14 So there are two sides to the hypercapnia story with the potential for benefit and the risk of harm. However, just as a pinch of salt can bring out the flavor in food where a fistful will ruin it, excess carbon dioxide has the potential for harm: hypercapnic acidosis has important off-target deleterious effects that limit its use in selected patients ( i.e., raised intracranial pressure and pulmonary hypertension), for prolonged periods (increased risk of infection) and at high dose (mitochondrial effects). 7, 8 In all these studies, the relative contribution of lung-protective ventilation or an increase in Pa co 2 could not be ascertained, although a post hoc analysis of one revealed an association between hypercapnia and improved survival. Eventually, two pivotal large randomized controlled trials indicated that low tidal volume mechanical ventilation improves survival in patients with ARDS. Comparable findings had been reported a decade before, whereby lowering tidal volumes in status asthmaticus 5 and in neonatal pulmonary hypertension 6 was associated with improved survival. 3, 4 first described the concept of “permissive hypercapnia” in two case series, wherein low tidal volume, pressure-limited mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) led to substantial elevations in Pa co 2 and a mortality that was significantly lower than that predicted by Apache II scores. Hypercapnia has been an unavoidable component of lung protection strategies in several key clinical studies over the past four decades. Arterial carbon dioxide tension (Pa co 2) represents the balance between carbon dioxide produced and eliminated. Carbon dioxide is essentially a “waste product” of aerobic cellular respiration.

Careful science, rather than caprice, has guided our understanding of the biology of carbon dioxide and the fundamental role it plays in normal physiology, adaptation to, and modulation of disease.

The goldilocks effect