Michael Stanchina

Weaning from mechanical ventilation

Weaning covers the entire process of liberating the patient from mechanical support and from the endotracheal tube. Many controversial questions remain concerning the best methods for conducting this process. An International Consensus Conference was held in April 2005 to provide recommendations regarding the management of this process. An 11-member international jury answered five pre-defined questions. 1) What is known about the epidemiology of weaning problems? 2) What is the pathophysiology of weaning failure? 3) What is the usual process of initial weaning from the ventilator? 4) Is there a role for different ventilator modes in more difficult weaning? 5) How should patients with prolonged weaning failure be managed? The main recommendations were as follows. 1) Patients should be categorised into three groups based on the difficulty and duration of the weaning process. 2) Weaning should be considered as early as possible. 3) A spontaneous breathing trial is the major diagnostic test to determine whether patients can be successfully extubated. 4) The initial trial should last 30 min and consist of either T-tube breathing or low levels of pressure support. 5) Pressure support or assist–control ventilation modes should be favoured in patients failing an initial trial/trials. 6) Noninvasive ventilation techniques should be considered in selected patients to shorten the duration of intubation but should not be routinely used as a tool for extubation failure.

Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea

Background: Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep. Methods: Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at “CPAP lung volume”, with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2). Results: The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001). Conclusion: An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.

How early in treatment is PAP adherence established? Revisiting night-to-night variability

Obstructive sleep apnea (OSA) is a serious disorder with significant daytime consequences. Treatment for OSA most commonly takes the form of positive airway pressure (PAP). Although effective, PAP adherence is often below expectations. Previous studies have suggested that early PAP use can predict long-term adherence, but these studies have not been replicated, nor has follow up been longer than 3 months. This article presents a replication study enhanced by a longer follow up and additional data to suggest that 6-month adherence can be predicted within the first days of PAP use. This article also discusses how this might relate to the experience of significant side effects of treatment.

Brief Behavioral Therapies Reduce Early Positive Airway Pressure Discontinuation Rates in Sleep Apnea Syndrome: Preliminary Findings

Sleep apnea syndrome (SAS) is a serious disorder with significant daytime consequences. Treatment for SAS most commonly takes the form of positive airway pressure (PAP). Although effective, PAP adherence is often below expectations. Previous studies have suggested that the provision of information on the importance of PAP use can enhance adherence. In this study, we compare 2 brief behavioral approaches—traditional education (ED) and a motivational enhancement therapy (MET)—designed from theories of behavior change to standard clinical care. PAP discontinuation and adherence are the primary outcome measures. Both brief therapies decreased PAP discontinuation compared to standard care. The MET therapy performed best under the condition of flexible delivery of PAP, although differences were not statistically significant. Implications are discussed.

Impact of CPAP use and age on mortality in patients with combined COPD and obstructive sleep apnea: the overlap syndrome.

BACKGROUND The overlap syndrome, defined by concurrent existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), is associated with poor outcomes. From a large outpatient cohort we aimed to define better the risk factors for increased mortality in the overlap syndrome and hypothesized that CPAP adherence would be associated with improved survival in patients with overlap syndrome. METHODS A post hoc analysis from an outpatient database of 10,272 patients from 2007-2010, identified 3,396 patients which were classified in 6 groups; patients both alive or deceased, with the known diagnosis of COPD, OSA, and the overlap of COPD plus OSA. Information regarding their gender, age, pulmonary function, obstructive sleep apnea parameters, and CPAP compliance was collected. A multivariate Cox proportional hazards model was generated for the determinants of mortality. RESULTS 1,112 COPD patients and 2,284 OSA patients were identified by diagnostic coding and then comprehensive chart review. Of these, 227 patients were identified with the overlap syndrome. From this group, 17 patients (7.4%) died. Multivariate analysis revealed hours of CPAP use and age as independent predictors of mortality (HR 0.71 and 1.14, p < 0.001, 0.002). Greater time on CPAP was associated with reduced mortality; although age did not correlate with CPAP use (p = 0.2), mean age of those with CPAP use < 2 hours per night was significantly higher than those using CPAP > 2 hours per night. CONCLUSIONS From this observational cohort, mortality in the overlap syndrome is impacted by CPAP use. Age is also an independent factor which has a negative association with survival and CPAP usage.

Clinical Use of Loop Gain Measures to Determine Continuous Positive Airway Pressure Efficacy in Patients with Complex Sleep Apnea. A Pilot Study

RATIONALE Measures of unstable ventilatory control (loop gain) can be obtained directly from the periodic breathing duty ratio on polysomnography in patients with Cheyne-Stokes respiration/central sleep apnea and can predict the efficacy of continuous positive airway pressure (CPAP) therapy. OBJECTIVES In this pilot study, we aimed to determine if this measure could also be applied to patients with complex sleep apnea (predominant obstructive sleep apnea, with worsening or emergent central apneas on CPAP). We hypothesized that loop gain was higher in patients whose central events persisted 1 month later despite CPAP treatment versus those whose events resolved over time. METHODS We calculated the duty ratio of the periodic central apneas remaining on the CPAP titration (or second half of the split night) while patients were on optimal CPAP with the airway open (obstructive apnea index < 1/h). Loop gain was calculated by the formula: LG = 2π/[(2πDR - sin(2πDR)]. Patients were followed on CPAP for 1 month. Post-treatment apnea-hypopnea index and compliance data were recorded from smart cards. MEASUREMENTS AND MAIN RESULTS Thirty-two patients with complex sleep apnea were identified, and 17 patients had full data sets. Eight patients continued to have a total of more than five events per hour (11.8 ± 0.5/h) (nonresponders). The remaining nine patients had an apnea-hypopnea index less than 5/h (2.2 ± 0.4/h) (responders). Loop gain was higher in the nonresponders versus responders (2.0 ± 0.1 vs. 1.7 ± 0.2, P = 0.026). Loop gain and the residual apnea-hypopnea index 1 month after CPAP were associated (r = 0.48, P = 0.02). CPAP compliance was similar between groups. CONCLUSIONS In this pilot study, loop gain was higher for patients with complex sleep apnea in whom central apneas persisted after 1 month of CPAP therapy (nonresponders). Loop gain measurement may enable an a priori determination of those who need alternative modes of positive airway pressure.

Treatment of Central Sleep Apnea with Adaptive Servoventilation in Chronic Heart Failure

EDITORIALS Treatment of Central Sleep Apnea with Adaptive Servoventilation in Chronic Heart Failure Patients with chronic heart failure and systolic dysfunction are at increased risk of having central sleep apnea (CSA) and Cheyne- Stokes respiration, which are associated with hypoxemia, sleep fragmentation, and mortality (1). Positive pressure devices (adaptive servoventilation or autoservoventilation [ASV]) have been designed to treat CSA and are often used in this patient population. These devices provide ventilatory support during periods of central apneas and hypopneas. ASV has been shown to be effective in improving sleep apnea severity, sleep quality, and cardiac function in short-term clinical trials (2). Given these short- term benefits, long-term treatment was hypothesized to result in improvements in robust clinical endpoints in patients with CHF . The SERVE-HF study was designed to address this hypothesis. The rationale and design of this study are described elsewhere (3, ClinicalTrials.gov NCT00733343). In brief, patients with chronic (.12 wk) symptomatic heart failure (New York Heart Association Class III or IV at enrollment, or II with at least one hospitalization for CHF in the last 24 mo) due to systolic dysfunction (left ventricular ejection fraction 10/h, apnea–hypopnea index > 15/h, and .50% central events) were enrolled. Participants were randomized to either standard medical therapy without treatment of CSA, or standard medical therapy with the addition of ASV. The trial completed enrollment with over 1,300 patients recruited and with preliminary results reported (4). No significant difference in the primary composite outcome of all-cause mortality or unplanned hospitalizations was identified (hazard ratio = 1.14, 0.97–1.33 ; P = 0.10); however, cardiovascular mortality was increased in patients in the ASV arm compared with participants in the control arm with an absolute annual mortality rate of 10% versus 7.5% (HR = 1.34, 1.07–1.67; P = 0.010). Although final and more in-depth analyses are still pending, the excess risk appears to be driven by outpatient deaths (likely sudden cardiac deaths). The increased risk of death seemed to be independent of perceived benefit from the device, with no worsening of clinical symptoms or need for hospitalization prior to the event. The results of SERVE-HF are surprising and contrary to the preliminary data showing short-term benefits in symptoms and physiology. More insight into the potential mechanisms for the increased mortality in the ASV arm will hopefully be available once the final results of the study are published; though open for speculation, potential explanations could include imbalances in randomization, hemodynamic effects of positive pressure, potential benefits of CSA (5), or a proarrhythmogenic effect through metabolic/electrolyte abnormalities. At this point, it is unknown whether certain subgroups might be at greater risk (e.g., lower ejection fraction, patients without an implantable defibrillator), but more insight into these issues will likely be available once the final results are published. Field Safety Notice Because of the results, a field safety notice was issued by ResMed, Inc., on May 13, 2015, that provided a number of recommendations (4). Specifically, they recommended that ASV should not be started in patients with symptomatic CHF and left ventricular ejection fraction < 45%, that is, heart failure with reduced ejection fraction (HFrEF), who have predominantly central sleep apnea. Similarly, before considering placing patients on ASV to treat central sleep apnea, a clinical evaluation for the presence of CHF should be done. Patients with suggestive signs and symptoms should be sent for further evaluation for HFrEF, and patients with HFrEF should not be initiated on ASV. Patients with symptomatic HFrEF currently using an ASV machine should be identified and contacted urgently to discuss discontinuation of the device. Ultimately, the decision on whether to continue ASV should be a joint one between the patient and physician balancing risks and benefits, but stopping ASV should be strongly considered given the increased cardiovascular mortality observed in this group. There are, however, a number of additional questions related to clinical management that should be considered in the context of these trial results. How Should ASV Be Discontinued? Given that positive airway pressure reduces ventricular preload and afterload, abrupt discontinuation may result in an exacerbation of heart failure. We would recommend careful assessment of volume status at the time of discontinuation, as this information may help with the timing of positive airway pressure discontinuation and optimization of medical therapy. How Should CSA Be Managed in Patients in Whom ASV Is Discontinued? Certainly, therapies such as supplemental oxygen, acetazolamide, or continuous positive airway pressure (CPAP) can be useful to correct hypoxemia and improve sleep apnea (6). However, the long-term effects of these therapies are unknown and may not be beneficial; for example, in a recent trial, oxygen was found to be potentially detrimental in nonhypoxemic patients with myocardial infarction (7). Clearly, the priority is to ensure that patients have their heart failure medical management optimized. Am J Respir Crit Care Med Vol jj, Iss jj, pp 1–2, jj jj, 2015 Copyright

Is Hyperinflation from Chronic Obstructive Pulmonary Disease “Protective” of Upper Airway Collapse in Obstructive Sleep Apnea?

Much interest has been generated by recent awareness that the co-occurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) results in a higher mortality rate than is predicted for either disease occurring independently (1). Also, more frequent COPD exacerbations and hospitalizations are observed when OSA is combined with COPD. These observations have given rise to the term OSA-COPD overlap syndrome. Positive airway pressure appears to reduce morbidity and mortality for patients with the overlap syndrome, but is not always tolerated. A better understanding of the physiological effect of lower airway dysfunction on upper airway patency should lead us to a better understanding of OSA-COPD overlap syndrome outcomes. A step forward in this process requires advances in understanding the pathophysiology behind upper airway collapse and the effect of hyperinflation on airway obstruction as lung function worsens. End-expiratory lung volume (EELV) is known to influence upper airway patency in animals through linkages to the thorax, with caudal traction being applied to the trachea during inspiration (2). In normal humans, when EELV is increased mechanically by application of negative extrathoracic pressure (3) or by external positive end-expiratory devices, the upper airway becomes more rigid, and thus less collapsible. It has also been shown that the apnea-hypopnea index (AHI) can be reduced in patients with OSA by increasing EELV, using a negative pressure ventilator (4). Continuous positive airway pressure reduces upper airway collapsibility in part by increasing lung volumes, as well as by increasing the transmural pressure of the pharyngeal airway. In this month’s issue of AnnalsATS, Krachman and colleagues (pp. 1129–1135) report on the relationship between upper airway patency and the degree of lung hyperinflation in a group of patients with COPD who also have OSA (5). These investigators determined that patients in the COPDgene study who had a higher percentage of emphysema and greater gas trapping had a lower AHI after controlling for other commonly known risk factors for OSA. Their relatively small study cohort of 51 patients was derived from a study population of more than 10,000 patients with COPD. Study participants were suspected clinically of having OSA, which was subsequently confirmed by overnight polysomnography. All participants also underwent high-resolution chest computed tomography (CT) imaging and spirometry. More than half of the patients in the study had moderately severe OSA, raising at least some likelihood of selection bias and missed cases. However, this was not a study of disease prevalence. In addition, although there was no clear increase in CT percentage emphysema or gas trapping in those with OSA, an inverse correlation was observed between AHI and the percentage of gas trapping seen on CT. This relationship was statistically significant and possibly also clinically relevant. As in many studies of OSA, sex and body mass index were also found to be contributing factors to AHI severity in the multivariate analysis. It is interesting to consider hyperinflation (or percentage gas trapping reported here) in COPD as potentially protective in patients with OSA. Hyperinflation in COPD is a common contributing factor to diaphragm fatigue, exercise limitation, and the work of breathing during minor tasks during wakefulness. In addition, the inspiratory volume to total lung capacity ratio (IC/TLC), a marker for static lung hyperinflation, has been shown to be an independent predictor of mortality in patients with COPD (6). During sleep, the EELV in patients with COPD remains constant from wakefulness to sleep (in contrast to the fall in EELV seen in normal individuals). Hyperinflation may have benefits (e.g., stenting open the upper airway), but may also have risk (e.g., leading to further hypoventilation, elevations of PaCO2 with pulmonary vasoconstriction, and right ventricular dysfunction). Treatments aimed at relieving hyperinflation during wakefulness that improve FEV1 and COPD morbidity, such as long-acting bronchodilators, could theoretically have a negative effect on the OSA. It is unclear what this means for mortality in the OSA-COPD overlap syndrome, and thus requires further research. Positive airway pressure therapy does work well to control both OSA and COPD, although mechanisms are unclear. Thus, there are likely trade-offs when considering therapies for the combination of disease states involving the upper and lower airways. The study by Krachman and coauthors also included cigarette smokers with OSA only. Thus, it is unclear whether the correlation between percentage emphysema and gas trapping would remain similar in