Strategies to improve hypoxaemia in the ventilated patient

Setting Positive End-Expiratory Pressure Despite the experimental data that provide striking evidence that PEEP may reduce the damages of mechanical ventilation, the largest studies comparing higher versus lower PEEP levels in unselected ALI/ARDS patients were unable to find any difference in outcome. It has been suggested that PEEP should be of benefit in patients with higher lung recruitability and useless or harmful in patients with low lung recruitability. Actually two meta-analyses seem to confirm this hypothesis. The meta-analysis by Phoenix et al. showed a trend towards improved survival in the high PEEP group with no evidence of increase in barotrauma. The other meta-analysis by Briel et al. on the largest 3 trials reported no treatment effect on hospital survival between higher and lower PEEP groups while a significant improved survival was found in patients in presence of ARDS defined as PaO2/FiO2 ≤ 200. In contrast, in patients with mild and moderate ARDS, higher PEEP seemed harmful. These results roughly account for what we know about the ARDS pathophysiology. In fact the putative beneficial effect of PEEP on survival should be related to the prevention of excessive regional stress and strain by keeping open lung regions that would otherwise collapse. When we studied lung recruitability in an unselected ALI/ARDS population, we found that it varied from 0% to more than 50% of the whole lung. We found that severity of lung injury was associated with higher lung recruitability and more severe hypoxemia, greater deadspace, and lower compliance of the respiratory system. By arbitrarily dividing the study population into patients with higher or lower lung recruitability, we first observed that in the latter, the amount of recruitable lung was almost negligible, amounting to about 50 g of tissue weight. The response to the application of higher levels of PEEP was minimal and much lower than that observed in patients with higher lung recruitability. Prone Position In the prone position, CT-scan densities redistribute from dorsal to ventral as the dorsal region tends to re-expand while the ventral zone tends to collapse. Although gravitational influence is similar in both positions, dorsal recruitment usually prevails over ventral de-recruitment, due to the need for the lung and its confining chest wall to conform to the same volume. The final result of proning is that the overall lung inflation is more homogeneous from dorsal to ventral than in the supine position with more homogeneously distributed stress and strain. As the distribution of perfusion remains nearly constant in both postures, proning usually improves oxygenation. Animal experiments clearly show that prone positioning delays or prevents ventilation-induced lung injury, likely due in large part to more homogeneously distributed stress and strain. Over the last 15 years, five major trials have been conducted to compare prone and supine position in ARDS regarding survival advantage. The sequence of trials enrolled patients who were progressively more hypoxemic, exposure to prone position was extended from 8 to 17 hours/day, and lung protective ventilation was more rigorously applied. Single patient and meta-analyses drawing from the four major trials showed significant survival benefit in patients with PaO2/FiO2 lower than 100. The latest PROSEVA trial confirmed these benefits in a formal randomized study. The bulk of data indicates that in severe ARDS, carefully performed prone positioning offers an absolute survival advantage of 10-17%, making this intervention highly recommended in this specific population subset.