Kathleen A. Ferguson

Suppression of Central Sleep Apnea by Continuous Positive Airway Pressure and Transplant-Free Survival in Heart Failure A Post Hoc Analysis of the Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure Trial (CANPAP)

Background— In the main analysis of the Canadian Continuous Positive Airway Pressure (CPAP) for Patients with Central Sleep Apnea (CSA) and Heart Failure Trial (CANPAP), CPAP had no effect on heart transplant–free survival; however, CPAP only reduced the mean apnea-hypopnea index to 19 events per hour of sleep, which remained above the trial inclusion threshold of 15. This stratified analysis of CANPAP tested the hypothesis that suppression of CSA below this threshold by CPAP would improve left ventricular ejection fraction and heart transplant–free survival. Methods and Results— Of the 258 heart failure patients with CSA in CANPAP, 110 of the 130 randomized to the control group and 100 of the 128 randomized to CPAP had sleep studies 3 months later. CPAP patients were divided post hoc into those whose apnea-hypopnea index was or was not reduced below 15 at this time (CPAP-CSA suppressed, n=57, and CPAP-CSA unsuppressed, n=43, respectively). Their changes in left ventricular ejection fraction and heart transplant–free survival were compared with those in the control group. Despite similar CPAP pressure and hours of use in the 2 groups, CPAP-CSA–suppressed subjects experienced a greater increase in left ventricular ejection fraction at 3 months (P=0.001) and significantly better transplant-free survival (hazard ratio [95% confidence interval] 0.371 [0.142 to 0.967], P=0.043) than control subjects, whereas the CPAP-CSA–unsuppressed group did not (for left ventricular ejection fraction, P=0.984, and for transplant-free survival, hazard ratio 1.463 [95% confidence interval 0.751 to 2.850], P=0.260). Conclusions— These results suggest that in heart failure patients, CPAP might improve both left ventricular ejection fraction and heart transplant–free survival if CSA is suppressed soon after its initiation.

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.

Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis.

Background: Cyclic variation of the heart rate is observed during apneic spells in obstructive sleep apnea (OSA). We hypothesized that autonomic changes would affect frequency‐domain measures of heart rate variability (HRV).

Associations among upper airway structure, body position, and obesity in skeletal Class I male patients with obstructive sleep apnea

Interactions between upper airway structure and posture in relation to obesity were studied in a sample of 61 adult Class I skeletal type male patients with obstructive sleep apnea (OSA) and 10 homologous control subjects. A pair of upright and supine lateral cephalometric films were taken for each subject. A Pearson correlation analysis identified significant r values for several demographic variables in patients with OSA such as apnea and hypopnea index, percentage of predicted neck circumference, minimum arterial oxygen saturation, and body mass index (BMI). The difference between cephalometric variables identified in upright and supine subjects was calculated. When patients with OSA changed their posture from upright to supine, significant correlations were observed between the cranial base to upper cervical column angle and the hypopharynx cross-sectional area and BMI. Moreover, the mandibular plane angle and the sella-nasion plane was significantly correlated with BMI. This occurred along with a significant positive correlation between the sella-nasion plane angle and BMI and a significant inverse correlation between the mandibular plane angle in reference to the absolute vertical and horizontal planes, with BMI after the positional change. Such correlations were not observed in control subjects. No correlations were observed between the variables related to the position of the hyoid bone with BMI in either patients with OSA or control subjects after the change in posture. On the basis of these findings, we propose that when patients with OSA change their body position from upright to supine (1) the patients neck is more extended, and (2) the hyoid bone moves more anterosuperiorly in conjunction with an upward and forward rotation of the mandible. This change in craniofacial structure may be a compensatory geometrical change in the upper airway to secure its patency.

The effect of the tongue retaining device on awake genioglossus muscle activity in patients with obstructive sleep apnea

Knowledge of how dental appliances alter upper airway muscle activity when they are used for the treatment of snoring and/or obstructive sleep apnea (OSA) is very limited. The purpose of this study was to define the effect of a tongue retaining device (TRD) on awake genioglossus (GG) muscle activity in 10 adult subjects with OSA and in 6 age and body mass index (BMI) matched symptom-free control subjects. The TRD is a custom-made appliance designed to allow the tongue to remain in a forward position between the anterior teeth by holding the tongue in an anterior bulb with negative pressure, during sleep. This pulls the tongue forward to enlarge the volume of the upper airway and to reduce upper airway resistance. In this study, two customized TRDs were used for each subject. The TRD-A did not have an anterior bulb but incorporated lingual surface electrodes to record the GG electromyographic (EMG) activity. The TRD-B contained an anterior bulb and two similar electrodes. The GG EMG activity was also recorded while patients used the TRD-B but were instructed to keep their tongue at rest outside the anterior bulb; this condition is hereafter referred to as TRD-X. The GG EMG activity and nasal airflow were simultaneously recorded while subjects used these customized TRDs during spontaneous awake breathing in both the upright and supine position. The following results were obtained and were consistent whether subjects were in the upright or the supine position. The GG EMG activity was greater with the TRD-B than with the TRD-A in control subjects (p < 0.05), whereas the GG EMG activity was less with the TRD-B than with the TRD-A in subjects with OSA (p < 0.01). Furthermore, there was no significant difference between the GG EMG activity of the TRD-A and the TRD-X in control subjects, whereas there was less activity with the TRD-X than with the TRD-A in subjects with OSA (p < 0.05). On the basis of these findings, it was concluded that the TRD has different effects on the awake GG muscle activity in control subjects and patients with OSA. The resultant change in the anatomic configuration of the upper airway caused by the TRD may be important in the treatment of OSA because such a change may alleviate the impaired upper airway function.

A tongue retaining device and sleep-state genioglossus muscle activity in patients with obstructive sleep apnea

To define the effect of a tongue retaining device (TRD) on genioglossus (GG) muscle activity in seven obstructive sleep apnea subjects, two overnight sleep studies were carried out with two TRDs. TRD-A had no anterior bulb and incorporated two electrodes to record GG electromyographic (EMG) activity. TRD-B had a bulb and it had electrodes similar to those in TRD-A. Episodes of apnea/hypopnea (AH) were analyzed during both rapid eye movement (REM) and non-REM (NREM) sleep. The peak GG muscle activity was measured for the breath immediately before the AH (pre-AH), for the first (first-E) and last (last-E) inspiratory efforts during the AH, and for the first breath after the AH (post-AH). The time lag between the peak GG EMG activity and the maximum inspiratory effort was calculated. The AH index decreased with both TRDs. The peak GG EMG activity preceded the maximum inspiratory effort throughout the periods, however the time lag changed considerably with TRD-A. The time lags with TRD-A and TRD-B differed significantly for the first-E and the last-E during NREM sleep and for the first-E during REM sleep. The TRD reduces AH severity, normalizes the time lag, and counteracts fluctuating GG EMG activity observed when no bulb is present.

Cephalometric characteristics of nonobese patients with severe OSA.

The purpose of this study was to determine the facial characteristics of nonobese patients with obstructive sleep apnea (OSA). Observational data on a cohort of patients was analyzed retrospectively. The subjects were classified into four groups: nonobese mild, obese mild, nonobese severe, and obese severe. The nonobese mild group included patients with a body mass index (BMI = kilogram/meter2) <25 and an apnea-hypopnea index (AHI) >5 and <15; the obese mild patients had a BMI >35 and an AHI >5 and <15; the nonobese severe patients had a BMI <25 and an AHI >40; the obese severe group had a BMI >35 and AHI >40. Thirty-three male patients referred for overnight polysomnography and lateral cephalometry who met the selection criteria were included. Between-group differences were examined pairwise by analysis of variance (ANOVA) with Bonferroni correction. Only two variables--lower facial height and overbite--were significantly different at p<0.05 between the nonobese severe group and the obese mild group. A discriminant analysis on the cephalometric measurements revealed that patients in the nonobese severe group could be distinguished from patients in other groups by their facial characteristics. OSA patients do not have a homogenous bony structure of the face. In particular, OSA severity in nonobese severe patients may be associated with a vertical skeletal disharmony.

Chapter 109 – Oral Appliances for Sleep-Disordered Breathing

Oral appliances are an established treatment option for snoring and mild obstructive sleep apnea–hypopnea (OSAH). Oral appliance therapy is a noninvasive, reversible approach to treatment. Oral appliances appear to work by increasing upper airway space, stabilizing the anterior position of the mandible, advancing the tongue or soft palate, or both, and possibly by changing upper airway muscle activity. Randomized, controlled trials of oral appliance therapy have shown a good efficacy in patients with mild to moderate OSAH and in some patients with more severe OSAH. In most of the studies, patients preferred the oral appliance over continuous positive airway pressure (CPAP), although CPAP was more effective in reducing the apnea–hypopnea index (AHI). Most patients report improved sleep quality and excessive daytime sleepiness with oral appliance therapy. Additionally, there is growing evidence of improvements in other important

Amiodarone Pulmonary, Neuromuscular and Ophthalmologic Toxicity

Amiodarone is an iodinated benzofuran derivative class III antiarrhythmic that is highly effective in suppressing ventricular and supraventricular arrhythmias. It is also associated with an imposing side effect profile, which often limits its use. Numerous adverse effects have been documented including skin discolouration, photosensitivity, hepatitis, thyroid dysfunction, corneal deposits, pulmonary fibrosis, bone marrow suppression and drug interactions. These side effects are thought to be correlated with the total cumulative dose of amiodarone, but idiopathic reactions have been reported. The majority of adverse reactions resolve with discontinuation of the drug; however, rapid progression may occur, which may be fatal. The present report documents a patient who had a combination of serious amiodarone toxicities that, once recognized, were treated and eventually resulted in a good outcome.

Prevalence of Sleep Disordered Breathing in a Population of Canadian Grainworkers

OBJECTIVES To determine the prevalence of sleep disordered breathing (SDB) in a Canadian population of industrial workers (grainworkers). To determine the clinical features that are predictive of SDB and the validity of self-reported snoring. DESIGN Cross-sectional, interviewer-administered questionnaire with selective recruitment of subjects for home sleep monitoring. SETTING Community setting, Vancouver, British Columbia. PARTICIPANTS All male grainworkers at grain elevators in Vancouver were approached for completion of a questionnaire. Eighty-three per cent of 524 subjects completed the questionnaire and were divided by presumed risk for SDB into four groups. All subjects in the highest risk group (group 1- frequent snoring and witnessed apneas) and a random sample of 40 subjects in the other three groups (group 2 - frequent snoring without witnessed apneas; group 3 - infrequent snoring rare; group 4 - nonsnoring) were approached for home sleep monitoring and 42% consented. INTERVENTIONS Interviewer-administered questionnaire and home sleep monitoring. RESULTS The overall prevalence of SDB in this relatively overweight group was estimated to be 25%, with a stepwise increase from group 4 to group 1 (7%, 29%, 40%, 60%). Presence of snoring and witnessed apneas, a greater body-mass index and a larger neck circumference were associated with SDB. Self-reported snoring was not found to be predictive. CONCLUSIONS This first study of the prevalence of SDB in Canada suggests that SDB is at least as prevalent in Canada as in other industrialized nations and may actually be more common than previously thought. Further studies are required to determine the morbidity, mortality and economic loss associated with SDB in industrial workers.