Effects of non-invasive ventilation on sleep in chronic hypercapnic respiratory failure.

Chronic respiratory disease can exacerbate the normal physiological changes in ventilation observed in healthy individuals during sleep, leading to sleep-disordered breathing, nocturnal hypoventilation, sleep disruption and chronic respiratory failure. Therefore, patients with obesity, slowly and rapidly progressive neuromuscular disease and chronic obstructive airways disease report poor sleep quality. Non-invasive ventilation (NIV) is a complex intervention used to treat sleep-disordered breathing and nocturnal hypoventilation with overnight physiological studies demonstrating improvement in sleep-disordered breathing and nocturnal hypoventilation, and clinical trials demonstrating improved outcomes for patients. However, the impact on subjective and objective sleep quality is dependent on the tools used to measure sleep quality and the patient population. As home NIV becomes more commonly used, there is a need to conduct studies focused on sleep quality, and the relationship between sleep quality and health-related quality of life, in all patient groups, in order to allow the clinician to provide clear patient-centred information.

A Core Outcome Set for Research Evaluating Interventions to Enable Communication in Patients With an Artificial Airway: An International Delphi Consensus Study (Comm-COS).

OBJECTIVES: Critically ill adults requiring artificial airways experience profound communication deficits. Studies of interventions supporting communication report disparate outcomes, creating subsequent challenges in the interpretation of their effectiveness. Therefore, we aimed to develop international consensus for a communication core outcome set (Comm-COS) for future trials of communication interventions in this population. DESIGN: 1) Systematic review, 2) patient/family interviews, 3) two-round modified Delphi, and 4) virtual consensus meetings with a final voting round. A multidisciplinary expert steering committee oversaw all stages. SETTING: Interviews and consensus meetings were conducted via videoconferencing. Digital methods were used for Delphi and final Comm-COS voting. SUBJECTS: Three stakeholder groups: 1) patient and family members with lived experience within 3 years, 2) clinicians with experience working in critical care, and 3) researchers publishing in the field. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We identified 59 outcomes via our systematic review, 3 unique outcomes from qualitative interviews, and 2 outcomes from our steering committee. Following item reduction, 32 outcomes were presented in Delphi round 1; 134 participants voted; 15 patient/family (11%), 91 clinicians (68%), and 28 researchers (21%). Nine additional outcomes were generated and added to round 2; 106 (81%) participants voted. Following completion of the consensus processes, the Comm-COS includes seven outcomes: 1) changes in emotions and wellbeing associated with ability to communicate, 2) physical impact of communication aid use, 3) time to functional communication, 4) ability to communicate healthcare needs (comfort/care/safety/decisions), 5) conversation agency, 6) ability to establish a communication connection to develop and maintain relationships, and 7) acceptability of the communication intervention. CONCLUSIONS: This is the first COS to specifically focus on communication for critically ill adults. Limitations for operationalization include selection of measures to use with these outcomes. Identification of suitable measures and adoption of the Comm-COS in future trials will help establish effective interventions to ameliorate the highly prevalent and negative experience of communicative incapacity.

Application of information from external data to correct for collider bias in a Covid-19 hospitalised cohort.

BACKGROUND: Throughout the Covid-19 pandemic, researchers have made use of electronic health records to research this disease in a rapidly evolving environment of questions and discoveries. These studies are prone to collider bias as they restrict the population of Covid-19 patients to only those with severe disease. Inverse probability weighting is typically used to correct for this bias but requires information from the unrestricted population. Using electronic health records from a South London NHS trust, this work demonstrates a method to correct for collider bias using externally sourced data while examining the relationship between minority ethnicities and poor Covid-19 outcomes. METHODS: The probability of inclusion within the observed hospitalised cohort was modelled based on estimates from published national data. The model described the relationship between patient ethnicity, hospitalisation, and death due to Covid-19 - a relationship suggested to be susceptible to collider bias. The obtained probabilities (as applied to the observed patient cohort) were used as inverse probability weights in survival analysis examining ethnicity (and covariates) as a risk factor for death due to Covid-19. RESULTS: Within the observed cohort, unweighted analysis of survival suggested a reduced risk of death in those of Black ethnicity - differing from the published literature. Applying inverse probability weights to this analysis amended this aberrant result to one more compatible with the literature. This effect was consistent when the analysis was applied to patients within only the first wave of Covid-19 and across two waves of Covid-19 and was robust against adjustments to the modelled relationship between hospitalisation, patient ethnicity, and death due to Covid-19 made as part of a sensitivity analysis. CONCLUSIONS: In conclusion, this analysis demonstrates the feasibility of using external publications to correct for collider bias (or other forms of selection bias) induced by the restriction of a population to a hospitalised cohort using an example from the recent Covid-19 pandemic.

Exploring the Experiences of Living With the Post-COVID Syndrome: A Qualitative Study.

INTRODUCTION: Many people experience persistent symptoms for more than 12 weeks following SARS-CoV-2 infection, which is known as post-COVID-19 condition (PCS) or Long COVID (LC). PCS can impair people's quality of life and daily functioning. However, there is a lack of in-depth research exploring the PCS patient journey, as well as gendered aspects of patients' experiences. METHODS: Nineteen semi-structured qualitative interviews were conducted with people living with PCS in the United Kingdom (13 women, 6 men). Interviews were transcribed verbatim and analysed inductively using reflexive thematic analysis. RESULTS: Five main themes were identified: 'Symptom dismissal', 'Lack of information and support', 'Life before and after Long COVID', 'Psychological impact' and 'Acceptance'. A shift overtime to self-management of symptoms was evident. These themes represent different stages of patients' PCS journey. Narratives indicated that women highlighted dismissal by healthcare professionals (HCPs), which was not as prominent in men's narratives. In addition, women went into more detail about the psychological impact of PCS compared to men. CONCLUSION: Women with PCS reported symptom dismissal by HCPs, which may have delayed their diagnosis and negatively affected their well-being. We were not able to explore the experiences of people from non-conforming gender groups. Raising awareness of these issues among HCPs, particularly general practitioners, could improve patient care in PCS. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement consisted of people who took part in the interviews and commented on the themes' interpretation and study conclusions.

A history of home mechanical ventilation: The past, present and future.

This state-of-the-art review provides an overview of the history of home mechanical ventilation (HMV), including early descriptions of mechanical ventilation from ancient and Renaissance perspectives and the mass development of ventilators designed for long-term use during the poliomyelitis epidemic. Seminal data from key clinical trials supports the application of HMV in certain patients with chronic obstructive pulmonary disease, neuromuscular disease and obesity-related respiratory failure. Innovative engineering coupled with refined physiological understanding now permits widespread delivery of home mechanical ventilation to a global population, using portable devices with advanced ventilatory modes and telemonitoring capabilities. Exponential growth in digital technology continues, and ongoing research is needed to understand how to harness clinical and physiological data to benefit patients and healthcare services in a clinically- and cost-effective manner.

Do patients internalize the positive regard they are offered? A dyadic test of a Rogerian condition.

OBJECTIVE: Positive regard (PR) reflects a therapist's unconditional prizing of their patient, which meta-analytically correlates positively with patient improvement. However, most research has been limited to single-participant ratings of PR at a specific time, which neglects the dyadic and dynamic nature of PR (i.e., fundamental to benefitting from therapist-offered PR is that a patient internalizes it). Testing this premise, we hypothesized that therapist-offered PR at one session would predict patient-felt PR at a subsequent session (two sessions later), which would in turn predict the patient's next-session outcome (within-patient mediation). METHOD: Eighty-four patients with generalized anxiety disorder received cognitive-behavioral therapy with or without motivational interviewing. Therapists and patients provided postsession ratings of their offered and felt PR, respectively, at odd-numbered sessions throughout treatment. Patients rated their worry following each even-numbered session. We used multilevel structural equation modeling to test our hypothesis. We explored whether treatment condition moderated the mediational path. RESULTS: As predicted, when a therapist regarded their patient more than usual following one session, the patient felt more regarded than usual. In turn, this internalized regard was negatively associated with worry. Treatment condition did not moderate this path. DISCUSSION: Results support internalized positive regard as a treatment-common, ameliorative relationship process.

Two-year prospective cohort of intensive care survivors enrolled on a digitally enabled recovery pathway focussed on individualised recovery goal attainment.

BACKGROUND: Despite substantial evidence documenting physical, psychological, and cognitive problems experienced by intensive care unit (ICU) survivors, few studies explore interventions supporting recovery after hospital discharge. Individualised recovery goal setting, the standard of care across many rehabilitation areas, is rarely used for ICU survivors. Digital health technologies may help to address current service fragmentation and gaps. We developed and implemented a digital ICU recovery pathway using the aTouchaway e-health platform. OBJECTIVES: The objective of this study was to explore recovery barriers and challenges; recovery goals set and achieved; self-reported patient outcomes; and healthcare costs of patients enrolled on a 12-week digital ICU recovery pathway after hospital discharge. METHODS: We conducted a prospective observational single-centre cohort study (June 2021 to May 2023) at a 90-bed tertiary critical care service in London, UK. We enrolled adults ventilated for ≥3 days who were able to participate in recovery activities. We ascertained baseline recovery challenges and identified recovery goals and achievement over 12 weeks. We collected patient-reported outcomes at 2-4, 12-14, 26-28 weeks and healthcare utilisation monthly for 28 weeks. RESULTS: We enrolled 105 participants (35% of eligible patients). Common rehabilitation challenges were standing balance (60%), walking indoors (56%), and washing (64%) and dressing (47%) abilities. Of 522 home recovery goals, 63% weekly, 48% monthly, and 38% aspirational goals were achieved. Most goals related to self-care: ability to move outside (91 goals, 55% achieved) and inside (45 goals, 47% achieved) the home and community access (65 goals, 48% achieved). Nottingham Extended Activities of Daily Living Scale scores improved from timepoints 1 to 2 (median [interquartile range]: 15 [7, 19] versus 19 [15, 21], P = 0.01). Total healthcare costs were £240,017 (median [interquartile range] cost per patient: £784 [£125, £4419]). CONCLUSIONS: This study found multiple ongoing functional deficits, challenges achieving recovery goals, and limited improvements in self-reported outcomes, with moderate healthcare costs after hospital discharge indicate substantial ongoing rehabilitative needs.

Cost-effectiveness of home non-invasive ventilation in patients with persistent hypercapnia after an acute exacerbation of COPD in the UK.

Home non-invasive mechanical ventilation (HMV) with home oxygen therapy (HOT) in patients with persistent hypercapnia following an acute exacerbation of chronic obstructive pulmonary disease delays hospital readmission. The economic impact of this treatment is unknown. We evaluated the cost-effectiveness of HMV in the UK healthcare system using data from a previously published efficacy trial. Quality-adjusted life-years (QALYs) were computed from EQ-5D-5L. Accounting for all direct patient costs HOT-HMV was £512 (95%CI £36 to £990) more expensive per patient per year than HOT-alone. This small increase in cost was accompanied by increased quality of life leading to an incremental cost-effectiveness ratio of £10 259 per QALY. HOT-HMV was cost-effective in this clinical population. Trial registration number: NCT00990132.

Cost-effectiveness of outpatient versus inpatient non-invasive ventilation setup in obesity hypoventilation syndrome: the OPIP trial.

BACKGROUND: Current guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective. METHODS: Patients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO2) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP). RESULTS: Between May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m2 and PaCO2 6.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO2 (difference -0.27 kPa, 95% CI -0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI -£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference -0.006, 95% CI -0.05 to 0.04). There were no differences in secondary outcomes. DISCUSSION: There was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference. TRIAL REGISTRATION NUMBERS: NCT02342899 and ISRCTN51420481.

Exercise-induced hypohydration impairs 3 km treadmill-running performance in temperate conditions.

Research assessing exercise-induced hypohydration on running performance in a temperate environment is scarce. Given the weight-bearing nature of running, the negative effects of hypohydration might be offset by the weight-loss associated with a negative fluid balance. Therefore, this study investigated the effect of exercise-induced hypohydration on running performance in temperate conditions. Seventeen intermittent games players (age 22 ± 1 y; VO2peak 52.5 ± 4.1 mL∙kg-1∙min-1) completed preliminary and familiarisation trials, and two experimental trials consisting of 12 blocks of 6 min of running (65% VO2peak; preload) with 1 min passive rest in-between, followed by a 3 km time trial (TT). During the preload, subjects consumed minimal fluid (60 mL) to induce hypohydration (HYP) or water to replace 95% sweat losses (1622 ± 343 mL; EUH). Body mass loss (EUH -0.5 ± 0.3%; HYP -2.2 ± 0.4%; P < 0.001), and other changes indicative of hypohydration, including increased serum osmolality, heart rate, thirst sensation, and decreased plasma volume (P ≤ 0.022), were apparent in HYP by the end of the preload. TT performance was ~6% slower in HYP (EUH 900 ± 87 s; HYP 955 ± 110 s; P < 0.001). Exercise-induced hypohydration of ~2% body mass impaired 3 km running TT performance in a temperate environment.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis.

BACKGROUND: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS). METHODS: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398). FINDINGS: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome. INTERPRETATION: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

The Noninvasive Ventilation Outcomes (NIVO) score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used. METHODS: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally noninvasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 1-4/5a/5b, time from admission to acidaemia >12 h, pH <7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation), a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort. DISCUSSION: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism and comparing risk-adjusted outcomes across centres.

Relationship Between Skeletal Muscle Area and Density and Clinical Outcome in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate the prevalence of low skeletal muscle index (area normalized for height) and density, their trajectory of change, and to determine associations with clinical outcome in adults with severe respiratory failure requiring venovenous extracorporeal membrane oxygenation. DESIGN: Prospective observational study. PATIENTS: Adults receiving venovenous extracorporeal membrane oxygenation for a minimum of 72 hours and a maximum of 6 months between September 2010 and June 2017, who had a CT scan which included the third lumbar vertebra. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle index and density was determined using Slice-O-Matic V5.0 (TomoVision, Montreal, QC, Canada). Low skeletal muscle index and density were defined using published criteria. Regression models were used to assess for associations between muscle index and density and clinical outcome. Two-hundred fifteen patients, median (interquartile range) age 46 years (35.0-57.0 yr) were included. Forty-five patients (21.1%) had low skeletal muscle index, and 48 (22.3%) had low skeletal muscle density on commencement of venovenous extracorporeal membrane oxygenation. Low skeletal muscle index was more prevalent in males (28.8% vs 11.6%; χ2 = 9.4; p = 0.002) and was associated with a longer duration of venovenous extracorporeal membrane oxygenation (B = 5.0; 95% CI, 0.2-9.9; p = 0.042). Higher skeletal muscle density was independently associated with ICU survival (odds ratio 1.6 per 10 Hounsfield units; 95% CI, 1.1-2.5; p = 0.025). No relationship was observed between skeletal muscle index nor density and physical function. Adequacy of energy and protein did not influence change in skeletal muscle index or density. CONCLUSIONS: Low skeletal muscle index at the commencement of venovenous extracorporeal membrane oxygenation was associated with a longer duration of venovenous extracorporeal membrane oxygenation, whereas preserved skeletal muscle density was associated with improved survival.

Respiratory follow-up of patients with COVID-19 pneumonia.

The COVID-19 pandemic has led to an unprecedented surge in hospitalised patients with viral pneumonia. The most severely affected patients are older men, individuals of black and Asian minority ethnicity and those with comorbidities. COVID-19 is also associated with an increased risk of hypercoagulability and venous thromboembolism. The overwhelming majority of patients admitted to hospital have respiratory failure and while most are managed on general wards, a sizeable proportion require intensive care support. The long-term complications of COVID-19 pneumonia are starting to emerge but data from previous coronavirus outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) suggest that some patients will experience long-term respiratory complications of the infection. With the pattern of thoracic imaging abnormalities and growing clinical experience, it is envisaged that interstitial lung disease and pulmonary vascular disease are likely to be the most important respiratory complications. There is a need for a unified pathway for the respiratory follow-up of patients with COVID-19 balancing the delivery of high-quality clinical care with stretched National Health Service (NHS) resources. In this guidance document, we provide a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia. We define two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge. To mitigate NHS pressures, virtual solutions have been embedded within the pathway as has safety netting of patients whose clinical trajectory deviates from the pathway. For all patients, we suggest a holistic package of care to address breathlessness, anxiety, oxygen requirement, palliative care and rehabilitation.

Long-term survival following initiation of home non-invasive ventilation: a European study.

INTRODUCTION: Although home non-invasive ventilation (NIV) is increasingly used to manage patients with chronic ventilatory failure, there are limited data on the long-term outcome of these patients. Our aim was to report on home NIV populations and the long-term outcome from two European centres. METHODS: Cohort analysis including all patients established on home NIV from two European centres between 2008 and 2014. RESULTS: Home NIV was initiated in 1746 patients to treat chronic ventilatory failure caused by (1) obesity hypoventilation syndrome±obstructive sleep apnoea (OHS±OSA) (29.5%); (2) neuromuscular disease (NMD) (22.7%); and (3) obstructive airway diseases (OAD) (19.1%). Overall cohort median survival following NIV initiation was 6.6 years. Median survival varied by underlying aetiology of respiratory failure: rapidly progressive NMD 1.1 years, OAD 2.7 years, OHS±OSA >7 years and slowly progressive NMD >7 years. Multivariate analysis demonstrated higher mortality in patients with rapidly progressive NMD (HR 4.78, 95% CI 3.38 to 6.75), COPD (HR 2.25, 95% CI 1.64 to 3.10), age >60 years at initiation of home NIV (HR 2.41, 95% CI 1.92 to 3.02) and NIV initiation following an acute admission (HR 1.38, 95% CI 1.13 to 1.68). Factors associated with lower mortality were NIV adherence >4 hours per day (HR 0.64, 95% CI 0.51 to 0.79), OSA (HR 0.51, 95% CI 0.31 to 0.84) and female gender (HR 0.79, 95% CI 0.65 to 0.96). CONCLUSION: The mortality rate following initiation of home NIV is high but varies significantly according to underlying aetiology of respiratory failure. In patients with chronic respiratory failure, initiation of home NIV following an acute admission and low levels of NIV adherence are poor prognostic features and may be amenable to intervention.

Autotitrating external positive end-expiratory airway pressure to abolish expiratory flow limitation during tidal breathing in patients with severe COPD: a physiological study.

BACKGROUND: The optimal noninvasive application of external positive end-expiratory pressure (EPAP) to abolish tidal-breathing expiratory flow limitation (EFLT) and minimise intrinsic positive end-expiratory pressure (PEEPi) is challenging in COPD patients. We investigated whether auto-titrating EPAP, using the forced oscillation technique (FOT) to detect and abolish EFLT, would minimise PEEPi, work of breathing and neural respiratory drive (NRD) in patients with severe COPD. METHODS: Patients with COPD with chronic respiratory failure underwent auto-titration of EPAP using a FOT-based algorithm that detected EFLT. Once optimal EPAP was identified, manual titration was performed to assess NRD (using diaphragm and parasternal intercostal muscle electromyography, EMGdi and EMGpara, respectively), transdiaphragmatic inspiratory pressure swings (ΔP di), transdiaphragmatic pressure-time product (PTPdi) and PEEPi, between EPAP levels 2 cmH2O below to 3 cmH2O above optimal EPAP. RESULTS: Of 10 patients enrolled (age 65±6 years; male 60%; body mass index 27.6±7.2 kg.m-2; forced expiratory volume in 1 s 28.4±8.3% predicted), eight had EFLT, and optimal EPAP was 9 (range 4-13) cmH2O. NRD was reduced from baseline EPAP at 1 cmH2O below optimal EPAP on EMGdi and at optimal EPAP on EMGpara. In addition, at optimal EPAP, PEEPi (0.80±1.27 cmH2O versus 1.95± 1.70 cmH2O; p<0.05) was reduced compared with baseline. PTPdi (10.3±7.8 cmH2O·s-1 versus 16.8±8.8 cmH2O·s-1; p<0.05) and ΔP di (12.4±7.8 cmH2O versus 18.2±5.1 cmH2O; p<0.05) were reduced at optimal EPAP+1 cmH2O compared with baseline. CONCLUSION: Autotitration of EPAP, using a FOT-based algorithm to abolish EFLT, minimises transdiaphragmatic pressure swings and NRD in patients with COPD and chronic respiratory failure.

Neurally adjusted ventilatory assist versus pressure support ventilation: a randomized controlled feasibility trial performed in patients at risk of prolonged mechanical ventilation.

BACKGROUND: The clinical effectiveness of neurally adjusted ventilatory assist (NAVA) has yet to be demonstrated, and preliminary studies are required. The study aim was to assess the feasibility of a randomized controlled trial (RCT) of NAVA versus pressure support ventilation (PSV) in critically ill adults at risk of prolonged mechanical ventilation (MV). METHODS: An open-label, parallel, feasibility RCT (n = 78) in four ICUs of one university-affiliated hospital. The primary outcome was mode adherence (percentage of time adherent to assigned mode), and protocol compliance (binary-≥ 65% mode adherence). Secondary exploratory outcomes included ventilator-free days (VFDs), sedation, and mortality. RESULTS: In the 72 participants who commenced weaning, median (95% CI) mode adherence was 83.1% (64.0-97.1%) and 100% (100-100%), and protocol compliance was 66.7% (50.3-80.0%) and 100% (89.0-100.0%) in the NAVA and PSV groups respectively. Secondary outcomes indicated more VFDs to D28 (median difference 3.0 days, 95% CI 0.0-11.0; p = 0.04) and fewer in-hospital deaths (relative risk 0.5, 95% CI 0.2-0.9; p = 0.032) for NAVA. Although overall sedation was similar, Richmond Agitation and Sedation Scale (RASS) scores were closer to zero in NAVA compared to PSV (p = 0.020). No significant differences were observed in duration of MV, ICU or hospital stay, or ICU, D28, and D90 mortality. CONCLUSIONS: This feasibility trial demonstrated good adherence to assigned ventilation mode and the ability to meet a priori protocol compliance criteria. Exploratory outcomes suggest some clinical benefit for NAVA compared to PSV. Clinical effectiveness trials of NAVA are potentially feasible and warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01826890. Registered 9 April 2013.

BPAP is an effective second-line therapy for obese patients with OSA failing regular CPAP: A prospective observational cohort study.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) is the most common treatment for obstructive sleep apnoea (OSA), but many patients fail long-term therapy. Bilevel positive airway pressure (BPAP) is a potential alternative. We hypothesized that BPAP could improve treatment adherence and outcomes in patients who cannot tolerate CPAP. METHODS: Patients with OSA who failed CPAP (usage < 4 h/day) and were referred to a tertiary sleep centre between 2014 and 2017 for BPAP were included. Age, gender, body mass index (BMI), co-morbidities, CPAP use and reasons for failure, Epworth Sleepiness Scale (ESS), sleep study data, spirometry data and average maximum nightly compliance were recorded. RESULTS: A total of 52 patients with OSA requiring CPAP > 15 cm H2 O (71% male, age: 58 (15) years, BMI: 42.6 (10.1) kg/m2 , apnoea-hypopnoea index (AHI): 51.1 (30.4)/h) were studied; 62% had respiratory co-morbidities affecting nocturnal breathing including obesity hypoventilation syndrome and COPD; 25% had neuromuscular conditions; and 17% had cardiovascular disease. CPAP was used for 199 (106-477) days prior to referral for BPAP. Reasons for CPAP failure were intolerant pressures (23%), uncontrolled symptoms (23%), mask problems (21%), adverse effects (13%), claustrophobia (8%), co-morbidities (8%) and other issues (4%). Lower expiratory positive airway pressures were needed with BPAP compared to CPAP (10 (8-12) vs 16.8 (15.7-19.2) cm H2 O, P = 0.001); patients achieved better adherence to BPAP (7.0 (4.0-8.5) vs 2.5 (1.6-6.7) h/night, P = 0.028) and better symptom control (ESS: 4.0 (1.0-7.0) vs 10.0 (6.0-17.0) points, P = 0.039). CONCLUSION: In patients with moderate-severe OSA who fail CPAP therapy due to low adherence, BPAP is well tolerated and achieves sufficient control of sleep-disordered breathing and its symptoms.

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.