Venous blood gases in the assessment of respiratory failure in patients undergoing sleep studies: a randomized study.

STUDY OBJECTIVES: Venous blood gases (VBGs) are not consistently considered suitable surrogates for arterial blood gases (ABGs) in assessing acute respiratory failure due to variable measurement error. The physiological stability of patients with chronic ventilatory failure may lead to improved agreement in this setting. METHODS: Adults requiring ABGs for sleep or ventilation titration studies had VBGs drawn before or after each ABG, in a randomized order. Veno-arterial correlation and agreement were examined for carbon dioxide tension (PCO2), pH, oxygen tension (PO2) and oxygen saturation (SO2). RESULTS: We analyzed 115 VBG-ABG pairs from 61 patients. Arterial and venous measures were correlated (with p<0.05) for PCO2 (r=0.84) and pH (r=0.72), but not for PO2 or SO2. Adjusted mean veno-arterial differences (95% limits of agreement) were +5.0mmHg (-4.4 to +14.4) for PCO2; -0.02 (-0.09 to +0.04) for pH; -34.3mmHg (-78.5 to +10.0) for PO2; and -23.9% (-61.3 to +13.5) for SO2. VBGs obtained from the dorsal hand demonstrated a lower mean PCO2 veno-arterial difference (p<0.01). A venous PCO2 threshold of ≥45.8mmHg was >95% sensitive for arterial hypercapnia, so measurements below this can exclude the diagnosis without an ABG. A venous PCO2 threshold of ≥53.7mmHg was >95% specific for arterial hypercapnia, so such readings can be assumed diagnostic. The area under the receiver operating characteristic curve of 0.91 indicated high discriminatory capacity. CONCLUSIONS: A venous PCO2 <45.8mmHg or ≥53.7mmHg would exclude or diagnose hypercapnia, respectively, in patients referred for sleep studies, but VBGs are poor surrogates for ABGs where precision is important. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Register; Name: A comparison of arterial and blood gas analyses in sleep studies; Identifier: ACTRN12617000562370; URL https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372717.

A Randomized Controlled Clinical Trial of Lung Volume Recruitment in Adults with Neuromuscular Disease.

Rationale: Clinical care guidelines advise that lung volume recruitment (LVR) be performed routinely by people with neuromuscular disease (NMD) to maintain lung and chest wall flexibility and slow lung function decline. However, the evidence base is limited, and no randomized controlled trials of regular LVR in adults have been published. Objectives: To evaluate the effect of regular LVR on respiratory function and quality of life in adults with NMD. Methods: A randomized controlled trial with assessor blinding was conducted between September 2015 and May 2019. People (>14 years old) with NMD and vital capacity <80% predicted were eligible, stratified by disease subgroup (amyotrophic lateral sclerosis/motor neuron disease or other NMDs), and randomized to 3 months of twice-daily LVR or breathing exercises. The primary outcome was change in maximum insufflation capacity (MIC) from baseline to 3 months, analyzed using a linear mixed model approach. Results: Seventy-six participants (47% woman; median age, 57 [31-68] years; mean baseline vital capacity, 40 ± 18% predicted) were randomized (LVR, n = 37). Seventy-three participants completed the study. There was a statistically significant difference in MIC between groups (linear model interaction effect P = 0.002, observed mean difference, 0.19 [0.00-0.39] L). MIC increased by 0.13 (0.01-0.25) L in the LVR group, predominantly within the first month. No interaction or treatment effects were observed in secondary outcomes of lung volumes, respiratory system compliance, and quality of life. No adverse events were reported. Conclusions: Regular LVR increased MIC in a sample of LVR-naive participants with NMD. We found no direct evidence that regular LVR modifies respiratory mechanics or slows the rate of lung volume decline. The implications of increasing MIC are unclear, and the change in MIC may represent practice. Prospective long-term clinical cohorts with comprehensive follow-up, objective LVR use, and clinically meaningful outcome data are needed. Clinical trial registered with anzctr.org.au (ACTRN12615000565549).

A Multidisciplinary Approach to Verbal Communication Interventions for Mechanically Ventilated Adults With a Tracheostomy.

There is developing evidence with regard to the feasibility, utility, and safety of verbal communication interventions with patients with tracheostomy who are invasively ventilated. In the past 2 decades, research efforts have focused on establishing evidence for communication interventions, including introducing an intentional leak into the ventilatory circuit such as with a fenestrated tube, leak speech or ventilator-adjusted leak speech, the use of a one-way valve in-line with the ventilator, and above cuff vocalization. This narrative review describes the benefits of a multi-disciplinary approach, summarizes verbal communication interventions, and provides guidance on the indications, contraindications and considerations for patient selection. Our clinical procedures based on collective clinical experience are shared. A multidisciplinary team approach enables holistic management across acuity, ventilation, airway, communication, and swallowing parameters. This collaborative approach is recommended to maximize the chance of successful opportunities for patients to communicate safely and effectively.

Filters Alter the Performance of Noninvasive Ventilators.

BACKGROUND: Noninvasive ventilation is recommended in hypercapnic respiratory failure secondary to ventilatory failure. Noninvasive ventilation may contribute to aerosol dispersion, which may increase the risk of transmission of COVID 2019. The addition of filters to the ventilator circuit has been recommended to reduce this risk. The aim of this benchtop study was to investigate the impact of adding filters to a ventilator circuit. METHODS: In this benchtop study, a breathing simulator was used with 4 commonly used ventilators. Ventilators were set to approximate the typical settings that are used for patients on long-term noninvasive ventilation. Ventilator performance was then evaluated with 3 circuit configurations in place: circuit A: no filter in situ; circuit B: 1 filter at the simulator end of the circuit; and circuit C: 1 filter at the simulator end of the circuit and a second filter at the ventilator end of the circuit. RESULTS: Ventilator variables were impacted by the addition of filters. Measurements of peak pressure (P < .001), tidal volume (P < .001), and peak flow (P < .001) decreased between circuit A and circuit C in all ventilators that were tested. Ventilator triggering was less sensitive in 3 of the 4 ventilators and the fourth ventilator did not trigger under the same simulator settings. CONCLUSIONS: This study demonstrated that ventilator settings established with filters in situ are not applicable if the ventilator is used without the filters. This is an important clinical consideration for patients who are hospitalized and require noninvasive ventilation in the COVID 2019 era.

Measuring Adherence to Long-Term Noninvasive Ventilation.

BACKGROUND: Obtaining benefits from long-term noninvasive ventilation (NIV) relies on achieving adequate adherence to treatment. Reported adherence to NIV is variable and could be influenced by high-volume users and attrition of nonusers and those who die. This observational study aimed to describe patterns of use and adherence rates in new unselected users of NIV. METHODS: All adults (> 18 y old) commencing long-term NIV were consecutively enrolled and followed for 6 months. Ventilator data were manually downloaded from devices and usage (minutes per day) was collected. Subjects were categorized into adherent users (≥ 4 h/d) and nonadherent users (< 4 h/d). RESULTS: Data were obtained from 86 subjects. Most (65%) had motor neuron disease, and most commenced NIV in an out-patient setting (72%). At one month after NIV implementation, overall average daily use was 302.1 min/d and categorical adherence was 57%. At 6 months or prior to death, overall average daily use increased (388.7 min/d), but categorical adherence was similar (62%). The majority of subjects (84%) remained in the same adherence category from their first month to their sixth month of use or death. Individuals with motor neuron disease demonstrated significantly lower rates of adherence compared to the rest of the cohort at 1 month (48% vs 73%, P = .03). In those who died within the study period (n = 19, all with motor neuron disease), this difference persisted to death (42% at death vs 73% at 6 months, P = .032). CONCLUSIONS: Average daily usage may conceal true prevalence of adherence or nonadherence to NIV within a population. Reporting both average daily use data and categorical adherence rates (using a threshold of 4 h/d) may improve transparency of reported outcomes from clinical trials and identifies a therapeutic target for home mechanical ventilation services for quality improvement.

Typical within and between person variability in non-invasive ventilator derived variables among clinically stable, long-term users.

BACKGROUND: Despite increasing capacity to remotely monitor non-invasive ventilation (NIV), how remote data varies from day to day and person to person is poorly described. METHODS: Single-centre, 2-month, prospective study of clinically stable adults on long-term NIV which aimed to document NIV-device variability. Participants were switched to a ventilator with tele-monitoring capabilities. Ventilation settings and masking were not altered. Raw, extensible markup language data files were provided directly from Philips Respironics (EncoreAnywhere). A nested analysis of variance was conducted on each ventilator variable to apportion the relative variation between and within participants. RESULTS: Twenty-nine people were recruited (four withdrew, one had insufficient data for analyses; 1364 days of data). Mean age was 54.0 years (SD 18.4), 58.3% male with body mass index of 37.0 kg/m2 (13.7). Mean adherence was 8.53 (2.23) hours/day and all participants had adherence >4 hours/day. Variance in ventilator-derived indices was predominantly driven by differences between participants; usage (61% between vs 39% within), Apnoea-Hypopnoea Index (71% vs 29%), unintentional (64% vs 36%) and total leak (83% vs 17%), tidal volume (93% vs 7%), minute ventilation (92% vs 8%), respiratory rate (92% vs 8%) and percentage of triggered breaths (93% vs 7%). INTERPRETATION: In this clinically stable cohort, all device-derived indices were more varied between users than the day-to-day variation within individuals. We speculate that normative ranges and thresholds for clinical intervention need to be individualised, and further research is necessary to determine the clinically important relationships between clinician targets for therapy and patient-reported outcomes.

Pneumothorax in neuromuscular disease associated with lung volume recruitment and mechanical insufflation-exsufflation.

A 25-year-old male with Duchenne muscular dystrophy and a 73-year-old male with motor neurone disease both presented with chest pain and increasing dyspnoea following routine mechanical insufflation-exsufflation or lung volume recruitment, on a background of long-term non-invasive ventilation. In each case, chest radiograph revealed a pneumothorax. In both cases the pneumothorax fully resolved following insertion of an intercostal catheter. There was no immediate recurrence and the patients were discharged home and ceased ongoing prophylactic respiratory therapy, although one person had recurrent pneumothoraces subsequently. This rare but serious complication highlights the need for careful risk/benefit analysis by clinicians prescribing these therapies.

Autocycling During Noninvasive Positive Pressure Ventilation Producing a Prolonged Severe Apnea and Syncope.

ABSTRACT: Autocycling is a form of patient-ventilator asynchrony that can occur during mechanical ventilation. In the case described, autocycling during noninvasive ventilation led to severe hyperventilation and subsequently produced a prolonged central apnea that resulted in syncope. This case represents the first description of a severe adverse event from autocycling during noninvasive ventilation.

Randomised controlled trial of polysomnographic titration of noninvasive ventilation.

Noninvasive ventilation (NIV) settings determined during wakefulness may produce patient-ventilator asynchrony (PVA) during sleep, causing sleep disruption and limiting tolerance. This study investigated whether NIV titrated with polysomnography (PSG) is associated with less PVA and sleep disruption than therapy titrated during daytime alone.Treatment-naive individuals referred for NIV were randomised to control (daytime titration followed by sham polysomnographic titration) or PSG (daytime titration followed by polysomnographic titration) groups. Primary outcomes were PVA and arousal indices on PSG at 10 weeks. Secondary outcomes included adherence, gas exchange, symptoms and health-related quality of life (HRQoL).In total, 60 participants were randomised. Most (88.3%) had a neuromuscular disorder and respiratory muscle weakness but minor derangements in daytime arterial blood gases. PVA events were less frequent in those undergoing polysomnographic titration (median (interquartile range (IQR)): PSG 25.7 (12-68) events·h-1 versus control 41.0 (28-182) events·h-1; p=0.046), but arousals were not significantly different (median (IQR): PSG 11.4 (9-19) arousals·h-1 versus control 14.6 (11-19) arousals·h-1; p=0.258). Overall adherence was not different except in those with poor early adherence (<4 h·day-1) who increased their use after polysomnographic titration (mean difference: PSG 95 (95% CI 29-161) min·day-1 versus control -23 (95% CI -86-39) min·day-1; p=0.01). Arterial carbon dioxide tension, somnolence and sleep quality improved in both groups. There were no differences in nocturnal gas exchange or overall measures of HRQoL.NIV titrated with PSG is associated with less PVA but not less sleep disruption when compared with therapy titrated during daytime alone.

A randomised controlled trial of CPAP versus non-invasive ventilation for initial treatment of obesity hypoventilation syndrome.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is the most common indication for home ventilation, although the optimal therapy remains unclear, particularly for severe disease. We compared Bi-level and continuous positive airways pressure (Bi-level positive airway pressure (PAP); CPAP) for treatment of severe OHS. METHODS: We conducted a multicentre, parallel, double-blind trial for initial treatment of OHS, with participants randomised to nocturnal Bi-level PAP or CPAP for 3 months. The primary outcome was frequency of treatment failure (hospital admission, persistent ventilatory failure or non-adherence); secondary outcomes included health-related quality of life (HRQoL) and sleepiness. RESULTS: Sixty participants were randomised; 57 completed follow-up and were included in analysis (mean age 53 years, body mass index 55 kg/m2, PaCO2 60 mm Hg). There was no difference in treatment failure between groups (Bi-level PAP, 14.8% vs CPAP, 13.3%, p=0.87). Treatment adherence and wake PaCO2 were similar after 3 months (5.3 hours/night Bi-level PAP, 5.0 hours/night CPAP, p=0.62; PaCO2 44.2 and 45.9 mm Hg, respectively, p=0.60). Between-group differences in improvement in sleepiness (Epworth Sleepiness Scale 0.3 (95% CI -2.8, 3.4), p=0.86) and HRQoL (Short Form (SF)36-SF6d 0.025 (95% CI -0.039, 0.088), p=0.45) were not significant. Baseline severity of ventilatory failure (PaCO2) was the only significant predictor of persistent ventilatory failure at 3 months (OR 2.3, p=0.03). CONCLUSIONS: In newly diagnosed severe OHS, Bi-level PAP and CPAP resulted in similar improvements in ventilatory failure, HRQoL and adherence. Baseline PaCO2 predicted persistent ventilatory failure on treatment. Long-term studies are required to determine whether these treatments have different cost-effectiveness or impact on mortality. TRIAL REGISTRATION NUMBER: ACTRN12611000874910, results.

Field Walking Tests Are Reliable and Responsive to Exercise Training in People With Non-Cystic Fibrosis Bronchiectasis.

PURPOSE: The 6-Minute Walk Test (6MWT) and Incremental Shuttle Walk Test (ISWT) are used to assess exercise capacity, but the reliability and responsiveness of these tests in individuals with non-cystic fibrosis (CF) bronchiectasis have not been determined. This study aimed to determine the reliability and responsiveness of both tests in adults with non-CF bronchiectasis. METHODS: Eighty-five participants completed 2 6MWTs and 2 ISWTs in random order. Testing was repeated at the conclusion of an 8-week intervention period of exercise training. Reliability was assessed using intraclass correlation coefficients (ICC) and Bland-Altman analysis. Responsiveness was measured by effect size (ES) and standardized response mean (SRM). RESULTS: At baseline, test-retest reliability was high for both tests (ICC ≥ 0.95). The mean (95% CI) increase in the 6MWT from test 1 to test 2 was 20 m (13-26 m): 3% (0-5%) change. The mean (95% CI) increase in the ISWT was 15 m (4-25m): 4% (2-6%) change. A significant learning effect persisted after 8 weeks for the 6MWT (P = .04), but not the ISWT (P = .61). The 6MWT ES was 0.32 and SRM was 0.68; for the ISWT, ES was 0.42 with SRM of 0.71. CONCLUSION: The 6MWT and ISWT are reliable measures of exercise capacity in non-CF bronchiectasis and responsive to exercise training. The small learning effect in both measures at baseline suggests that 2 of each test are necessary to correctly assess exercise capacity. Completion of 2 6MWTs at followup may minimize the risk of underestimating a treatment effect.

The short and long term effects of exercise training in non-cystic fibrosis bronchiectasis--a randomised controlled trial.

BACKGROUND: Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis. METHODS: Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months. RESULTS: Eighty-five participants (mean FEV1 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1-3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1-3]) compared to the control group (2[1-3]) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p = 0.047). CONCLUSIONS: Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months. TRIAL REGISTRY: ClinicalTrials.gov (NCT00885521).

Improved survival with an ambulatory model of non-invasive ventilation implementation in motor neuron disease.

Non-invasive ventilation (NIV) increases survival and quality of life in motor neuron disease (MND). NIV implementation historically occurred during a multi-day inpatient admission at this institution; however, increased demand led to prolonged waiting times. The aim of this study was to evaluate the introduction of an ambulatory model of NIV implementation. A prospective cohort study was performed. Inclusion criteria were referral for NIV implementation six months pre- or post-commencement of the Day Admission model. This model involved a 4-h stay to commence ventilation with follow-up in-laboratory polysomnography titration and outpatient attendance. Outcome measures included waiting time, hospital length of stay, adverse events and polysomnography data. Results indicated that after changing to the Day Admission model the median waiting time fell from 30 to 13.5 days (p < 0.04) and adverse events declined (4/17 pre- (three deaths, one acute admission) vs. 0/12 post-). Survival was also prolonged (median (IQR) 278 (51-512) days pre- vs 580 (306-1355) days post-introduction of the Day Admission model; hazard ratio 0.41, p = 0.04). Daytime PaCO2 was no different. In conclusion, reduced waiting time to commence ventilation and improved survival were observed following introduction of an ambulatory model of NIV implementation in people with MND, with no change in the effectiveness of ventilation.

Inpatient and long-term outcomes of individuals admitted for weaning from mechanical ventilation at a specialized ventilation weaning unit.

BACKGROUND: Weaning from invasive mechanical ventilation (IMV) in specialized weaning units has been demonstrated to be safe and cost-effective. Success rates and outcomes vary widely, probably relating to patient factors and unit expertise. METHODS: An audit was undertaken of patients admitted for weaning from IMV at the Austin Hospital Ventilation Weaning Unit (VWU) between March 2002 and January 2008. Weaning success, complications and both in-hospital and long-term mortality were examined and regression analysis was undertaken to examine factors related to these outcomes. RESULTS: Seventy-eight patients were admitted to the VWU after a median of 27 days of IMV at their referring centre. Weaning success rate (ventilator free or nocturnal non-invasive ventilation only) was 78.2% (n = 61). Inpatient mortality was 10.2% (n = 8) and serious complications were infrequent. Progressive neuromuscular disease (odds ratio 0.10) and sepsis during admission to the VWU (odds ratio 0.09) were predictive of weaning failure at discharge. Overall survival at 12 months following discharge from the VWU was 66.7% (n = 52) with most survivors residing in the community. Increasing age (hazard ratio 1.93), referral from rural or outer metropolitan centres (hazard ratio 3.57 and 2.37 respectively) and a diagnosis of chronic obstructive pulmonary disease were associated with increased long-term mortality. CONCLUSION: High rates of weaning success with infrequent complications and low mortality were achieved in this specialized non-intensive care unit-based weaning unit. The VWU may provide a useful template for the development of similar units elsewhere.

The effects of pulmonary rehabilitation in patients with non-cystic fibrosis bronchiectasis: protocol for a randomised controlled trial.

BACKGROUND: Non-cystic fibrosis bronchiectasis is characterised by sputum production, exercise limitation and recurrent infections. Although pulmonary rehabilitation is advocated for this patient group, its effects are unclear. The aims of this study are to determine the short and long term effects of pulmonary rehabilitation on exercise capacity, cough, quality of life and the incidence of acute pulmonary exacerbations. METHODS/DESIGN: This randomised controlled trial aims to recruit 64 patients with bronchiectasis from three tertiary institutions. Participants will be randomly allocated to the intervention group (supervised, twice weekly exercise training with regular review of airway clearance therapy) or a control group (twice weekly telephone support). Measurements will be taken at baseline, immediately following the intervention and at six and 12 months following the intervention period by a blinded assessor. Exercise capacity will be measured using the incremental shuttle walk test and the six-minute walk test. Quality of life and health status will be measured using the Chronic Respiratory Questionnaire, Leicester Cough Questionnaire, Assessment of Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale. The rate of hospitalisation will be captured as well as the incidence of acute pulmonary exacerbations using a daily symptom diary. DISCUSSION: Results from this study will help to determine the efficacy of supervised twice-weekly pulmonary rehabilitation upon exercise capacity and quality of life in patients with bronchiectasis and will contribute to clinical practice guidelines for physiotherapists in the management of this population. TRIAL REGISTRATION: This study protocol is registered with ClinicalTrials.gov (NCT00885521).