Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial

Michael A Austin, Karen E Wills, Leigh Blizzard, Eugene H Walters, Richard Wood-Baker, Michael A Austin, Karen E Wills, Leigh Blizzard, Eugene H Walters, Richard Wood-Baker

Abstract

Objectives: To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.

Design: Cluster randomised controlled parallel group trial.

Setting: Ambulance service in Hobart, Tasmania, Australia.

Participants: 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.

Interventions: High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.

Main outcome measure: Prehospital or in-hospital mortality.

Results: In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure -33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.

Conclusions: Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.

Trial registration: Australian New Zealand Clinical Trials Register ACTRN12609000236291.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4787644/bin/ausm765461.f1_default.jpg
Flow of participants through study. COPD=chronic obstructive pulmonary disease; FEV1=forced expiratory volume in one second; FVC=forced vital capacity; ITT=intention to treat; TPP=treatment per protocol

References

    1. World Health Organization. Chronic obstructive pulmonary disease (COPD). 2010. .
    1. American Lung Association. Chronic obstructive pulmonary disease COPD. 2010. .
    1. British Lung Foundation. Invisible lives: chronic obstructive pulmonary disease (COPD)—finding the missing millions. British Lung Foundation, 2007 (available at ).
    1. Halpern MT, Stanford RH, Borker R. The burden of COPD in the USA: results from the Confronting COPD Survey. Respir Med 2003;97:81-9S.
    1. McKenzie D, Frith P, Burdon J, Town G. The COPDX plan: Australian and New Zealand guidelines for the management of chronic obstructive pulmonary disease. Med J Aust 2003;178:1-40S.
    1. Mittmann N, Kuramoto L, Seung SJ, Haddon JM, Bradley-Kennedy C, FitzGerald JM. The cost of moderate and severe COPD exacerbations to the Canadian healthcare system. Respir Med 2008;102:413-21.
    1. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J 2008;25:773-6.
    1. O’Driscoll BR, Howard LS, Davison AG. BTS guideline for emergency oxygen use in adult patients. Thorax 2008;63:vi1-68.
    1. Becker HF, Polo O, McNamara SG, Berthon-Jones M, Sullivan CE. Effect of different levels of hyperoxia on breathing in healthy subjects. J Appl Physiol 1996;81:1683-90.
    1. Lambertsen CJ, Kough RH, Cooper DY, Emmel GL, Loeschcke HH, Schmidt CF. Oxygen toxicity: effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport, cerebral circulation and cerebral metabolism. J Appl Physiol 1953;5:471-86.
    1. Sassoon CSH, Hassell KT, Mahutte CK. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987;135:907-11.
    1. Westlake EK, Simpson T, Kaye M. Carbon dioxide narcosis in emphysema. Q J Med 1955;24:155-73.
    1. Donald K. Neurological effects of oxygen. Lancet 1949;257:1056-7.
    1. Campbell E. The J Burns Amberson lecture: the management of acute respiratory failure. Am Rev Respir Dis 1967;96:626-39.
    1. Jeffrey AA, Warren PM, Flenley DC. Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease—risk-factors and use of guidelines for management. Thorax 1992;47:34-40.
    1. Denniston A, O’Brien C, Stableforth D. The use of oxygen in acute exacerbations of chronic obstructive pulmonary disease: a prospective audit of pre-hospital and hospital emergency management. Clin Med 2002;2:449-51.
    1. Joosten EA. The effects of oxygen therapy in patients presenting to an emergency department with exacerbation of chronic obstructive pulmonary disease. Med J Aust 2007;5:235-8.
    1. Robinson T, Young I. The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163:1524-9.
    1. Plant PK, Owen JL, Elliott MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration. Thorax 2000;55:550-4.
    1. Wijesinghe M, Perrin K, Healy B, Hart K, Clay J, Weatherall M, et al. Pre-hospital oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease. Intern Med J 2009;39:1-18.
    1. Gooptu B, Ward L, Ansari SO, Eraut CD, Law D, Davison AG. Oxygen alert cards and controlled oxygen: preventing emergency admissions at risk of hypercapnic acidosis receiving high inspired oxygen concentrations in ambulances and A & E departments. Emerg Med J 2006;23:636-8.
    1. Austin M, Wood-Baker R. Oxygen therapy in the pre-hospital setting for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006;3:CD005534.
    1. Hurd S, Pauwels R. Global initiative for chronic obstructive lung disease (GOLD). Pulm Pharmacol Ther 2002;14:353-5.
    1. Elliott DMWE. A prospective randomised controlled trial of oxygen targeted to maintain an oxygen saturation between 88 and 92% compared with standard therapy for patients with COPD during ambulance transfer to hospital. Leeds Teaching Hospitals NHS Trust, 2004.
    1. Eiser DN. Comparison of controlled oxygen with standard oxygen therapy for COPD patients during ambulance transfer to hospital. London Ambulance Service NHS Trust, 2004.
    1. Lumb A, Pearl R. Nunn’s applied respiratory physiology. 6th ed. Elsevier, 2005.
    1. Ak A, Ogun CO, Bayir A, Kayis SA, Koylu R. Prediction of arterial blood gas values from venous blood gas values in patients with acute exacerbation of chronic obstructive pulmonary disease. Tohoku J Exp Med 2006;210:285-90.
    1. Gunen H, Hacievliyagil SS, Kosar F, Mutlu LC, Gulbas G, Pehlivan E, et al. Factors affecting survival of hospitalised patients with COPD. Eur Respir J 2005;26:234-41.
    1. Price LC, Lowe D, Hosker HS, Anstey K, Pearson MG, Roberts CM. UK national COPD audit 2003: impact of hospital resources and organisation of care on patient outcome following admission for acute COPD exacerbation. Thorax 2006;61:837-42.
    1. Soler-Cataluna JJ, Martinez-Garcia MA, Sanchez PR, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-31.
    1. Plant PK, Owen JL, Elliott MW. Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome. Thorax 2001;56:708-12.
    1. Jeffrey AA, Warren PM, Flenley DC. Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management. Thorax 1992;47:34-40.
    1. New A. Oxygen: kill or cure? Pre-hospital hyperoxia in the COPD patient. Emerg Med J 2005;23:144-6.
    1. Scales DC, Adhikari NKJ. Lost in (knowledge) translation: “all breakthrough, no follow through”? Crit Care Med 2008;36:1654-5.
    1. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients’ care. Lancet 2003;362:1225-.30.

Source: PubMed

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