PaCO₂ as a Possible Treatable Trait in Acute Respiratory Failure: A Scoping Review

Acute respiratory failure (ARF) often leads to ICU admission, ventilatory support, illness, and death. The usual classification into hypoxemic and hypercapnic types does not capture its full complexity. Precision medicine uses the idea of “treatable traits” to guide care based on traits that are clinically relevant, identifiable, measurable, and possibly changeable. Arterial carbon dioxide pressure (PaCO₂) reflects factors like alveolar ventilation, dead space, respiratory mechanics, and how patients respond to ventilatory support. This makes it a clinically relevant variable in selected situations in certain situations. We carried out a scoping review using PRISMA-ScR and JBI guidelines (OSF post hoc protocol https://osf.io/vszkg) to summarize evidence on hypocapnia and hypercapnia as prognostic, stratification, or clinically relevant variables during respiratory support. We searched PubMed/MEDLINE, ScienceDirect, and Web of Science (1994–2025), and checked references by hand. Thirty-four studies met our criteria and were grouped into four areas: pre-intubation or early acute presentation, non-invasive support (NIV/HFNC), invasive mechanical ventilation, and weaning or post-extubation. In summary, hypocapnia was linked to worse outcomes or failure of support in hypoxemic or cardiogenic cases. Hypercapnia helped identify patients who benefited from NIV, such as those with COPD or obesity-hypoventilation. For invasive mechanical ventilation, the effects depended on the presence and severity of acidosis and how long it lasted. We found that PaCO₂ is measurable and clinically important, but whether it can be targeted for treatment depends on the situation. More research is needed to set safe limits and practical targets.