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      Noninvasive mechanical ventilation with high pressure strategy remains a “double edged sword”?

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          Dear editor We read with great interest the original work by Murphy et al analyzing the effects of two treatment strategies for delivery of noninvasive mechanical ventilation in hypercapnic patients with chronic obstructive pulmonary disease.1 High pressure and high intensity noninvasive mechanical ventilation were compared in a short-term crossover trial to assess whether high intensity noninvasive mechanical ventilation (inspiratory pressure > 25 cm H2O associated with a high backup ventilator rate) may improve adherence, physiological, and subjective outcomes when compared with delivery of high pressure noninvasive mechanical ventilation (without elevated backup respiratory rate). The authors concluded that both strategies are equivalent in all the recorded outcomes, showing thus that driving pressure, but not backup respiratory rate, is essential to gain physiological and clinical benefits in this population when in a chronic stable condition. Despite previous randomized studies showing the potential benefits of long-term noninvasive mechanical ventilation in hypercapnic patients with chronic obstructive pulmonary disease, current research has still not clearly indicated the best strategy to improve the patient’s adherence with treatment.2,3 Overall, dropout during noninvasive mechanical ventilation remains a serious clinical problem.4 This study provides valuable information in this regard, suggesting that sufficiently high-pressure delivery is enough to achieve useful clinical and physiological goals. This notwithstanding, we believe that some of the expectations following the adoption of these different noninvasive mechanical ventilation strategies have not been adequately addressed in the present study. Therefore, we consider that it would be useful, from a practical point of view, to underline some points in this regard. First, the authors did not determine what effects the highest respiratory backup rate used in their study may have had. Although there have been no major studies published on application of high levels of backup that have proved to be useful in patients with severe chronic obstructive pulmonary disease, this is the best indication for hypoventilation syndromes, ie, obesity and overlap syndromes. In fact, we cannot exclude that addition of a high backup respiratory rate may help to resolve “overlap” when present at a subclinical level in patients with chronic obstructive pulmonary disease, or that it has not been adequately assessed before. However, it seems that the authors selected backup respiratory rate levels on a clinical basis without any physiological assessment in their study population. Despite patients in the present study not appearing to show any abnormal increase in their body mass index, the extrapolated conclusion of a lack of additional benefit from a well assessed strategy, including adequate backup respiratory rate, cannot be firmly excluded in such “extreme” cases.5 Second, there was a lack of complementary tests in this study that might have helped in analysis of the data. Indeed, the authors selected patients with a FEV1 (forced expiratory volume in one second) that could worsen with high backup and pressure, especially with the auto-positive end-expiratory pressure mechanism. It is not clear how selection of expiratory-positive airway pressure was made in the study population. Similarly, the authors did not take into account any potential auto-positive end-expiratory pressure effects during the 6-week period of observation. Third, the authors arbitrarily selected a population of hypercapnic patients with chronic obstructive pulmonary disease (daytime PaCO2 > 6 kPa) which would not be universally recognized as the most appropriate in terms of risk of frequency of exacerbations and clinical instability, and it is not clear whether any other additional clinical factors behind cardiac dysfunction may have interfered at admission or over the study period.6 Indeed, three of the five patients who withdrew did so because of factors other than mere mask/pressure intolerance (see Table E1).1 Final, there was no analysis of potential implications of air leakage in the observed results. No mention was made of measurement or monitoring of leakage during application of noninvasive mechanical ventilation. This aspect could have been potentially relevant and interfered with the results, especially during application of such high-pressure delivery, which is known to increase mask leakages.4 To conclude, we recognize that the paper by Murphy et al1 will add information to the complex process of setting and titration of noninvasive mechanical ventilation in the population of stable hypercapnic patients with chronic obstructive pulmonary disease. However, given the observations discussed, we are convinced that further studies of longer duration and including larger numbers of patients are needed to determine which physiological effects should be assessed and expected during application of both strategies. Currently, high-pressure strategies remain a “double edged sword” in daily practice.

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          Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial.

          Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD. A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) 46 mm Hg and on LTOT for at least 3 months) and age 20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood. 144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01-5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and PaCO2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour. Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life. ACTRN12605000205639.
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            The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients.

            Chronic obstructive pulmonary disease (COPD) patients with chronic ventilatory failure (CVF) are more likely to develop exacerbations, which are an important determinant of health-related quality of life (HRQL). Long-term noninvasive positive-pressure ventilation (NPPV) has been proposed in addition to long-term oxygen therapy (LTOT) to treat CVF but little information is available on its effects on HRQL and resource consumption. Therefore, the current authors undertook a 2-yr multicentric, prospective, randomised, controlled trial to assess the effect of NPPV+ LTOT on: 1) severity of hypercapnia; 2) use of healthcare resources, and 3) HRQL, in comparison with LTOT alone. One hundred and twenty-two stable hypercapnic COPD patients on LTOT for > or = 6 months were consecutively enrolled. After inclusion and 1-month run-in, 90 patients were randomly assigned to NPPV+LTOT (n=43) or to LTOT alone (n=47). Arterial blood gases, hospital and intensive care unit (ICU) admissions, total hospital and ICU length of stay and HRQL were primary outcome measures; survival and drop-out rates, symptoms (dyspnoea and sleep quality) and exercise tolerance were secondary outcome measures. Follow-up was performed at 3-month intervals up to 2 yrs. Lung function, inspiratory muscle function, exercise tolerance and sleep quality score did not change over time in either group. By contrast the carbon dioxide tension in arterial blood on usual oxygen, resting dyspnoea and HRQL, as assessed by the Maugeri Foundation Respiratory Failure Questionnaire, changed differently over time in the two groups in favour of NPPV+LTOT. Hospital admissions were not different between groups during the follow-up. Nevertheless, overall hospital admissions showed a different trend to change in the NPPV+LTOT (decreasing by 45%) as compared with the LTOT group (increasing by 27%) when comparing the follow-up with the follow-back periods. ICU stay decreased over time by 75% and 20% in the NPPV+LTOT and LTOT groups, respectively. Survival was similar. Compared with long-term oxygen therapy alone, the addition of noninvasive positive-pressure ventilation to long-term oxygen therapy in stable chronic obstructive pulmonary disease patients with chronic ventilatory failure: 1) slightly decreased the trend to carbon dioxide retention in patients receiving oxygen at home and 2) improved dyspnoea and health-related quality of life. The results of this study show some significant benefits with the use of nocturnal, home noninvasive positive-pressure ventilation in patients with chronic ventilatory failure due to advanced chronic obstructive pulmonary disease patients. Further work is required to evaluate the effect of noninvasive positive-pressure ventilation on reducing the frequency and severity of chronic obstructive pulmonary disease exacerbation.
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              High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial.

              The conventional approach of low-intensity non-invasive positive pressure ventilation (NPPV) produces only minimal physiological and clinical benefits in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). To determine whether the novel approach of high-intensity NPPV is superior to low-intensity NPPV in controlling nocturnal hypoventilation. A randomised controlled crossover trial comparing 6 weeks of high-intensity NPPV (using controlled ventilation with mean inspiratory pressures of 28.6+/-1.9 mbar) with low-intensity NPPV (using assisted ventilation with mean inspiratory pressures of 14.6+/-0.8 mbar) was performed in 17 patients with severe stable hypercapnic COPD. Two patients refused low-intensity NPPV and two patients dropped out while on low-intensity NPPV. Thirteen patients (mean forced expiratory volume in 1 s (FEV(1)) 0.76+/-0.29 l) completed the trial. High-intensity NPPV produced higher pneumotachographically-measured expiratory volumes, with a mean treatment effect of 96 ml (95% CI 23 to 169) (p=0.015). This resulted in a mean treatment effect on nocturnal arterial carbon dioxide tension (Paco(2)) of -9.2 mm Hg (95% CI -13.7 to -4.6) (p=0.001) in favour of high-intensity NPPV. Daily use of NPPV was increased in high-intensity NPPV compared with low-intensity NPPV, with a mean difference of 3.6 h/day (95% CI 0.6 to 6.7) (p=0.024). In addition, compared with baseline, only high-intensity NPPV resulted in significant improvements in exercise-related dyspnoea, daytime Paco(2), FEV(1), vital capacity and the Severe Respiratory Insufficiency Questionnaire Summary Score. High-intensity NPPV is better tolerated by patients with severe chronic hypercapnic COPD and has been shown to be superior to the conventional and widely-used form of low-intensity NPPV in controlling nocturnal hypoventilation. High-intensity NPPV therefore offers a new promising therapeutic option for these patients.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                27 May 2013
                : 8
                : 255-256
                [1 ]Intensive Care Unit, Hospital Morales Meseguer, Murcia,
                [2 ]Department of Medical and Surgical Sciences, University of Modena, Pavullo-Modena, Italy
                [1 ]Lane Fox Clinical Respiratory Physiology Group, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
                [2 ]Department of Thoracic Medicine, King’s College Hospital, London, UK
                [3 ]Sleep and Ventilation Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UK
                [4 ]Guy’s and St Thomas’ NHS Foundation Trust and Kings College London NIHR Comprehensive Biomedical Research Centre, London, UK
                Author notes
                Correspondence: Antonio M Esquinas, Intensive Care Unit, Hospital Morales Meseguer, Avenida Marques Velez s/n, Murcia, 30008, Spain, Email antmesquinas@
                Correspondence: Patrick Murphy, Lane Fox Respiratory Unit, St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH, UK, Tel +44 20 7188 8070, Fax +44 20 7188 6116, Email patrick.b.murphy@
                © 2013 Esquinas et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.


                Respiratory medicine


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