Hypercatabolism, hypercapnia, and brain injury: The role of stress-induced inflammation and high caloric load in neurological patients

Background: Patients with acute brain injury frequently enter a hypercatabolic state driven by stress-induced inflammation. While high caloric nutrition is often prescribed to counteract muscle wasting, excessive caloric delivery may inadvertently worsen hypercapnia by increasing carbon dioxide production (VCO₂), potentially exacerbating cerebral injury.
Objective: To investigate the relationship between high caloric intake, hypercapnia, and clinical outcomes in hypercatabolic patients with acute brain injury.
Methods: A retrospective cohort study of 459 adult patients with acute brain injury (TBI, ischemic stroke, ICH, or post-cardiac arrest syndrome) admitted between January 2023 and December 2024. Patients were stratified into high caloric (≥25 kcal/kg/day, n=218) and standard caloric (15–24 kcal/kg/day, n=241) groups. Hypercapnia defined as PaCO₂ >45 mmHg. Primary outcomes included hypercapnia incidence, mechanical ventilation duration, ICU LOS, and neurological outcome (Glasgow Outcome Scale).
Results: The high caloric group demonstrated significantly higher hypercapnia rates (42.7% vs. 24.9%, p<0.001) and higher mean PaCO₂ (47.8±5.4 vs. 43.2±4.6 mmHg, p<0.001). Hypercapnia was independently associated with high caloric intake (aOR=2.48, 95% CI: 1.68–3.66, p<0.001). Hypercapnic patients had longer ventilator days (median 12 vs. 7 days, p<0.001), prolonged ICU stay (median 16 vs. 10 days, p<0.001), and worse neurological outcomes (48.6% vs. 29.8% poor outcome, p<0.001). Patients with baseline malnutrition risk (PNI <38) derived greatest benefit from standard caloric targets.
Conclusion: High caloric enteral nutrition (≥25 kcal/kg/day) is associated with increased hypercapnia risk, prolonged ventilation, and worse neurological outcomes compared to standard caloric targets (15–24 kcal/kg/day). These findings support moderate caloric targets (18–22 kcal/kg/day) in acute neurological patients.