Administration of pharmacological sleep aids prior to, during and following critical illness.

BACKGROUND: Sleep in the intensive care unit (ICU) is frequently disturbed and this may have a detrimental effect on recovery. AIM: To determine the use of pharmacological sleep aids in critically ill patients prior to, during and after ICU admission. METHODS: We conducted a single-centre period prevalence study of all adult patients admitted to a university-associated adult medical-surgical ICU for more than two nights in a 3-month period ending September 2019. The major outcome of interest was the proportion of ICU patients who had a pharmacological sleep aid administered prior to, during and after ICU admission. Associations of selected patient variables with sleep aid prescription in the ICU were summarised both as unadjusted univariable comparisons and as adjusted effect estimates returned by a multivariable logistic regression model. RESULTS: During the study period, 370 patients met all eligibility criteria. A pharmacological sleep aid was identified prior to hospital admission in 34 (9%) patients and in 62 (17%) patients during ICU admission. Of the 340 ICU survivors, 292 remained in the same hospital. Of these, 96 (33%) received a pharmacological sleep aid at least once during their post-ICU general hospital ward stay. Pre-hospital sleep aid use, male sex, longer ICU admission and higher APACHE (Acute Physiology and Chronic Health Evaluation) III scores were associated with sleep aid prescription in the ICU. CONCLUSIONS: Pharmacological sleep aids are administered frequently in the ICU with administration increasing substantially after ICU discharge.

Sleep apnoea has a dose-dependent effect on atrial remodelling in paroxysmal but not persistent atrial fibrillation: a high-density mapping study.

AIMS: Obstructive sleep apnoea (OSA) associates with atrial fibrillation (AF), but the relationship of OSA severity and AF phenotype with the atrial substrate remains poorly defined. We sought to define the atrial substrate across the spectrum of OSA severity utilizing high-density mapping. METHODS AND RESULTS: Sixty-six consecutive patients (male 71%, age 61 ± 9) having AF ablation (paroxysmal AF 36, persistent AF 30) were recruited. All patents underwent formal overnight polysomnography and high-density left atrial (LA) mapping (mean 2351 ± 1244 points) in paced rhythm. Apnoea-hypopnoea index (AHI) (mean 21 ± 18) associated with lower voltage (-0.34, P = 0.005), increased complex points (r = 0.43, P < 0.001), more low-voltage areas (r = 0.42, P < 0.001), and greater voltage heterogeneity (r = 0.39, P = 0.001), and persisted after multivariable adjustment. Atrial conduction heterogeneity (r = 0.24, P = 0.025) but not conduction velocity (r = -0.09, P = 0.50) associated with AHI. Patchy regions of low voltage that co-localized with slowed conduction defined the atrial substrate in paroxysmal AF, while a diffuse atrial substrate predominated in persistent AF. The association of AHI with remodelling was most apparent among paroxysmal AF [LA voltage: paroxysmal AF -0.015 (-0.025, -0.005), P = 0.004 vs. persistent AF -0.006 (-0.017, 0.005), P = 0.30]. Furthermore, in paroxysmal AF an AHI ≥ 30 defined a threshold at which atrial remodelling became most evident (nil-mild vs. moderate vs. severe: 1.92 ± 0.42 mV vs. 1.84 ± 0.28 mV vs. 1.34 ± 0.41 mV, P = 0.006). In contrast, significant remodelling was observed across all OSA categories in persistent AF (1.67 ± 0.55 mV vs. 1.50 ± 0.66 mV vs. 1.55 ± 0.67 mV, P = 0.82). CONCLUSION: High-density mapping observed that OSA associates with marked atrial remodelling, predominantly among paroxysmal AF cohorts with severe OSA. This may facilitate the identification of AF patients that stand to derive the greatest benefit from OSA management.

Characteristics of patients who progress from bridging to long-term oxygen therapy.

BACKGROUND: Patients with persistent hypoxia following an acute hospital admission may be discharged with 'bridging' domiciliary oxygen as per criteria defined by the Thoracic Society of Australia and New Zealand. The need for continuous long-term oxygen therapy (LTOT) is then reassessed at a clinic review 1-2 months later. AIM: To describe the characteristics of patients discharged from an acute hospital admission with continuous short-term oxygen therapy (STOT), and subsequently to investigate for differences between subjects who proceeded to qualify for continuous LTOT versus those who were able to cease STOT at review. METHODS: This is a retrospective cohort study involving all subjects discharged from Alfred Health between 2011 and 2015 inclusive with bridging domiciliary oxygen. Multiple biochemical, physiological and demographic characteristics were collated and analysed. RESULTS: Of all patients prescribed continuous STOT at time of discharge, 47.3% qualified for LTOT at outpatient review. This cohort had a significantly lower PaO2 measurement at time of discharge, compared with those who no longer qualified. CONCLUSION: PaO2 at time of discharge provides a signal with the potential to identify who will require continuous LTOT following an acute hospital admission. Additionally, this study highlights the need to re-evaluate patients' oxygen requirements during a period of clinical stability.

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.

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

Loop gain as a means to predict a positive airway pressure suppression of Cheyne-Stokes respiration in patients with heart failure.

RATIONALE: Patients with heart failure (HF) and Cheyne-Stokes respiration or periodic breathing (PB) often demonstrate improved cardiac function when treatment with continuous positive airway pressure (CPAP) resolves PB. Unfortunately, CPAP is successful in only 50% of patients, and no known factor predicts responders to treatment. Because PB manifests from a hypersensitive ventilatory feedback loop (elevated loop gain [LG]), we hypothesized that PB persists on CPAP when LG far exceeds the critical threshold for stable ventilation (LG = 1). OBJECTIVES: To derive, validate, and test the clinical utility of a mathematically precise method that quantifies LG from the cyclic pattern of PB, where LG = 2π/(2πDR - sin2πDR) and DR (i.e., duty ratio) = (ventilatory duration)/(cycle duration) of PB. METHODS: After validation in a mathematical model of HF, we tested whether our estimate of LG changes with CPAP (n = 6) and inspired oxygen (n = 5) as predicted by theory in an animal model of PB. As a first test in patients with HF (n = 14), we examined whether LG predicts the first-night CPAP suppression of PB. MEASUREMENTS AND MAIN RESULTS: In lambs, as predicted by theory, LG fell as lung volume increased with CPAP (slope = 0.9 ± 0.1; R(2) = 0.82; P < 0.001) and as inspired-arterial PO(2) difference declined (slope = 1.05 ± 0.12; R(2) = 0.75; P < 0.001). In patients with HF, LG was markedly greater in 8 CPAP nonresponders versus 6 responders (1.29 ± 0.04 versus 1.10 ± 0.01; P < 0.001); LG predicted CPAP suppression of PB in 13/14 patients. CONCLUSIONS: Our novel LG estimate enables quantification of the severity of ventilatory instability underlying PB, making possible a priori selection of patients whose PB is immediately treatable with CPAP therapy.

Impact of CPAP on the Atrial Fibrillation Substrate in Obstructive Sleep Apnea: The SLEEP-AF Study.

BACKGROUND: Observational studies report that obstructive sleep apnea (OSA) is associated with an increasingly remodeled atrial substrate in atrial fibrillation (AF). However, the impact of OSA management on the electrophysiologic substrate has not been evaluated. OBJECTIVES: In this study, the authors sought to determine the impact of OSA management on the atrial substrate in AF. METHODS: We recruited 24 consecutive patients referred for AF management with at least moderate OSA (apnea-hypopnea index [AHI] ≥15). Participants were randomized in a 1:1 ratio to commence continuous positive airway pressure (CPAP) or no therapy (n = 12 CPAP; n = 12 no CPAP). All participants underwent invasive electrophysiologic study (high-density right atrial mapping) at baseline and after a minimum of 6 months. Outcome variables were atrial voltage (mV), conduction velocity (m/s), atrial surface area <0.5 mV (%), proportion of complex points (%), and atrial effective refractory periods (ms). Change between groups over time was compared. RESULTS: Clinical characteristics and electrophysiologic parameters were similar between groups at baseline. Compliance with CPAP therapy was high (device usage: 79% ± 19%; mean usage/day: 268 ± 91 min) and resulted in significant AHI reduction (mean reduction: 31 ± 23 events/h). There were no differences in blood pressure or body mass index between groups over time. At follow-up, the CPAP group had faster conduction velocity (0.86 ± 0.16 m/s vs 0.69 ± 0.12 m/s; P (time × group) = 0.034), significantly higher voltages (2.30 ± 0.57 mV vs 1.94 ± 0.72 mV; P < 0.05), and lower proportion of complex points (8.87% ± 3.61% vs 11.93% ± 4.94%; P = 0.011) compared with the control group. CPAP therapy also resulted in a trend toward lower proportion of atrial surface area <0.5 mV (1.04% ± 1.41% vs 4.80% ± 5.12%; P = 0.065). CONCLUSIONS: CPAP therapy results in reversal of atrial remodeling in AF and provides mechanistic evidence advocating for management of OSA in AF.

Heart failure and the lung.

Heart failure (HF) is a highly prevalent disease that leads to significant morbidity and mortality. There is increasing evidence that the symptoms of HF are exacerbated by its deleterious effects on lung function. HF appears to cause airway obstruction acutely and leads to impaired gas diffusing capacity and pulmonary hypertension in the longer term. It is postulated that this is the result of recurrent episodes of elevated pulmonary capillary pressure leading to pulmonary oedema and pulmonary capillary stress fracture, which produces lung fibrosis. It is likely that impaired lung function impairs the functional status of HF patients and makes them more prone to central sleep apnoea.

Effectiveness of a Novel Sleep Clinical Pathway in an Inpatient Musculoskeletal Rehabilitation Cohort: A Pilot Randomized Controlled Trial.

OBJECTIVE: Sleep disturbance in hospital is common. This pilot randomized controlled trial assessed a sleep clinical pathway compared with standard care in improving sleep quality, engagement in therapy and length of stay in musculoskeletal inpatient rehabilitation. METHODS: Participants (n = 51) were randomized to standard care ("control", n =29) or sleep clinical pathway ("intervention", n = 22). Outcome measures included: Pittsburgh Sleep Quality Index (PSQI), Hopkins Rehabilitation Engagement Rating Scale (HRERS), Fatigue Severity Scale (FSS), Patient Satisfaction with Sleep Scale, and actigraphy. Assessment time-points were at admission and before discharge from rehabilitation. RESULTS: No significant differences were found between groups for any outcome measure. As a cohort (n = 51), there were significant improvements from admission to discharge in sleep quality (PSQI (-2.31; 95% confidence interval (95% CI) -3.33 to -1.30; p <0.001)], fatigue (FSS (-8.75; 95% CI -13.15 to -4.34; p <0.001)], engagement with therapy (HRERS-Physiotherapists (+1.37; 95% CI 0.51-3.17; p =0.037), HRERS-Occupational Therapists (+1.84; 95% CI 0.089-2.65; p = 0.008)), and satisfaction with sleep (+0.824; 95% CI 0.35-1.30; p = 0.001). Actigraphy findings were equivocal. CONCLUSION: The sleep clinical pathway did not improve sleep quality compared with standard care. Larger studies and studies with alternate methodology such as "cluster randomization" are needed.

Heart failure and sleep-disordered breathing: mechanisms, consequences and treatment.

PURPOSE OF REVIEW: This review examines the recently published articles pertaining to sleep-disordered breathing (SDB) and heart failure. RECENT FINDINGS: The recent findings can be classified into pulmonary, upper airway and treatment trials. Pulmonary complications of heart failure include loss of surfactant, increased pulmonary dry weight and reduced lung volume, which are likely to increase plant gain and thus predispose to central sleep apnea with Cheyne-Stokes respiration. Upper airway narrowing in normal individuals has been shown to occur with lower limb compression and the supine body position, thus suggesting that rostral fluid shifts may narrow the upper airway and aggravate obstructive sleep apnea. Extrapolating this to congestive heart failure (CHF), it is possible that CHF fluid status may impact upon obstructive sleep apnea severity. Following the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnoea and Heart Failure trial, further SDB intervention studies have been reported using adaptive servo-ventilation. Although encouraging, small, short-term studies are discussed, however long-term randomized trials with objective cardiac outcomes are still lacking. SUMMARY: The relationship between CHF and SDB is likely to be bidirectional, CHF impacting on SDB severity and vice versa. Identification of SDB in the CHF population appears to be important as it is probably associated with greater mortality, but whether SDB intervention significantly influences CHF survival still remains to be determined.

Sleep apnoea - a general practice approach.

BACKGROUND: Snoring and sleepiness are common presentations in general practice. OBJECTIVE: To describe the frequency, clinical findings, investigations and management options for obstructive sleep apnoea. DISCUSSION: Obstructive sleep apnoea should be considered in a range of presentations. Diagnosis is based on history, examination, investigation and, occasionally, a trial of therapy. Management options should start with lifestyle management. Further options include surgery, dental splints and continuous positive airway pressure. Continuous positive airway pressure requires long term input by both the patient and the general practitioner. Common issues with the use of machines for the management of sleep apnoea are also discussed.

Comparison of Commonly Used Questionnaires to Identify Obstructive Sleep Apnea in a High-Risk Population.

STUDY OBJECTIVES: Sleep apnea is associated with adverse health outcomes. Despite being an important comorbidity in obesity, type 2 diabetes, heart failure, and resistant hypertension, it is underdiagnosed in these patient groups. An inexpensive and readily accessible sleep apnea screening tool would help address this problem. We sought to compare three commonly used screening tools. METHODS: We recruited 812 patients who had not previously been investigated for sleep apnea from our institution's diabetes (n = 512), obesity (n = 129), resistant hypertension (n = 74) and heart failure (n = 43) clinics. Patients completed three frequently used sleep apnea screening questionnaires (STOP-BANG, Berlin, and OSA50). A total of 758 patients had a valid (> 4 hours' duration) level 3 home sleep study. Studies were reported by a sleep physician and were deemed positive if they recorded a respiratory event index (REI) ≥ 15 events/h. RESULTS: The 758 patients with valid sleep studies were age 59 ± 11 years and 63% were male. A total of 38% of patients had a positive test. The respective sensitivities and specificities of the screening questionnaires at the recommended screening thresholds (REI ≥ 15 events/h) were STOP-BANG ≥ 3 (95% and 19%), STOP-BANG ≥ 5 (60% and 69%), Berlin (75% and 38%), and OSA50 (88% and 21%). We identified six independent predictors (age, sex, body mass index, neck circumference, snoring ≥ 3 days per week, observed apnea ≥ 3 days per week). However, combining these factors was no better than the STOP-BANG in predicting sleep apnea. All patients with a STOP-BANG < 3 had an REI < 30 events/h. CONCLUSIONS: There is a high prevalence of undiagnosed symptomatic sleep apnea in high-risk patient groups. The STOP-BANG questionnaire appeared superior, though all questionnaires had significant limitations. Incorporation of STOP-BANG ≥ 3 in this high-risk population might reduce the need for sleep testing in a resource-constrained setting.

Maximal exercise does not increase ventilation heterogeneity in healthy trained adults.

The effect of exercise on ventilation heterogeneity has not been investigated. We hypothesized that a maximal exercise bout would increase ventilation heterogeneity. We also hypothesized that increased ventilation heterogeneity would be associated with exercise-induced arterial hypoxemia (EIAH). Healthy trained adult males were prospectively assessed for ventilation heterogeneity using lung clearance index (LCI), Scond, and Sacinat baseline, postexercise and at recovery, using the multiple breath nitrogen washout technique. The maximal exercise bout consisted of a maximal, incremental cardiopulmonary exercise test at 25 watt increments. Eighteen subjects were recruited with mean ± SDage of 35 ± 9 years. There were no significant changes inLCI, Scond, or Sacinfollowing exercise or at recovery. While there was an overall reduction in SpO2with exercise (99.3 ± 1 to 93.7 ± 3%,P < 0.0001), the reduction in SpO2was not associated with changes inLCI, Scondor Sacin Ventilation heterogeneity is not increased following a maximal exercise bout in healthy trained adults. Furthermore,EIAHis not associated with changes in ventilation heterogeneity in healthy trained adults.

Ventilation heterogeneity is increased in patients with chronic heart failure.

In the healthy lung, ventilation is distributed heterogeneously due to factors such as anatomical asymmetry and gravity. This ventilation heterogeneity increases pathologically in conditions such as asthma, chronic obstructive lung disease, and cystic fibrosis. In chronic heart failure, lung biopsy demonstrates evidence of peripheral lung fibrosis and small airways narrowing and distortion. We hypothesized that this would lead to increased ventilation heterogeneity. Furthermore, we proposed that rostral fluid shifts when seated patients lie supine would further increase ventilation heterogeneity. We recruited 30 ambulatory chronic heart failure patients (57 ± 10 years, 83% male, left ventricular ejection fraction 31 ± 12%) as well as 10 healthy controls (51 ± 13 years, 90% male). Heart failure patients were clinically euvolemic. Subjects underwent measurement of ventilation heterogeneity using the multiple-breath nitrogen washout technique in the seated position, followed by repeat measurements after 5 and 45 min in the supine position. Ventilation heterogeneity was calculated using the lung clearance index (LCI), Sacin and Scond which represent overall, acinar, and small conducting airway function, respectively. Lung clearance index (9.6 ± 1.2 vs. 8.6 ± 1.4 lung turnovers, P = 0.034) and Scond (0.029 ± 0.014 vs. 0.006 ± 0.016/L, P = 0.007) were higher in the heart failure patients. There was no difference in Sacin (0.197 ± 0.171 vs. 0.125 ± 0.081/L, P = 0.214). Measures of ventilation heterogeneity did not change in the supine position. This study confirms the presence of peripheral airway pathology in patients with chronic heart failure. This leads to subtle but detectable functional abnormalities which do not change after 45 min in the supine position.

Intermittent positive pressure ventilation increases diastolic pulmonary arterial pressure in advanced COPD.

OBJECTIVES: To measure the impact of intermittent positive pressure ventilation (IPPV) on diastolic pulmonary arterial pressure (dPAP) and pulmonary pulse pressure in patients with advanced COPD. BACKGROUND: The physiological effects of raised intrathoracic pressures upon the pulmonary circulation have not been fully established. METHODS: 22 subjects with severe COPD receiving IPPV were prospectively assessed with pulmonary and radial arterial catheterization. Changes in dPAP were assessed from end-expiration to early inspiration during low and high tidal volume ventilation. RESULTS: Inspiration during low tidal volume IPPV increased the median [IQR] dPAP by 3.9 [2.5-4.8] mm Hg (P < 0.001). During high tidal volume, similar changes were observed. The IPPV-associated change in dPAP was correlated with baseline measures of PaO2 (rho = 0.65, P = 0.005), pH (rho = 0.64, P = 0.006) and right atrial pressure (rho = -0.53, P = 0.011). CONCLUSIONS: In severe COPD, IPPV increases dPAP and reduces pulmonary pulse pressure during inspiration.