Nicholas Oscroft

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial

Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (PaCO2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] PaCO2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; Pu2009=u2009.002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration clinicaltrials.gov Identifier: NCT00990132

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6u2005weeks of treatment with three non-adjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4u2005weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20u2005000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39u2005800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice. Trial registration number ISRCTN02309506.

A Randomised Crossover Trial Comparing Volume Assured and Pressure Preset Noninvasive Ventilation in Stable Hypercapnic COPD

ABSTRACT Recent randomised controlled trials suggest non-invasive ventilation may offer benefit in the long-term management of ventilatory failure in stable COPD. The best mode of ventilation is unknown and newer volume assured modes may offer advantages by optimising ventilation overnight when treatment is delivered. This study compares volume assured with pressure preset non-invasive ventilation. Randomised crossover trial including twenty five subjects previously established on long-term non-invasive ventilation to manage COPD with chronic ventilatory failure. Two 8-week treatment periods of volume assured and pressure preset non-invasive ventilation. The primary outcomes were daytime arterial blood gas tensions and mean nocturnal oxygen saturation. Secondary outcomes included lung function, exercise capacity, mean nocturnal transcutaneous carbon dioxide, health status and compliance. No significant differences were seen in primary or secondary outcomes following 8 weeks of treatment when comparing volume assured and pressure preset ventilation. Primary outcomes assessed: mean (standard deviation) PaO2 7.8 (1.2) vs 8.1(1) kPa, PaCO2 6.7 (1.1) vs 6.3 (1.2) kPa and mean nocturnal oxygenation 90 (4) vs 91 (3)% volume assured versus pressure preset, respectively. Volume assured and pressure preset non-invasive ventilation appear equally effective in the long-term management of ventilatory failure associated with stable COPD.

A bench test to confirm the core features of volume-assured non-invasive ventilation.

Background and objective:u2003 Volume‐assured non‐invasive positive pressure ventilation (va‐NIPPV) is a novel mode designed to adapt pressure support (PS) to achieve a target minute ventilation (TgV). This may optimize ventilation; however, no data confirm that va‐NIPPV compensates appropriately for the changes in pulmonary mechanics and circuit leak seen in clinical practice. Bench testing assessed these principles.

Volume assured versus pressure preset non-invasive ventilation for compensated ventilatory failure in COPD

BACKGROUNDnThe addition of domiciliary non-invasive ventilation (NIV) to standard therapy in chronic obstructive pulmonary disease (COPD) patients with compensated ventilatory failure (CVF) is reported to have beneficial effects. Compliance with NIV is an important factor. Volume assured NIV (va-NIV) may improve compliance and ventilation during sleep by automatically titrating ventilatory pressures.nnnMETHODSnA prospective single centre, randomised, parallel group trial comparing va-NIV and pressure preset NIV (pp-NIV) in COPD patients with CVF naïve to domiciliary NIV was performed (ISCRTN91892415). The primary outcomes were arterial blood gases, mean overnight oximetry (mSpO2) and compliance after three months. Secondary outcomes included pulmonary function, exercise capacity and health-related quality of life assessment.nnnRESULTSnForty patients were randomised in a 1:1 ratio. The va-NIV median target minute ventilation was 8.4xa0L/min and pp-NIV median inspiratory pressure was 28 cmH2O. There were no significant differences between groups in primary or secondary outcomes after three months. Mean (SD) PaO2 8.7 (1.7) versus 7.9 (1.7) kPa (pxa0=xa00.19), PaCO2 6.7 (0.5) versus 7.3 (1.1) kPa (pxa0=xa00.1), mSpO2 89.7 (4.2) versus 89.8 (3.9) % (pxa0=xa00.95), compliance 5.0 (3.1) versus 4.7 (3.2) hours (pxa0=xa00.8) in va-NIV versus pp-NIV respectively. Patients allocated va-NIV spent fewer days in hospital initiating therapy 3.3 (1.6) versus 5.2 (2.8) (pxa0=xa00.02). Both groups showed significant improvements in PaCO2 and mSpO2 after three months treatment.nnnCONCLUSIONSnDomiciliary va-NIV and pp-NIV have similar effects on physiological outcomes in COPD patients with CVF and both are well tolerated.

Long‐term non‐invasive ventilation to manage persistent ventilatory failure after COPD exacerbation

Background and objective:u2003 Patients with ventilatory failure at discharge from hospital following an exacerbation of COPD (ECOPD) have increased work of breathing and reduced inspiratory muscle strength compared with those with a normal arterial carbon dioxide tension (PaCO2). They also have a significantly worse prognosis. Long‐term non‐invasive positive pressure ventilation (NIPPV) may offer a treatment strategy but benefits have not been established.

Weaning from prolonged invasive ventilation in motor neuron disease: analysis of outcomes and survival

Introduction Non-invasive ventilation (NIV) improves prognosis in patients with motor neuron disease (MND) in the absence of major bulbar involvement. However, some experience a rapid and unexpected decline in respiratory function and may undergo emergency tracheal intubation. Weaning from invasive ventilation can be difficult, and reported independence from invasive ventilation is uncommon with poor prognosis. The outcomes of patients with MND referred to a specialist weaning service following emergency tracheal intubation were examined and compared with MND patients electively initiating NIV. Methods A case note review was performed on all patients with MND invasively ventilated and referred to a specialist weaning service between 1992 and 2007. Outcomes were compared with those electively commenced on NIV during the same period. Results Thirty patients were referred for weaning from invasive ventilation which was started in 17 before MND was diagnosed. Fourteen patients (47%) were weaned from invasive ventilation but still required NIV, 13 failed to wean, and three died. Seventeen were discharged home from hospital. The median survival from tracheal intubation was 13.7 months (95% CI 0 to 30.8) for those previously diagnosed and 7.2u2005months (95% CI 5.1 to 9.4) for those not previously known to have MND. Comparison with patients initiated electively on NIV demonstrated similar survival estimates to that from emergency intubation (median 9.4 (95% CI 6.9 to 12.0) vs 7.8 (95% CI 2.6 to 12.9) months respectively). Conclusion The prognosis in MND following acute respiratory failure and intubation is not always complete ventilator dependence if patients are offered a comprehensive weaning programme.

The impact of changing people with sleep apnea using CPAP less than 4 h per night to a Bi-level device.

Pressure intolerance is a reason for poor acceptance and subsequent compliance in some patients starting treatment with continuous positive airway pressure (CPAP). In unselected populations initiating CPAP; different types of pressure generating device have not been found to improve compliance. We hypothesized that using Bi-level PAP for patients who reported pressure related discomfort as a cause for poor compliance with CPAP might increase their hours of treatment use. Patients using CPAP <4 h/night with symptoms to suggest pressure intolerance were randomized to receive either a Bi-level PAP device or a new CPAP for 4 weeks. Following a washout period of 2 weeks, they were crossed over to the other device for 4 weeks. Twenty eight volunteers completed the protocol. Compared to the baseline (mean 1.49 h per night), improvement in compliance was noticed when changed to a new CPAP (2.23 h, p = 0.006) or Bi-level PAP (2.73 h, p < 0.001). The trend suggesting superior compliance with a Bi-level PAP device compared to new CPAP was not significant (p = 0.059) and there were no differences in subjective or objective measures of sleepiness. The results of this study suggest that routine intervention with Bi-level PAP in this group of sub-optimally compliant individuals was not very effective in improving PAP usage. There is however a subgroup of patients who complains of difficulty with exhalation; where favorable trends towards improved compliance were observed on Bi-level PAP.

The effects of withdrawing long-term nocturnal non-invasive ventilation in COPD patients.

ABSTRACT Patients with ventilatory failure due to chronic obstructive pulmonary disease (COPD) are increasingly managed with long-term non-invasive positive pressure ventilation (NIPPV) and this may improve survival. NIPPV can frequently be interrupted but there are few data detailing the short-term effects and none on the longer-term consequences of treatment withdrawal. Ten patients withdrew from NIPPV for 1 week and were randomised to restart NIPPV or to continued withdrawal for up to 6 months. Outcomes assessed included daytime blood gases, nocturnal ventilation, lung function, exercise capacity and health status. After 1 week of withdrawal PaO2, PaCO2, nocturnal oximetry, lung function and exercise capacity did not change, but mean nocturnal transcutaneous CO2 (6.3 (1) vs. 7.6 (1.1) kPa p = 0.04) and daytime blood gas bicarbonate (30.3 (4.5) vs. 31.2 (3.9) mmol/L p = 0.04) rose. During a 6-month period of withdrawal of nocturnal NIPPV, daytime PaCO2 (6 (1.1) vs. 7.5 (1.3) kPa p = 0.002) increased and health status (total St Georges Respiratory Questionnaire score 55.5 (6.3) vs. 65.6 (10) p = 0.006) worsened. Three out of five patients met a priori criteria to restart NIPPV in the continued withdrawal group. Short interruptions to domiciliary NIPPV used to manage chronic ventilatory failure as a consequence of COPD do not cause a rapid clinical deterioration but nocturnal ventilation worsens and daytime bicarbonate levels increase following 1 weeks cessation. Thereafter, daytime PaCO2 rises and health status worsens, supporting the role of long-term NIPPV in the management of such patients.

Hospital outcomes and long-term survival after referral to a specialized weaning unit

Background.nProlonged invasive mechanical ventilation (IMV) is a frequent challenge, and an increasing number of patients are transferred from intensive care units to long-term acute care hospitals or specialized weaning units. There are few published data for discharge home rates, use of noninvasive ventilation (NIV), or long-term survival.nnnMethods.nA case-note and database review was conducted of patients admitted to a UK national specialized weaning unit for weaning from IMV between 1992 and 2012. Patients were grouped into diagnostic categories according to the predominant cause of weaning failure. Weaning outcomes and long-term survival were assessed according to diagnostic group and mode of ventilation on discharge.nnnResults.nFour hundred and fifty-eight patients were transferred for weaning from IMV. Four hundred and seventeen (91%) survived to hospital discharge, of whom at least 343 (82%) were ultimately discharged to their own home. Three hundred and thirty (72%) weaned from IMV, of whom 142 weaned from all ventilation and 188 weaned to nocturnal NIV. Weaning success was highest for patients with chronic obstructive pulmonary disease and chest wall disorders. Median survival from unit discharge was 25 months (interquartile range 5-74), with the longest survival seen for patients discharged with nocturnal NIV [37 (12-81) months].nnnConclusions.nThese results confirm successful weaning outcomes for patients transferred to a specialized weaning and long-term ventilation service. In contrast to other service models, most patients achieved discharge to their own home.