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

Disclosures

BMJ 

In This Article

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.

Introduction

Chronic obstructive pulmonary disease is a major public health problem in many countries. The World Health Organization estimates that 210 million people have moderate to severe chronic obstructive pulmonary disease and that three million people died of the condition in 2005.[1] Chronic obstructive pulmonary disease is associated with a substantial economic burden; estimates of cost include $49.9 (£31.5; €36.3) billion in the United States in 2010 and $1.5 billion in the United Kingdom in 2004.[2,3] The course of the disease is characterised by episodes, known as acute exacerbations, when symptoms of cough, sputum production, and breathlessness become much worse. These are a frequent cause of admission to hospital, estimated to cost approximately $73 billion a year in the United States and $700 million a year in Australia and Canada.[4,5,6] Standard prehospital management of an acute exacerbation of chronic obstructive pulmonary disease includes nebulised bronchodilators (usually driven by 6-8 l/min of oxygen), corticosteroids, and oxygen.

Oxygen is commonly administered to patients with an acute exacerbation of chronic obstructive pulmonary disease, as well as for a range of other medical emergencies,[7,8] and can save lives by preventing severe hypoxaemia. Administration of high flow oxygen to normal people leads to an increase in the minute ventilation (the volume of air inspired into or expired out of the lungs in one minute) and a decrease in end tidal carbon dioxide concentration.[9,10] However, even in patients with stable chronic obstructive pulmonary disease, hyperoxia leads to a decrease in minute ventilation and an increase in transcutaneous carbon dioxide.[11] These changes are postulated to occur as a result of either depression of ventilation or worsening inequality in ventilation-perfusion due to recruitment of poorly ventilated lung units (alveolus and associated pulmonary capillaries where gas exchange takes place) by reversal of local hypoxic pulmonary vasoconstriction subsequently releasing sequestered carbon dioxide.[8] Oxygen induced changes in carbon dioxide concentrations in chronic obstructive pulmonary disease were first shown in 1955,[12] several years after a report on the deleterious effects of oxygen in this condition.[13] Campbell was then fundamental in establishing the in-hospital practice of titrating oxygen treatment by using venturi masks.[14] Subsequently, mortality in acute exacerbations of chronic obstructive pulmonary disease was reported to be associated with an increase in chronic stable levels of arterial carbon dioxide pressure, rather than the absolute level of hypercapnia.[15]

More recently, audits of hospital management have shown that the administration of high flow oxygen during acute exacerbations of chronic obstructive pulmonary disease has been associated with increases in mortality, length of hospital stay, requirement for ventilation, and admission to high dependency units.[16,17,18,19,20] Furthermore, the use of titrated oxygen treatment has been associated with less acidosis, a lower requirement for assisted ventilation, and reduced mortality.[15,20] A one year prevalence study showed that the injudicious use of oxygen treatment caused acidosis in patients with acute exacerbations of chronic obstructive pulmonary disease, but a proportion of these patients were rapidly able to correct their pH once the fraction of inspired oxygen was reduced.[19] Despite the accumulating evidence, high flow oxygen treatment continued to be the standard of care in Australia and other countries up to the time this trial started.[7,17,20,21] In recent years, awareness of the potential harm of routine use of high flow oxygen has increased, and attempts have been made to modify practice. Concern about the routine use of high flow oxygen to relieve breathlessness in emergency settings has prompted the release of the first international guidelines for the emergency use of oxygen,[8] but the need for randomised controlled trials is widely acknowledged.[8,16,19,22,23] A recent Cochrane review on oxygen treatment and acute exacerbations of chronic obstructive pulmonary disease in the prehospital setting identified two ongoing trials, reinforcing the medical community’s recognition of the need for evidence in this area.[22,24,25]

Despite published guidelines, the lack of clear evidence showing the benefit of titrated oxygen treatment may be responsible for the lack of widespread cultural change among practitioners, authorities, and opinion leaders. The difficulty in modifying practice in the prehospital setting is compounded by the lack of equipment capable of delivering controlled oxygen treatment while administering nebulised drugs in ambulances. This study was motivated by the need for quantitative evidence on the dangers of high flow oxygen, to support recommendations for the use of titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease. Our ultimate objective is to improve the quality of care for patients. The aim of this study was 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.

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