American Journal of Respiratory and Critical Care Medicine

What are the risk factors for recurrent exacerbations of hypercapnic respiratory failure, and how do we minimize them? Although there is frequently emphasis on controlling arterial blood gas tensions and reducing pulmonary infection, in this issue of the Journal, Adler and colleagues (pp. 200–207) have now shown the importance of systematic evaluation for comorbidities in both patients with chronic obstructive pulmonary disease (COPD) and patients without COPD who have experienced a severe hypercapnic exacerbation requiring intensive care unit (ICU) admission (1). Importantly, they have demonstrated that these comorbidities are not only underrecognized, despite patients being frequently hospitalized, but may be associated with poor outcome.

In a prospective, single-center study, the authors assessed pulmonary function, cardiac function using echocardiography, and the presence of sleep-disordered breathing using polysomnography in 78 consecutive chronic respiratory patients discharged from ICU after a hypercapnic exacerbation necessitating mechanical ventilation (invasive or noninvasive). Patients without COPD predominantly had obesity hypoventilation syndrome. Heart failure with preserved ejection fraction was found to be previously undiagnosed in 44% of patients, and hypertension had not been recognized before admission in 67%. The prevalence of severe obstructive sleep apnea (OSA) was surprisingly high in patients with COPD, at 51%, with an even greater prevalence in patients without COPD, at 81%.

Only a minority of patients with COPD had previously been diagnosed on spirometry, although a third of the total population had previously been hospitalized for respiratory failure. More than half of the patients studied had three or more morbidities (e.g., COPD, heart failure, obesity, and severe OSA). Multiple morbidities were associated with longer hospital admissions, and there was a trend to higher hospital-free survival in those with fewer comorbidities compared with those with a greater number of comorbidities.

How applicable are these results to general ICU practice and acute pulmonary care? As investigations for comorbidity were carried out after the index admission, only survivors could be studied, and it is not clear how representative they are of the total group admitted to ICU. Indeed, around 18% of the 197 patients screened for eligibility were not admitted to ICU, as the outcome was judged likely to be poor or futile (life expectancy estimated at <3 months), so coexisting problems are likely to be even more prevalent in this group with acute hypercapnic decompensation. Median pH on admission for the total patient cohort was 7.29 (interquartile range, 7.23–7.34), and in some centers, patients with a pH >7.26 would be managed with noninvasive ventilation (NIV) on acute pulmonary wards or high-dependency units, and not admitted to ICU (2, 3). There was no difference in outcome in patients treated with NIV or invasive ventilation, but only a minority required the latter.

Although pulmonary function tests were performed in all patients, 41 of 78 patients were unable to attend a sleep laboratory for polysomnography 3 months after discharge. The members of this group were older than those who did undergo polysomnography, which may have caused an underestimate of degree of sleep-disordered breathing. In a small subset of patents, simpler respiratory polygraphy was successfully performed, and as this may be sufficient for diagnosis of OSA, polygraphy rather than polysomnography may be a more practical and cost-effective solution to maximize the diagnosis of OSA. It is notable that only 29% of patients had previously been diagnosed with OSA, and less than a third with such a finding were being treated with continuous positive airway pressure or NIV before admission.

There was a preexisting diagnosis of heart failure in 21% of patients. In the 57/78 patients who underwent echocardiography postdischarge, the most notable finding was of heart failure with preserved ejection fraction in 44% (95% confidence interval, 31–58%). Right ventricular dilation was highly prevalent, at 42% in both COPD and non-COPD groups.

A limitation of the study is that the non-COPD group primarily consisted of obese patients, and other causes of hypercapnic respiratory failure such as neuromuscular disease were excluded. However, the prevalence of obesity in the Western world is increasing rapidly, and in many countries, obesity hypoventilation syndrome is now the prime indication for long-term NIV (46). The authors have extensive experience in home NIV and report that 67% of patients with multiple comorbidities were discharged with home NIV or continuous positive airway pressure, and a significant number of those with fewer comorbidities also received home ventilatory support. This high use of home NIV may not be representative of ventilatory practice in other centers, but the use of home continuous positive airway pressure or NIV did not seem to decrease or prevent readmissions.

Until recently, the evidence that home NIV in COPD influences survival and readmissions has been mixed. Köhnlein and colleagues (7) showed that long-term NIV improved survival and health-related quality of life in chronically hypercapnic patients with COPD, but Struik and colleagues (8) found no advantage to discharging patients on home NIV after an acute hypercapnic exacerbation, probably because these individuals were still recovering with normalization of Pco2 in the weeks postdischarge. Early results from a further trial (HOT-HMV UK [Home Oxygen Therapy–Home Mechanical Ventilation UK]) (9), in which patients were randomly assigned to NIV plus long-term oxygen therapy or long-term oxygen therapy alone after an acute hypercapnic exacerbation if hypercapnia persisted more than 2 weeks after discharge, have shown a considerable benefit in reducing admissions/death in the NIV group. This persistently hypercapnic COPD group seems to be a relatively small severe subgroup. Interestingly, arterial Pco2 on discharge in both patients with COPD and patients without COPD in the current study by Adler and colleagues (1) was normal, but that is likely to be influenced by ongoing NIV use in many patients. In patients with obesity hypoventilation, as the authors point out, there is evidence from cohort series that patients receiving long-term NIV experience a correction of sleep-disordered breathing and arterial blood gas tensions. However, the role of comorbidities is evident, as cardiovascular risk remains high despite NIV (10), and in one series of patients with obesity hypoventilation with acute or chronic hypercapnic respiratory failure treated with NIV, use of cardiovascular medication was the only factor independently associated with a higher risk for mortality (11).

Although the authors convincingly demonstrate that comorbidities are significantly underdiagnosed, the data on whether treatment of these reduces readmission are less convincing, although a trend in reduction was seen, and crucially, symptom relief from optimizing the management of heart failure, chronic airflow obstruction, and sleep-disordered breathing is likely to improve quality of life. It remains clear, however, that a focus on simply correcting arterial blood gas tensions both acutely and long term, without understanding the contribution of comorbidities to current and future illness trajectory, is a missed opportunity.

1. Adler D, Pépin J-L, Dupuis-Lozeron E, Espa-Cervena K, Merlet-Violet R, Muller H, Janssens J-P, Brochard L. Comorbidities and subgroups of patients surviving severe acute hypercapnic respiratory failure in the intensive care unit. Am J Respir Crit Care Med 2017;196:200207.
2. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet 2000;355:19311935.
3. Carlucci A, Delmastro M, Rubini F, Fracchia C, Nava S. Changes in the practice of non-invasive ventilation in treating COPD patients over 8 years. Intensive Care Med 2003;29:419425.
4. Janssens JP, Derivaz S, Breitenstein E, De Muralt B, Fitting JW, Chevrolet JC, Rochat T. Changing patterns in long-term noninvasive ventilation: a 7-year prospective study in the Geneva Lake area. Chest 2003;123:6779.
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6. Garner DJ, Berlowitz DJ, Douglas J, Harkness N, Howard M, McArdle N, Naughton MT, Neill A, Piper A, Yeo A, et al. Home mechanical ventilation in Australia and New Zealand. Eur Respir J 2013;41:3945.
7. Köhnlein T, Windisch W, Köhler D, Drabik A, Geiseler J, Hartl S, Karg O, Laier-Groeneveld G, Nava S, Schönhofer B, et al. Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial. Lancet Respir Med 2014;2:698705.
8. Struik FM, Sprooten RT, Kerstjens HA, Bladder G, Zijnen M, Asin J, Cobben NA, Vonk JM, Wijkstra PJ. Nocturnal non-invasive ventilation in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure: a randomised, controlled, parallel-group study. Thorax 2014;69:826834.
9. Murphy PB, Rehal S, Arbane G, Bourke S, Calverley PMA, Crook AM, Dowson L, Duffy N, Gibson GJ, Hughes PD, et al. Effect of noninvasive ventilation with oxygen therapy vs oxygen therapy alone on hospital readmission or death after an acute COPD exacerbation: a randomized clinical trial. JAMA [online ahead of print] 21 May 2017; DOI:10.1001/jama.2017.4451.
10. Borel J-C, Tamisier R, Gonzalez-Bermejo J, Baguet J-P, Monneret D, Arnol N, Roux-Lombard P, Wuyam B, Levy P, Pépin JL. Noninvasive ventilation in mild obesity hypoventilation syndrome: a randomized controlled trial. Chest 2012;141:692702.
11. Borel J-C, Burel B, Tamisier R, Dias-Domingos S, Baguet JP, Levy P, Pepin JL. Comorbidities and mortality in hypercapnic obese under domiciliary noninvasive ventilation. PLoS One 2013;8:e52006.

Author disclosures are available with the text of this article at

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American Journal of Respiratory and Critical Care Medicine

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