivery systems for patients with chronic non‐malignant pain are intended to improve pain and quality of life and reduce side effects of systemic use. A subset of patients may have escalating pain, functional decline, and/or intolerable side effects even as IT opioid doses are increased. Discontinuation of IT medications may represent a viable treatment option but strategies to accomplish this are needed. Subjects and Interventions: Three patients with intrathecal drug delivery systems (IDDS), inadequate pain control, and declining functionality underwent abrupt IT opioid cessation. This was accomplished through a standardized protocol with symptom‐triggered administration of clonidine and buprenorphine, monitored using the clinical opiate withdrawal scale. Results: Symptoms of IT withdrawal were similar in all patients and included diuresis, agitation, hyperalgesia, mild diarrhea, yawning, and taste and smell aversion. Hypertension and tachycardia were effectively controlled by clonidine administration. Classic symptoms of withdrawal, such as piloerection, chills, severe diarrhea, nausea, vomiting, diaphoresis, myoclonus, and mydriasis, were not noted. At 2 to 3 months follow‐up, patients reported decreased, but ongoing pain, with improvements in functional capacity and quality of life. Conclusions: This preliminary work demonstrates the safety of abrupt IT opioid cessation utilizing standardized inpatient withdrawal protocols. To our knowledge, these are among the first reported cases of intentional, controlled IT opioid cessation without initiation of an opioid bridge: self‐reported pain scores, functional capacity, and quality of life improved. The IT opioid withdrawal syndrome is characterized based upon our observations and a review of the literature.     

Piloting Smart Home Sensors to Detect Overnight Respiratory and Withdrawal Symptoms in Adults Prescribed Opioids

BackgroundNovel strategies are needed to curb the opioid overdose epidemic. Smart home sensors have been successfully deployed as digital biomarkers to monitor health conditions, yet they have not been used to assess symptoms important to opioid use and overdose risks.AimThis study piloted smart home sensors and investigated their ability to accurately detect clinically pertinent symptoms indicative of opioid withdrawal or respiratory depression in adults prescribed methadone.MethodsParticipants (n = 4; 3 completed) were adults with opioid use disorder exhibiting moderate levels of pain intensity, withdrawal symptoms, and sleep disturbance. Participants were invited to two 8-hour nighttime sleep opportunities to be recorded in a sleep research laboratory, using observed polysomnography and ambient smart home sensors attached to lab bedroom walls. Measures of feasibility included completeness of data captured. Accuracy was determined by comparing polysomnographic data of sleep/wake and respiratory status assessments with time and event sensor data.ResultsSmart home sensors captured overnight data on 48 out of 64 hours (75% completeness). Sensors detected sleep/wake patterns in alignment with observed sleep episodes captured by polysomnography 89.4% of the time. Apnea events (n = 118) were only detected with smart home sensors in two episodes where oxygen desaturations were less severe (>80%).ConclusionsSmart home technology could serve as a less invasive substitute for biologic monitoring for adults with pain, sleep disturbances, and opioid withdrawal symptoms. Supplemental sensors should be added to detect apnea events. Such innovations could provide a step forward in assessing overnight symptoms important to populations taking opioids.     

Obstructive sleep-disordered breathing in children

Obstructive sleep-disordered breathing in children is a spectrum of disorders of breathing during sleep characterized by snoring and upper airway obstruction. In its most severe form, obstructive sleep apnea, prolonged complete upper airway obstruction occurs, disrupting normal ventilation and sleep patterns. The hallmark feature of the disorder is habitual and loud snoring. Adenotonsillar hypertrophy is the most common cause of obstructive sleep-disordered breathing. Left untreated, obstructive sleep-disordered breathing may lead to problems related to sleep disruption such as inattention, poor learning, behavioral problems, and attention deficit/hyperactivity disorder or may cause more serious morbidity, including growth failure and pulmonary hypertension. The diagnosis of obstructive sleep-disordered breathing in most children is made through a thorough sleep-based history and physical examination. Adenotonsillectomy, the cardinal treatment for obstructive sleep-disordered breathing, is curative in a large proportion of patients and markedly improves quality of life for children with the disorder.