Predictive factors for sleep apnoea in patients on opioids for chronic pain.

Background: The risk of death is elevated in patients taking opioids for chronic non-cancer pain. Respiratory depression is the main cause of death due to opioids and sleep apnoea is an important associated risk factor. Methods: In chronic pain clinics, we assessed the STOP-Bang questionnaire (a screening tool for sleep apnoea; Snoring, Tiredness, Observed apnoea, high blood Pressure, Body mass index, age, neck circumference and male gender), Epworth Sleepiness Scale, thyromental distance, Mallampati classification, daytime oxyhaemoglobin saturation (SpO2) and calculated daily morphine milligram equivalent (MME) approximations for each participant, and performed an inlaboratory polysomnogram. The primary objective was to determine the predictive factors for sleep apnoea in patients on chronic opioid therapy using multivariable logistic regression models. Results: Of 332 consented participants, 204 underwent polysomnography, and 120 (58.8%) had sleep apnoea (AHI ≥5) (72% obstructive, 20% central and 8% indeterminate sleep apnoea), with a high prevalence of moderate (23.3%) and severe (30.8%) sleep apnoea. The STOP-Bang questionnaire and SpO2 are predictive factors for sleep apnoea (AHI ≥15) in patients on opioids for chronic pain. For each one-unit increase in the STOP-Bang score, the odds of moderate-to-severe sleep apnoea (AHI ≥15) increased by 70%, and for each 1% SpO2 decrease the odds increased by 33%. For each 10 mg MME increase, the odds of Central Apnoea Index ≥5 increased by 3%, and for each 1% SpO2 decrease the odds increased by 45%. Conclusion: In patients on opioids for chronic pain, the STOP-Bang questionnaire and daytime SpO2 are predictive factors for sleep apnoea, and MME and daytime SpO2 are predictive factors for Central Apnoea Index ≥5. Trial registration number: NCT02513836.

Profile of CPAP treated patients in Ontario, Canada, 2006-2013: a population-based cohort study.

RATIONALE: Many studies have demonstrated the benefits of treating obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP). However, both recognition of OSA and acceptance of treatment are suboptimal. Current data on CPAP initiation at a population level is lacking. OBJECTIVES: The objectives were to determine the rate of CPAP initiations in Ontario, Canada (population ∼13,000,000), and to profile these individuals over time. METHODS: We conducted a population based cohort study between 2006 and 2013. All adults who initiated CPAP for OSA were included. Patient characteristics, comorbidities and health care utilization at the time of CPAP initiation were derived from provincial health administrative data. Changes in patient characteristics over time were assessed. RESULTS: Over eight years, 216,514 individuals initiated CPAP therapy in comparison to 802,188 individuals who underwent diagnostic polysomnography (PSG) during that time. The rate of new CPAP initiations increased from 18.6/10,000 in 2006 to 28.7/10,000 in 2008 and then plateaued with an annual increase of less than 1/10,000 from 2008 to 2013. More women and middle aged (50+) individuals initiated CPAP as did more low income Ontarians. Comorbidities were common and the frequency of congestive heart failure, chronic kidney disease, and cancer increased during the study period. CONCLUSIONS: Over an eight year period CPAP initiation appears to have plateaued in spite of increasing PSG testing; however, those receiving treatment with CPAP are increasingly complex and a greater proportion are women.

Continuous positive airway pressure treatment of sleepy patients with milder obstructive sleep apnea: results of the CPAP Apnea Trial North American Program (CATNAP) randomized clinical trial.

RATIONALE: Twenty-eight percent of people with mild to moderate obstructive sleep apnea experience daytime sleepiness, which interferes with daily functioning. It remains unclear whether treatment with continuous positive airway pressure improves daytime function in these patients. OBJECTIVES: To evaluate the efficacy of continuous positive airway pressure treatment to improve functional status in sleepy patients with mild and moderate obstructive sleep apnea. METHODS: Patients with self-reported daytime sleepiness (Epworth Sleepiness Scale score >10) and an apnea-hypopnea index with 3% desaturation and from 5 to 30 events per hour were randomized to 8 weeks of active or sham continuous positive airway pressure treatment. After the 8-week intervention, participants in the sham arm received 8 weeks of active continuous positive airway pressure treatment. MEASUREMENTS AND MAIN RESULTS: The Total score on the Functional Outcomes of Sleep Questionnaire was the primary outcome measure. The adjusted mean change in the Total score after the first 8-week intervention was 0.89 for the active group (n = 113) and -0.06 for the placebo group (n = 110) (P = 0.006). The group difference in mean change corresponded to an effect size of 0.41 (95% confidence interval, 0.14-0.67). The mean (SD) improvement in Functional Outcomes of Sleep Questionnaire Total score from the beginning to the end of the crossover phase (n = 91) was 1.73 ± 2.50 (t[90] = 6.59; P < 0.00001) with an effect size of 0.69. CONCLUSIONS: Continuous positive airway pressure treatment improves the functional outcome of sleepy patients with mild and moderate obstructive sleep apnea.

A 2-week, polysomnographic, safety study of sodium oxybate in obstructive sleep apnea syndrome.

PURPOSE: Sodium oxybate (SXB) is approved for cataplexy and excessive daytime sleepiness in narcolepsy. Obstructive sleep apnea syndrome (OSAS) affects ∼9-50% of narcoleptics. Effects of 2-week SXB administration on apnea-hypopnea index (AHI), oxygen saturation (SaO(2)), and sleep architecture were investigated in OSAS patients. METHODS: OSAS patients (n = 48) received 2-week SXB or placebo (PBO) treatment with polysomnography at baseline and day 14. The primary outcome measure was change from baseline in mean AHI. Secondary outcomes included changes from baseline in SaO(2), and sleep architecture. RESULTS: Compared with PBO, SXB significantly increased reduction in mean AHI and obstructive apnea index with SXB (-0.8 ± 13.3 vs. -8.2 ± 10.0; p = 0.0327 and 3.54 ± 11.1 vs. -4.72 ± 7.7; p = 0.0054, respectively) and significantly increased change in slow wave sleep duration (5.2 ± 25.0 min vs. 29.4 ± 37.0 min; p = 0.0038). There were no differences between treatments in SaO2, central apneic events, or other measures. Adverse events, most commonly headache, were noted in nine of 27 (33%) and six of 23 (26%) patients receiving SXB and PBO, respectively. CONCLUSIONS: Short-term use of 4.5 g/night SXB did not generate respiratory depressant effects in OSAS patients as measured by AHI, obstructive apnea events, central apneas, and SaO2. Extended use of SXB in higher therapeutic doses in OSAS has not been studied, and merits caution.

Sleep apnea, daytime somnolence, and idiopathic dizziness--a novel association.

OBJECTIVES/HYPOTHESIS: To determine if an association exists between sleep apnea, daytime somnolence, and chronic idiopathic dizziness. STUDY DESIGN: Case-control study of new patients presenting to a tertiary neuro-otologic practice. A total of 46 subjects with idiopathic dizziness (ID), 20 positive controls with dizziness (benign paroxysmal positional vertigo [BPV]), and 69 negative controls with hearing loss (HL) but no dizziness were enrolled. METHODS: Participants who were patients diagnosed with the above conditions and who met all other inclusion criteria completed a sleep questionnaire and had a complete physical exam and investigations to establish or exclude a neuro-otologic diagnosis. They were subsequently evaluated for risk of symptomatic sleep disturbance based on the Epworth Sleepiness Scale (ESS), the Berlin Questionnaire, and the Multivariable Apnea Risk Index (MAP). Statistical analysis was carried out using SPSS (SPSS Inc., Chicago, IL). RESULTS: There was no significant demographic difference among the groups in terms of age, sex, body mass index, neck size, alcohol consumption, or smoking. Using a cutoff of both 10 and 12 on the ESS, the ID were more likely to have significant daytime somnolence than the HL group, with a likelihood ratio (LR) of 7.8 for the ESS 12 score (P = .021) and 7.1 for the ESS 10 score (P = .029). Using the MAP score, a statistically significant difference between the ID group and both the BPV group (LR 3.99, P = .046) and the HL group (LR 5.46, P = .019) was found. CONCLUSIONS: This study suggests that a previously undescribed link between idiopathic dizziness, daytime somnolence, and sleep apnea might exist. Prospective investigation is warranted to determine whether treatment of any sleep issues resolves symptoms of idiopathic dizziness.

Evaluation of sham-CPAP as a placebo in CPAP intervention studies.

STUDY OBJECTIVES: To evaluate the use of sham-continuous positive airway pressure (CPAP) treatment as a placebo intervention. DESIGN AND SETTING: Analysis of polysomnograms performed in fixed order without sham-CPAP and on the first night of the sham-CPAP intervention in participants in the CPAP Apnea Trial North American Program (CATNAP), a randomized, placebo controlled trial evaluating the effects of CPAP treatment on daytime function in adults with newly diagnosed mild to moderate obstructive sleep apnea (apnea hypopnea index (AHI) 5-30). PARTICIPANTS: The first 104 CATNAP participants randomized to the sham-CPAP intervention arm. MEASUREMENTS AND RESULTS: Compared to the polysomnographic measures without sham-CPAP, the study on the first night with sham-CPAP had statistically significant differences that suggested a decrease in sleep quality: decreased sleep efficiency, increased arousal index, increased time in stage 1 NREM sleep, and prolonged latency to REM sleep. However, all of these differences had a relatively small effect size. Compared to the polysomnogram without sham-CPAP, the number of hypopneas on the sham-CPAP polysomnogram was significantly increased and the number of apneas significantly decreased. Relatively minor differences in AHI with and without sham-CPAP were present and were dependent on the criteria used to score hypopneas. CONCLUSION: Comparison of polysomnograms with and without sham-CPAP revealed differences that, although statistically significant, were small in magnitude and had relatively low effect sizes suggesting minimal clinical significance. The results support the use of sham-CPAP as a placebo intervention in trials evaluating the effects of CPAP treatment in patients with obstructive sleep apnea. CLINICAL TRIAL INFORMATION: This paper was a secondary analysis of clinical trial data. CATNAP: CPAP Apnea Trial North American Program, the trial from which the data were obtained, is registered with clinicaltrial.gov. Registration #NCT00089752.

A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing.

OBJECTIVE: Sodium oxybate (SXB) is an approved drug for the treatment of excessive daytime sleepiness (EDS) and cataplexy in narcolepsy. Obstructive sleep apnea syndrome (OSAS) is a condition that frequently co-occurs with narcolepsy. Given the known central nervous system (CNS) depressant effects of SXB, this study aimed to examine its effects on sleep-disordered breathing (SDB) and sleep architecture in patients with OSAS. METHODS: Sixty patients with a history of mild to moderate OSAS (apnea-hypopnea index [AHI]>or=10 and or=75%) received one of four treatments of the following: (1) 9g SXB, (2) 9g SXB/modafinil 200mg, (3) zolpidem 10mg, and (4) placebo (PBO) in a randomized, crossover design on four consecutive nights followed by overnight polysomnography. RESULTS: Forty-two patients (70%) completed the study. The mean change from baseline in AHI and mean SaO(2) was not significantly different among groups following treatment. Central apneas in patients treated with SXB increased, and clinically significant oxygen desaturations were seen in three patients with SXB treatment. The most common treatment related adverse events were headache and nausea. CONCLUSION: These results suggest that nighttime administration of 9g SXB in patients with mild to moderate OSAS does not negatively impact SDB, as measured by mean change from baseline in AHI and SaO(2), but might increase central apneas and cause oxygen desaturation in some individuals and should be used with caution.

Sleep apnea, alertness, and motor vehicle crashes.

Sleep apnea causes impairment in performance and is associated with an increased risk of motor vehicle crashes compared with the general population of drivers. Despite this increased risk, the actual number of accidents is still quite low, although the implications are significant in commercial vehicle drivers. It is difficult for physicians to assess risk and ability to drive in many patients with sleep apnea, yet physicians are often mandated to make these assessments with obvious implications for patients. Because many patients may never have a crash, it is not practical or feasible to restrict all untreated patients from driving, unless they operate commercial vehicles. Thresholds of disease severity that prompt driving restriction need to be established for sleep apnea much like they have been for alcohol. Until more data emerge, continued educational efforts about sleep apnea are needed to convince government and insurance organizations to provide appropriate resources for diagnosis and treatment of sleep apnea, because apnea risk is minimized with successful apnea treatment.

Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning.

STUDY OBJECTIVES: Evidence suggests that, to maintain treatment effects, nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) needs to be used every night. What remains unknown is the nightly duration of use required to normalize functioning. This study, employing probit analyses and piecewise regression to estimate dose-response functions, estimated likelihoods of return to normal levels of sleepiness and daily functioning relative to nightly duration of CPAP. DESIGN: Multicenter, quasi-experimental study. SETTING: Seven sleep centers in the United States and Canada. PARTICIPANTS: Patients with severe OSA (total cohort n = 149; the numbers of included participants from 85 - 120, depending on outcome analyzed.) INTERVENTIONS: CPAP. MEASUREMENTS AND RESULTS: Before treatment and again after 3 months of therapy, participants completed a day of testing that included measures of objective and subjective daytime sleepiness and functional status. There were significant differences in mean nightly CPAP duration between treatment responders and nonresponders across outcomes. Thresholds above which further improvements were less likely relative to nightly duration of CPAP were identified for Epworth Sleepiness Scale score (4 hours), Multiple Sleep Latency Test (6 hours), and Functional Outcomes associated with Sleepiness Questionnaire (7.5 hours). A linear dose-response relationship (P < 0.01) between increased use and achieving normal levels was shown for objective and subjective daytime sleepiness, but only up to 7 hours use for functional status. CONCLUSIONS: Our analyses suggest that a greater percentage of patients will achieve normal functioning with longer nightly CPAP durations, but what constitutes adequate use varies between different outcomes.

Impaired performance in commercial drivers: role of sleep apnea and short sleep duration.

Sleepiness plays an important role in major crashes of commercial vehicles. Because determinants are likely to include inadequate sleep and sleep apnea, we evaluated the role of short sleep durations over 1 wk at home and sleep apnea in subjective sleepiness (Epworth Sleepiness Scale), objective sleepiness (reduced sleep latency as determined by the Multiple Sleep Latency Test), and neurobehavioral functioning (lapses in performance, tracking error in Divided Attention Driving Task) in commercial drivers. Studies were conducted in 247 of 551 drivers at higher risk for apnea and in 159 of 778 drivers at lower risk. A multivariate linear association between the sets of outcomes and risk factors was confirmed (p < 0.0001). Increases in subjective sleepiness were associated with shorter sleep durations but not with increases in severity of apnea. Increases in objective sleepiness and performance lapses, as well as poorer lane tracking, were associated with shorter sleep durations. Associations with sleep apnea severity were not as robust and not strictly monotonic. A significant linear association with sleep apnea was demonstrated only for reduced sleep latency. The effects of severe apnea (apnea-hypopnea index, at least 30 episodes/h), which occurred in 4.7%, and of sleep duration less than 5 h/night, which occurred in 13.5%, were similar in terms of their impact on objective sleepiness. Thus, addressing impairment in commercial drivers requires addressing both insufficient sleep and sleep apnea, the former being more common.

Sleepiness and relationships in obstructive sleep apnea.

This is a qualitative analysis of data from a multisite study of 156 participants with Obstructive Sleep Apnea (OSA). Participants completed a battery of tests, including the Functional Outcomes of Sleep Questionnaire (FOSQ) that contains an item assessing the impact of OSA on relationships. Approximately one third of participants wrote comments; they were predominately male, mean age 44.7, with severe OSA. Interpersonal themes expressed included work and marital problems and social life restriction. Intrapersonal themes included embarrassment and poor mood. This report adds specific details to previous reports of impaired relationships in OSA, and stresses the importance of assessing this critical area.

Physiologic pacing in patients with obstructive sleep apnea: a prospective, randomized crossover trial.

OBJECTIVES: This study was designed to assess the impact of prevention of bradycardia with physiologic pacing on the severity of obstructive sleep apnea. BACKGROUND: Apneic episodes during sleep are associated with slowing of the heart rate during apnea and tachycardia with subsequent arousal. Patients with permanent pacemakers may have reduced episodes of sleep apnea when their pacemaker rate is set faster than their spontaneous nocturnal heart rate. METHODS: We conducted a prospective, randomized, single-blind crossover trial of temporary atrial pacing in obstructive sleep apnea to reduce the apnea hypopnea index (AHI). Fifteen patients (age 60 +/- 13 years, 12 men) with moderate to severe obstructive sleep apnea (AHI 34 +/- 14) underwent insertion of an externalized atrial permanent pacing system via the left subclavian vein. Patients underwent overnight respiratory sleep studies in hospital, during atrial pacing at 75 beats/min, and with pacing turned off. The order of pacing mode was randomized, with crossover the subsequent night to the other mode. Patients were blinded to pacing mode, and the analysis of sleep recordings was blind to pacing mode. RESULTS: Pacing was tolerated without complications in all patients. Overnight physiologic pacing did not affect the AHI (pacing 39 +/- 21/h vs. control 42 +/- 21/h, p = 0.23, 95% confidence interval -9.3 to 2.5 for difference), desaturation time (pacing 3.8 +/- 6.0% vs. control 3.5 +/- 4.3%, p = 0.70), or the minimum SaO(2) (pacing 75 +/- 10% vs. control 77 +/- 11%, p = 0.38). There was a borderline significant reduction in circulatory time with pacing (pacing 23.4 +/- 3.2 s vs. control 25.5 +/- 4.4 s, p = 0.09). CONCLUSIONS: Temporary atrial pacing does not appear to improve respiratory manifestations of obstructive sleep apnea. Permanent atrial pacing in this patient population does not appear to be justified.

Sleep and motor performance in on-call internal medicine residents.

STUDY OBJECTIVES: To compare vigilance and performance among internal medicine residents doing in-house call versus residents not doing in-house call. DESIGN: Prospective study of resident cohorts with repeated testing. SETTING: University Teaching Hospital. PARTICIPANTS: Internal medicine residents doing in-house call and residents not doing in-house call (pathology, endocrinology) (controls). MEASUREMENTS AND RESULTS: Subjective sleepiness scores (daily Stanford Sleepiness Scale and Epworth Sleepiness Scale at start and end of the test period), actigraphy, and daily sleep logs as well as regular psychomotor vigilance testing using a Palm version (Walter Reed Army Institute of Research) of the Psychomotor Vigilance Test (PVT). Subjects were enrolled for a period of 28 to 32 days, which included 4 to 6 on-call nights for the internal medicine residents. Controls took call from home. Participants were compensated for their time. RESULTS: Twenty residents were evaluated, 13 internal medicine and 7 controls. Overall median reaction time was slower in the internal medicine residents (264.7 +/- 102.9 vs 239.2 +/- 26.1 milliseconds; P < .001). Internal medicine residents showed no difference in reaction time postcall versus other periods (269.9 +/- 131.2 vs 263.6 +/- 95.6; P = .65). Actigraphic sleep time was shorter during on-call than noncall nights and in internal medicine residents as compared with controls (287.48 +/- 143.8 vs 453.49 +/- 178.5 and 476.08 +/- 71.9 minutes; P < .001). Internal medicine residents had significantly greater major and minor reaction-time lapses compared with controls (1.26 +/- 3.4 vs 0.53 +/- 1.1 & 2.4 +/- 7.4 vs 0.45 +/- 1.0; P < .001). They reported increased sleepiness on postcall days compared with the start of their call (Stanford Sleepiness Scale: 3.26 +/- 1.2 vs 2.22 +/- 0.8; P < .001) but had scores similar to those of controls by their next call (2.22 +/- 0.8 vs 2.07 +/- 0.8; P = .13). CONCLUSIONS: Internal medicine residents have impaired reaction time and reduced vigilance compared with controls. Despite subjective improvements in sleepiness postcall, there was no change in their objective performance across the study period, suggesting no recovery. Internal medicine residents did not get extra sleep on postcall nights in an attempt to recover their lost sleep time. Implications for residents' well-being and patient care remain unclear.

Sleep and breathing in professional football players.

OBJECTIVES: To evaluate sleep in professional football players and describe clinical features of players at risk for sleep for sleep-disordered breathing (SDB). METHODS: The Multivariable Apnea Prediction (MAP) index was used to stratify players into high (MAP> or =0.5) and low (MAP<0.5) risk for SDB. Players from both risk groups were randomly selected for overnight polysomnography, with over-sampling from the High-risk group. Of 302 players from eight professional football teams; 52 underwent attended polysomnography. Anthropometrics including neck circumference, airway size (Mallampati score, maxillary overjet) and sleepiness measured by Epworth scores (ESS) were recorded. The primary outcome measures were ESS and an apnea-hypopnea index (AHI) > or =10. RESULTS: Ninety-two percent of players were <30 years old (mean (SD) age: 25.5+/-2.7 years) with large necks (45.2+/-3.6 cm) and elevated BMI (31.5+/-4.6). More than 20% of players had an ESS>10 with ESS highest in habitual snorers. An AHI of > or =10 was found in 13 (34%, 95% confidence interval (CI) 21-50%) high-risk players but only one (7%, 95% CI 1-31%) of 14 low-risk players. Offensive (9) or defensive (3) linemen accounted for the majority of the positive cases. Based on our sample, we estimate the prevalence of SDB to be 14% (2-25%). CONCLUSIONS: Excessive daytime sleepiness (EDS) is present in a large fraction of professional football players. Some but not all of this may be due to an increased prevalence of SDB. Further study is required to understand all of the factors responsible for EDS and to determine which of the biggest players will have SDB, which may impact not only performance and productivity but also future health.