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Re-examining Permissive Hypercapnia in ARDS: A Narrative Review. Lung-protective ventilation (LPV) has become the cornerstone of management in patients with ARDS. A subset of patients is unable to tolerate LPV without significant CO2 elevation. In these patients, permissive hypercapnia is used. Although thought to be benign, it is becoming increasingly evident that elevated CO2 levels have significant physiological effects. In this narrative review, we highlight clinically relevant end-organ effects in both animal models and clinical studies. We also explore the association between elevated CO2, acute cor pulmonale, and ICU mortality. We conclude with a brief review of alternative therapies for CO2 management currently under investigation in patients with moderate to severe ARDS.