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Association of Hypercapnic and Nonrespiratory Acidemia With Hospital Mortality in Mechanically Ventilated Patients

Ravindranath Tiruvoipati^1,2,3, Jason Zheng¹, Sachin Gupta^1,2

¹Department of Intensive Care Medicine, Frankston Hospital, Frankston, VIC, Australia.

Critical Care Medicine

|March 5, 2026

Abstract

Objectives:

The mortality among patients admitted with sepsis remains high and varies depending on the site of infection. The impact of hypercapnia and acidemia on clinical outcomes in mechanically ventilated patients with sepsis is not well understood.

Design:

Multicenter, binational, retrospective study assessed the association of compensated hypercapnia, hypercapnic acidemia, and nonrespiratory acidemia, in mechanically ventilated patients with mortality in sepsis.

Setting:

Data were extracted from the "Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient" database over a 17-year period (from January 2006 to December 2022) from 201 ICUs.

Patients:

Patients were classified into four mutually exclusive groups based on a combination of arterial pH and arterial C o2 recorded during the first 24 hours of ICU stay: normocapnia with normal pH, fully compensated hypercapnia, hypercapnic acidemia, and nonrespiratory acidemia. Logistic regression and Cox proportional hazards regression were used to examine the association of compensated hypercapnia, hypercapnic, and nonrespiratory academia to hospital mortality.

Interventions:

None.

Measurements And Main Results:

Fifty-two thousand four hundred five patients were included. Overall compensated hypercapnia (odds ratio [OR], 1.39; 95% CI, 1.24-1.55; p < 0.001), hypercapnic acidemia (OR, 1.68; 95% CI, 1.57-1.80; p < 0.001), and nonrespiratory acidemia (OR, 1.75; 95% CI, 1.61-1.90; p < 0.001) was associated with increased risk of hospital mortality as compared with patients with normocapnia and normal pH. The risk of increased hospital mortality associated with hypercapnic and nonrespiratory acidemia persisted in all prespecified diagnostic subgroups when compared with patients who had normal pH and normocapnia. Compensated hypercapnia was associated with increased mortality risk in neurologic and unspecified subgroups of sepsis.

Conclusions:

Hypercapnic acidemia and nonrespiratory acidemia within the first 24 hours of ICU admission are associated with increased risk of hospital mortality in mechanically ventilated patients with sepsis. This association remains consistent in all diagnostic subgroups of sepsis.

Keywords:

hypercapnia mortality nonrespiratory acidemia respiratory acidemia sepsis

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