In the previous issue of Critical Care, Nakos and colleagues presented interesting experimental research in sheep, reporting beneficial effects of the prone position on the damage of mechanical ventilation (MV) on lung tissue and apoptosis in several vital organs 1. These observations are an interesting addition to a number of experimental and clinical studies showing that MV can initiate as well as exacerbate lung injury, and can worsen other vital organ function 23. Ventilator-induced injury (VILI) can thereby contribute to an unfavourable outcome. At least two different basic mechanisms are involved in VILI and peripheral organ dysfunction: direct mechanical lung damage and enhancement of inflammatory changes in pulmonary tissue 4. As a result, subsequent pathophysiological pathways contribute to clinical symptoms and morbidity, including translocation of inflammatory mediators, endotoxins and bacteria from the lung to the systemic circulation 4. The clinical relevance of VILI in the intensive care unit is confirmed by the beneficial effects on outcome of protective ventilatory techniques 56, including the use of lower tidal volumes and plateau pressures, as well as higher levels of positive end-expiratory pressure.
The study of Nakos and colleagues 1 expands the findings of two recent publications on potentially beneficial effects of the prone position on VILI and its systemic complications 78. In an experimental work on normal rats, Valenza and colleagues 7 observed a more homogeneous distribution of lung strain during MV in the prone position, assessed by computed tomography. These data suggest that a better distribution of alveolar ventilation in the prone position could be the cause of the delayed occurrence of VILI compared with the supine position 7. In the other recent investigation, Mentzelopoulos and colleagues 8 examined the overall parenchymal lung stress and strain, estimated from the transpulmonary plateau pressure and the tidal volume to end-expiratory lung volume ratio, in 10 patients with severe ARDS. Both of these indexes were reduced in the prone position compared with the semirecumbant position. This suggests that lung tissue damage by VILI can be reduced by the prone position 9.
In the aforementioned study of VILI in normal sheep, Nakos and colleagues add information on function and apoptotic changes in other vital organs 1. It is noteworthy that the type of MV used (tidal volume of 15 ml/kg body weight and positive end-expiratory pressure of 3 cmH2O) for a duration of only 90 minutes did produce marked alterations in the lung and certain distal organs. The prone position made a significant difference only for the lung, the liver and the diaphragm. In contrast, apoptotic changes in the kidney, the brain and the intestine were no different between the supine and prone positions.
How could these findings be explained? First, the modifications of lung histology observed are in line with some earlier studies 79101112 and could be explained by differences in the distribution of ventilation, in tissular stress and strain as well as in changes of interactions between the weight of the heart and underlying lung tissue in the supine and prone positions. More novel approaches may be needed to explain the different intensities of apoptosis observed in different organs. Although such observations have been reported previously 13, little is known about the causes of programmed cell death in this situation. One of the suggested mechanisms could be the increased systemic plasma levels of inflammatory mediators and proaptotic soluble factors such as Fas ligand 5613, but this does not explain the profound differences between some organs. Other factors such as different sensibility for these circulating proteins and/or differences in organ perfusion between the supine and prone positions may explain the more protective effect of the prone position for the liver and the diaphragm than for the kidney and the intestine epithelial cells.
These changes in cell biology induced by MV and the protective role of the body position seem an exciting area for further research. The optimal position in an intensive care unit patient in regard to VILI remains to be defined, and it could be different from the sheep model studied by Nakos and colleagues.