JCSM Articles

Entering the Age of Portable Monitoring

EDITORIAL - Entering the Age of Portable Monitoring

Adaptive Pressure Support Servoventilation: a Novel Treatment for Sleep Apnea Associated with Use of Opioids

Rationale:

Opioids have become part of contemporary treatment in the management of chronic pain. However, chronic use of opioids has been associated with high prevalence of sleep apnea which could contribute to morbidity and mortality of such patients.

Objectives:

The main aim of this study was to treat sleep apnea in patients on chronic opioids.

Methods:

Five consecutive patients who were referred for evaluation of obstructive sleep apnea underwent polysomnography followed by a second night therapy with continuous positive airway pressure (CPAP) device. Because CPAP proved ineffective, patients underwent a third night therapy with adaptive pressure support servoventilation.

Main Results:

The average age of the patients was 51 years. They were habitual snorers with excessive daytime sleepiness. Four suffered from chronic low back pain and one had trigeminal neuralgia. They were on opioids for 2 to 5 years before sleep apnea was diagnosed. The average apnea-hypopnea index was 70/hr. With CPAP therapy, the apnea-hypopnea index decreased to 55/hr, while the central apnea index increased from 26 to 37/hr. The patients then underwent titration with adaptive pressure support servoventilation. At final pressure, the hypopnea index was 13/hr, with central and obstructive apnea index of 0 per hour.

Conclusions:

Opioids may cause severe sleep apnea syndrome. Acute treatment with CPAP eliminates obstructive apneas but increases central apneas. Adaptive pressure support servoventilation proves to be effective in the treatment of sleep related breathing disorders in patients on chronic opioids. Long-term studies on a large number of patients are necessary to determine if treatment of sleep apnea improves quality of life, decreases daytime sleepiness, and ultimately decreases the likelihood of unexpected death of patients on opioids.

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

Background:

Adaptive servoventilation (ASV) can be effective therapy for specific types of central apnea such as Cheyne-Stokes respiration (CSR). Patients treated chronically with opioids develop central apneas and ataxic breathing patterns (Biot’s respiration), but therapy with CPAP is usually unsuccessful. There are no published studies of ASV in patients with sleep apnea complicated by chronic opioid therapy.

Methods:

Retrospective analysis of 22 consecutive patients referred for evaluation and treatment of sleep apnea who had been using opioid medications for at least 6 months, had an apnea-hypopnea index (AHI) >20/h, and had been tested with ASV. Baseline polysomnography was compared with CPAP and ASV. Outcome variables: AHI, central apnea index (CAI), obstructive apnea index (OAI), hypopnea index (HI), desaturation index, mean SpO2, lowest SpO2, time SpO2 <90%, and degree of Biot’s respiration.

Results:

Mean (SD) AHI measured 66.6/h (37.3) at baseline, 70.1/h (32.6) on CPAP, and 54.2/h (33.0) on ASV. With ASV, the mean OAI was significantly decreased to 2.4/h (p < 0.0001), and the mean HI increased significantly to 35.7/h (p < 0.0001). The decrease of CAI from 26.4/h to 15.6/h was not significant (p = 0.127). Biot’s breathing persisted, and oxygenation parameters were unimproved with ASV.

Conclusions:

Due to residual respiratory events and hypoxemia, ASV was considered insufficient therapy in these patients. Persistence of obstructive events could be due to suboptimal pressure settings (end expiratory and/or maximal inspiratory). Residual central events could be related to fundamental differences in the pathophysiology of CSR compared to opioid induced breathing disturbances.

The Quest for Stability in an Unstable World: Adaptive Servoventilation in Opioid Induced Complex Sleep Apnea Syndrome
Commentary on Javaheri S, et al. Adaptive pressure support servoventilation: a novel treatment for sleep apnea
associated with use of opioids. J Clin Sleep Med 2008;4(4):305-10 and Farney RJ, 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):311-19.

COMMENTARY - The Quest for Stability in an Unstable World: Adaptive Servoventilation in Opioid Induced Complex Sleep Apnea Syndrome

Serum Angiotensin Converting Enzyme and the Obstructive Sleep Apnea Hypopnea Syndrome

Study Objectives:

We wanted to see if the obstructive sleep apnea hypopnea syndrome (OSAHS) causes hypertension and endothelial dysfunction through activation of the angiotensin-converting enzyme (ACE).

Methods:

A cross-sectional followed by a prospective, interventional study in a sleep disordered breathing clinic in a UK Hospital. We measured baseline serum ACE activity and ACE allele frequencies in 26 consecutive (untreated) OSAHS patients, 26 consecutive Sleepy Snorers, and 26 healthy (non-sleepy) controls. The OSAHS and Sleepy Snorers had serum ACE repeated after 6 months, with the OSAHS group receiving CPAP in the interim.

Results:

There was no difference in baseline mean serum ACE among OSAHS (33 IU/L), sleepy snorers (36 IU/L), and healthy controls (32 IU/L), p = 0.63. There was no difference in serum ACE activity between OSAHS and sleepy snorers after 6 months (p = 0.9) and no change in serum ACE from baseline in either group. In particular, there was no change in ACE activity in the OSAHS group on an intention to treat basis or when limiting analysis was limited to only “good” CPAP users (n = 16, p = 0.68), despite significant improvements in their Epworth scores and blood pressure and normalization of the 4% dip-rate.

Conclusions:

Changes in serum ACE activity do not occur in OSAHS; therefore it is unlikely to be associated with the hypertension and other cardiovascular dysfunction often reported in OSAHS.

Persistence of Obstructive Sleep Apnea After Surgical Weight Loss

Study Objectives:

Weight loss may reduce the severity of obstructive sleep apnea (OSA), but persistence of OSA following surgical weight loss has not been defined. We sought to clarify the impact of bariatric surgery on OSA. We hypothesized that, despite substantial weight loss and reductions in the apnea-hypopnea index (AHI), many will have persistent disease.

Methods:

Consecutive patients referred for preoperative sleep evaluation underwent polysomnography before and 1 year following bariatric surgery. We compared the effects of weight loss on body mass, OSA, and continuous positive airway pressure requirements. We defined OSA severity using the AHI (normal < 5 events per hour, mild 5 to 14 events per hour, moderate 15 to 29 events per hour, and severe 30 or more events per hour). We identified predictors of OSA severity following weight loss and assessed compliance with therapy.

Results:

Twenty-four patients (aged 47.9 ± 9.3 years; 75% women) were enrolled. At baseline, all subjects had OSA, the majority of which was severe. Weight loss reduced body mass index from 51.0 ± 10.4 kg/m2 to 32.1 ± 5.5 kg/m2 (p < 0.001) and the AHI from 47.9 ± 33.8 to 24.5 ± 18.1 events per hour (p < 0.001). At follow-up, only 1 patient (4%) experienced resolution of OSA. The majority (71%) had moderate or severe disease. The most important predictor of the follow-up AHI was the baseline AHI (R2 = 0.603). All patients with residual OSA required continuous positive airway pressure to ablate apneic events, but the required pressures decreased from 11.5 ± 3.6 cm H2o to 8.4 ± 2.1 cm H2o (p = 0.001). Only 6 patients were compliant with continuous positive airway pressure therapy at the follow-up visit.

Conclusions:

Surgical weight loss reduces the AHI, but many patients have residual OSA one year after bariatric surgery.

Morbid Obesity and Sleep Apnea. Is Weight Loss the Answer?
Commentary on Lettieri CJ et al. Persistence of obstructive sleep apnea after surgical weight loss. J Clin Sleep Med 2008;4(4):333-338.

COMMENTARY - Morbid Obesity and Sleep Apnea. Is Weight Loss the Answer?

Autoadjusting Positive Pressure Trial in Adults with Sleep Apnea Assessed by a Simplified Diagnostic Approach

Study Objectives:

To describe our clinical experience with autoadjusting positive airway pressure (APAP) trials carried out on patients with moderate-to-severe obstructive sleep apnea (OSA).

Methods:

Consecutive CPAP-naïve adults underwent a non-attended home APAP trial (ResMed, Autoset, Spirit). Diagnoses of OSA were established by simplified polygraphy.

Results:

Data from 208 men and 71 women. The median age (interquartile range) was 51 years (41-59), with an Epworth Sleepiness Scale score of 13.5 (9-19), body mass index of 33 kg/m2 (29-38) and respiratory disturbance index (RDI) of 53 events/h (35-74). The APAP trial results included: hours used per night, 5.5 (4-7); 95th percentile pressure, 10.6 cm H2O (9.4-11.7); 95th percentile leak, 0.3 L/sec (0.1-0.6); residual RDI, 6.2 events/h (3.9-11.4); and percentage change in RDI, 87% (74-93). The proportion of patients with residual RDI >10 events/h was 29% (95% CI 23.6-34.3). Adherence (≥70% of nights and ≥4 h/night) was observed in 72.4% of subjects (95% CI 67-78). Patients with APAP adherence tended to require higher CPAP pressures, had higher rates of residual RDI, and had a lower percentage change in RDI than those with no adherence. As the 95th percentile CPAP pressure increased so too did residual RDI.

Conclusions:

The APAP trial was effective in decreasing RDI with an acceptable adherence rate; however, residual OSA was a frequent finding. Our results support that in up to one-third of patients evaluated by a simplified diagnostic approach, CPAP titration based on 95th percentile pressure may not be sufficient if residual RDI <10 events/his considered as a therapeutic target.

Characterizing Sleep Structure Using the Hypnogram

Objectives:

Research on the effects of sleep-disordered breathing (SDB) on sleep structure has traditionally been based on composite sleep-stage summaries. The primary objective of this investigation was to demonstrate the utility of log-linear and multistate analysis of the sleep hypnogram in evaluating differences in nocturnal sleep structure in subjects with and without SDB.

Methods:

A community-based sample of middle-aged and older adults with and without SDB matched on age, sex, race, and body mass index was identified from the Sleep Heart Health Study. Sleep was assessed with home polysomnography and categorized into rapid eye movement (REM) and non-REM (NREM) sleep. Log-linear and multistate survival analysis models were used to quantify the frequency and hazard rates of transitioning, respectively, between wakefulness, NREM sleep, and REM sleep.

Results:

Whereas composite sleep-stage summaries were similar between the two groups, subjects with SDB had higher frequencies and hazard rates for transitioning between the three states. Specifically, log-linear models showed that subjects with SDB had more wake-to-NREM sleep and NREM sleep-to-wake transitions, compared with subjects without SDB. Multistate survival models revealed that subjects with SDB transitioned more quickly from wake-to-NREM sleep and NREM sleep-to-wake than did subjects without SDB.

Conclusions:

The description of sleep continuity with log-linear and multistate analysis of the sleep hypnogram suggests that such methods can identify differences in sleep structure that are not evident with conventional sleep-stage summaries. Detailed characterization of nocturnal sleep evolution with event history methods provides additional means for testing hypotheses on how specific conditions impact sleep continuity and whether sleep disruption is associated with adverse health outcomes.

Depression and Sleep-Related Symptoms in an Adult, Indigenous, North American Population

Study Objectives:

Symptoms related to sleep disorders are common and may have substantial adverse impacts on mental health. Indigenous North Americans (American Indian) are a medically vulnerable population with reduced access to healthcare services. The purposes of this study were to assess (1) the prevalence of sleep symptoms and (2) the relationships between symptoms and depression in this population.

Methods:

We performed a community-based, door-to-door, crosssectional survey of 3 indigenous North American groups (Gitxsan, Nisga’a and Tsimshian) living in the northwestern part of British Columbia. Between May and September of 2006, subjects completed a comprehensive questionnaire that included questions about sleep habits, medical history, subjective sleepiness (Epworth Sleepiness Scale), and depression (Personal Health Questionnaire [PHQ-9]). Weights and heights were also measured.

Results:

Four hundred thirty adults participated in the study (response rate = 42%). Their mean age was 43.2 years. Three hundred ninetythree agreed to have heights and weights measured. Their mean body mass index (BMI) was 31.0 ± 9.2 kg/m2; 45% of them (177/393) were obese (BMI > 30 kg/m2), and 11% (43/393) were morbidly obese (BMI > 40 kg/m²). The prevalence of sleep complaints was high; insomnia symptoms was reported by 17.2%, symptoms of restless legs syndrome (RLS) by 17.7%, and frequent witnessed apneas reported (i.e., being told they stopped breathing at least 3 nights per week) by 7.6%. Of the 76 patients who had RLS symptoms, only 3 (3.9%) reported having received a diagnosis of RLS from a physician. Thirty-three subjects reported having frequent witnessed apneas, but only 5 of them (15.1%) reported having received a diagnosis of OSA from a physician. The mean PHQ9 score was 4.86 ± 5.13 (reported by 389 subjects). Twenty-eight subjects (7.20%) had moderate to severe depression, with a PHQ-9 score of 15 or greater. In multivariable linear regression analysis, insomnia symptoms, witnessed apneas, and RLS symptoms were independently associated with an increase in PHQ9 score; frequent witnessed apneas were associated with an increase in PHQ9 by 2.46 (95% confidence interval: 0.47-4.46), insomnia symptoms by 4.49 (95% confidence interval: 3.14-5.83), and RLS symptoms by 1.82, (95% confidence interval: 0.53-3.12).

Conclusions:

Sleep symptoms and depression are common in the indigenous North American population of northern British Columbia. Sleep-related symptoms (insomnia symptoms, witnessed nocturnal apneas, and RLS symptoms) are independently associated with depression scores. Improving access to sleep-related diagnostic and therapeutic services may substantially improve mental health in this
vulnerable patient population.

Sleep Pattern Differences Between Older Adult Dementia Caregivers and Older Adult Noncaregivers Using Objective and Subjective Measures

Study Objectives:

Informal caregivers of persons with dementia often complain about poor quality sleep; however, studies on caregivers have mixed results when examining sleep values. The purpose of this study was to describe the sleep patterns in a subset of dementia caregivers who provide care during the night, and compare those patterns to noncaregiving adults.

Methods:

Data from a study on dementia caregivers and from a study of sleep in older adults were used. Both studies used objective and subjective methods to measure sleep in the home setting over a 7-day period. Participants were over 60 years old and relatively healthy.

Results:

Older dementia caregivers had worse objectively measured sleep than noncaregiving older adults, characterized by fewer minutes asleep and longer time to fall asleep. For subjectively measured sleep, depressive symptoms were the only predictive factor, with depressed participants reporting longer total sleep time, greater sleep onset latency, and wake after sleep onset. Caregivers’ sleep had greater night-to-night variability.

Conclusions:

Caregivers consistently report poorer quality sleep and greater fatigue than noncaregivers. However, when sleep is measured objectively and subjectively, a mixed picture emerges regarding sleep deficits. Thus sleep changes are caused by a multitude of factors affecting sleep in a variety of ways. It is important for health care providers to assess sleep adequacy and depression in caregivers.

Adverse Effects of Ropinirole-Treated Restless Leg Syndrome (RLS) During Smoking Cessation

The impact of nicotine on drug metabolism should be carefully considered, including its impact on ropinirole. The author presents a case in which a patient with RLS effectively treated with ropinirole (Requip) experienced profound side effects from ropinirole when she stopped smoking.

A Severely Sleep Deprived Patient

SLEEP MEDICINE PEARLS - A Severely Sleep Deprived Patient

The Harvard Medical School Guide to a Good Night’s Sleep
By Lawrence J. Epstein, M.D., with Steven Mardon, 272 pp, $14.95, ISBN: 0071467432. The McGraw-Hill Companies,
New York, NY

BOOK REVIEW - The Harvard Medical School Guide to a Good Night’s Sleep

SLEEP MEDICINE NEWS AND UPDATES