Meme Wijesinghe

Routine use of oxygen in the treatment of myocardial infarction: systematic review

Context: International guidelines recommend the routine use of oxygen therapy in the treatment of myocardial infarction (MI). Objective: To undertake a systematic review and meta-analysis of randomised placebo-controlled trials of oxygen therapy in MI. Data sources: Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, EMBASE and CINHAL. Study selection: Randomised placebo-controlled trials of oxygen therapy in MI. Data extraction: The primary clinical outcome was mortality. Results: Two of 51 potential studies met the inclusion criteria. The one study with substantive clinical outcome data reported that in uncomplicated MI, high-flow oxygen was associated with a non-significant increased risk of death (risk ratio 2.9, 95% CI 0.8 to 10.3, p = 0.08) and a greater serum aspartate aminotransferase level (difference 19.2 IU/ml, 95% CI 0 to 38.4, p = 0.05) than room air. Conclusion: The limited evidence that does exist suggests that the routine use of high-flow oxygen in uncomplicated MI may result in a greater infarct size and possibly increase the risk of mortality.

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy

Background: There is concern that long-acting β agonist (LABA) drugs may increase the risk of asthma mortality. Methods: A meta-analysis was conducted of asthma deaths in randomised controlled clinical trials from the GlaxoSmithKline database that compared salmeterol with a non-LABA comparator treatment in asthma. The Peto one-step method was used to determine the risk overall (all studies) and in derived datasets based on inhaled corticosteroid (ICS) use. Results: There were 35 asthma deaths in 215 studies with 106 575 subjects. Two studies (SMART and SNS) contributed 30/35 (86%) asthma deaths, the overall findings largely reflecting the characteristics of these studies. The odds ratio for risk of asthma mortality with salmeterol was 2.7 (95% CI 1.4 to 5.3). In 54 placebo controlled studies the risk of death from asthma in patients not prescribed ICS was 7.3 (95% CI 1.8 to 29.4). In 127 studies in which patients were prescribed ICS, the risk of asthma death was 2.1 (95% CI 0.6 to 7.9). In 63 studies in which patients were randomised to receive the combination salmeterol/fluticasone propionate inhaler or ICS, there were no asthma deaths among 22 600 patients. Conclusions: Salmeterol monotherapy in asthma increases the risk of asthma mortality and this risk is reduced with concomitant ICS therapy. There is no evidence that combination salmeterol/fluticasone propionate therapy is associated with an increased risk of asthma mortality, although this interpretation is limited by the low statistical power of available studies.

The Effect of Supplemental Oxygen on Hypercapnia in Subjects With Obesity-Associated Hypoventilation: A Randomized, Crossover, Clinical Study

BACKGROUND It is unknown whether oxygen therapy causes worsening hypercapnia in patients with obesity-associated hypoventilation (OAH), similar to the response observed in COPD. The objectives of this study were to investigate whether breathing 100% oxygen results in an increase in hypercapnia in patients with OAH and the mechanisms of any effect. METHODS In this double-blind, randomized, controlled, crossover trial, 24 outpatients with newly diagnosed OAH inhaled 100% oxygen or room air for 20 min on 2 separate days. Transcutaneous CO(2) tension (Ptco(2)), minute ventilation, and volume of dead space to tidal volume ratio were measured at baseline and at 20 min. A mixed linear model was used to determine differences between the two treatments. RESULTS The study was terminated in three subjects breathing 100% oxygen due to a Ptco(2) increase ≥ 10 mm Hg, which occurred after 10:35, 13:20, and 15:51 min. Ptco(2) increased by 5.0 mm Hg (95% CI, 3.1-6.8; P < .001) with oxygen compared with room air. Minute ventilation decreased by 1.4 L/min (95% CI, 0.11-2.6 L/min; P = .03), and volume of dead space to tidal volume ratio increased by 0.067 (95% CI, 0.035-0.10; P < .001) with oxygen compared with room air. CONCLUSIONS Breathing 100% oxygen causes worsening hypercapnia in stable patients with OAH. TRIAL REGISTRY Australia New Zealand Clinical Trials Registry; No.: ACTRN 12608000592347; URL: www.anzctr.org.au.

Dose–response relationship for risk of non-vertebral fracture with inhaled corticosteroids

Objective To determine the strength of association between the dose of inhaled corticosteroids (ICS) and risk of non‐vertebral fracture in adults.

Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma

Background The effect on Paco2 of high concentration oxygen therapy when administered to patients with severe exacerbations of asthma is uncertain. Methods 106 patients with severe exacerbations of asthma presenting to the Emergency Department were randomised to high concentration oxygen (8 l/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93% and 95%) for 60 min. Patients with chronic obstructive pulmonary disease or disorders associated with hypercapnic respiratory failure were excluded. The transcutaneous partial pressure of carbon dioxide (Ptco2) was measured at 0, 20, 40 and 60 min. The primary outcome variable was the proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min. Results The proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min was significantly higher in the high concentration oxygen group, 22/50 (44%) vs 10/53 (19%), RR 2.3 (95% CI 1.2 to 4.4, p<0.006). The high concentration group had a higher proportion of patients with a rise in Ptco2 ≥8 mm Hg, 11/50 (22%) vs 3/53 (6%), RR 3.9 (95% CI 1.2 to 13.1, p=0.016). All 10 patients with a final Ptco2 ≥45 mm Hg received high concentration oxygen therapy, and in five there was an increase in Ptco2 ≥10 mm Hg. Conclusion High concentration oxygen therapy causes a clinically significant increase in Ptco2 in patients presenting with severe exacerbations of asthma. A titrated oxygen regime is recommended in the treatment of severe asthma, in which oxygen is administered only to patients with hypoxaemia, in a dose that relieves hypoxaemia without causing hyperoxaemia. Clinical trial number ACTRN12607000131459.

Original ResearchCritical CareThe Effect of Supplemental Oxygen on Hypercapnia in Subjects With Obesity-Associated Hypoventilation: A Randomized, Crossover, Clinical Study

BACKGROUND It is unknown whether oxygen therapy causes worsening hypercapnia in patients with obesity-associated hypoventilation (OAH), similar to the response observed in COPD. The objectives of this study were to investigate whether breathing 100% oxygen results in an increase in hypercapnia in patients with OAH and the mechanisms of any effect. METHODS In this double-blind, randomized, controlled, crossover trial, 24 outpatients with newly diagnosed OAH inhaled 100% oxygen or room air for 20 min on 2 separate days. Transcutaneous CO(2) tension (Ptco(2)), minute ventilation, and volume of dead space to tidal volume ratio were measured at baseline and at 20 min. A mixed linear model was used to determine differences between the two treatments. RESULTS The study was terminated in three subjects breathing 100% oxygen due to a Ptco(2) increase ≥ 10 mm Hg, which occurred after 10:35, 13:20, and 15:51 min. Ptco(2) increased by 5.0 mm Hg (95% CI, 3.1-6.8; P < .001) with oxygen compared with room air. Minute ventilation decreased by 1.4 L/min (95% CI, 0.11-2.6 L/min; P = .03), and volume of dead space to tidal volume ratio increased by 0.067 (95% CI, 0.035-0.10; P < .001) with oxygen compared with room air. CONCLUSIONS Breathing 100% oxygen causes worsening hypercapnia in stable patients with OAH. TRIAL REGISTRY Australia New Zealand Clinical Trials Registry; No.: ACTRN 12608000592347; URL: www.anzctr.org.au.

Pre‐hospital oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

Background: High concentration oxygen is commonly administered during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study was to determine the association between oxygen, severity markers and poor outcomes in AECOPD.

Accuracy of patient self-report as a measure of inhaled asthma medication use

Measuring adherence to inhaled asthma treatment is a key priority for asthma care. The aim of this study was to determine the relationship between self‐report and actual medication use as measured by electronic monitoring for single and combination inhaled corticosteroid (ICS) and long‐acting beta‐agonist (LABA) metered‐dose inhaler therapy.

International Trends in Asthma Mortality Rates in the 5- to 34-Year Age Group: A Call for Closer Surveillance

BACKGROUND International time trends in asthma mortality have played an important sentinel role in the identification of two epidemics of asthma mortality in some countries in the 1960s and the 1970s and 1980s. Since then, little attention has been paid to the ongoing international time trends. METHODS Country-specific data on asthma mortality rates since 1960 in the 5- to 34-year-old age group were collated. To be included in the analysis, countries were required to have data available prior to 1980. A scatter plot smoothing technique was used to model the change in asthma mortality rates with time. RESULTS Asthma mortality rates from 20 countries were included in the analysis. An increase in asthma mortality rates was found in the 1960s, with a mean increase of 53% from 0.55 per 100,000 in 1960 and 1961 to a peak of 0.84 in 1966 and 1967. This trend was followed by a progressive decline to a nadir of 0.45 per 100,000 in 1974 and 1975. A gradual increase was then found in asthma mortality rates to a peak of 0.62 per 100,000 in 1985 and 1986, with a mean increase of 38% during this period. Since the late 1980s, there has been a widespread and progressive reduction in mortality rates to a level of 0.23 per 100,000 in 2004 and 2005, with a mean reduction of 63% during this period. CONCLUSIONS The widespread increase in asthma mortality in the 1980s and the subsequent, even greater reduction has largely gone unrecognized. We propose that awareness of such trends and their causes is important and that they are investigated contemporaneously.

The risk of asthma mortality with inhaled long acting β-agonists

This article reviews the available evidence as to whether inhaled long acting β-agonists (LABA) increase the risk of asthma mortality and considers the implications for the use of this treatment in the management of asthma. Randomised controlled trials suggest that LABAs prescribed as monotherapy may increase the risk of asthma death in certain circumstances, such as the unsupervised “off-label” use without concomitant inhaled corticosteroid (ICS) treatment in patients with unstable asthma. However, there is also evidence that the use of LABAs in conjunction with ICS treatment in adult asthma as recommended in current guidelines is not associated with an increased risk of asthma mortality. The only way in which a prescriber can ensure that a patient with asthma takes LABA treatment in conjunction with ICS is through a combination ICS/LABA product, an approach which may have additional therapeutic advantages. We propose that in the management of asthma, a case can now be made to limit the availability of LABAs to combination LABA/ICS therapy.