William Tunnicliffe

High-frequency oscillation for acute respiratory distress syndrome.

BACKGROUND Patients with the acute respiratory distress syndrome (ARDS) require mechanical ventilation to maintain arterial oxygenation, but this treatment may produce secondary lung injury. High-frequency oscillatory ventilation (HFOV) may reduce this secondary damage. METHODS In a multicenter study, we randomly assigned adults requiring mechanical ventilation for ARDS to undergo either HFOV with a Novalung R100 ventilator (Metran) or usual ventilatory care. All the patients had a ratio of the partial pressure of arterial oxygen (PaO) to the fraction of inspired oxygen (FiO) of 200 mm Hg (26.7 kPa) or less and an expected duration of ventilation of at least 2 days. The primary outcome was all-cause mortality 30 days after randomization. RESULTS There was no significant between-group difference in the primary outcome, which occurred in 166 of 398 patients (41.7%) in the HFOV group and 163 of 397 patients (41.1%) in the conventional-ventilation group (P=0.85 by the chi-square test). After adjustment for study center, sex, score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the initial PaO:FiO ratio, the odds ratio for survival in the conventional-ventilation group was 1.03 (95% confidence interval, 0.75 to 1.40; P=0.87 by logistic regression). CONCLUSIONS The use of HFOV had no significant effect on 30-day mortality in patients undergoing mechanical ventilation for ARDS. (Funded by the National Institute for Health Research Health Technology Assessment Programme; OSCAR Current Controlled Trials number, ISRCTN10416500.).

Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial

Summary Background In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS. Methods We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2/FIO2) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86. Findings We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03–2·08). Interpretation Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended. Funding UK Medical Research Council, UK Department of Health, UK Intensive Care Foundation.

Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome

BackgroundKerbs von Lungren 6 antigen (KL-6) is expressed on the surface of alveolar type II cells, and elevated plasma and epithelial lining fluid levels of KL-6 have previously been shown to correlate with the severity of disease and survival in acute respiratory distress syndrome (ARDS). The relationship between alveolar inflammation and KL-6 measurements has not been ascertained. We hypothesized that the elevation of KL-6 in ARDS is dependent upon the severity of neutrophilic inflammation. Furthermore we were interested in the relationship between significant alveolar infection and KL-6 levels.MethodsPlasma arterial samples were collected from ARDS patients on day 1 and when possible on day 4 along with bronchoalveolar lavage fluid (BALF) samples on the same day. Bacterial growth in the BALF was determined by quantitative cultures and was defined as significant at counts >1 × 104 colony-forming units.ResultsPlasma KL-6 levels in ARDS patients were elevated compared with at-risk control individuals (P = 0.014) and with normal control individuals (P = 0.02). The plasma KL-6 level correlated with the Murray Lung Injury Score (r = 0.68, P = 0.001) and with BALF KL-6 (r = 0.3260, P = 0.04). The BALF KL-6 level was detectable in all ARDS cases and was lower on both day 0 and day 4 in those who survived. BALF KL-6 also correlated with the BALF myeloperoxidase activity (r = 0.363, P = 0.027), with the BALF cell count per millilitre (r = 0.318, P = 0.038), with BALF epithelial-cell-derived neutrophil attractant 78; (r = 0.37, P = 0.016) and with BALF vascular endothelial growth factor (r = 0.35, P = 0.024). The BALF KL-6 level of ARDS patients with significant pathogenic bacterial growth was similar compared with those without significant infection.ConclusionKL-6 may represent a useful marker of alveolar type II cell dysfunction in ARDS since the levels reflect the severity of lung injury and neutrophilic inflammation. KL-6 release across the alveolar epithelial barrier is associated with a poor prognosis. The pathophysiological roles of KL-6 in the development of ARDS warrant further study.

A randomised controlled trial and cost-effectiveness analysis of high-frequency oscillatory ventilation against conventional artificial ventilation for adults with acute respiratory distress syndrome. The OSCAR (OSCillation in ARDS) study.

BACKGROUND Patients with the acute respiratory distress syndrome (ARDS) require artificial ventilation but this treatment may produce secondary lung damage. High-frequency oscillatory ventilation (HFOV) may reduce this damage. OBJECTIVES To determine the clinical benefit and cost-effectiveness of HFOV in patients with ARDS compared with standard mechanical ventilation. DESIGN A parallel, randomised, unblinded clinical trial. SETTING UK intensive care units. PARTICIPANTS Mechanically ventilated patients with a partial pressure of oxygen in arterial blood/fractional concentration of inspired oxygen (P : F) ratio of 26.7 kPa (200 mmHg) or less and an expected duration of ventilation of at least 2 days at recruitment. INTERVENTIONS Treatment arm HFOV using a Novalung R100(®) ventilator (Metran Co. Ltd, Saitama, Japan) ventilator until the start of weaning. Control arm Conventional mechanical ventilation using the devices available in the participating centres. MAIN OUTCOME MEASURES The primary clinical outcome was all-cause mortality at 30 days after randomisation. The primary health economic outcome was the cost per quality-adjusted life-year (QALY) gained. RESULTS One hundred and sixty-six of 398 patients (41.7%) randomised to the HFOV group and 163 of 397 patients (41.1%) randomised to the conventional mechanical ventilation group died within 30 days of randomisation (p = 0.85), for an absolute difference of 0.6% [95% confidence interval (CI) -6.1% to 7.5%]. After adjustment for study centre, sex, Acute Physiology and Chronic Health Evaluation II score, and the initial P : F ratio, the odds ratio for survival in the conventional ventilation group was 1.03 (95% CI 0.75 to 1.40; p = 0.87 logistic regression). Survival analysis showed no difference in the probability of survival up to 12 months after randomisation. The average QALY at 1 year in the HFOV group was 0.302 compared to 0.246. This gives an incremental cost-effectiveness ratio (ICER) for the cost to society per QALY of £88,790 and an ICER for the cost to the NHS per QALY of £ 78,260. CONCLUSIONS The use of HFOV had no effect on 30-day mortality in adult patients undergoing mechanical ventilation for ARDS and no economic advantage. We suggest that further research into avoiding ventilator-induced lung injury should concentrate on ventilatory strategies other than HFOV. TRIAL REGISTRATION Current Controlled Trials ISRCTN10416500.

Applied Lung Physiology

This chapter has been written by two clinicians with immense experience in the measurement and interpretation of lung function testing; one a physician and one a physiologist, but both extremely passionate about educating others in understanding lung function. As an introduction to lung function testing for the trainee respiratory physician, this chapter covers some of the essential questions including “Why test lung function?”, “What’s normal and abnormal lung function?”, and “What are the basic principles of the main lung function tests?”

High-Frequency Oscillation for Acute Respiratory Distress Syndrome

*John Radcliffe Hospital and the †University of Oxford, Oxford, ‡Bristol Royal Infirmary, Bristol, §Queen Elizabeth Hospital, Birmingham, and ||Warwick Clinical Trials, University of Warwick, Warwick, and ¶Intensive Care National Audit and Research Centre, London, UK; and #Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and the Department of Anesthesiology, University of Toronto, Toronto, Ontario, Canada. Copyright * 2013 by Lippincott Williams & Wilkins DOI: 10.1097/01.SA.0000435572.01496.5c