Inter-night variability of in-home, overnight pulse oximetry screening in an asymptomatic older adult population.

PURPOSE: Obstructive sleep apnoea (OSA) is common, yet often undiagnosed. Self-administered, overnight pulse oximetry (OPO) could screen for OSA in asymptomatic, older populations. However, the inter-night variability of OPO in an asymptomatic, older population is unknown. We determined the inter-night variability of home OPO parameters in an older population and correlated with sleep questionnaires. METHODS: Participants > 50 years without a diagnosis of OSA undertook home OPO for three consecutive nights and completed two sleep questionnaires (STOP-BANG (SBQ) and Epworth Sleepiness Score (ESS)). Analysis was performed with linear mixed models and Spearman's correlation coefficient. RESULTS: There was no difference in oxygen desaturation index (ODI), MeanSpO2, MinimumSpO2, and time spent with SpO2 < 90% (T90) across two or three nights (P ≥ 0.282). However, the variability of all parameters across nights increased with the magnitude of departure from normal values (P ≤ 0.002). All OPO parameters were associated with age (P ≤ 0.034) and body mass index (P ≤ 0.049). There was a weak correlation between three OPO parameters and SBQ (absolute ρ = 0.22 to 0.32; P ≤ 0.021), but not ESS (P ≥ 0.254). CONCLUSION: Inter-night variability of home OPO was minimal when values were near-normal in an older population. However, as values depart from normal, the inter-night variability increases, indicating the need for multiple night recordings. Low correlation to sleep questionnaires suggest the need for more robust OSA questionnaires in an asymptomatic population.

Sleep apnoea and heart failure.

Heart failure and sleep disordered breathing (SDB) are two common conditions that frequently overlap and have been studied extensively in the past three decades. Obstructive sleep apnoea (OSA) may result in myocardial damage due to intermittent hypoxia that leads to increased sympathetic activity and transmural pressures, low-grade vascular inflammation, and oxidative stress. On the other hand, central sleep apnoea and Cheyne-Stokes respiration (CSA-CSR) occurs in heart failure, irrespective of ejection fraction, either reduced (HFrEF), preserved (HFpEF) or mildly reduced (HFmrEF). The pathophysiology of CSA-CSR relies on several mechanisms leading to hyperventilation, breathing cessation and periodic breathing. Pharyngeal collapse may result at least in part from fluid accumulation in the neck, owing to daytime fluid retention and overnight rostral fluid shift from the legs. Although both OSA and CSA-CSR occur in heart failure, the symptoms are less suggestive than in typical (non-heart failure-related) OSA. Overnight monitoring is mandatory for a proper diagnosis, with accurate measurement and scoring of central and obstructive events, since the management will be different depending on whether the sleep apnoea in heart failure is predominantly OSA or CSA-CSR. SDB in heart failure is associated with worse prognosis, including higher mortality, than in patients with heart failure but without SDB. However, there is currently no evidence that treating SDB improves clinically important outcomes in patients with heart failure, such as cardiovascular morbidity and mortality.

Sleep-disordered breathing was associated with lower health-related quality of life and cognitive function in a cross-sectional study of older adults.

BACKGROUND AND OBJECTIVE: The clinical significance of sleep-disordered breathing (SDB) in older age is uncertain. This study determined the prevalence and associations of SDB with mood, daytime sleepiness, quality of life (QOL) and cognition in a relatively healthy older Australian cohort. METHODS: A cross-sectional analysis was conducted from the Study of Neurocognitive Outcomes, Radiological and retinal Effects of Aspirin in Sleep Apnoea. Participants completed an unattended limited channel sleep study to measure the oxygen desaturation index (ODI) to define mild (ODI 5-15) and moderate/severe (ODI ≥ 15) SDB, the Centre for Epidemiological Studies Scale, the Epworth Sleepiness Scale, the 12-item Short-Form for QOL and neuropsychological tests. RESULTS: Of the 1399 participants (mean age 74.0 years), 36% (273 of 753) of men and 25% (164 of 646) of women had moderate/severe SDB. SDB was associated with lower physical health-related QOL (mild SDB: beta coefficient [ß] -2.5, 95% CI -3.6 to -1.3, p < 0.001; moderate/severe SDB: ß -1.8, 95% CI -3.0 to -0.6, p = 0.005) and with lower global composite cognition (mild SDB: ß -0.1, 95% CI -0.2 to 0.0, p = 0.022; moderate/severe SDB: ß -0.1, 95% CI -0.2 to 0.0, p = 0.032) compared to no SDB. SDB was not associated with daytime sleepiness nor depression. CONCLUSION: SDB was associated with lower physical health-related quality of life and cognitive function. Given the high prevalence of SDB in older age, assessing QOL and cognition may better delineate subgroups requiring further management, and provide useful treatment target measures for this age group.

Research Priorities for Patients with Heart Failure and Central Sleep Apnea. An Official American Thoracic Society Research Statement.

Background: Central sleep apnea (CSA) is common among patients with heart failure and has been strongly linked to adverse outcomes. However, progress toward improving outcomes for such patients has been limited. The purpose of this official statement from the American Thoracic Society is to identify key areas to prioritize for future research regarding CSA in heart failure.Methods: An international multidisciplinary group with expertise in sleep medicine, pulmonary medicine, heart failure, clinical research, and health outcomes was convened. The group met at the American Thoracic Society 2019 International Conference to determine research priority areas. A statement summarizing the findings of the group was subsequently authored using input from all members.Results: The workgroup identified 11 specific research priorities in several key areas: 1) control of breathing and pathophysiology leading to CSA, 2) variability across individuals and over time, 3) techniques to examine CSA pathogenesis and outcomes, 4) impact of device and pharmacological treatment, and 5) implementing CSA treatment for all individualsConclusions: Advancing care for patients with CSA in the context of heart failure will require progress in the arenas of translational (basic through clinical), epidemiological, and patient-centered outcome research. Given the increasing prevalence of heart failure and its associated substantial burden to individuals, society, and the healthcare system, targeted research to improve knowledge of CSA pathogenesis and treatment is a priority.

Cough syncope as a cause of motor vehicle crash: fatal distraction?

Coughing is a rare cause of syncope that can contribute to motor vehicle crashes. The precise pathophysiological mechanisms responsible for the syncope are unclear. We report six occasions in which motor vehicle drivers have been involved in serious crashes and cough syncope was cited as the cause. In each occasion, an alternative cause leading to the crash could be identified. Cough as a cause of syncope should be a diagnosis of exclusion and used with great caution as a medico-legal defence. A suggested criterion for confirmation of cough syncope is recommended.

Exercise oscillatory ventilation during autonomic blockade in young athletes and healthy controls.

PURPOSE: Exercise oscillatory ventilation (EOV) is a form of periodic breathing that is associated with a poor prognosis in heart failure patients, but little is known about EOV in other populations. We sought to provide insights into the phenomenon of EOV after it was observed in young healthy subjects, including athletes, after the administration of dual autonomic blockade (DAB). METHODS: From 29 participants who completed cardiopulmonary exercise testing (CPET) with and without DAB (0.04 mg/kg atropine and 0.2 mg/kg metoprolol), 5 subjects developed EOV (age = 29 ± 5 years; 3/5 were athletes) according to American Heart Association criteria. For each case, we identified 2 non-EOV healthy controls (age = 34.2 ± 8.3; 7/10 were athletes) that were subsequently age- and sex-matched. RESULTS: No participants had EOV during exercise without DAB. The 5 participants (4 male, 1 female) who demonstrated EOV with DAB had lower mean tidal volume (1.7 ± 0.5 L/min vs. 1.8 ± 0.5 L/min; p = 0.04) compared to participants in the non-EOV group and a decrease in peak tidal volume (2.9 ± 0.6 L/min to 2.2 ± 0.7 L/min; p = 0.004) with DAB. There were few other differences in CPET measures between EOV and non-EOV participants, although the PETCO2 tended to be higher in the EOV group (p = 0.07). CONCLUSION: EOV can be elucidated in young healthy subjects, including athletes, during cardiopulmonary exercise testing, suggesting that it may not be an ominous sign in all populations.

The future of sleep-disordered breathing: A public health crisis.

Find the whole series here https://onlinelibrary.wiley.com/doi/toc/10.1111/(ISSN)1440-1843.new-frontiers-in-sleep-disordered-breathing See cover image.

Perioperative considerations in the management of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is characterised by repetitive compromise of the upper airway, causing impaired ventilation, sleep fragmentation, and daytime functional impairment. It is a heterogeneous condition encompassing different phenotypes. The prevalence of OSA among patients presenting for elective surgery is growing, largely attributable to an increase in age and obesity rates, and most patients remain undiagnosed and untreated at the time of surgery. This condition is an established risk factor for increased perioperative cardiopulmonary morbidity, heightened in the presence of concurrent medical comorbidities. Therefore, it is important to perform preoperative OSA screening and risk stratification - using the STOP-Bang screening questionnaire, nocturnal oximetry, and ambulatory and in-laboratory polysomnography, for example. Postoperative risk assessment is an evolving process that encompasses evaluation of upper airway compromise, ventilatory control instability, and pain-sedation mismatch. Optimal postoperative OSA management comprises continuation of regular positive airway pressure, a multimodal opioid-sparing analgesia strategy to limit respiratory depression, avoidance of supine position, and cautious intravenous fluid administration. Supplemental oxygen does not replace a patient's regular positive airway pressure therapy and should be administered cautiously to avoid risk of hypoventilation and worsening of hypercapnia. Continuous pulse oximetry monitoring with specified targets of peripheral oxygen saturation measured by pulse oximetry is encouraged.

The Role of Weight Management in the Treatment of Adult Obstructive Sleep Apnea. An Official American Thoracic Society Clinical Practice Guideline.

BACKGROUND: Overweight/obesity is a common, reversible risk factor for obstructive sleep apnea severity (OSA). The purpose of this guideline is to provide evidence-based recommendations for the management of overweight/obesity in patients with OSA. METHODS: The Grading of Recommendations, Assessment, Development and Evaluation approach was used to evaluate the literature. Clinical recommendations were formulated by a panel of pulmonary, sleep medicine, weight management, and behavioral science specialists. RESULTS: Behavioral, pharmacological, and surgical treatments promote weight loss and can reduce OSA severity, reverse common comorbidities, and improve quality of life, although published studies have methodological limitations. After considering the quality of evidence, feasibility, and acceptability of these interventions, the panel made a strong recommendation that patients with OSA who are overweight or obese be treated with comprehensive lifestyle intervention consisting of 1) a reduced-calorie diet, 2) exercise or increased physical activity, and 3) behavioral guidance. Conditional recommendations were made regarding reduced-calorie diet and exercise/increased physical activity as separate management tools. Pharmacological therapy and bariatric surgery are appropriate for selected patients who require further assistance with weight loss. CONCLUSIONS: Weight-loss interventions, especially comprehensive lifestyle interventions, are associated with improvements in OSA severity, cardiometabolic comorbidities, and quality of life. The American Thoracic Society recommends that clinicians regularly assess weight and incorporate weight management strategies that are tailored to individual patient preferences into the routine treatment of adult patients with OSA who are overweight or obese.

Models of care for non-invasive ventilation in the Acute COPD Comparison of three Tertiary hospitals (ACT3) study.

BACKGROUND AND OBJECTIVE: Non-invasive ventilation (NIV) improves clinical outcomes in hypercapnic acute exacerbations of COPD (AECOPD), but the optimal model of care remains unknown. METHODS: We conducted a prospective observational non-inferiority study comparing three models of NIV care: general ward (Ward) (1:4 nurse to patient ratio, thrice weekly consultant ward round), a high dependency unit (HDU) (1:2 ratio, twice daily ward round) and an intensive care unit (ICU) (1:1 ratio, twice daily ward round) model in three similar teaching tertiary hospitals. Changes in arterial blood gases (ABG) and clinical outcomes were compared and corrected for differences in AECOPD severity (Blood urea > 9 mmol/L, Altered mental status (Glasgow coma scale (GCS) < 14), Pulse > 109 bpm, age > 65 (BAP-65)) and co-morbidities. An economic analysis was also undertaken. RESULTS: There was no significant difference in age (70 ± 10 years), forced expiratory volume in 1 s (FEV1 ) (0.84 ± 0.35 L), initial pH (7.29 ± 0.08), partial pressure of CO2 in arterial blood (PaCO2 ) (72 ± 22 mm Hg) or BAP-65 scores (2.9 ± 1.01) across the three models. The Ward achieved an increase in pH (0.12 ± 0.07) and a decrease in PaCO2 (12 ± 18 mm Hg) that was equivalent to HDU and ICU. However, the Ward treated more patients (38 vs 28 vs 15, P < 0.001), for a longer duration in the first 24 h (12.3 ± 4.8 vs 7.9 ± 4.1 vs 8.4 ± 5.3 h, P < 0.05) and was more cost-effective per treatment day ($AUD 1231 ± 382 vs 1745 ± 2673 vs 2386 ± 1120, P < 0.05) than HDU and ICU. ICU had a longer hospital stay (9 ± 11 vs 7 ± 7 vs 13 ± 28 days, P < 0.002) compared with the Ward and HDU. There was no significant difference in intubation rate or survival. CONCLUSION: In acute hypercapnic Chronic obstructive pulmonary disease (COPD) patients, the Ward model of NIV care achieved equivalent clinical outcomes, whilst being more cost-effective than HDU or ICU models.

Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease.

RATIONALE: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. OBJECTIVES: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease. METHODS: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow-up, and the urinary albumin-to-creatinine ratio was measured at study exit. MEASUREMENTS AND MAIN RESULTS: In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m2), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m2/yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (-4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between-group differences in end-of-study urinary albumin-to-creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings. CONCLUSIONS: CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).

Mood disorders are highly prevalent in patients investigated with a multiple sleep latency test.

PURPOSE: Excessive daytime sleepiness (EDS) is a debilitating symptom which occurs commonly in both primary sleep and mood disorders. The prevalence of mood disorders in patients with EDS, evaluated objectively with a mean sleep latency test (MSLT), has not been reported. We hypothesize that mood disorders are highly prevalent in patients being investigated for EDS. This study aims to report the prevalence of mood disorder in the MSLT population and investigate the association between mood disorder and objective and subjective scores of sleepiness. METHODS: A retrospective multicenter study of adults with a MSLT and Hospital Anxiety and Depression Score (HADS) identified over a 3-year period. The HADS is a validated questionnaire in detecting depression (HADS-D ≥ 8) and anxiety (HADS-A ≥ 11) in the sleep clinic population. Data collected included demographics, medical, and sleep study information. Mood disorder prevalence was compared to the general sleep clinic population. Correlation between measures of sleepiness and mood was performed. RESULTS: Two hundred twenty patients were included with mean age 41.1 ± 15.7 years, mean body mass index 28.6 kg/m2 of whom 30% had anxiety (HADS-A > 11) and 43% depression (HADS-D > 8). Mean results for the cohort are ESS 13.7, mean sleep latency 11.5 min, HADS-A 8.2, and HADS-D 7. There was no significant correlation between objective sleepiness, as measured by the mean sleep latency, and either HADS-A (-0.006, p = 0.93) or HADS-D score (0.002, p = 0.98). There was, however, a weak correlation between subjective sleepiness, as measured by the ESS, and the mean sleep latency (-0.25, p < 0.01), HADS-A (0.15, p = 0.03), and HADS-D (0.2, p = 0.004). There was no significant association between diagnosis of hypersomnia disorders and presence of anxiety (p = 0.71) or depression (p = 0.83). CONCLUSIONS: Mood disorders are highly prevalent in the MSLT population. There was a weak correlation found between subjective measures of sleepiness and mood disorders, but not between objective measures of sleepiness and mood disorders. Routine screening for mood disorders in patients with hypersomnolence should be considered.

Physician Decision Making and Clinical Outcomes With Laboratory Polysomnography or Limited-Channel Sleep Studies for Obstructive Sleep Apnea: A Randomized Trial.

BACKGROUND: The clinical utility of limited-channel sleep studies (which are increasingly conducted at home) versus laboratory polysomnography (PSG) for diagnosing obstructive sleep apnea (OSA) is unclear. OBJECTIVE: To compare patient outcomes after PSG versus limited-channel studies. DESIGN: Multicenter, randomized, noninferiority study. (Australian New Zealand Clinical Trials Registry: ACTRN12611000926932). SETTING: 7 academic sleep centers. PARTICIPANTS: Patients (n = 406) aged 25 to 80 years with suspected OSA. INTERVENTION: Sleep study information disclosed to sleep physicians comprised level 1 (L1) PSG data (n = 135); level 3 (L3), which included airflow, thoracoabdominal bands, body position, electrocardiography, and oxygen saturation (n = 136); or level 4 (L4), which included oxygen saturation and heart rate (n = 135). MEASUREMENTS: The primary outcome was change in Functional Outcomes of Sleep Questionnaire (FOSQ) score at 4 months. Secondary outcomes included the Epworth Sleepiness Scale (ESS), the Sleep Apnea Symptoms Questionnaire (SASQ), continuous positive airway pressure (CPAP) compliance, and physician decision making. RESULTS: Change in FOSQ score was not inferior for L3 (mean difference [MD], 0.01 [95% CI, -0.47 to 0.49; P = 0.96]) or L4 (MD, -0.46 [CI, -0.94 to 0.02; P = 0.058]) versus L1 (noninferiority margin [NIM], -1.0). Compared with L1, change in ESS score was not inferior for L3 (MD, 0.08 [CI, -0.98 to 1.13; P = 0.89]) but was inconclusive for L4 (MD, 1.30 [CI, 0.26 to 2.35; P = 0.015]) (NIM, 2.0). For L4 versus L1, there was less improvement in SASQ score (-17.8 vs. -24.7; P = 0.018), less CPAP use (4.5 vs. 5.3 hours per night; P = 0.04), and lower physician diagnostic confidence (P = 0.003). LIMITATION: Limited-channel studies were simulated by extracting laboratory PSG data and were not done in the home. CONCLUSION: The results support manually scored L3 testing in routine practice. Poorer outcomes with L4 testing may relate, in part, to reduced physician confidence. PRIMARY FUNDING SOURCE: National Health and Medical Research Council and Repat Foundation.

Sleep apnoea in heart failure: To treat or not to treat?

Heart failure (HF) and sleep apnoea are common disorders which frequently coexist. Two main types of apnoea occur: one is obstructive which, through recurring episodes of snoring, hypoxaemia, large negative intra-thoracic pressures and arousals from sleep leading to downstream inflammatory and autonomic nervous system changes, is thought to be a causative factor to the development of systemic hypertension and HF. The other type of apnoea, Cheyne-Stokes respiration with central sleep apnoea (CSR-CSA), is characterized by an oscillatory pattern of ventilation with a prevailing hyperventilation-induced hypocapnia, often in the absence of significant hypoxaemia and snoring, and is thought to be a consequence of advanced HF-related low cardiac output, high sympathetic nervous system activation and pulmonary congestion. CSR-CSA may be a compensatory response to advanced HF. Rostral fluid shift during sleep may play an important role in the pathogenesis of both obstructive sleep apnoea (OSA) and CSA. Studies of positive airway pressure (PAP) treatment of OSA and CSA in HF have shown short-term improvements in cardiac and autonomic function; however, there is no evidence of improved survival. Loop gain may provide useful marker of continuous PAP (CPAP) responsiveness in patients with central apnoea. A greater understanding of the pathophysiology of the interaction between obstructive and central apnoea and the various types of HF, and the mechanisms of therapies, such as PAP, is required to develop new strategies to overcome the disabling symptoms, and perhaps improve the mortality, that accompany HF with sleep apnoea.

Increased Dead Space Ventilation Mediates Reduced Exercise Capacity in Systolic Heart Failure.

RATIONALE: Patients with chronic heart failure have limited exercise capacity, which cannot be completely explained by markers of cardiac dysfunction. Reduced pulmonary diffusing capacity at rest and excessively high ventilation during exercise are common in heart failure. We hypothesized that the reduced pulmonary diffusing capacity in patients with heart failure would predict greater dead space ventilation during exercise and that this would lead to impairment in exercise capacity. OBJECTIVES: To determine the relationship between pulmonary diffusing capacity at rest and dead space ventilation during exercise, and to examine the influence of dead space ventilation on exercise in heart failure. METHODS: We analyzed detailed cardiac and pulmonary data at rest and during maximal incremental cardiopulmonary exercise testing from 87 consecutive heart transplant assessment patients and 18 healthy control subjects. Dead space ventilation was calculated using the Bohr equation. MEASUREMENTS AND MAIN RESULTS: Pulmonary diffusing capacity at rest was a significant predictor of dead space ventilation at maximal exercise (r = -0.524, P < 0.001) in heart failure but not in control subjects. Dead space at maximal exercise also correlated inversely with peak oxygen consumption (r = -0.598, P < 0.001), peak oxygen consumption per kilogram (r = -0.474, P < 0.001), and 6-minute-walk distance (r = -0.317, P = 0.021) in the heart failure group but not in control subjects. CONCLUSIONS: Low resting pulmonary diffusing capacity in heart failure is indicative of high dead space ventilation during exercise, leading to excessive and inefficient ventilation. These findings would support the concept of pulmonary vasculopathy leading to altered ventilation perfusion matching (increased dead space) and resultant dyspnea, independent of markers of cardiac function.

The Effect of Treatment of Obstructive Sleep Apnea on Glycemic Control in Type 2 Diabetes.

RATIONALE: There is uncertainty about the effects of treating obstructive sleep apnea on glycemic control in patients with type 2 diabetes. OBJECTIVES: To determine whether treatment of obstructive sleep apnea in patients with type 2 diabetes improves glycemic control. METHODS: In this trial, we randomized patients with type 2 diabetes and no previous diagnosis of obstructive sleep apnea, with a glycated hemoglobin level of 6.5-8.5%, and an oxygen desaturation index of 15 or more events per hour to positive airway pressure therapy or to usual care. MEASUREMENTS AND MAIN RESULTS: A total of 416 patients met the entry criteria as determined by each site and were randomized. Of the 298 participants who met centrally adjudicated entry criteria, no differences between the study groups were seen for change in glycated hemoglobin. Furthermore, there were no between-group differences when analyses were restricted to those with poorer baseline glycemic control, those with more severe sleep apnea, or those who were adherent to therapy. A greater fall in diastolic blood pressure occurred in the positive airway pressure group than in the usual care group (-3.5 mm Hg vs. -1.5 mm Hg; P = 0.07). This difference was significant in those who were adherent to positive airway pressure therapy (-4.4 mm Hg vs. -1.6 mm Hg; P = 0.02). There was a significant reduction in sleepiness in the positive airway pressure therapy group (P < 0.0001). Quality of life assessment revealed improvements in vitality, mental health, and mental component summary scores in the positive airway pressure therapy group. CONCLUSIONS: This trial showed no effect of positive airway pressure therapy on glycemic control in patients with relatively well-controlled type 2 diabetes and obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT00509223).

Control theory prediction of resolved Cheyne-Stokes respiration in heart failure.

Cheyne-Stokes respiration (CSR) foretells deleterious outcomes in patients with heart failure. Currently, the size of therapeutic intervention is not guided by the patient's underlying pathophysiology. In theory, the intervention needed to resolve CSR, as a control system instability (loop gain >1), can be predicted knowing the baseline loop gain and how much it falls with therapy.In 12 patients with heart failure, we administered an inspiratory carbon dioxide fraction of 1-3% during CSR (n=95 interventions) as a means to reduce loop gain. We estimated the loop gain on therapy (LGtherapy), using the baseline loop gain (using hyperpnoea length/cycle length) and its expected reduction (18% per 1% inspired carbon dioxide), and tested the specific hypothesis that LGtherapy predicts CSR persistence (LGtherapy >1) versus resolution (LGtherapy <1).As predicted, when LGtherapy >1.0, CSR continued during therapy in 23 out of 25 (92%) trials. A borderline loop gain zone (0.8