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For Outpatients , Does Regional Anesthesia Truly Shorten the Hospital Stay , and How Should We Define Postanesthesia Care Unit Bypass Eligibility ?

A Key for the Future or Pandora’s Box? IN this issue of ANESTHESIOLOGY, Whitehead et al. bring experimental evidence suggesting that a high tidal volume ventilation can markedly reduce the release of inflammatory cytokines in response to intratracheal lipopolysaccharide. They attribute this paradoxical effect to a reduction of the alveolar macrophage population and hypothesize that injurious ventilation may increase susceptibility to infection, a detrimental effect that may participate in ventilator-induced lung injury. Clinicians have long known some of the risks of mechanical ventilation. The classic and well-known manifestations of gross barotrauma (air leaks) and the adverse hemodynamic effects of high pressure/volume mechanical ventilation were described shortly after the generalization of mechanical ventilators in intensive care units. More recently, severe histologic distension of bronchoalveolar structures, lung overinflation, large air cysts, and extended bronchiectasis have been reported in acute respiratory distress syndrome (ARDS) patients mechanically ventilated with high tidal volumes and pressures. One of the most important breakthroughs in the ventilatory management of such patients was the recognition of another iatrogenic potential of mechanical ventilation, which has been termed ventilator-induced lung injury (VILI). The concept was derived from animal studies that clearly showed that mechanical ventilation with high airway pressure and tidal volume rapidly caused a permeability-type pulmonary edema with diffuse alveolar damage and was accompanied by severe lung inflammation when protracted. High lung volume rather than pressure was identified as responsible for these abnormalities, hence the term volutrauma. In the 1970s, the recommendation was to deliver generous tidal volumes in the range of 15–20 ml/kg to patients with acute lung injury to provide adequate carbon dioxide elimination and counterbalance the formation of atelectasis with ensuing development of lung regions with low ventilation/perfusion ratios. In the following years, practices progressively moved toward a reduction of tidal volume to values lower than 10 ml/kg, and, interestingly, a decrease in ARDS mortality was simultaneously observed. These progressive changes in ventilation modalities over time were supported by solid pathophysiologic foundations that form the concept of VILI. Definite proof of a causal relation between mortality and ventilatory strategy was given by the results of a multicenter randomized controlled trial that showed better survival in patients ventilated with a 6-ml/kg rather than a 12-ml/kg tidal volume. In addition to the permeability alterations and diffuse alveolar damage observed during VILI, the possibility that lung cell overstretching induced a biochemical reaction was soon investigated. Indeed, lung cell stretch elicits many responses, including opening of ion channels, increased lipid trafficking in cell membranes, and CXC chemokine release. The release of many cytokines by lungs subjected ex vivo to injurious ventilatory modalities was also reported. These findings led to the hypothesis that the multiple organ system dysfunction observed in many patients with ARDS was the result of uncontrolled production of inflammatory cytokines by the lungs and their systemic diffusion because of the alveolocapillary barrier alterations produced by injurious ventilation. Should this hypothesis prove to be true, it would offer both an interesting explanation for the reduced mortality observed with lung-protective ventilation strategies during ARDS and an exciting avenue for the search for newer treatments for this deadly disease. Some authors strongly advocated the use of antiinflammatory therapies during mechanical ventilation of patients with ARDS to decrease the risk and severity of associated organ failure. Given the high costs of such therapies and their potential for adverse effects, their administration should be based on strong and concordant experimental and clinical data. This may not be the case for the time being. Too many inconsistencies and contradictions exist that preclude making a straightforward link between cell responses to stress, VILI, organ failure, and their putative treatments. Detailing these conceptual problems is beyond the scope of this editorial, but several aspects deserve mentioning. Pulmonary and systemic cytokine release was found highly variable during experimental VILI, even when experiments were performed under the same conditions and by the same team. For example, the concentration of tumor necrosis factor in bronchoalveolar lavage was found higher than 1,000 pg/ml after This Editorial View accompanies the following article: Whitehead TC, Zhang H, Mullen B, Slutsky AS: Effect of mechanical ventilation on cytokine response to intratracheal lipopolysaccharide. ANESTHESIOLOGY 2004; 101:52–8.