Tidal volumes during general anesthesia: size does matter!

I N this issue of ANESTHESIOLOGY, Lellouche et al. report on the results of a prospective observational trial that investigated the effects of low, traditional, and high tidal volumes (less than 10, 10– 12, and more than 12 ml/kg of predicted body weight [PBW], respectively) delivered after admission into the intensive care unit on the development of organ dysfunction after cardiac surgery. Organ dysfunction was defined as mechanical ventilation exceeding 24 h (prolonged mechanical ventilation), use of vasopressors or inotropes for more than 48 h after surgery (hemodynamic instability), or increase in creatinine levels more than 50 M after surgery compared with baseline values (renal failure), according to the Society of Thoracic Surgeons. ‡ Authors found that low tidal volumes, i.e., less than 10 ml/kg of PBW, have been used in only about 21% of 3,434 patients included in the study, whereas the vast majority received tidal volumes more than 10 ml/kg, or even more than 12 ml/kg of PBW. Such findings are not really surprising and mirror clinical practice worldwide, where protective ventilation has been regarded as superfluous, because uninjured lungs shall be robust enough to overcome tidal volumes of that magnitude. The striking finding by Lellouche et al., however, is that such common practice (tidal volumes of more than 10 ml/kg of PBW) was associated with prolonged mechanical ventilation, hemodynamic instability, higher incidence of renal failure, and prolonged stay in the intensive care unit among patients who underwent cardiac surgery, compared with low tidal volumes. In addition, high tidal volumes (more than 12 ml/kg of PBW) were an independent risk factor for multiple organ failure. Organ failure was associated with increased intensive care unit stay, hospital mortality, and long-term mortality. Authors concluded that prophylactic protective ventilatory strategies should be provided in populations with an inflammatory state (virtually all critically ill patients) who are at risk of developing ventilator-associated lung injury. In patients suffering from acute lung injury and its more severe form, the acute respiratory distress syndrome, the importance of mechanical ventilation with tidal volumes in the range of 4–8 ml/kg of PBW is undisputed. This clinical data has been extensively supported by studies on the mechanisms of ventilator-associated lung injury. According to those studies, straining of the lung tissue beyond a certain limit results in a level of stress that may induce cells to release inflammatory cytokines, a phenomenon known as mechanotransduction. Strain is defined as the deformation of a material with elastic properties relative to its initial length (or volume). However, a given tidal volume (volumetric strain) will result in different levels of stress depending on the resting end-expiratory lung volume at airway pressure of 0 cm H2O. Thus, a tidal volume higher than 10 ml/kg may not induce harmful stress, provided the resting end-expiratory lung volume is also proportionally high. Recent studies in healthy animals showed that ventilator-associated lung injury develops only when a strain greater than 1.5–2 is reached or exceeded, and stress reaches the total lung capacity. Inflammation seems to modulate the response of alveolar epithelial cells to strain. Accordingly, the release of inflammatory cytokines as a response to mechanical stress is very dependent on previous activation of the inflammation signaling. In clinical practice, such phenomenon has been translated as “double hit theory,” and high tidal volumes need an “inflammatory background” or previous injury in order to be harmful. Taken together, these mechanisms suggest that there is no need for use of protective mechanical ventilation in the absence of previous lung injury. How then to explain the findings by Lellouche et al. in light of that body of knowledge? First, the concept of stress