• Martina Ni Chonghaile, Brendan Higgins, and John G Laffey.
• Department of Anaesthesia, Clinical Sciences Institute and National Centre for Biomedical Engineering Sciences, National University of Ireland, Galway, Ireland.
• Curr Opin Crit Care. 2005 Feb 1; 11 (1): 56-62.

Purpose Of ReviewHypercapnia is a central component of current protective ventilatory strategies. This review aims to present and interpret data from recent clinical and experimental studies relating to hypercapnia and its role in protective ventilatory strategies.Recent FindingsIncreasing clinical evidence supports the use of permissive hypercapnia, particularly in acute lung injury/acute respiratory distress syndrome, status asthmaticus, and neonatal respiratory failure. However, there are no clinical data examining the contribution of hypercapnia per se to protective ventilatory strategies. Recent experimental studies provide further support for the concept of therapeutic hypercapnia, whereby deliberately elevated PaCO2 may attenuate lung and systemic organ injury. CO2 administration attenuates experimental acute lung injury because of adverse ventilatory strategies, mesenteric ischemia reperfusion, and pulmonary endotoxin instillation. Hypercapnic acidosis attenuates key effectors of the inflammatory response and reduces lung neutrophil infiltration. At the genomic level, hypercapnic acidosis attenuates the activation of nuclear factor-kappaB, a key regulator of the expression of multiple genes involved in the inflammatory response. The physiologic effects of hypercapnia, both beneficial and potentially deleterious, are increasingly well understood. In addition, reports suggest that humans can tolerate extreme levels of hypercapnia for relatively prolonged periods without adverse effects.SummaryThe potential for hypercapnia to contribute to the beneficial effects of protective lung ventilatory strategies is clear from experimental studies. However, the optimal ventilatory strategy and the precise contribution of hypercapnia to this strategy remain unclear. A clearer understanding of its effects and mechanisms of action is central to determining the safety and therapeutic utility of hypercapnia in protective lung ventilatory strategies.

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