"Permissive
hypercapnia" is an inherent
element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of
hypercapnia per se, independent of
ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for
hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First, we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second, we examine whether hypercapnic
acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO(2), in the absence of protective ventilation, is beneficial or deleterious. Fourth, we address the current evidence regarding the buffering of hypercapnic
acidosis in ARDS. These perspectives reveal that the potential exists for
hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO(2) is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of
hypercapnia. At present, protective ventilatory strategies that involve
hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that
hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic
acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of
hypercapnia in ARDS.