Michelle Ramsay

Neural respiratory drive predicts clinical deterioration and safe discharge in exacerbations of COPD

Rationale Hospitalised patients with acute exacerbation of COPD may deteriorate despite treatment, with early readmission being common. Objectives To investigate whether neural respiratory drive, measured using second intercostal space parasternal muscle electromyography (EMGpara), would identify worsening dyspnoea and physician-defined inpatient clinical deterioration, and predict early readmission. Methods Patients admitted to a single-site university hospital with exacerbation of COPD were enrolled. Spirometry, inspiratory capacity (IC), EMGpara, routine physiological parameters, modified early warning score (MEWS), modified Borg scale for dyspnoea and physician-defined episodes of deterioration were recorded daily until discharge. Readmissions at 14 and 28 days post discharge were recorded. Measurements and main results 120 patients were recruited (age 70±9 years, forced expiratory volume in 1 s (FEV1) of 30.5±11.2%). Worsening dyspnoea, defined as at least one-point increase in Borg scale, was associated with increases in EMGpara%max and MEWS, whereas an increase in EMGpara%max alone was associated with physician-defined inpatient clinical deterioration. Admission-to-discharge change (Δ) in the normalised value of EMGpara (ΔEMGpara%max) was inversely correlated with ΔFEV1 (r=−0.38, p<0.001) and ΔIC (r=−0.44, p<0.001). ΔEMGpara%max predicted 14-day readmission (OR 1.13, 95% 1.03 to 1.23) in the whole cohort and 28-day readmission in patients under 85 years (OR 1.09, 95% CI 1.01 to 1.18). Age (OR 1.08, 95% CI 1.03 to 1.14) and 12-month admission frequency (OR 1.29, 1.01 to 1.66), also predicted 28-day readmission in the whole cohort. Conclusions Measurement of neural respiratory drive by EMGpara represents a novel physiological biomarker that may be helpful in detecting inpatient clinical deterioration and identifying the risk of early readmission among patients with exacerbations of COPD. Trial registration NCT01361451.

Parasternal electromyography to determine the relationship between patient-ventilator asynchrony and nocturnal gas exchange during home mechanical ventilation set-up

Introduction Patient-ventilator asynchrony (PVA) can adversely affect the successful initiation of non-invasive home mechanical ventilation (HMV). The aim of this observational study was to quantify the prevalence of PVA during initiation of HMV and to determine the relationship between PVA and nocturnal gas exchange. Method Type and frequency of PVA were measured by surface parasternal intercostal muscle electromyography, thoracoabdominal plethysmography and mask pressure during initiation of HMV. Severe PVA was defined, as previously, as asynchrony affecting ≥10% of breaths. Results 28 patients (18 male) were enrolled aged 61±15 years and with a body mass index of 35±9 kg/m2. Underlying diagnoses were neuromuscular disease with or without chest wall disease (n=6), obesity related chronic respiratory failure (n=12) and COPD (n=10). PVA was observed in all patients with 79% of patients demonstrating severe PVA. Triggering asynchrony was most frequent, observed in 24% (IQR: 11–36%) of breaths, with ineffective efforts accounting for 16% (IQR: 4–24%). PVA types were similar between disease groups, with the exception of auto-triggering, which was higher in patients with COPD (12% (IQR: 6–26%)). There was no correlation observed between PVA and time spent with oxygen saturations ≤90%, mean oxygen saturations or transcutaneous carbon dioxide levels during overnight ventilation. Conclusions Severe PVA was identified in the majority of patients, irrespective of pathophysiological disease state. This was not associated with ineffective ventilation as evidenced by gas exchange.

Current opinions on non-invasive ventilation as a treatment for chronic obstructive pulmonary disease

Purpose of review This review examines the current reports, the evidence and the issues surrounding the use of non-invasive ventilation (NIV) for the treatment of chronic obstructive pulmonary disease (COPD) in both the acute and domiciliary setting. Recent findings With the increasing use of NIV, more recent studies have focused on investigating the outcomes of our current practice. Although overall morbidity and mortality outcomes in the acute setting have improved, patients who initially stabilize but then deteriorate during an acute exacerbation of COPD have a poor prognosis. The focus must be on phenotyping this high-risk group to investigate other potential rescue treatments, including extracorporeal carbon dioxide removal. Indeed, phenotyping appears to favour the obese COPD patient, which may have a protective role in reducing the risk of NIV failure and recurrent hospital admissions. Randomized controlled trial evidence to support the use of NIV in a domiciliary setting as a treatment for COPD is awaited, and until the data from a number of ongoing clinical trials are available, the wide variation in global practice will continue. Increased understanding of patient ventilator asynchrony has improved domiciliary NIV set up, which is expected to enhance the tolerability of NIV, promoting patient adherence. Summary NIV is the established standard of care to treat acute hypercapnic exacerbations of COPD postoptimal medical management. NIV as a long-term treatment for COPD remains controversial based on the evidence from the published randomized controlled trials. With increasing experience of NIV therapy, patient outcomes are improving; however, further work is still required to better characterize and target the patients who will most benefit from NIV.

Hot Topics in Noninvasive Ventilation: Report of a Working Group at the International Symposium on Sleep-Disordered Breathing in Leuven, Belgium

During the last few decades, attention has increasingly focused on noninvasive ventilation (NIV) in the treatment of chronic respiratory failure. The University of Leuven and the University Hospitals Leuven therefore chose this topic for a 2-day working group session during their International Symposium on Sleep-Disordered Breathing. Numerous European experts took part in this session and discussed (1) NIV in amyotrophic lateral sclerosis (when to start NIV, NIV and sleep, secretion management, and what to do when NIV fails), (2) recent insights in NIV and COPD (high-intensity NIV, NIV in addition to exercise training, and NIV during exercise training), (3) monitoring of NIV (monitoring devices, built-in ventilator software, leaks, and asynchronies) and identifying events during NIV; and (4) recent and future developments in NIV (target-volume NIV, electromyography-triggered NIV, and autoregulating algorithms).

Safety and efficacy of auto-titrating noninvasive ventilation in COPD and obstructive sleep apnoea overlap syndrome

The deleterious effects of comorbid chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) have long been recognised and are frequently encountered as a clinical scenario [1, 2]. Although continuous positive airways pressure can be used in order to abolish upper airways obstruction in OSA, it can have adverse effects on pulmonary mechanics in patients with airways obstruction [3]. Auto-titrating modes of noninvasive ventilation (NIV) that monitor tidal volume, respiratory rate and upper airway patency and can vary back up rate, inspiratory and expiratory positive airway pressure (IPAP and EPAP, respectively) may have clinical benefits. However, these auto-titration modes and the software algorithms driving the ventilators are being engineered and modified at a rapid rate. The clinician, therefore, needs to be reassured that these novel modes have an established safety and efficacy profile. We hypothesised that auto-titrating NIV would enhance overnight gas exchange, sleep quality, and patient comfort when compared to standard fixed-level NIV in COPD-OSA patients with chronic respiratory failure. Auto-titrating NIV controls sleep disordered breathing and augments patient sleep comfort in COPD-OSA overlap http://ow.ly/NtL24

Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO): a pilot randomised controlled trial

Background Respiratory management of obesity hypoventilation syndrome (OHS) focusses on the control of sleep-disordered breathing rather than the treatment of obesity. Currently, there are no data from randomised trials of weight loss targeted rehabilitation programmes for patients with OHS. Intervention A 3-month multimodal hybrid inpatient–outpatient motivation, exercise and nutrition rehabilitation programme, in addition to non invasive ventilation (NIV), would result in greater per cent weight loss compared with standard care. Methods A single-centre pilot randomised controlled trial allocated patients to either standard care or standard care plus rehabilitation. Primary outcome was per cent weight loss at 12 months with secondary exploratory outcomes of weight loss, exercise capacity and health-related quality of life (HRQOL) at the end of the rehabilitation programme to assess the intervention effect. Results Thirty-seven patients (11 male, 59.8±12.7 years) with a body mass index of 51.1±7.7 kg/m2 were randomised. At 12 months, there was no between-group difference in per cent weight loss (mean difference −5.9% (95% CI −14.4% to 2.7%; p=0.17)). At 3 months, there was a greater per cent weight loss (mean difference −5% (95% CI −8.3% to −1.4%; p=0.007)), increased exercise capacity (6 min walk test 60 m (95% CI 29.5 to 214.5) vs 20 m (95% CI 11.5 to 81.3); p=0.036) and HRQL (mean difference SF-36 general health score (10 (95% CI 5 to 21.3) vs 0 (95% CI −5 to 10); p=0.02)) in the rehabilitation group. Conclusion In patients with OHS, a 3-month comprehensive rehabilitation programme, in addition to NIV, resulted in improved weight loss, exercise capacity and QOL at the end of the rehabilitation period, but these effects were not demonstrated at 12 months, in part, due to the limited retention of patients at 12 months. Trial registration number Pre-results; NCT01483716.

Comparative study of linear and curvilinear ultrasound probes to assess quadriceps rectus femoris muscle mass in healthy subjects and in patients with chronic respiratory disease

Introduction Ultrasound measurements of rectus femoris cross-sectional area (RFCSA) are clinically useful measurements in chronic obstructive pulmonary disease (COPD) and critically ill patients. Technical considerations as to the type of probe used, which affects image resolution, have limited widespread clinical application. We hypothesised that measurement of RFCSA would be similar with linear and curvilinear probes. Methods Four studies were performed to compare the use of the curvilinear probe in measuring RFCSA. Study 1 investigated agreement of RFCSA measurements using linear and curvilinear probes in healthy subjects, and in patients with chronic respiratory disease. Study 2 investigated the intra-rater and inter-rater agreement using the curvilinear probe. Study 3 investigated the agreement of RFCSA measured from whole and spliced images using the linear probe. Study 4 investigated the applicability of ultrasound in measuring RFCSA during the acute and recovery phases of an exacerbation of COPD. Results Study 1 showed demonstrated no difference in the measurement of RFCSA using the curvilinear and linear probes (308±104 mm2 vs 320±117 mm2, p=0.80; intraclass correlation coefficient (ICC)>0.97). Study 2 demonstrated high intra-rater and inter-rater reliability of RFCSA measurement with ICC>0.95 for both. Study 3 showed that the spliced image from the linear probe was similar to the whole image RFCSA (308±103.5 vs 263±147 mm2, p=0.34; ICC>0.98). Study 4 confirmed the clinical acceptability of using the curvilinear probe during an exacerbation of COPD. There were relationships observed between admission RFCSA and body mass index (r=+0.65, p=0.018), and between RFCSA at admission and physical activity levels at 4 weeks post-hospital discharge (r=+0.75, p=0.006). Conclusions These studies have demonstrated that clinicians can employ whole and spliced images from the linear probe or use images from the curvilinear probe, to measure RFCSA. This will extend the clinical applicability of ultrasound in the measurement of muscle mass in all patient groups.

Patient ventilator asynchrony and sleep disruption during non-invasive ventilation

Patient-ventilator asynchrony (PVA) are a common phenomenon affecting all patients receiving long-term domiciliary ventilation. The interruption of synchrony between the patient and the ventilator has been reported to be a possible cause of nocturnal sleep disruption leaking to arousals, awakenings and reduced periods of stage 3 and REM sleep overnight. The cause of PVA is multi-factorial driven frequently by leak at the interface, changing respiratory breathing patterns and changes in sleep stages. It currently remains unclear as to whether the PVA is the cause of sleep fragmentation or if PVA is purely a marker of unsuccessful ventilatory control, patient discomfort and underlying sleep disruption.

Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO)

Introduction We have previously shown that treatment of obesity hypoventilation syndrome (OHS) with non-invasive ventilation (NIV) results in weight reduction and an increase in physical activity (Murphy et al., 2012). We therefore hypothesised that a multi-modal rehabilitation programme, in addition to NIV, would lead to enhanced weight loss. Method We conducted a randomised controlled trial of NIV alone vs. NIV and a personalised rehabilitation programme in patients with OHS. Subjects in the intervention group received a bespoke diet and exercise regime, from a dietician and physiotherapist. All patients, in both groups, were reviewed monthly for 3 months. Anthropometrics, exercise capacity and health related quality of life (HQRL) were measured at baseline and at 3 months. The primary outcome measure at 3 months was weight loss. Secondary outcomes included: body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC) blood pressure (BP), rectus femoris cross-sectional area (RFCSA) and quadriceps maximal voluntary contraction (QMVC), 6 min walk distance (6MWD) and HRQL measures. Results 37 subjects were randomised with data from 30 patients analysed at 3 months (15 in each group). There were no differences between the groups in all parameters measured at baseline. The intervention group showed greater weight loss than the control group (-11.9 ± 6.7 vs. -2.4 ± 6.2 kg; p < 0.0001). There were also differences in NC, WC and HC (all p < 0.001, Table 1) with an improvement in BP observed in the intervention group (Table 1). In addition, there was an increase in weight corrected RFCSA and muscle strength (p < 0.0001, Table 1) with an increase in 6MWD in the intervention group (122 ± 161 vs. 46 ± 60 m; p = 0.005; Table 1). Finally, HRQL improved in the intervention group as evidenced by a greater reduction in Epworth sleepiness score, an increase in severe respiratory insufficiency questionnaire sum score and a greater decrease in the hospital and anxiety depression score (Table 1, all p < 0.0001).Abstract S30 Table 1 Changes in anthropometrics, blood pressure, peripheral muscle area, peripheral muscle strength and exercise capacity Conclusion In patients with OHS, the addition of a hospital-home hybrid personalised diet and exercise programme to standard NIV was shown to enhance weight loss as well as, skeletal muscle area and strength, exercise capacity and HRQL. Reference 1 Murphy PB, Davidson C, Hind MD, et al. Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial. Thorax. 2012;67:727–34

S87 The effect of on patient comfort and neural respiratory drive (NRD) of ventilator trigger delay during non-invasive ventilation (NIV)

Introduction Optimising patient-ventilator interaction (PVI) has been shown to enhance patient comfort and respiratory muscle unloading. A major cause of poor PVI is ventilator trigger delay, defined as an extended response time in the delivery of airway pressure following initiation of inspiratory effort by the patient. Although bench tests of ventilators have demonstrated variation in trigger response times (120–500ms), there are limited data reporting the effect of trigger delay on a subject’s NRD and comfort. We therefore investigated the relationship between ventilator trigger delay, NRD and comfort perception. Methods A custom-made NIPPY3 + ventilator (B&D Electromedical, Stratford-upon-Avon, UK) with modifiable trigger delay was used. A standardised protocol of 10cm H20 inspiratory positive airway pressure, 4cm H20 expiratory positive airway pressure and back up rate of 6 breaths per minute was utilised in healthy subjects familiarised with NIV. Subjects were blinded to the settings and asked to assess perceived comfort using a visual analogue score (VAS) at 20 randomised trigger delay timings ranging from 10ms to 1000ms following a 2 minute assessment period. Second intercostal space electromyography (EMGpara%max), as a marker of NRD, mask pressure and flow were used to assess PVI. Transcutaneous carbon dioxide and oxygen saturations were controlled within limits of 0.5 kPa and 4% respectively of the subject’s baseline values to minimise changes in the biochemical drive to breathe. Results 5 subjects (1 male) were enrolled to date with a mean age of 34 ± 8years, BMI 22 ± 3kgm2, FEV1 105 ± 11%predicted and FVC 114 ± 13%predicted. 500 breaths were analysed. The EMGpara%max was lowest at a trigger delay setting of 400ms 5.9%(4.8–8.0) and largest at a trigger delay of 800ms 10.1%(6.0–16.5). (Figure 1). There was a corresponding decrease in the VAS score from 78cm (63.5–92.5) at 400ms trigger delay to 47cm (30–66) at 1000ms trigger delay. The highest comfort score was 89cm (52–92) observed at 170ms trigger delay. Abstract S87 Figure 1. Graph representing the changes in comfort and neural respiratory drive with increasing trigger delay Conclusion This is the first study to comprehensively investigate NIV trigger delay in healthy subjects. Based on NRD, these data suggest that the optimal NIV trigger response time was up to 400ms. This challenges previous bench studies that reported ventilators with response times over 100–150ms have limited clinical utility.