Despite intense clinical and scientific scrutiny, clinicians have yet to standardize mechanical ventilatory therapy of acute lung injury (ALI).94, 95 The absence of carefully controlled clinical trials, coupled with the existence of multiple causes for acute respiratory distress syndrome (ARDS), has contributed to the development of different ventilatory approaches. Conventional mechanical ventilation (CMV) of ARDS targets normalization of arterial blood gases by using supraphysiologic (10–15 mL/kg) tidal volumes (VT) and positive end-expiratory pressure (PEEP). PEEP is titrated to achieve a minimum arterial oxygen saturation (Sa o2) of 90% at an acceptable inspired O2 concentration (F io2), and ventilatory frequency is adjusted to maintain eucapnia (Pa co2 about 40 mm Hg). Various aspects of CMV never have been tested in a prospective clinical trial.
In some centers, the mortality of patients with ARDS treated with CMV has remained relatively unchanged. Zapol and colleagues,165 for example, observed a mortality rate of 67% between 1978 and 1988 in patients with moderate to severe ARDS, which was similar to that reported (66%) in the National Heart, Lung and Blood Institute (NHLBI)–sponsored multicenter study of extracorporeal membrane oxygenation (ECMO) therapy of ARDS conducted between 1975 and 1977.34 Some investigators recently have noted a trend in improved survival in ARDS, however, and have attributed that outcome to the introduction and wider application of a lung protective ventilatory strategy.140
Growing experimental evidence indicates that cyclic alveolar overdistention can damage the air–alveolar interface, producing ALI similar to that observed in ARDS.32, 91, 94, 124 This form of barotrauma (also referred to as volutrauma32) is distinct from the sequelae of alveolar rupture and gas extravasation, a phenomenon that may produce pneumothorax, pneumomediastinum, or systemic gas embolism. The risk of ventilator-induced lung injury (VILI) is greatest in the setting of pre-existing lung tissue damage, when high airway opening pressures routinely are required during mechanical ventilation to achieve adequate gas exchange.
In ARDS, measurements of respiratory mechanics and CT images suggest that lung injury is distributed nonhomogeneously.44, 45, 46, 90, 92 Pulmonary infiltrates initially tend to concentrate in dependent regions, whereas nondependent areas radiographically appear to remain spared and normally distensible. Certain lung regions retain normal compliance and ventilation-to-perfusion (V˙/Q˙) characteristics, whereas other regions lose compliance and volume because of pulmonary edema, cellular infiltration, and atelectasis. Conceptually, aerated lung in ARDS should be viewed as smaller rather than stiffer than normal.41, 48, 92 Under these conditions, targeting normal Pa co2 and Pa o2 during mechanical ventilation with application of conventional tidal volumes (10–15 mL/kg) could overdistend mechanically normal lung regions, leading to alveolar rupture and parenchymal injury.59, 91, 94, 126 Because lung units normally reach their maximum physiologic volume at total lung capacity (TLC) at a transpulmonary pressure of approximately 30 cm H2O, it is reasonable to limit operating airway pressure to values that do not expose the functional alveoli to pressures higher than 30 to 35 cm H2O.95 During tidal breathing, reopening of collapsed lung regions can generate excessive shear forces at the alveolar level that may contribute to VILI. On the deflation side, a certain minimal level of end-expiratory volume may be required to prevent collapse of unstable airways and alveoli.46, 93, 95
In animal models, mechanical ventilation strategies that overdistend normal lung tissue (peak airway pressures of 30–50 cm H2O) while allowing repeated closure and reopening of damaged unstable lung units cause injury that resembles the early phase of ARDS.32, 95, 124 Consequently, the magnitude of volume fluctuations (tidal volume) and the level of end-expiratory lung volume may be important in generating and propagating lung injury.
Lung protective ventilatory strategy adjusts VT and PEEP according to the pressure–volume (PV) characteristics of the respiratory system to achieve ventilation between the lower inflection and upper deflection points of the static PV curve of the respiratory system. This strategy aims to minimize overdistention, cyclic collapse, and reopening of lung tissue. To improve oxygenation, operating lung volume is adjusted by extending the duty cycle not by further incrementing PEEP. Periodic recruiting breaths may be necessary in some patients to overcome atelectasis. This strategy accepts hypercapnia in preference to violating the guidelines of controlled alveolar pressure.
Although the management strategy put forward in a lung protective ventilatory strategy for ALI is rooted firmly in the theoretic and experimental literature, the clinical value of the suggested strategy (and to the authors' knowledge, of every other newer technique for the support of such patients) is untested, and several aspects remain open to question. The goal of the lung protective strategy is to avoid VILI by limiting the distention of alveoli to a level below their total volumetric capacity while maintaining their volume above a critical end-expiratory value that preserves alveolar recruitment. By design, this strategy chooses to limit the tidal volumetric excursion of the respiratory system. In severe ALI, the allowed VT may be too small to accomplish alveolar ventilation (V˙A) sufficient to provide eucapnia.60, 61, 62 Rather than increasing minute ventilation (V˙E) to increase V˙A, the lung protective ventilatory strategy allows Pa co2 to drift upward. A major outcome of this approach is the development of respiratory acidosis (permissive hypercapnia).2, 60, 61, 71 The magnitude of respiratory acidosis is minimized if the strategy is employed from the onset of mechanical ventilatory support. Nevertheless, under certain clinical situations, hypercarbia is contraindicated (e.g., cerebral pathology) or poorly tolerated (e.g., pulmonary hypertension). The effects of acute or gradual hypercapnia in critically ill patients are unknown.
In some patients with ARDS, the application of a lung protective ventilatory strategy may lead to severe hypercapnia and, possibly, hypoxemia. In such cases, adjunctive ventilatory techniques may allow the physician to maintain acceptable cardiopulmonary function within the restrictions imposed by the lung protective strategy. Adjuncts to mechanical ventilation have been developed in parallel to a lung protective strategy and only recently has work progressed in the application of these techniques to address one or more of the gas-exchange consequences of the lung protective strategy.
Most adjunctive techniques enhance the elimination of CO2 or improve the distribution of V˙/Q˙ of the lungs (thereby increasing Pa o2). Three techniques are available that can be used as adjuncts to mechanical ventilation to enhance CO2 clearance—tracheal gas insufflation (TGI), extracorporeal carbon dioxide removal (ECCO2R), and intravena-caval oxygen exchanger (IVOX). Many other adjunctive techniques have been developed to improve oxygenation of ventilated patients. Some of them are highly invasive (such as ECMO) and others are rather easy to perform with the proper equipment (e.g., inhaled nitric oxide [NO]). The techniques that use a semipermeable membrane and introduce an external or internal surface area where additional gas exchange can take place may improve Pa co2 and Pa o2. In the following sections, the authors discuss the operational characteristics of some of the most promising adjunctive techniques.
