PaCO₂: a treatable trait in acute respiratory failure

Treatable traits are a cornerstone of personalized (precision) medicine. Arterial carbon dioxide tension (PaCO₂) is a fundamental measure in acute respiratory failure. We aimed to determine whether PaCO₂ can be considered a treatable trait in patients with acute respiratory failure.

We performed an electronic search to identify studies addressing hypercapnia and hypocapnia as clinically actionable features in respiratory insufficiency, including their prognostic value and role as potential treatment targets. A systematic snowball approach (backward and forward citation tracking) was applied to capture additional relevant articles. Evidence was synthesized narratively to contextualize findings within the conceptual framework of PaCO₂ as a treatable trait.

PaCO₂ supports classification of acute respiratory failure as hypercapnic or non-hypercapnic, informs prognosis, and helps define non-invasive management with high-flow nasal cannula or non-invasive ventilation. In intubated patients, PaCO₂ contributes to monitoring ventilatory strategies such as lung-protective ventilation and prone positioning, and it helps interpret outcome-relevant variables such as ventilatory ratio and mechanical power. Across the peri-extubation period, PaCO₂ is associated with clinically meaningful outcomes before, during, and after ventilator weaning and can guide selection of post-extubation non-invasive support to reduce reintubation risk.

PaCO₂ may be considered a treatable trait across the pre-intubation, invasively ventilated, and post-extubation phases of acute respiratory failure. Further research is needed to define clinically actionable limits and targets in relevant patient subgroups, including safety margins in relation to pH and exposure time.