NIHR Signal Pre-hospital non-invasive ventilation for people with acute respiratory failure

Published on 19 August 2015

This NIHR-funded systematic review and cost-effectiveness study found that pre-hospital (i.e. in the ambulance) non-invasive ventilation in the form of continuous positive airway pressure for people with acute respiratory failure, can reduce both the risk of dying and the need for ventilation in intensive care. The small device used by trained ambulance personnel was more effective than standard care, giving oxygen and standard medical treatment only, but was more expensive. No trials in the review were based in the UK. Emergency care services between countries may vary substantially, thus limiting the applicability of the findings to the NHS.

The implementation of a change in practice for people with acute respiratory failure is likely to require extra resources such as equipment, training and reorganisation of emergency service in the NHS, but based on this study it seems like it could be value for money.  Further UK-based evidence is likely to be required before pre-hospital non-invasive ventilation in the NHS can be recommended.

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Why was this study needed?

Acute respiratory failure is a common life-threatening medical emergency, particularly in older people, with low levels of oxygen and raised carbon dioxide in the blood. It can be caused by a range of heart and lung conditions such as heart failure, chronic obstructive pulmonary disease (COPD), and pneumonia or acute lower respiratory infection. In 2009   379,731 people went to hospital in England for these conditions with about 14% of people dying within 30 days.

One hospital-based treatment device delivers continuous positive airway pressure (CPAP) using a tight-fitting mask over their mouth and nose. This helps patients with various problems breathe more easily. People with respiratory failure are often given oxygen treatment in the ambulance on the way to the hospital. The risk of death in people with respiratory problems has been found to increase with distance travelled to hospital. The NIHR funded this study to find out whether giving oxygen using either of two non-invasive devices in the ambulance (pre-hospital) reduced the risk of people with acute respiratory failure dying or needing to be put on a ventilator when they got to hospital, and to see how the extra costs weighed up against the benefits.

What did this study do?

This systematic review identified two quasi-randomised and eight randomised controlled trials comparing pre-hospital non-invasive ventilation with standard care - giving oxygen and standard medical treatment only. Two types of device were investigated: continuous positive airway pressure (CPAP) in six trials and bilevel inspiratory positive airway pressure (BiPAP) in four trials. CPAP provides constant pressure as the person breathes in and out, while BiPAP provides high pressure when they breathe in and low pressure when they breathe out. Treatments were compared directly within trials, and indirectly across trials, using network meta-analysis. This gives an overall measure of the effect of one treatment compared to another treatment, even if trials did not compare treatments directly. 

The trials included in the review were generally small and might represent selected patient groups. The treatments compared varied across the trials, and the pooled analysis may not have been able to detect potentially important differences in outcomes.

The review included a cost-effectiveness analysis where they looked at the costs of giving pre-hospital CPAP for each future year of life that the person lived in good health (a quality adjusted life year, QALY).

What did it find?

  • The pooled results of six trials found that pre-hospital CPAP reduced the risk of dying compared with standard care (odds ratio [OR] 0.41, 95% Credible Interval [CrI] 0.20 to 0.77). Follow-up times ranged from 30 days to hospital discharge or death.
  • The pooled results of five trials also found that pre-hospital CPAP reduced the risk of being put on a ventilator compared with standard care (OR 0.32, 95% CrI 0.17 to 0.62).
  • For BiPAP, there were no significant differences compared with standard care for risk of death (three trials) or needing a ventilator (four trials). 
  • Pre-hospital CPAP was more effective than standard care but also more expensive. Pre-hospital CPAP cost £20,514 per QALY gained. Results meant that it had almost a 50% chance of being cost effective at the £20,000 per QALY threshold normally set for determining whether treatments are a good use of NHS resources.

What does current guidance say on this issue?

Pre-hospital ventilation is not usually used by UK NHS ambulance service. The 2013 update of the UK Ambulance Services Clinical Practice Guidelines for the first time recommended the use of pre-hospital CPAP on the basis of expert consensus. This treatment has not been researched extensively in settings outside of hospitals.

What are the implications?

This systematic review found that pre-hospital CPAP was more effective than standard care for the two outcomes examined, and was reasonable value for money compared to alternatives for the NHS (at the usual £20,000 per QALY NHS threshold).

Importantly, none of the trials took place in an NHS setting, and they were limited by small sample sizes and differences in the treatment offered.

With the current level of evidence it is uncertain whether the implementation of pre-hospital CPAP would be appropriate for the NHS. For example, the implementation for people with acute respiratory failure is likely to require substantial resources of equipment, training and reorganisation of emergency service in the NHS. 

Citation

Pandor A, Thokala P, Goodacre S, et al. Pre-hospital non-invasive ventilation for acute respiratory failure: a systematic review and cost-effectiveness evaluation. Health Technol Assess. 2015 Jun;19(42):1-102.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 11/36/09)

Bibliography

BMJ Best practice. Acute respiratory failure. London: BMJ Publishing Group; 2014

Joint Royal Colleges Ambulance Liaison Committee. UK Ambulance Services Clinical Practice Guidelines 2013. London: Association of Ambulance Chief Executives; 2013

Stefan MS, Shieh MS, Pekow PS, et al. Epidemiology and outcomes of acute respiratory failure in the United States, 2001 to 2009: a national survey. J Hosp Med. 2013;8:76-82.

Why was this study needed?

Acute respiratory failure is a common life-threatening medical emergency, particularly in older people, with low levels of oxygen and raised carbon dioxide in the blood. It can be caused by a range of heart and lung conditions such as heart failure, chronic obstructive pulmonary disease (COPD), and pneumonia or acute lower respiratory infection. In 2009   379,731 people went to hospital in England for these conditions with about 14% of people dying within 30 days.

One hospital-based treatment device delivers continuous positive airway pressure (CPAP) using a tight-fitting mask over their mouth and nose. This helps patients with various problems breathe more easily. People with respiratory failure are often given oxygen treatment in the ambulance on the way to the hospital. The risk of death in people with respiratory problems has been found to increase with distance travelled to hospital. The NIHR funded this study to find out whether giving oxygen using either of two non-invasive devices in the ambulance (pre-hospital) reduced the risk of people with acute respiratory failure dying or needing to be put on a ventilator when they got to hospital, and to see how the extra costs weighed up against the benefits.

What did this study do?

This systematic review identified two quasi-randomised and eight randomised controlled trials comparing pre-hospital non-invasive ventilation with standard care - giving oxygen and standard medical treatment only. Two types of device were investigated: continuous positive airway pressure (CPAP) in six trials and bilevel inspiratory positive airway pressure (BiPAP) in four trials. CPAP provides constant pressure as the person breathes in and out, while BiPAP provides high pressure when they breathe in and low pressure when they breathe out. Treatments were compared directly within trials, and indirectly across trials, using network meta-analysis. This gives an overall measure of the effect of one treatment compared to another treatment, even if trials did not compare treatments directly. 

The trials included in the review were generally small and might represent selected patient groups. The treatments compared varied across the trials, and the pooled analysis may not have been able to detect potentially important differences in outcomes.

The review included a cost-effectiveness analysis where they looked at the costs of giving pre-hospital CPAP for each future year of life that the person lived in good health (a quality adjusted life year, QALY).

What did it find?

  • The pooled results of six trials found that pre-hospital CPAP reduced the risk of dying compared with standard care (odds ratio [OR] 0.41, 95% Credible Interval [CrI] 0.20 to 0.77). Follow-up times ranged from 30 days to hospital discharge or death.
  • The pooled results of five trials also found that pre-hospital CPAP reduced the risk of being put on a ventilator compared with standard care (OR 0.32, 95% CrI 0.17 to 0.62).
  • For BiPAP, there were no significant differences compared with standard care for risk of death (three trials) or needing a ventilator (four trials). 
  • Pre-hospital CPAP was more effective than standard care but also more expensive. Pre-hospital CPAP cost £20,514 per QALY gained. Results meant that it had almost a 50% chance of being cost effective at the £20,000 per QALY threshold normally set for determining whether treatments are a good use of NHS resources.

What does current guidance say on this issue?

Pre-hospital ventilation is not usually used by UK NHS ambulance service. The 2013 update of the UK Ambulance Services Clinical Practice Guidelines for the first time recommended the use of pre-hospital CPAP on the basis of expert consensus. This treatment has not been researched extensively in settings outside of hospitals.

What are the implications?

This systematic review found that pre-hospital CPAP was more effective than standard care for the two outcomes examined, and was reasonable value for money compared to alternatives for the NHS (at the usual £20,000 per QALY NHS threshold).

Importantly, none of the trials took place in an NHS setting, and they were limited by small sample sizes and differences in the treatment offered.

With the current level of evidence it is uncertain whether the implementation of pre-hospital CPAP would be appropriate for the NHS. For example, the implementation for people with acute respiratory failure is likely to require substantial resources of equipment, training and reorganisation of emergency service in the NHS. 

Citation

Pandor A, Thokala P, Goodacre S, et al. Pre-hospital non-invasive ventilation for acute respiratory failure: a systematic review and cost-effectiveness evaluation. Health Technol Assess. 2015 Jun;19(42):1-102.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 11/36/09)

Bibliography

BMJ Best practice. Acute respiratory failure. London: BMJ Publishing Group; 2014

Joint Royal Colleges Ambulance Liaison Committee. UK Ambulance Services Clinical Practice Guidelines 2013. London: Association of Ambulance Chief Executives; 2013

Stefan MS, Shieh MS, Pekow PS, et al. Epidemiology and outcomes of acute respiratory failure in the United States, 2001 to 2009: a national survey. J Hosp Med. 2013;8:76-82.

Pre-hospital non-invasive ventilation for acute respiratory failure: a systematic review and cost-effectiveness evaluation

Published on 24 June 2015

Pandor, A.,Thokala, P.,Goodacre, S.,Poku, E.,Stevens, J. W.,Ren, S.,Cantrell, A.,Perkins, G. D.,Ward, M.,Penn-Ashman, J.

Health Technol Assess Volume 19 , 2015

BACKGROUND: Non-invasive ventilation (NIV), in the form of continuous positive airway pressure (CPAP) or bilevel inspiratory positive airway pressure (BiPAP), is used in hospital to treat patients with acute respiratory failure. Pre-hospital NIV may be more effective than in-hospital NIV but requires additional ambulance service resources. OBJECTIVES: We aimed to determine the clinical effectiveness and cost-effectiveness of pre-hospital NIV compared with usual care for adults presenting to the emergency services with acute respiratory failure and to identify priorities for future research. DATA SOURCES: Fourteen electronic databases and research registers (including MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to August 2013, supplemented by hand-searching reference lists and contacting experts in the field. REVIEW METHODS: We included all randomised or quasi-randomised controlled trials of pre-hospital NIV in patients with acute respiratory failure. Methodological quality was assessed according to established criteria. An aggregate data network meta-analysis (NMA) of mortality and intubation was used to jointly estimate intervention effects relative to usual care. A NMA, using individual patient-level data (IPD) and aggregate data where IPD were not available, was carried out to assess whether or not covariates were treatment effect modifiers. A de novo economic model was developed to explore the costs and health outcomes when pre-hospital NIV (specifically CPAP provided by paramedics) and standard care (in-hospital NIV) were applied to a hypothetical cohort of patients with acute respiratory failure. RESULTS: The literature searches identified 2284 citations. Of the 10 studies that met the inclusion criteria, eight were randomised controlled trials and two were quasi-randomised trials (six CPAP; four BiPAP; sample sizes 23-207 participants). IPD were available from seven trials (650 patients). The aggregate data NMA suggested that CPAP was the most effective treatment in terms of mortality (probability = 0.989) and intubation rate (probability = 0.639), and reduced both mortality [odds ratio (OR) 0.41, 95% credible interval (CrI) 0.20 to 0.77] and intubation rate (OR 0.32, 95% CrI 0.17 to 0.62) compared with standard care. The effect of BiPAP on mortality (OR 1.94, 95% CrI 0.65 to 6.14) and intubation rate (OR 0.40, 95% CrI 0.14 to 1.16) compared with standard care was uncertain. The combined IPD and aggregate data NMA suggested that sex was a statistically significant treatment effect modifier for mortality. The economic analysis showed that pre-hospital CPAP was more effective and more expensive than standard care, with an incremental cost-effectiveness ratio of pound20,514 per quality-adjusted life-year (QALY) and a 49.5% probability of being cost-effective at the pound20,000-per-QALY threshold. Variation in the incidence of eligible patients had a marked impact on cost-effectiveness and the expected value of sample information for a future randomised trial. LIMITATIONS: The meta-analysis lacked power to detect potentially important differences in outcome (particularly for BiPAP), the intervention was not always compared with the best alternative care (in-hospital NIV) in the primary studies and findings may not be generalisable. CONCLUSIONS: Pre-hospital CPAP can reduce mortality and intubation rates, but cost-effectiveness is uncertain and the value of further randomised evaluation depends on the incidence of suitable patients. A feasibility study is required to determine if a large pragmatic trial of clinical effectiveness and cost-effectiveness is appropriate. STUDY REGISTRATION: The study is registered as PROSPERO CRD42012002933. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A 2013 US epidemiological study found that there was shift away from invasive mechanical ventilation as the use of non-invasive ventilation for treatment of people with acute respiratory failure in hospitals has increased by 169% in the period from 2001 to 2009.

Non-invasive ventilation is widely used in NHS hospitals to treat people with acute respiratory failure, and is usually delivered in the emergency department, critical care units or respiratory wards.

To deliver pre-hospital treatment ambulances need to be equipped with CPAP devices and paramedics need to be properly trained. The costs of pre-hospital CPAP would vary depending on the number of people each year needing the treatment. The study estimated that in an average sized ambulance service, if 175 people needed pre-hospital treatment each year this would save about 11 lives and cost £235, 683. If 2000 needed treatment each year this would save about 124 lives and cost £582,300.

Author commentary

This study showed that pre-hospital CPAP can reduce mortality and intubation rates in patients with acute respiratory failure, but these findings need to be confirmed in an NHS setting. The cost-effectiveness of pre-hospital CPAP is uncertain and depends upon the incidence of patients able to benefit from treatment. Current evidence is therefore inadequate to support implementation of pre-hospital CPAP across the NHS. A pragmatic randomised trial and economic evaluation is required to determine the effectiveness and cost-effectiveness of pre-hospital CPAP in the NHS.

Professor Steve Goodacre, Professor of Emergency Medicine, School of Health and Related Research (ScHARR), University of Sheffield