Conservative versus Interventional Treatment for Spontaneous Pneumothorax.

BACKGROUND: Whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax is unknown. METHODS: In this open-label, multicenter, noninferiority trial, we recruited patients 14 to 50 years of age with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients were randomly assigned to immediate interventional management of the pneumothorax (intervention group) or a conservative observational approach (conservative-management group) and were followed for 12 months. The primary outcome was lung reexpansion within 8 weeks. RESULTS: A total of 316 patients underwent randomization (154 patients to the intervention group and 162 to the conservative-management group). In the conservative-management group, 25 patients (15.4%) underwent interventions to manage the pneumothorax, for reasons prespecified in the protocol, and 137 (84.6%) did not undergo interventions. In a complete-case analysis in which data were not available for 23 patients in the intervention group and 37 in the conservative-management group, reexpansion within 8 weeks occurred in 129 of 131 patients (98.5%) with interventional management and in 118 of 125 (94.4%) with conservative management (risk difference, -4.1 percentage points; 95% confidence interval [CI], -8.6 to 0.5; P = 0.02 for noninferiority); the lower boundary of the 95% confidence interval was within the prespecified noninferiority margin of -9 percentage points. In a sensitivity analysis in which all missing data after 56 days were imputed as treatment failure (with reexpansion in 129 of 138 patients [93.5%] in the intervention group and in 118 of 143 [82.5%] in the conservative-management group), the risk difference of -11.0 percentage points (95% CI, -18.4 to -3.5) was outside the prespecified noninferiority margin. Conservative management resulted in a lower risk of serious adverse events or pneumothorax recurrence than interventional management. CONCLUSIONS: Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events. (Funded by the Emergency Medicine Foundation and others; PSP Australian New Zealand Clinical Trials Registry number, ACTRN12611000184976.).

Asthma and Respiratory Foundation NZ adult asthma guidelines: a quick reference guide.

The purpose of the Asthma and Respiratory Foundation NZ Adult Asthma Guidelines is to provide simple, practical and evidence-based recommendations for the diagnosis, assessment and management of asthma in adults (aged 16 and over) in a quick reference format. The intended users are health professionals responsible for delivering asthma care in the community and hospital Emergency Department settings, and those responsible for the training of such health professionals.

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax.

INTRODUCTION: Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP. METHODS AND ANALYSIS: This multicentre, prospective, randomised, open label, parallel group, non-inferiority study will randomise 342 participants with a first large PSP to conservative or interventional management. To maintain allocation concealment, randomisation will be performed in real time by computer and stratified by study site. Conservative management will involve a period of observation prior to discharge, with intervention for worsening symptoms or physiological instability. Interventional treatment will involve insertion of a small bore drain. If drainage continues after 1 hour, the patient will be admitted. If drainage stops, the drain will be clamped for 4 hours. The patient will be discharged if the lung remains inflated. Otherwise, the patient will be admitted. The primary end point is the proportion of participants with complete lung re-expansion by 8 weeks. Secondary end points are as follows: days in hospital, persistent air leak, predefined complications and adverse events, time to resolution of symptoms, and pneumothorax recurrence during a follow-up period of at least 1 year. The study has 95% power to detect an absolute non-inferiority margin of 9%, assuming 99% successful expansion at 8 weeks in the invasive treatment arm. The primary analysis will be by intention to treat. ETHICS AND DISSEMINATION: Local ethics approval has been obtained for all sites. Study findings will be disseminated by publication in a high-impact international journal and presentation at major international Emergency Medicine and Respiratory meetings. TRIAL REGISTRATION NUMBER: ACTRN12611000184976; Pre-results.

Randomized controlled trial of the effect of regular paracetamol on influenza infection.

BACKGROUND AND OBJECTIVE: Anti-pyretic treatment is recommended in the management of influenza infection. In animal models anti-pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection. METHODS: This is a randomized, double-blind, placebo-controlled trial of adults aged 18-65 years with influenza-like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT-PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5-14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log10 viral load from Baseline to Day 5. RESULTS: A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR-positive in placebo and in paracetamol groups respectively. Mean (SD) AUC PCR log10 viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was -0.24, 95% CI: -0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR. CONCLUSION: Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR-confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection. CLINICAL TRIAL REGISTRATION: ACTRN12611000497909 at the Australian New Zealand Clinical Trials Registry.

Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease.

During the last decade, there have been major advances in knowledge of the effects of oxygen therapy in patients with acute exacerbations of chronic obstructive pulmonary disease. This includes a randomised controlled trial of oxygen therapy in the pre-hospital setting, which showed that high concentration oxygen therapy leads to a 2.4-fold increased risk of mortality compared with titrated oxygen therapy to maintain oxygen saturations (SpO2) within a target range of 88-92%. Professional guidelines now recommend the use of supplementary oxygen in acute exacerbations of chronic obstructive pulmonary disease only if the SpO2 is less than 88%, with titration to achieve an SpO2 of 88-92%, and the delivery of bronchodilators by air-driven nebulisation or metered dose inhaler with a spacer. The aim of this review is to provide an overview of the evidence base that underpins these recommendations. We suggest that their implementation will require important changes to current clinical practice in which there is an entrenched culture of the use of high concentration oxygen therapy.

The effect of 1g of acetaminophen twice daily for 12 weeks on alanine transaminase levels--A randomized placebo-controlled trial.

OBJECTIVE: Acetaminophen is often used on a regular, daily basis for the treatment of chronic pain; however, the safety of regular acetaminophen is still debated. This study determined whether 12 weeks of treatment with acetaminophen at half the maximum recommended daily dose causes an increase in alanine transaminase (ALT) in healthy adults participating in a clinical trial of the effect of acetaminophen on asthma control and severity. DESIGN AND METHODS: 94 healthy adults aged 18-65 years with mild to moderate asthma and with no history of previous liver dysfunction and an ALT within 1.5 times the upper limit of normal at baseline participated in a randomized, double-blind, placebo-controlled, parallel-group, clinical trial of 1g of acetaminophen twice daily or placebo twice daily for 12 weeks. Liver function monitoring was undertaken at baseline, weeks 2, 4, 6 and 12. The primary outcome variable was mean ALT levels at week 12 compared to baseline in the acetaminophen group versus placebo group. RESULTS: 94 participants were randomized and commenced study treatment. One participant in each treatment group was withdrawn due to an increase in ALT to greater than three times the upper limit of normal. Mean ALT at week 12 was 25.4I U/L (SD 9.7) in the acetaminophen group (N=31) and 19.0 IU/L (SD 6.0) in the placebo group (N=54). After controlling for baseline this represented a statistically significant difference of 3.6 IU/L (95% CI 1.3 to 6.0, P=0.003). There was no progressive increase in ALT demonstrated throughout the trial. CONCLUSIONS: Regular, daily use of acetaminophen at half the maximum recommended daily dose for 12 weeks in a healthy adult population is associated with a small elevation in mean ALT of no probable clinical significance. Further assessment of the effects on liver function of the maximum recommended dose of acetaminophen is required.

Comparative audit of oxygen use in the prehospital setting in acute COPD exacerbation over 5†years.

BACKGROUND: In 2009 the Wellington Free Ambulance implemented an education programme to reduce high concentration oxygen delivery to patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The aim of this audit was to compare pre-hospital oxygen delivery to patients with AECOPD before and after the programme. METHODS: An audit of patients who presented to Wellington Regional Hospital by ambulance with an AECOPD in 2005 and then in 2010, after implementation of the education programme. Oxygen therapy was categorised as: HIGH, supplemental high concentration oxygen therapy ≥3 L/min and/or delivery via high concentration mask; NEB, high concentration oxygen only during nebuliser use; or LOW, neither of these. RESULTS: In 2005 those in the HIGH, NEB and LOW categories were 81 (75.0%), 18 (16.7%) and 9 (8.3%) of 108 identified patients. In 2010 those in the HIGH, NEB and LOW categories were 80 (44.0%), 61 (33.5%) and 41 (22.5%) of 182 identified patients. The proportions of patients in the three oxygen groups were significantly different between 2005 and 2010 (p<0.001). CONCLUSIONS: The proportion of patients administered supplemental high concentration oxygen therapy markedly decreased between 2005 and 2010 following implementation of the education programme. However, in 2010 more than half of the patients not managed with high concentration oxygen therapy were still exposed to high concentration oxygen through the use of oxygen-driven nebulisers. To reduce exposure to high concentration oxygen in AECOPD the use of air-driven nebulisers or metered dose inhalers with spacers is required.

A retrospective case series of 44 patients with community-acquired Staphylococcus aureus pneumonia.

AIM: Staphylococcus aureus (S. aureus) community-acquired pneumonia (CAP) is a potentially devastating and life-threatening infection. Early detection and appropriate treatment is important to prevent morbidity and death. The aim of this case series was to investigate the patient demographics, clinical features, antibiotic treatment and complications of cases of community-acquired S. aureus pneumonia occurring in the Wellington region. METHOD: The case records of patients with radiographically confirmed community-acquired pneumonia and laboratory evidence to support S. aureus as the causative organism admitted to Wellington Regional Hospital over a 5-year period (2007-2012) were retrospectively reviewed. RESULTS: A total of 48 presentations in 44 patients met the inclusion criteria. The majority of patients (63.6%) had underlying comorbidities. Although the mean CURB65 score was only one and fever was uncommon, 30% of patients were admitted to ICU and 16% died in hospital. Significant infective complications occurred in 48% with new lung cavitation in 20%. CONCLUSION: This series of patients with staphylococcal pneumonia confirms the significant morbidity and mortality of the infection. A low CURB65 score and lack of objective fever should not detract from the possibility of S. aureus. The presence of bacteraemia in patients with S. aureus pneumonia needs to be regarded as a potentially deleterious finding that may necessitate a change in treatment.

Randomised placebo-controlled study of the effect of paracetamol on asthma severity in adults.

OBJECTIVE: To investigate the effect of regular paracetamol on bronchial hyper-responsiveness (BHR) and asthma control in adult asthma. SETTING: Single research-based outpatient clinic. PARTICIPANTS: 94 adults with mild-to-moderate asthma received randomised treatment; 85 completed the study. Key inclusion criteria were age 18-65 years, forced expiratory volume in 1 s (FEV1) >70% predicted, provocation concentration of methacholine causing a 20% reduction in FEV1 (PC20) between 0.125 and 16 mg/mL. Key exclusion criteria included an asthma exacerbation within the previous 2 months, current regular use of paracetamol, use of high-dose aspirin or non-steroidal anti-inflammatory drugs, current or past cigarette smoking >10 pack-years. INTERVENTIONS: In a 12-week randomised, double-blind, placebo-controlled, parallel-group study, participants received 12 weeks of 1 g paracetamol twice daily or placebo twice daily. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was BHR, measured as the PC20 at week 12. Secondary outcome variables included FEV1, fractional exhaled nitric oxide (FeNO) and asthma control questionnaire (ACQ) score. RESULTS: At 12 weeks, the mean (SD) logarithm base two PC20 was 1.07 (2.36) in the control group (N=54) and 0.62 (2.09) in the paracetamol group (N=31). After controlling for baseline PC20, the mean difference (paracetamol minus placebo) was -0.48 doubling dose worsening in BHR in the paracetamol group (95% CI -1.28 to 0.32), p=0.24. There were no statistically significant differences (paracetamol minus placebo) in log FeNO (0.09 (95% CI -0.097 to 0.27)), FEV1 (-0.07 L (95% CI -0.15 to 0.01)) or ACQ score (-0.04 (95% CI -0.27 to 0.18)). CONCLUSIONS: There was no significant effect of paracetamol on BHR and asthma control in adults with mild-to-moderate asthma. However, the study findings are limited by low power and the upper confidence limits did not rule out clinically relevant adverse effects. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry Number: NZCTR12609000551291.

Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial.

BACKGROUND: The Single combination budesonide-formoterol inhaler Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations in patients, but whether the high doses of corticosteroid and ß agonist increase the risk of adverse effects with both short-term and cumulative exposure is not certain. Our aim was to investigate whether the SMART regimen would reduce the risk of overuse of ß agonist, reduce the likelihood of patients to seek medical review when such episodes occurred, and if any reduction in severe asthma exacerbations would be at the cost of a higher burden of systemic corticosteroid. METHODS: In this 24-week trial undertaken at four primary health-care practices and one hospital in New Zealand, patients (aged 16-65 years) with a recent asthma exacerbation were randomly assigned in a 1:1 ratio to the SMART or standard fixed-dose regimen. Treatment in the SMART group consisted of two actuations of budesonide-formoterol (200 µg and 6 µg, respectively, per actuation) twice daily, delivered through a combination metered dose inhaler (MDI), with one extra actuation as needed for relief of symptoms; treatment in the standard group consisted of two actuations of budesonide-formoterol (200 µg and 6 µg, respectively, per actuation) twice daily through a combination MDI with one to two actuations of salbutamol (100 µg per actuation) by MDI as needed for relief of symptoms. MDIs were monitored electronically to measure actual use of medication. The allocation sequence for randomisation was computer generated, with a block size of eight per site. Participants, investigators, and the statistician were not masked to group assignment. The primary outcome was the proportion of participants with at least one high-use episode of ß agonist (more than eight actuations per day of budesonide-formoterol in addition to the four maintenance doses in the SMART group or more than 16 actuations per day of salbutamol in the standard group). Analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000515099. FINDINGS: 303 patients were randomly assigned to the SMART (n=151) or standard group (n=152). No significant difference was noted between the SMART and standard groups in the proportion of participants with at least one high-use episode of ß agonist (84 [56%] vs 68 [45%], respectively, relative risk 1·24 [95% CI 0·99-1·56]; p=0·058). There were fewer days of high use in the SMART group (mean 5·1 days [SD 14·3] vs 8·9 days [20·9], relative rate 0·58 [0·39-0·88]; p=0·01). Of the patients who had at least one high-use episode, those in the SMART group had fewer days of high use without medical review (8·5 days [17·8] vs 18·3 days [24·8], 0·49 [0·31-0·75]; p=0·001). The SMART regimen resulted in higher inhaled corticosteroid exposure (943·5 µg budesonide per day [1502·5] vs 684·3 µg budesonide per day [390·5], respectively; ratio of means 1·22 [1·06-1·41]; p=0·006), but reduced oral corticosteroid exposure (77·5 mg prednisone [240·5] vs 126·6 mg prednisone [382·1], respectively; p=0·011), with no significant difference in composite systemic corticosteroid exposure (793·7 mg prednisone equivalent per year [893·1] vs 772·1 mg prednisone equivalent per year [1062·7], respectively; 1·03 [0·86-1·22]; p=0·76). Participants in the SMART group had fewer severe asthma exacerbations (35 [weighted mean rate per year 0·53] vs 66 [0·97]; relative rate 0·54 [0·36-0·82]; p=0·004). INTERPRETATION: The SMART regimen has a favourable risk-to-benefit profile and can be recommended for use in adults at risk of severe asthma exacerbations. FUNDING: Health Research Council of New Zealand.

Use of metered-dose inhaler electronic monitoring in a real-world asthma randomized controlled trial.

BACKGROUND: Electronic monitoring of inhaled asthma medications is one method to measure medication adherence and patterns of use. Information on the performance of monitors in a randomized controlled trial allows researchers and clinicians to understand their utility and limitations. The Smartinhaler Tracker is an electronic monitor for metered-dose inhalers (MDIs) that records the date, time, and number of actuations. OBJECTIVE: To determine the performance of the Smartinhaler monitors used in a 24-week randomized controlled trial of 303 patients with asthma in a real-world setting. METHODS: Prestudy use checks involved 2 actuations of the MDI, with a further 2 performed 2 hours later. Within-study monitor checks, performed before dispensing at clinic visits 2 to 4, included a computerized check of monitor clock function, actuation accuracy, and battery life. Within-study data checks involved computerized checks of monitor clock function before data upload. RESULTS: Two thousand six hundred seventy-eight of 2728 monitors (98.2%) passed prestudy use checks. Seventy-six of 2642 monitors (2.9%) dispensed to participants failed within-study monitor checks. Fifty-one of 2642 monitors (1.9%) malfunctioned before data upload, mostly as a result of fluid immersion. Ninety-three of 2642 monitors (3.5%) were lost or thrown away by participants. Complete data was available from 2498 of 2642 dispensed monitors (94.5%) and 2498 of 2549 returned monitors (98.0%). CONCLUSIONS: The Smartinhaler Tracker is a reliable monitor for measuring MDI use in a real-world setting. Use of extensive monitor and data-checking protocols reduces data loss. In a research or clinical setting, the use of a validated and reliable electronic monitor represents the reference standard for assessing patterns of medication use.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: In this retrospective analysis from a previously completed prospective 24-week randomized, controlled trial of single or combination ICS/LABA therapy, medication use in the week prior to study visits determined by self-report questionnaire and electronic monitoring was compared. One hundred eleven participants received 125 µg fluticasone dipropionate and 25 µg salmeterol, two actuations twice daily, by either separate or combination ICS/LABA inhalers. Paired data for self-report and electronic monitoring were analysed. Measurement of agreement was by Bland-Altman-like plots by visit with calculation of limits of agreement. RESULTS: For single and combination ICS/LABA therapy, self-report consistently overestimated actual inhaler use assessed by electronic monitoring by a mean of 2.2-8.4 inhalations over a 1-week period, with limits of agreement ranging from ±15.8 to 25.6 inhalations. Participants who underused their inhalers tended to overreport their use, while those who overused tended to underreport their medication use. The greater the degree of underuse, the greater the magnitude of overreport, and likewise, the greater the degree of overuse, the greater the magnitude of underreport. CONCLUSIONS: Self-report is inaccurate in measuring actual use of inhaled asthma treatment with patients who underuse their maintenance therapy overreporting their use and those who overuse their therapy underreporting their use.

The effect of high concentration oxygen therapy on PaCO2 in acute and chronic respiratory disorders.

There is evidence that the potential for high concentration oxygen therapy to increase PaCO2 is not limited to stable and acute exacerbations of COPD, but also to other acute respiratory disorders with abnormal gas exchange such as asthma and pneumonia, and chronic respiratory conditions with hypercapnia such as obesity hypoventilation syndrome. This evidence forms the basis of consensus guidelines which recommend that oxygen therapy is titrated in COPD and other respiratory conditions, to ensure the maximal benefits of oxygen therapy are achieved while reducing the potential for harm due to hyperoxia.

The risk of serious adverse outcomes associated with hypoxaemia and hyperoxaemia in acute exacerbations of COPD.

BACKGROUND: Prehospital high concentration oxygen therapy leads to worse clinical outcomes in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Less is known about the risks of hypoxaemia despite oxygen treatment. Current respiratory and ambulance guidelines recommend titration of supplemental oxygen to a target oxygen saturation range of 88%-92%. AIM: To explore the association between PaO(2) and risk of serious adverse clinical outcomes in AECOPD. METHODS: A retrospective review of consecutive patients presenting via ambulance to the Wellington Regional Hospital Emergency Department with AECOPD between June 2005 and January 2008. Patients with an arterial blood gas taken within 4 h of triage were included in the study and were categorised as hypoxaemic (PaO(2)<60 mm Hg), normoxaemic (PaO(2) 60-100 mm Hg) or hyperoxaemic (PaO(2)>100 mm Hg). Serious adverse outcome was defined as a composite of hypercapnic respiratory failure, assisted ventilation or inpatient death. Multivariate logistic regression analysis examined the association between PaO(2) category and the composite outcome. RESULTS: Of the 680 patients presenting with AECOPD in the review period, 254 presentations in 180 patients had data suitable for analysis. Hyperoxaemia occurred in 61/254 (24%) presentations and was strongly associated with serious adverse outcome compared with normoxaemia (OR 9.17, 95% CI 4.08 to 20.6). Hypoxaemia was also associated with an increased risk of serious adverse outcome compared with normoxaemia (OR 2.16, 95% CI 1.11 to 4.20). Compared with the recommended target oxygen saturation range of 88%-92%, the risk of a serious adverse outcome was increased in both the <88% group (OR 2.0, 95% CI 1.03 to 3.80) and the >96% group (OR 2.37, 95% CI 1.34 to 4.20). CONCLUSIONS: In patients presenting via ambulance to the Emergency Department with AECOPD, serious adverse clinical outcomes are associated with both hypoxaemia and hyperoxaemia. These data provide further support for the principle of titrating supplemental oxygen therapy to target oxygen saturations.

Proposed MHRA changes to UK children's paracetamol dosing recommendations: modelling study.

OBJECTIVES: Paracetamol is the most commonly administered medicine to children. A recent study highlighted the risk of overdose of paracetamol using British National Formulary for Children (BNFC) age-based dosing guidelines. This current study assesses the safety of changes to the UK paracetamol product dosing system proposed by the Medicines and Healthcare products Regulatory Authority (MHRA) which include a larger number of narrower age bands and a single dose per age band. DESIGN: Theoretical comparison of the proposed MHRA dosing system with the product dosing instructions of a commonly prescribed form of paracetamol in the UK. SETTING: United Kingdom Participants Proposed MHRA dosing recommendations and current product dosing instructions were compared using a previously validated model. MAIN OUTCOME MEASURES: For both dosing recommendations, single and cumulative daily doses of paracetamol for boys and girls at the 9th, 50th and 91st centiles for weight were calculated for 3 month, 1 year, 6 year and 12 year age groups. RESULTS: With the current product dosing instructions, underweight children are at risk of receiving approximately two times the recommended single and cumulative daily dose of paracetamol, particularly at age 1 year and 6 years. This risk is negligible when the same model is applied to the proposed MHRA dosing system, whereby underweight, average weight and overweight children at all ages receive doses marginally above or within the recommended dose range or limit. CONCLUSION: The proposed MHRA dosing recommendations for paracetamol use in children are effective at reducing the risk of paracetamol overdose in children of all ages, when compared with current product dosing instructions.

Randomized controlled trial of high concentration oxygen in suspected community-acquired pneumonia.

OBJECTIVE: To determine whether high concentration oxygen increases the PaCO(2) in the treatment of community-acquired pneumonia. DESIGN: Randomized controlled clinical trial in which patients received high concentration oxygen (8 L/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93 and 95%) for 60 minutes. Transcutaneous CO(2) (PtCO(2)) was measured at 0, 20, 40 and 60 minutes. SETTING: The Emergency Departments at Wellington, Hutt and Kenepuru Hospitals. PARTICIPANTS: 150 patients with suspected community-acquired pneumonia presenting to the Emergency Department. Patients with chronic obstructive pulmonary disease (COPD) or disorders associated with hypercapnic respiratory failure were excluded. MAIN OUTCOME VARIABLES: The primary outcome variable was the proportion of patients with a rise in PtCO(2) ≥4 mmHg at 60 minutes. Secondary outcome variables included the proportion of patients with a rise in PtCO(2) ≥8 mmHg at 60 minutes. RESULTS: The proportion of patients with a rise in PtCO(2) ≥4 mmHg at 60 minutes was greater in the high concentration oxygen group, 36/72 (50.0%) vs 11/75 (14.7%), relative risk (RR) 3.4 (95% CI 1.9 to 6.2), P < 0.001. The high concentration group had a greater proportion of patients with a rise in PtCO(2) ≥8 mmHg, 11/72 (15.3%) vs 2/75 (2.7%), RR 5.7 (95% CI 1.3 to 25.0), P = 0.007. Amongst the 74 patients with radiological confirmation of pneumonia, the high concentration group had a greater proportion with a rise in PtCO(2) ≥4 mmHg, 20/35 (57.1%) vs 5/39 (12.8%), RR 4.5 (95% CI 1.9 to 10.6) P < 0.001. CONCLUSIONS: We conclude that high concentration oxygen therapy increases the PtCO(2) in patients presenting with suspected community-acquired pneumonia. This suggests that the potential increase in PaCO(2) with high concentration oxygen therapy is not limited to COPD, but may also occur in other respiratory disorders with abnormal gas exchange.

High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomized controlled trial.

BACKGROUND: The optimal approach to oxygen therapy in ST-elevation myocardial infarction (STEMI) is uncertain. METHODS: A randomized controlled trial was undertaken in which 136 patients presenting with their first STEMI uncomplicated by cardiogenic shock or marked hypoxia were randomized to receive high-concentration (6 L/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturation 93%-96%) for 6 hours after presentation. The main outcome variables were 30-day mortality and infarct size assessed by troponin T level at 72 hours. Secondary outcomes included a meta-analysis of mortality data from this study and previous randomized controlled trials, and infarct size was assessed by magnetic resonance imaging at 4 to 6 weeks. RESULTS: There were 1 of 68 and 2 of 68 deaths in the high-concentration and titrated oxygen groups, respectively; a meta-analysis including these data with those from the 2 previous studies showed an odds ratio for mortality of high-concentration oxygen compared with room air or titrated oxygen of 2.2 (95% CI 0.8-6.0). There was no significant difference between high-concentration versus titrated oxygen in troponin T (ratio of mean levels 0.74, 95% CI 0.50-1.1, P = .14), infarct mass (mean difference -0.8 g, 95% CI -7.6 to 6.1, P = .82), or percent infarct mass (mean difference -0.6%, 95% CI -5.6 to 4.5, P = .83). CONCLUSION: This study found no evidence of benefit or harm from high-concentration compared with titrated oxygen in initially uncomplicated STEMI. However, our estimates have wide CIs, and as a result, large randomized controlled trials are required to resolve the clinical uncertainty.