Sleep Apnea Syndromes: Hanly P

Fleetham J, Ayas N, Bradley D, Ferguson K, Fitzpatrick M, George C, Hanly P, Hill F, Kimoff J, Kryger M, Morrison D, Series F, Tsai W, Anonymous00098. · Comité des troubles respiratoires du sommeil de la SCT. · Can Respir J. · Pubmed #17315056 links to  free full text

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Fleetham J, Ayas N, Bradley D, Ferguson K, Fitzpatrick M, George C, Hanly P, Hill F, Kimoff J, Kryger M, Morrison D, Series F, Tsai W, Anonymous00045. · Respiratory Medicine, Diamond Health Care Centre, Vancouver, British Columbia V5Z 1M9. · Can Respir J. · Pubmed #17036094 links to  free full text

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Hanly P. · Sleep Centre, Foothills Medical Centre, Calgary, Alberta, Canada. · Curr Opin Pulm Med. · Pubmed #18812831 No free full text.

Abstract: PURPOSE OF REVIEW: To provide an update on the prevalence and clinical importance of sleep disorders in patients with end-stage renal disease (ESRD) and to highlight recent findings on their pathogenesis and treatment. RECENT FINDINGS: Although poor sleep quality is common in patients with ESRD, it is underrecognized. In addition to causing impaired quality of life, poor sleep is associated with increased cardiovascular mortality. There is evidence that sleep quality may be improved by cognitive-behavioral therapy that may help to reduce the frequent use of hypnotic medication. There are differences in the clinical presentation of sleep apnea in patients with ESRD compared with patients with normal renal function. The pathogenesis of sleep apnea in patients with ESRD appears to be related both to increased chemosensitivity, which destabilizes the control of breathing, and narrowing of the upper airway, which predisposes to closure of the airway during sleep. Although renal transplantation corrects periodic leg movements, it does not always correct sleep apnea. SUMMARY: Sleep disorders are common in patients with ESRD. Although our understanding of their pathogenesis and clinical presentation has grown in recent years, further research is required to determine their impact on clinical outcomes in this patient population.

Hanly P. · Division of Respirology, Room 6049, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8. · Semin Dial. · Pubmed #15043611 No free full text.

Abstract: Sleep disorders are common in patients with end-stage renal disease (ESRD). The prevalence of sleep apnea is 10 times greater in patients with ESRD than in the general population. Although sleep apnea is not improved by conventional modes of dialysis, it is corrected by nocturnal hemodialysis, which provides a new and unique model to study its pathophysiology in this patient population. In addition to causing sleep disruption and impairment of daytime function, sleep apnea may also increase the cardiovascular morbidity and mortality that is commonly found in patients with ESRD. "Pathological" daytime sleepiness is found in 50% of patients with ESRD. Although its pathogenesis has been related both to sleep apnea and periodic limb movements, it has also been attributed to a variety of metabolic factors, including the severity of uremia. Further research is required to evaluate the impact of sleep disorders on the clinical outcome of patients with ESRD.

Hanly P, Chan C, Pierratos A. · Sleep Clinic, St. Michael's Hospital, Toronto, Ontario, Canada. · Nephrol News Issues. · Pubmed #12847958 No free full text.

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Bradley TD, Logan AG, Kimoff RJ, Sériès F, Morrison D, Ferguson K, Belenkie I, Pfeifer M, Fleetham J, Hanly P, Smilovitch M, Tomlinson G, Floras JS, Anonymous00277. · Department of Medicine, University of Toronto, Toronto. · N Engl J Med. · Pubmed #16282177 links to  free full text

Abstract: BACKGROUND: The Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure trial tested the hypothesis that continuous positive airway pressure (CPAP) would improve the survival rate without heart transplantation of patients who have central sleep apnea and heart failure. METHODS: After medical therapy was optimized, 258 patients who had heart failure (mean age [+/-SD], 63+/-10 years; ejection fraction, 24.5+/-7.7 percent) and central sleep apnea (number of episodes of apnea and hypopnea per hour of sleep, 40+/-16) were randomly assigned to receive CPAP (128 patients) or no CPAP (130 patients) and were followed for a mean of two years. During follow-up, sleep studies were conducted and measurements of the ejection fraction, exercise capacity, quality of life, and neurohormones were obtained. RESULTS: Three months after undergoing randomization, the CPAP group, as compared with the control group, had greater reductions in the frequency of episodes of apnea and hypopnea (-21+/-16 vs. -2+/-18 per hour, P<0.001) and in norepinephrine levels (-1.03+/-1.84 vs. 0.02+/-0.99 nmol per liter, P=0.009), and greater increases in the mean nocturnal oxygen saturation (1.6+/-2.8 percent vs. 0.4+/-2.5 percent, P<0.001), ejection fraction (2.2+/-5.4 percent vs. 0.4+/-5.3 percent, P=0.02), and the distance walked in six minutes (20.0+/-55 vs. -0.8+/-64.8 m, P=0.016). There were no differences between the control group and the CPAP group in the number of hospitalizations, quality of life, or atrial natriuretic peptide levels. An early divergence in survival rates without heart transplantation favored the control group, but after 18 months the divergence favored the CPAP group, yet the overall event rates (death and heart transplantation) did not differ (32 vs. 32 events, respectively; P=0.54). CONCLUSIONS: Although CPAP attenuated central sleep apnea, improved nocturnal oxygenation, increased the ejection fraction, lowered norepinephrine levels, and increased the distance walked in six minutes, it did not affect survival. Our data do not support the use of CPAP to extend life in patients who have central sleep apnea and heart failure.

Beecroft J, Zanon S, Lukic D, Hanly P. · Sleep Disorders Clinic, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8. · Chest. · Pubmed #14665501 links to  free full text

Abstract: BACKGROUND: Nasal continuous positive airway pressure (CPAP) is the most definitive medical therapy for obstructive sleep apnea (OSA). Many patients have difficulty tolerating nasal CPAP due to nasal airway problems, mouth leak, and general discomfort from the mask and headgear. These limitations may be overcome by an oral mask (Oracle; Fisher & Paykel Healthcare; Languna Hills, CA) that does not require headgear. We performed a study to compare the Oracle mask to conventional nasal and oronasal masks in the effectiveness of CPAP delivery and patient satisfaction and adherence. METHODS: Ninety-eight, consecutive CPAP-naïve patients with OSA diagnosed by overnight polysomnography (apnea-hypopnea index [AHI] > 5) were referred for CPAP therapy. All patients were presented with a variety of CPAP masks, including nasal, oronasal, and Oracle, and reasons for mask choice were documented. After 3 weeks of acclimatization to the mask of their choice, patients had a CPAP titration sleep study to determine their optimal CPAP level. Further follow-up was obtained 2 months and 6 months later with a subjective patient assessment of CPAP use and efficacy, mask comfort, and upper airway dryness. RESULTS: Patients were predominantly male (70%), middle aged (50.6 +/- 11.7 years), and moderately obese (body mass index, 32.5 +/- 9.0) with severe OSA (AHI, 40.6 +/- 25.8/h) [mean +/- SD]. Patients were classified into three groups based on their choice of mask: nasal (66%), Oracle (27%), and oronasal (7%). Baseline characteristics did not differ significantly between groups. Optimal CPAP was not significantly different between mask groups (nasal, 7.7 +/- 2.1 cm H(2)O; Oracle, 8.0 +/- 2.0 cm H(2)O; oronasal, 9.7 +/- 3.2 cm H(2)O; p = 0.267). Subjective ratings of adherence, efficacy, and mask comfort were also similar between groups. However, the Oracle group had more complaints of upper airway dryness and "rain-out." The oronasal group had a disproportionately greater number of dropouts from CPAP therapy than the Oracle group (57% vs 19%, p = 0.046). Nine patients changed from the Oracle mask to a nasal mask during the study, whereas no patients changed from their nasal or oronasal masks. CONCLUSIONS: The Oracle mask is an efficacious interface for long-term CPAP therapy in patients with OSA. The main limitations of the mask are upper airway dryness and rain-out associated with heated humidification, which may be improved by further technical modifications. Oracle may be more acceptable than oronasal masks for patients who cannot rely exclusively on the nasal airway for CPAP therapy.

Younes M, Ostrowski M, Atkar R, Laprairie J, Siemens A, Hanly P. · Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada. · J Appl Physiol. · Pubmed #17823298 links to  free full text

Abstract: The response to chemical stimuli (chemical responsiveness) and the increases in respiratory drive required for arousal (arousal threshold) and for opening the airway without arousal (effective recruitment threshold) are important determinants of ventilatory instability and, hence, severity of obstructive apnea. We measured these variables in 21 obstructive apnea patients (apnea-hypopnea index 91 +/- 24 h(-1)) while on continuous-positive-airway pressure. During sleep, pressure was intermittently reduced (dial down) to induce severe hypopneas. Dial downs were done on room air and following approximately 30 s of breathing hypercapneic and/or hypoxic mixtures, which induced a range of ventilatory stimulation before dial down. Ventilation just before dial down and flow during dial down were measured. Chemical responsiveness, estimated as the percent increase in ventilation during the 5(th) breath following administration of 6% CO(2) combined with approximately 4% desaturation, was large (187 +/- 117%). Arousal threshold, estimated as the percent increase in ventilation associated with a 50% probability of arousal, ranged from 40% to >268% and was <120% in 12/21 patients, indicating that in many patients arousal occurs with modest changes in chemical drive. Effective recruitment threshold, estimated as percent increase in pre-dial-down ventilation associated with a significant increase in dial-down flow, ranged from zero to >174% and was <110% in 12/21 patients, indicating that in many patients reflex dilatation occurs with modest increases in drive. The two thresholds were not correlated. In most OSA patients, airway patency may be maintained with only modest increases in chemical drive, but instability results because of a low arousal threshold and a brisk increase in drive following brief reduction in alveolar ventilation.

Arzt M, Floras JS, Logan AG, Kimoff RJ, Series F, Morrison D, Ferguson K, Belenkie I, Pfeifer M, Fleetham J, Hanly P, Smilovitch M, Ryan C, Tomlinson G, Bradley TD, Anonymous00003. · University of Toronto, Toronto, Ontario, Canada. · Circulation. · Pubmed #17562959 links to  free full text

Abstract: 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.

Chan CT, Hanly P, Gabor J, Picton P, Pierratos A, Floras JS. · Division of Nephrology, University Health Network, Toronto, Ontario, Canada. · Kidney Int. · Pubmed #14717939 No free full text.

Abstract: BACKGROUND: Nocturnal hemodialysis (NHD) alleviates uremia-related sleep apnea, a condition characterized by increased sympathetic activity and diminished heart rate (HR) variability. We tested the hypothesis that NHD reduces both hypoxemia and sympathetic neural contributions to HR variability during sleep. METHODS: Episodes of apnea and hypopnea and the duration of nocturnal hypoxemia during sleep were determined in 9 end-stage renal disease (ESRD) patients (age: 44 +/- 2) (mean +/- SEM) before and after conversion from conventional hemodialysis (CHD) to NHD, and in 10 control subjects (age: 45 +/- 3) with normal renal function and without sleep apnea. Low frequency (LF) (0.05-0.15 Hz) and high frequency (HF) (0.15-0.5 Hz) HR spectral power during stage 2 sleep was calculated (Fast Fourier transformation). Patients were studied 4 times (1 day before and on the night after their CHD session) and 6-15 months after conversion to NHD, while receiving NHD and on a non-dialysis night. RESULTS: NHD decreased the frequency of apnea and hypopnea (from 29.7 +/- 9.3 to 8.2 +/- 2.0 episodes per hour, P= 0.02), and duration of nocturnal hypoxemia (from 13.9 +/- 5.2 to 2.6 +/- 1.9% of total sleep time, P= 0.02). As CHD recipients, ESRD patients had faster nocturnal heart rates (79 +/- 2 vs. 58 +/- 1 min-1, P= 0.03) and lower HF (vagal) (78 +/- 27 vs. 6726 +/- 4556 ms2, P= 0.001) spectral power than control subjects. After conversion to NHD, HR fell (from 79 +/- 2 to 66 +/- 1 min-1, P= 0.03) and HF power increased (from 78 +/- 27 to 637 +/- 139 ms2, P= 0.001). The HF/HF+LF ratio, an index of vagal HR modulation, was lower during CHD (0.16 +/- 0.03 vs. 0.42 +/- 0.05 in control subjects, P < 0.05) and increased (to 0.45 +/- 0.05, P < 0.001) after conversion to NHD. The LF/HF ratio, a representation of sympathetic HR modulation, which was significantly higher during CHD than in control subjects (2.77 +/- 0.82 vs. 0.71 +/- 0.11, P < 0.05), was also normalized by NHD (0.74 +/- 0.12, P < 0.05, compared with CHD). CONCLUSION: Higher heart rates and impaired vagal and augmented sympathetic HR modulation during sleep in ESRD patients are normalized by NHD. Potential mechanisms for these observations include attenuation of surges in sympathetic outflow elicited by apnea and hypoxia during sleep, normalization of nocturnal breathing patterns that influence HRV, and removal, by increased dialysis, of a sympatho-excitatory stimulus of renal origin.