An 63 year old woman with a history of bronchiectasis required intubation for a community acquired pneumonia. Several days into her ICU admission she developed a rapid worsening in her oxygenation and new bilateral pulmonary infiltrates. She also required increasing vasopressor support and began to develop multiorgan failure. She was paralysed and ventilated with inverse ratios but remained profoundly hypoxic. She was proned with no effect on oxygenation. She was commenced on inhaled nitric oxide with no effect. She continued to rapidly deteriorate and died shortly after.
Does prone ventilation in ARDS improve mortality?
David Garry
ARDS is characterised by hypoxaemia, pulmonary congestion and a decrease in lung compliance. It is associated with substantial morbidity; according to the new Berlin definition (1) the mortality ranges from 27% for mild ARDS to 45% for severe ARDS.
Prone ventilation for acute respiratory distress syndrome has been increasingly used since a 1976 study on five patients showed an improvement in oxygenation with no adverse effects. Prone position optimises both lung recruitment and ventilation-perfusion matching. There is less gravitational collapse of the ventral lung segments in the prone position than that of dorsal lung segments in the supine position, and lung perfusion in the prone position is more evenly distributed. Other benefits may arise from enhanced postural drainage of secretions and a decrease in alveolar overdistension. Prone positioning has been shown in randomised controlled trials to improve oxygenation (2,3) and prevent ventilator induced lung injury (4,5,6). Individual trials have until recently failed to translate these physiological benefits into better patient outcomes (7-10), with survival benefits only seen in meta-analyses (3,11).
Guerin et al (12) conducted a prospective multicentre randomised controlled trial of early prone positioning in severe ARDS that was published in 2013. Four hundred and sixty six patients were included from 27 ICUs. The inclusion criteria were severe ARDS (defined as a PaO2:FiO2 ratio < 150mmHg, with an FiO2 > 0.06, a PEEP > 5 and a tidal volume of 6ml/kg of predicated body weight) and mechanical ventilation for ARDS less than 36 hours. Two hundred and thirty seven patients were assigned to the prone group, they were turned to the prone position within the first hour of randomisation, for a minimum of 16 consecutive hours. Two hundred and twenty nine patients were assigned to the supine group, they were maintained in the semi-recumbent position. Patients in both groups were ventilated with a tidal volume of 6ml/kg of predicted body weight, and PEEP levels according to a PEEP-FiO2 table. Ventilation targets included a maximal plateau pressure of 30 and pH of 7.20-7.45. Prone treatment was stopped if the patient showed an improvement in oxygenation in the supine position or if there were complications during a prone session leading to its immediate interruption (accidental extubation, endobronchial intubation, endotracheal tube obstruction, haemoptysis, desaturation, cardiac arrest and cardiovascular instability). Patients in the prone group received an average of 4+/-4 sessions per patient, with a mean duration of 17+/-3 hours per session. They spent an average of 73% of their time on a mechanical ventilator in the prone position from the start of the first session to the end of the last session. When patients in the prone group were turned to the supine position they were assessed at 4 hours for resumption of the prone position (or earlier if criteria for oxygenation were met). This strategy was continued for 28 days, after which it was used at the clinician’s discretion. Patients in the supine position were crossed over as a rescue measure once they met a pre-specified set of criteria (including an FiO2 of 1.0, inhaled nitric oxide, an infusion of almitrine bismesylate and recruitment manoeuvres). The results were analysed using an intention to treat basis. The primary endpoint was mortality at 28 days, secondary endpoints were mortality at 90 days, rate of successful extubation, time to successful extubation, length of stay in the ICU, complications, use of non-invasive ventilation, tracheotomy rate, number of organ failure free days, ventilator settings, arterial blood gases and respiratory mechanics.
Mortality at 28 days was significantly lower in the prone group (16.0% vs 32.8%, p<0.001). This survival benefit persisted at 90 days (23.6% vs 41.0%, p<0.001). It also persisted when the 2 groups were adjusted for the SOFA score, use of neuromuscular blocking agents and vasopressors. The prone group also had a significantly higher rate of successful extubation. In terms of complications, the only significant difference was in the rate of cardiac arrests (16 in the prone group vs 31 in the supine group, p=0.02).
Lessons learnt
Prior randomised controlled trials have demonstrated that proning leads to an improvement in oxygenation, and is a safe manoeuvre with little incidence of complications. The study by Guerin et al. was consistent with the findings of the 2 meta-analyses, showing a survival benefit. It did not show any complications associated with proning, with a significantly lower rate of cardiac arrest in the prone group. Patients with ARDS and severe hypoxaemia can benefit from prone treatment when it is used early and in relatively long sessions.
References
1 The ARDS Definition Task Force. Acute Respiratory Distress Syndrome, The Berlin Definition. JAMA, June 20, 2012—Vol 307, No. 23
2 Abroug F, Ouanes-Besbes L, Elatrous S, Brochard L. The effect of prone posi- tioning in acute respiratory distress syndrome or acute lung injury: a meta-analysis: areas of uncertainty and recommendations for research. Intensive Care Med 2008; 34: 1002-11.
3 Sud S, Friedrich JO, Taccone P, et al. Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis. Intensive Care Med 2010; 36: 585-99.
4 Broccard A, Shapiro RS, Schmitz LL, Adams AB, Nahum A, Marini JJ. Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs. Crit Care Med 2000; 28: 295-303.
5 Mentzelopoulos SD, Roussos C, Zakynthinos SG. Prone position reduces lung stress and strain in severe acute respiratory distress syndrome. Eur Respir J 2005; 25: 534-44.
6 Galiatsou E, Kostanti E, Svarna E, et al. Prone position augments recruitment and prevents alveolar overinflation in acute lung injury. Am J Respir Crit Care Med 2006; 174: 187-97.
7 Papazian L, Gainnier M, Marin V, et al. Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome. Crit Care Med 2005; 33: 2162-71.
8 Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001; 345: 568-73.
9 Guerin C, Gaillard S, Lemasson S, et al. Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 2004; 292: 2379-87.
10 Mancebo J, Fernández R, Blanch L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med 2006; 173: 1233-9.
11 Gattinoni L, Carlesso E, Taccone P, Polli F, Guérin C, Mancebo J. Prone posi- tioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis. Minerva Anestesiol 2010; 76: 448-54.
12 Guerin C, Reigner J, Richard JC et al. Prone positioning in severe acute respiratory distress syndrome. NEJM. http://www.nejm.org/doi/full/10.1056/NEJMoa1214103#t=articleTop. Accessed on 30/05/13
ICM Case Summaries 