Is carbon dioxide harmful or helpful in ARDS?

Arterial CO₂ tension (PaCO₂) represents a balance between CO₂ production and elimination via the lungs, and in health is maintained within a tight range (3.5-4.5 kPa). Traditional approaches to CO₂ management in the critically ill focused on maintaining tidal and minute ventilation to avoid the risks of hypercapnia. The demonstration that high lung stretch directly injures the lungs heralded the use of more protective ventilatory strategies that reduce lung stretch, and have been proven to improve survival in patients with acute respiratory distress syndrome (ARDS). Consequently, hypercapnia (HC)-and its associated hypercapnic acidosis (HCA)-is prevalent in the critically ill, and “permitted” order to realize the benefits of lower lung stretch. Experimental and clinical investigations have generated key advances in our understanding of the effects of HC, which is a potent biologic agent, with the potential to exert both beneficial and potentially harmful effects. HC modulates the innate immune response, with inhibition of nuclear factor κ-B, a key transcriptional protein in injury, inflammation, and repair, mediating the diverse effects of HC. Advances in extracorporeal technologies have made possible the direct removal of CO₂ while maintaining lung protective ventilation, a promising, though as yet unproven, approach. Consequently, it is important to understand the biology of HC, in order to best understand when it should be encouraged, tolerated, or avoided in patients with ARDS.