Amanda J. Piper

Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation

Background: Untreated, obesity hypoventilation is associated with significant use of health care resources and high mortality. It remains unclear whether continuous positive airway pressure (CPAP) or bilevel ventilatory support (BVS) should be used as initial management. The aim of this study was to determine if one form of positive pressure is superior to the other in improving daytime respiratory failure. Methods: A prospective randomised study was performed in patients with obesity hypoventilation referred with respiratory failure. After exclusion of patients with persisting severe nocturnal hypoxaemia (Spo2 <80% for >10 min) or carbon dioxide retention (>10 mm Hg) despite optimal CPAP, the remaining patients were randomly assigned to receive either CPAP or BVS over a 3-month period. The primary outcome was change in daytime carbon dioxide level. Secondary outcome measures included daytime sleepiness, quality of life, compliance with treatment and psychomotor vigilance testing. Results: Thirty-six patients were randomised to either home CPAP (n = 18) or BVS (n = 18). The two groups did not differ significantly at baseline with regard to physiological or clinical characteristics. Following 3 months of treatment, daytime carbon dioxide levels decreased in both groups (CPAP 6 (8) mm Hg; BVS 7 (7) mm Hg) with no between-group differences. There was no difference in compliance between the two treatment groups (5.8 (2.4) h/night CPAP vs 6.1 (2.1) h/night BVS). Although both groups reported an improvement in daytime sleepiness, subjective sleep quality and psychomotor vigilance performance were better with BVS. Conclusions: Both CPAP and BVS appear to be equally effective in improving daytime hypercapnia in a subgroup of patients with obesity hypoventilation syndrome without severe nocturnal hypoxaemia. Trial registration number: Australian Clinical Trials Registry ACTRN01205000096651.

Obesity hypoventilation syndrome: mechanisms and management.

Obesity hypoventilation syndrome describes the association between obesity and the development of chronic daytime alveolar hypoventilation. This syndrome arises from a complex interaction between sleep-disordered breathing, diminished respiratory drive, and obesity-related respiratory impairment, and is associated with significant morbidity and mortality. Therapy directed toward reversing these abnormalities leads to improved daytime breathing, with available treatment options including positive pressure therapy, weight loss, and pharmacological management. However, a lack of large-scale, well-designed studies evaluating these various therapies has limited the development of evidence-based treatment recommendations. Although treatment directed toward improving sleep-disordered breathing is usually effective, not all patients tolerate mask ventilation and awake hypercapnia may persist despite effective use. In the longer term, weight loss is desirable, but data on the success and sustainability of this approach in obesity hypoventilation are lacking. The review outlines the major mechanisms believed to underlie the development of hypoventilation in this subgroup of obese patients, their clinical presentation, and current therapy options.

Obesity Hypoventilation Syndrome

Obesity hypoventilation syndrome describes the association between obesity and the development of chronic daytime alveolar hypoventilation. This syndrome arises from a complex interaction between sleep-disordered breathing, diminished respiratory drive, and obesity-related respiratory impairment, and is associated with significant morbidity and mortality. Therapy directed toward reversing these abnormalities leads to improved daytime breathing, with available treatment options including positive pressure therapy, weight loss, and pharmacological management. However, a lack of large-scale, well-designed studies evaluating these various therapies has limited the development of evidence-based treatment recommendations. Although treatment directed toward improving sleep-disordered breathing is usually effective, not all patients tolerate mask ventilation and awake hypercapnia may persist despite effective use. In the longer term, weight loss is desirable, but data on the success and sustainability of this approach in obesity hypoventilation are lacking. The review outlines the major mechanisms believed to underlie the development of hypoventilation in this subgroup of obese patients, their clinical presentation, and current therapy options.

Obesity and the lung: 2 · Obesity and sleep-disordered breathing

As the prevalence of obesity increases in both the developed and the developing world, the respiratory consequences are often underappreciated. This review discusses the presentation, pathogenesis, diagnosis and management of the obstructive sleep apnoea, overlap and obesity hypoventilation syndromes. Patients with these conditions will commonly present to respiratory physicians, and recognition and effective treatment have important benefits in terms of patient quality of life and reduction in healthcare utilisation. Measures to curb the obesity epidemic are urgently required.

Treatment of Obesity Hypoventilation Syndrome and Serum Leptin

Background: Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels. Objectives: The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations. Method: We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study. Results: The average age of the subjects was (mean ± SE) 62 ± 13 years, BMI 40.9 ± 2.2 kg/m2, PaCO2 6.7 ± 0.2 kPa, PaO2 8.9 ± 0.4 kPa and total respiratory disturbance index 44 ± 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6–3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred. Conclusion: Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

Big breathing: the complex interaction of obesity, hypoventilation, weight loss, and respiratory function

Obesity places a significant load on the respiratory system, affecting lung volumes, respiratory muscle function, work of breathing, and ventilatory control. Despite this, most morbidly obese individuals maintain eucapnia. However, a subgroup of morbidly obese individuals will develop chronic daytime hypercapnia, described as the obesity hypoventilation syndrome (OHS). While obesity is obviously a crucial component of this syndrome, the relationship between excess fat accumulation and the development of awake hypercapnia is complex and extends beyond simply impairments of pulmonary mechanics and lung volumes as a consequence of obesity. Various compensatory mechanisms operate to maintain eucapnia even in the presence of extreme obesity. However, if compensation is impaired, hypoventilation will ensue. While obesity alone does not account for the development of hypoventilation, weight loss will produce significant improvements in lung function and awake gas exchange. Such improvements have the potential to substantially reduce morbidity and mortality in these individuals. Nevertheless, many individuals remain overweight despite substantial weight loss, with persistence of upper airway obstruction. Attention to this residual abnormality is important given the high incidence of cardiovascular abnormalities, including pulmonary hypertension, in individuals with OHS.

Prognosis and sleep disordered breathing in heart failure

Abnormal breathing in heart failure as originally described by Cheyne1 and subsequently by Stokes2 was observed in apparently awake patients as an agonal breathing pattern. “. . . The only peculiarity in the last period of his illness was in the state of the respiration. For several days his breathing was irregular, then it would become perceptible, though very low, then by degrees it became heaving and quick, and then it would cease again: this revolution in the state of his breathing occupied about a minute, during which there were about 30 acts of respiration (Cheyne, 1818) . . .” The patient described in this report was an obese, elderly, alcoholic who had suffered a substantial, and ultimately, fatal stroke. He probably had obstructive sleep apnoea prior to the stroke and developed central apnoea subsequently. In the literature subsequent to these reports periodic respiration associated with central apnoeas was believed to be a terminal consequence of end stage heart failure.3-5 More recently it has been recognised that central apnoeas occur commonly in heart failure, especially during sleep, being reported in 40–50% of patients, predominantly men, with stable, medically treated congestive heart failure.6 This sleep breathing abnormality leads to sleep fragmentation, alterations in sleep architecture—with relative increases in stage 1 and 2 sleep and reduction in REM sleep—and a clinical sleep disorder with symptoms of tiredness and sleepiness in some patients.7 The sleep disorder in central sleep apnoea is a consequence of the development of congestive heart failure. Although the pathophysiology is not completely understood, hyperventilation,8 increased chemoreceptor drive,9 and increased circulation time4 10 11 are all believed to be important factors promoting this sleep disorder. Identification of obstructive sleep apnoea (OSA) in patients with primarily left ventricular (LV) dysfunction and clinical heart …

Noninvasive pressure preset ventilation for the treatment of Cheyne-Stokes respiration during sleep

Cheyne-Stokes respiration (CSR) during sleep is common in patients with congestive heart failure (CHF). This pattern of breathing fragments sleep, leading to daytime symptoms of sleepiness and fatigue. It was hypothesized that by controlling CSR with noninvasive pressure preset ventilation (NPPV), there would be a decrease in sleep fragmentation and an improvement in sleep quality. Nine patients (eight males, one female; mean +/- SD 65 +/- 11 yrs) with symptomatic CSR diagnosed on overnight polysomnography (apnoea/hypopnoea index (AHI) 49 +/- 10 x h(-1), minimum arterial oxygen saturation (Sa,O2, 77 +/- 7%) and CHF (left ventricular ejection fraction 25 +/- 8%) were studied. After a period of acclimatization to NPPV (variable positive airway pressure (VPAP) II ST, Sydney, NSW, Australia and bilevel positive airway pressure (BiPAP), Murraysville, PA, USA), sleep studies were repeated on therapy. NPPV almost completely abolished CSR in all patients with a reduction in AHI from 49 +/- 10 to 6 +/- 5 x h(-1) (p<0.001). Residual respiratory events were primarily due to upper airway obstruction at sleep on-set. Arousal index was markedly decreased from 42 +/- 6 to 17 +/- 7 x h(-1) (p <0.001). Sleep architecture showed a trend toward improvement with a reduction in stage 1 and 2 (79 +/- 7% during the diagnostic night versus 72 +/- 10% during NPPV, (p=0.057)), whilst sleep efficiency, slow-wave sleep (SWS), and rapid eye movement (REM) were not altered. Controlling Cheyne-Stokes respiration with noninvasive pressure preset ventilation resulted in reduced arousal and improved sleep quality in the patients with congestive heart failure. Noninvasive pressure preset ventilation should be considered a potential therapy for Cheyne-Stokes respiration in congestive heart failure in those patients who do not respond or fail to tolerate nasal continuous positive airway pressure therapy.

Home mechanical ventilation in australia and new zealand

This study aims to describe the pattern of home mechanical ventilation (HMV) usage in Australia and New Zealand. 34 centres providing HMV in the region were identified and asked to complete a questionnaire regarding centre demographics, patient diagnoses, HMV equipment and settings, staffing levels and methods employed to implement and follow-up therapy. 28 (82%) centres responded, providing data on 2,725 patients. The minimum prevalence of HMV usage was 9.9 patients per 100,000 population in Australia and 12.0 patients per 100,000 population in New Zealand. Variation existed across Australian states (range 4–13 patients per 100,000 population) correlating with population density (r=0.82; p<0.05). The commonest indications for treatment were obesity hypoventilation syndrome (OHS) (31%) and neuromuscular disease (NMD) (30%). OHS was more likely to be treated in New Zealand, in smaller, newer centres, whilst NMD was more likely to be treated in Australia, in larger, older centres. Chronic obstructive pulmonary disease was an uncommon indication (8.0%). No consensus on indications for commencing treatment was found. In conclusion, the prevalence of HMV usage varies across Australia and New Zealand according to centre location, size and experience. These findings can assist HMV service planning locally and highlight trends in usage that may be relevant in other countries.

Nasal versus full face mask for noninvasive ventilation in chronic respiratory failure

This study was undertaken to determine the efficacy of nasal mask (NM) versus full face mask (FFM) for the delivery of noninvasive ventilation (NIV) in subjects with nocturnal hypoventilation. A total of 16 patients (11 males) were enrolled, all with nocturnal hypoventilation currently treated at home with NIV via pressure preset devices. Subjects underwent full polysomnography on three occasions; on the first night current therapy on NM was reviewed, followed by two experimental studies in randomised order using either NM or FFM. NIV settings and oxygen flow rate were the same under both conditions. Notably, 14 of the 16 subjects required the use of a chinstrap to minimise oral leak. Apnoea-hypopnoea indices were within normal limits under both conditions (1.7±3.4 NM versus 1.6±2.4 h FFM). The type of interface did not significantly affect gas exchange during sleep (minimum average arterial oxyhaemoglobin saturation total sleep time 93.4±2.1 NM versus 92.8±2.5% FFM, Delta transcutaneous carbon dioxide nonrapid eye movement sleep to rapid eye movement sleep (0.58±0.36 NM versus 0.50±0.40 kPa FFM). Sleep efficiency was significantly reduced on the FFM (78±9 NM versus 70±14% FFM), although arousal indices were comparable under both conditions (15.6±9.8 NM versus 15.8±8.8 h FFM). Full face masks appear to be as effective as nasal masks in the delivery of noninvasive ventilation to patients with nocturnal hypoventilation. However, a chinstrap was required to reduce oral leak in the majority of subjects using the nasal mask.