NIHR Signal Use of a facemask ventilator can reduce deaths in severe flare-ups of COPD

Published on 19 September 2017

People admitted to hospital with a severe exacerbation of chronic obstructive pulmonary disease (COPD) were 46% less likely to die if they received non-invasive ventilation. Only 12% of those receiving non-invasive ventilation needed subsequent invasive ventilation via a tube, compared to 34% of those who had usual care.

This review identified 17 trials of adults with a severe acute exacerbation of COPD with high carbon dioxide levels. Trials compared usual care, including steroids and antibiotics with usual care plus non-invasive ventilation, which delivers air at high pressure via a mask. Airways are forced open and respiratory muscles can rest.

This updated review shows benefits of immediate treatment with non-invasive ventilation for people with COPD admitted with respiratory failure. The results do not apply to patients in respiratory failure from other causes.

Acceptability of the treatment to patients, quality of life and cost measures need further exploration.

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Why was this study needed?

Chronic obstructive pulmonary disease (COPD) affects about three million people in the UK, mostly smokers over 40 years old. It accounts for about 30,000 deaths annually and costs the NHS £1.9 billion per year.

COPD is an irreversible condition. It incorporates emphysema (damage to the lung air sacs), and chronic bronchitis (long-term airways inflammation). An exacerbation of COPD causes severe breathlessness, confusion, low blood oxygen levels and can cause high carbon dioxide levels.

Non-invasive ventilation pushes air into the lungs via a facemask. Unlike invasive ventilation, patients are not sedated and do not need a tube inserted into the windpipe. There is a lower risk of complications, such as pneumonia than with invasive ventilation.

Non-invasive ventilation is increasingly being used for people admitted to hospital with acute exacerbations of COPD in severe respiratory failure. This review aimed to gather evidence on the effectiveness of this approach.

What did this study do?

This systematic review found 17 randomised controlled trials involving 1,264 adults admitted to hospital with a severe exacerbation of chronic obstructive pulmonary disease. This was defined as a low blood pH (less than 7.35) and high levels of carbon dioxide (6kPa or more).

Non-invasive ventilation was delivered with a Bilevel Positive Airway Pressure machine on a hospital ward. Usual care involved typical medical treatment without ventilation. People with pneumonia were excluded.

The review looked primarily at mortality during the hospital admission and the need to insert a tube into the windpipe.

The evidence was rated as moderate quality. The intervention made blinding difficult although this was unlikely to affect the primary objective outcomes. Treatment duration and the type of ward setting varied somewhat between studies.

What did it find?

  • Participants who received ventilation were 46% less likely to die during that hospital admission than those who just received usual care (risk ratio [RR] 0.54, 95% confidence interval [C.I] 0.38 to 0.76). During the 10% (42/434) of participants who received ventilation and usual care died compared with 18% (77/420) who received usual care. This pooled analysis was from 12 studies.
  • Intubation was required by 12% (67/559) people who received ventilation, compared with 34% (186/546) of those with usual care alone (RR 0.36, 95% CI 0.28 to 0.46). These results were from 17 studies.
  • Pooled results from ten studies involving 888 participants found that people who initially received ventilation stayed in the for on average 14.1 days compared to 17.5 days for usual care alone (mean difference -3.39, 95% CI -5.93 to -0.85).
  • Six studies, 346 participants, found that people were less likely to tolerate non-invasive ventilation than usual care. This result given the nature of ventilation delivery (risk difference 0.11, 95% CI 0.04 to 0.17).

What does current guidance say on this issue?

NICE 2010 guidance recommends using non-invasive ventilation as the treatment of choice for persistent respiratory failure despite optimal medical therapy. It should be delivered in a dedicated setting with trained staff who are experienced in its use. There should be a clear plan covering what to do in the event of deterioration and ceilings of therapy should be agreed. The 2008 guideline from the Royal College of Physicians, British Thoracic Society and Intensive Care Society recommends that non-invasive ventilation should be considered if the blood acidity remains low despite a maximum of one hour of standard medical therapy.

What are the implications?

This review suggests that prompt non-invasive ventilation during admission could save lives and avoid invasive ventilation. This may have training implications as it should only be delivered by staff proficient in its use and who understand its limitations. There may also be issues around availability of Bilevel Positive Airways Pressure machines.

The results don’t apply to people who are coming off invasive ventilation therapy or those in respiratory failure not due to chronic obstructive pulmonary disease.

There was no cost analysis, but reduced hospital stays suggest potential financial savings. It would be useful to see patient-centred outcomes in the future including the acceptability of these devices and quality of life.

Citation and Funding

Osadnik CR, Tee VS, Carson-Chahhoud KV, et al. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7:CD004104.

This project was funded by the National Institute for Health Research via Cochrane infrastructure funding to the Cochrane Airways Group.

Bibliography

British Lung Foundation. Estimating the economic burden of respiratory illness in the UK. London: British Lung Foundation; 2017.

National Clinical Guideline Centre. Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre; 2010.

NCEPOD. Acute Non-Invasive Ventilation: Inspiring Change. London: National Confidential Enquiry into Patient Outcome and Death; 2017.

NHS Choices. Chronic obstructive pulmonary disease (COPD). London: Department of Health; 2016.

NICE. Chronic Obstructive Pulmonary Disease in over 16s: diagnosis and management. CG101. London: National Institute for Health and Care Excellence; 2010.

Patient. Chronic Obstructive Pulmonary Disease. Leeds: Patient; 2015.

Royal College of Physicians, British Thoracic Society, Intensive Care Society. Chronic obstructive pulmonary disease: non-invasive ventilation with bi-phasic positive airways pressure in the management of patients with acute type 2 respiratory failure. Concise Guidance to Good Practice series, No 11. London: RCP; 2008.

Why was this study needed?

Chronic obstructive pulmonary disease (COPD) affects about three million people in the UK, mostly smokers over 40 years old. It accounts for about 30,000 deaths annually and costs the NHS £1.9 billion per year.

COPD is an irreversible condition. It incorporates emphysema (damage to the lung air sacs), and chronic bronchitis (long-term airways inflammation). An exacerbation of COPD causes severe breathlessness, confusion, low blood oxygen levels and can cause high carbon dioxide levels.

Non-invasive ventilation pushes air into the lungs via a facemask. Unlike invasive ventilation, patients are not sedated and do not need a tube inserted into the windpipe. There is a lower risk of complications, such as pneumonia than with invasive ventilation.

Non-invasive ventilation is increasingly being used for people admitted to hospital with acute exacerbations of COPD in severe respiratory failure. This review aimed to gather evidence on the effectiveness of this approach.

What did this study do?

This systematic review found 17 randomised controlled trials involving 1,264 adults admitted to hospital with a severe exacerbation of chronic obstructive pulmonary disease. This was defined as a low blood pH (less than 7.35) and high levels of carbon dioxide (6kPa or more).

Non-invasive ventilation was delivered with a Bilevel Positive Airway Pressure machine on a hospital ward. Usual care involved typical medical treatment without ventilation. People with pneumonia were excluded.

The review looked primarily at mortality during the hospital admission and the need to insert a tube into the windpipe.

The evidence was rated as moderate quality. The intervention made blinding difficult although this was unlikely to affect the primary objective outcomes. Treatment duration and the type of ward setting varied somewhat between studies.

What did it find?

  • Participants who received ventilation were 46% less likely to die during that hospital admission than those who just received usual care (risk ratio [RR] 0.54, 95% confidence interval [C.I] 0.38 to 0.76). During the 10% (42/434) of participants who received ventilation and usual care died compared with 18% (77/420) who received usual care. This pooled analysis was from 12 studies.
  • Intubation was required by 12% (67/559) people who received ventilation, compared with 34% (186/546) of those with usual care alone (RR 0.36, 95% CI 0.28 to 0.46). These results were from 17 studies.
  • Pooled results from ten studies involving 888 participants found that people who initially received ventilation stayed in the for on average 14.1 days compared to 17.5 days for usual care alone (mean difference -3.39, 95% CI -5.93 to -0.85).
  • Six studies, 346 participants, found that people were less likely to tolerate non-invasive ventilation than usual care. This result given the nature of ventilation delivery (risk difference 0.11, 95% CI 0.04 to 0.17).

What does current guidance say on this issue?

NICE 2010 guidance recommends using non-invasive ventilation as the treatment of choice for persistent respiratory failure despite optimal medical therapy. It should be delivered in a dedicated setting with trained staff who are experienced in its use. There should be a clear plan covering what to do in the event of deterioration and ceilings of therapy should be agreed. The 2008 guideline from the Royal College of Physicians, British Thoracic Society and Intensive Care Society recommends that non-invasive ventilation should be considered if the blood acidity remains low despite a maximum of one hour of standard medical therapy.

What are the implications?

This review suggests that prompt non-invasive ventilation during admission could save lives and avoid invasive ventilation. This may have training implications as it should only be delivered by staff proficient in its use and who understand its limitations. There may also be issues around availability of Bilevel Positive Airways Pressure machines.

The results don’t apply to people who are coming off invasive ventilation therapy or those in respiratory failure not due to chronic obstructive pulmonary disease.

There was no cost analysis, but reduced hospital stays suggest potential financial savings. It would be useful to see patient-centred outcomes in the future including the acceptability of these devices and quality of life.

Citation and Funding

Osadnik CR, Tee VS, Carson-Chahhoud KV, et al. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7:CD004104.

This project was funded by the National Institute for Health Research via Cochrane infrastructure funding to the Cochrane Airways Group.

Bibliography

British Lung Foundation. Estimating the economic burden of respiratory illness in the UK. London: British Lung Foundation; 2017.

National Clinical Guideline Centre. Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre; 2010.

NCEPOD. Acute Non-Invasive Ventilation: Inspiring Change. London: National Confidential Enquiry into Patient Outcome and Death; 2017.

NHS Choices. Chronic obstructive pulmonary disease (COPD). London: Department of Health; 2016.

NICE. Chronic Obstructive Pulmonary Disease in over 16s: diagnosis and management. CG101. London: National Institute for Health and Care Excellence; 2010.

Patient. Chronic Obstructive Pulmonary Disease. Leeds: Patient; 2015.

Royal College of Physicians, British Thoracic Society, Intensive Care Society. Chronic obstructive pulmonary disease: non-invasive ventilation with bi-phasic positive airways pressure in the management of patients with acute type 2 respiratory failure. Concise Guidance to Good Practice series, No 11. London: RCP; 2008.

Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease

Published on 14 July 2017

Osadnik, C. R.,Tee, V. S.,Carson-Chahhoud, K. V.,Picot, J.,Wedzicha, J. A.,Smith, B. J.

Cochrane Database Syst Rev Volume 7 , 2017

BACKGROUND: Non-invasive ventilation (NIV) with bi-level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory failure (AHRF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). OBJECTIVES: To compare the efficacy of NIV applied in conjunction with usual care versus usual care involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The aim of this review is to update the evidence base with the goals of supporting clinical practice and providing recommendations for future evaluation and research. SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and PsycINFO, and through handsearching of respiratory journals and meeting abstracts. This update to the original review incorporates the results of database searches up to January 2017. SELECTION CRITERIA: All randomised controlled trials that compared usual care plus NIV (BiPAP) versus usual care alone in an acute hospital setting for patients with AECOPD due to AHRF were eligible for inclusion. AHRF was defined by a mean admission pH < 7.35 and mean partial pressure of carbon dioxide (PaCO2) > 45 mmHg (6 kPa). Primary review outcomes were mortality during hospital admission and need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in arterial blood gases. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the selection criteria to determine study eligibility, performed data extraction, and determined risk of bias in accordance with Cochrane guidelines. Review authors undertook meta-analysis for data that were both clinically and statistically homogenous, and analysed data as both one overall pooled sample and according to two predefined subgroups related to exacerbation severity (admission pH between 7.35 and 7.30 vs below 7.30) and NIV treatment setting (intensive care unit-based vs ward-based). We reported results for mortality, need for endotracheal intubation, and hospital length of stay in a 'Summary of findings' table and rated their quality in accordance with GRADE criteria. MAIN RESULTS: We included in the review 17 randomised controlled trials involving 1264 participants. Available data indicate that mean age at recruitment was 66.8 years (range 57.7 to 70.5 years) and that most participants (65%) were male. Most studies (12/17) were at risk of performance bias, and for most (14/17), the risk of detection bias was uncertain. These risks may have affected subjective patient-reported outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.Use of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N = 17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality owing to uncertainty regarding risk of bias for several studies. Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome. NIV use was also associated with reduced length of hospital stay (mean difference (MD) -3.39 days, 95% CI -5.93 to -0.85; N = 10 studies), reduced incidence of complications (unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of oxygen (PaO2) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one hour. A trend towards improvement in PaCO2 was observed, but this finding was not statistically significant (MD -4.62 mmHg, 95% CI -11.05 to 1.80 mmHg; N = 8 studies). Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the NIV group than in the usual care group). Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of NIV on PaCO2. Treatment intolerance was significantly greater in the NIV group than in the usual care group (risk difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis showed a non-significant trend towards reduction in dyspnoea with NIV compared with usual care (standardised mean difference (SMD) -0.16, 95% CI -0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between-group differences. AUTHORS' CONCLUSIONS: Data from good quality randomised controlled trials show that NIV is beneficial as a first-line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD). The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH < 7.30), and when NIV is applied within the intensive care unit (ICU) or ward setting.

Bilevel Positive Airways Pressure involved delivering air at high pressure via a nasal cannula (a tube in the nose) or a facemask. It increases oxygen levels and helps the wearer breathe out more carbon dioxide. It also helps to rest respiratory muscles.

Expert commentary

When people with chronic obstructive pulmonary disease have a severe flare-up of their condition, they may develop respiratory failure. Respiratory failure is when they are unable to move enough air in and out to stop carbon dioxide accumulating. Left untreated this can be fatal.

Invasive ventilation is where a tube is inserted into the person’s throat to support their breathing. Researchers reviewed clinical trials of a type of support, delivered via a tight-fitting mask, called non-invasive ventilation.

This is confirmed to be an effective treatment in this situation, reducing the risk of death and shortening the time in hospital.

Dr Nicholas Hopkinson, Clinical Senior Lecturer, Imperial College London; Honorary Consultant Chest Physician, The Royal Brompton Hospital

Expert commentary

Non-invasive ventilation is a NICE recommended therapy for patients suffering from acidotic acute exacerbations of chronic obstructive pulmonary disease. This Cochrane review updates the evidence behind that. The National Confidential Enquiry into Patient Outcome and Death recently published the results of a large-scale study into its use in regular clinical practice. Interestingly they recommend a 1:2 nurse to patient ratio usually only available in a high dependency unit or intensive therapy unit (ITU) setting.

In the review, the authors find non-invasive ventilation in ITU less beneficial than on a general ward. Perhaps this is the difference between being in a trial rather than receiving routine NHS care. Further study is probably required. 

Dr John White, Consultant Physician, York NHS Foundation Trust