minimising ventilator - induced lung injury while providing optimal respiratory support remains challenging . limiting tidal volumes to 6 ml / kg ( predicted body weight ) has been widely adopted , in theory at least , but numerous other debates remain  perhaps most contentiously  regarding positive end - expiratory pressure ( peep ) . two large trials investigating the optimal ventilatory approach to patients with acute lung injury have recently been published . in the first , a combined canadian , australian and saudi arabian multicentre study , 983 patients were randomised to a 6 ml / kg ( predicted body weight ) tidal volume with either established ardsnet peep settings or a ' high peep strategy with recruitment manoeuvres ' . of note , plateau pressures in the lower peep group were limited to 30 cmh2o whilst those in the high - peep group were limited to 40 cmh2o . the protocol produced a significantly higher average peep in the experimental group , with consequently higher plateau pressures . there was no difference between the two groups with regard to the 28-day mortality , ventilator days , intensive care unit days or days of hospitalisation . there was a significant reduction in the high - peep group in the incidence of refractory hypoxaemia and the use of rescue therapies . in short , the high - peep strategy did no harm  and may have done some good , in terms of improvements in short - term physiology  but these results did not translate into statistically significant outcome improvements , although there was a trend suggesting that a significantly larger trial might produce such an outcome . the second study , a french multicentre randomised control trial , investigated 767 patients with acute lung injury . the patients were randomised to either a minimal distension strategy ( intrinsic plus extrinsic peep 5 to 9 cmh2o ) or a recruitment strategy , in which the peep was maximised and plateau pressures were maintained between 28 and 30 cmh2o . there was a significant reduction in ventilator - free days , organ - failure - free days and the need for adjunctive therapies in the recruitment group . in short , two large studies asking similar questions with significantly different , detailed , protocols reach the same conclusion  that setting a higher peep is noninjurious and is possibly beneficial , but only in secondary endpoints . of note , due to the real - world practicalities of trial recruitment , the majority of patients had received many hours of ' routine ' mechanical ventilation prior to study entry , thus potentially missing the vital early effect of any strategy . alongside these impressive studies are two editorials that discuss not only these two papers but also the wider problem of how to investigate complex care in the critically ill patient . a series of similar papers and editorials have also appeared over the past few months . there appears to be a growing consensus that trials , such as the two discussed above , represent a huge amount of work but are rarely , if ever , likely to result in clear evidence upon which to base the treatment of an individual patient . for example , if one takes lung - protective ventilation to its logical extreme , then alternative modes of ventilation such as airway pressure release ventilation or high - frequency oscillatory ventilation should provide even greater benefit than a low - tidal - volume high - peep strategy , yet they remain principally the province of enthusiasts or are reserved for rescue modalities . similarly , the use of permissive hypoxaemia and hypercapnia in such patients results in less injurious ventilation strategies , but awaits large - scale investigation . to conclude , despite the very great efforts employed by the investigators of these two studies , there remain more questions than answers . 2-agonists have been shown to enhance the clearance of alveolar and interstitial pulmonary oedema in a number of experimental settings . , 24 patients undergoing elective lung resection , who were preoperatively assessed to be at high risk of postoperative pulmonary oedema , were given nebulised salbutamol and ipratropium at 6-hourly intervals in a randomised order and in a blinded fashion . the oxygenation index , cardiac index , extravascular lung water index and pulmonary vascular permeability index were assessed preoperatively and postoperatively as well as pre and 50 minutes post each nebulised therapy . salbutamol , but not ipratropium , induced on average a 20% reduction in both parameters , together with a sustained improvement in the oxygenation index and cardiac index . in the second study , a rat model of acute lung injury was used to test the effects of terbutaline instillation versus systemic administration . radiolabelled proteins were quantified in various body compartments over time to assess the flux across the alveolar epithelium and pulmonary capillary endothelium . in a complex series of experiments involving a variety of injurious ventilation strategies , pulmonary instillation of terbutaline reduced protein flux across both barriers whereas systemic terbutaline only reduced the flux from the circulation into the alveoli  in essence , suggesting that 2-agonists may be more efficacious when nebulised rather than when administered systemically . in stark contrast to the large acute lung injury trials described above , a small trial has been published investigating the effects of complete diaphragmatic inactivity coupled , of course , with mechanical ventilatory support . the investigators took diaphragm biopsies from 14 brain - dead organ donors and compared them with eight patients having elective thoracic surgery . the former had been ventilated for 18 to 69 hours , and the control group for 2 to 3 hours . the study adds significantly to a number of previous small studies suggesting that maintaining at least some spontaneous breathing effort in mechanically patients should be attempted . the diaphragmatic injury caused by mandatory ventilatory modes coupled with the sedation and sometimes neuromuscular blockade required to achieve them may well have been underestimated , to say nothing of the deleterious effects on ventilation and perfusion in the dependent lung . ventilator - induced diaphragm injury appears to be yet another potentially avoidable , organ - supportive , iatrogenic injury to add to the seemingly ever - growing list . to round off the respiratory theme , a simple but elegant study has been published that examines the added value of measuring b - type natriuretic peptide ( bnp ) before and after a spontaneous breathing trial in predicting extubation failure . there has been a plethora of studies assessing the diagnostic value of bnp testing in the patient presenting with dyspnoea , with elevated levels being associated with cardiac dysfunction and , most usefully , with a negative predictive value rather than a positive one . in the critically ill patient , however , bnp is merely a marker of cardiac strain and is universally elevated in hyperdynamic and shocked patients , regardless of the aetiology . in this study , 41 patients who met a standard set of criteria for extubation were subjected to a 2-hour t - piece trial to assess their suitability . bnp levels were measured just prior to and at the end of the trial . a greater than 20% increase in bnp levels accurately and reliably predicted extubation failure . this cutoff value was then prospectively tested in a further cohort of 49 patients with almost identical results . with the potential advent of near - patient testing for bnp , this may prove to be a valuable adjunctive assessment to promote both a more successful and possibly a more aggressive approach to liberating patients from mechanical ventilation . as i have previously commented in this series of editorials , oxygen  perhaps the first therapy we instigate in critically ill patients  remains poorly understood in terms of both benefit and injury . to highlight this subject , another detailed animal experiment has been published suggesting that hyperoxia has significant beneficial effects as a component of early resuscitation in severe sepsis . barth and colleagues induced faecal peritonitis in 20 anaesthetised pigs , and randomised one - half to receive just enough oxygen to maintain arterial haemoglobin oxygen saturations  90% and the other half to receive 100% inspired oxygen . the animals were very intensively monitored and continuously resuscitated with fluids and vasopressors for 24 hours before being euthanised . the hyperoxic pigs showed no evidence of oxygen toxicity but instead demonstrated attenuated end - organ dysfunction in the lungs , liver and kidney . whether an anesthetised pig with continuous and aggressive haemodynamic support represents a good model for the shocked human is debateable , but with the increasing evidence in favour of hyperoxia and very limited data of oxygen toxicity in humans , this simple , cheap and easily available therapy warrants investigation in patients . bnp = b - type natriuretic peptide ; peep = positive end - expiratory pressure .
recent papers discussed include two large , multicentre , high - positive end - expiratory pressure trials in acute lung injury and reflects upon the usefulness of such trial designs . 
 further papers considered include the emerging story of 2-agonists for pulmonary oedema , highlights the newly described , iatrogenic demon , of ventilator - induced diaphragm injury , promotes the addition of b - type natriuretic peptide testing to the prediction of extubation success , and muses again over the oxygen debate .