An Exploratory Analysis of the Association between Hypercapnia and Hospital Mortality in Critically Ill Patients with Sepsis

Ravindranath Tiruvoipati, Ary Serpa Neto, Marcus Young, Nada Marhoon, John Wilson, Sachin Gupta, David Pilcher, Michael Bailey, Rinaldo Bellomo

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6 Citations (Scopus)


Rationale: Hypercapnia may affect the outcome of sepsis. Very few clinical studies conducted in noncritically ill patients have investigated the effects of hypercapnia and hypercapnic acidemia in the context of sepsis. The effect of hypercapnia in critically ill patients with sepsis remains inadequately studied. Objectives: To investigate the association of hypercapnia with hospital mortality in critically ill patients with sepsis. Methods: This is a retrospective study conducted in three tertiary public hospitals. Critically ill patients with sepsis from three intensive care units between January 2011 and May 2019 were included. Five cohorts (exposure of at least 24, 48, 72, 120, and 168 hours) were created to account for immortal time bias and informative censoring. The association between hypercapnia exposure and hospital mortality was assessed with multivariable models. Subgroup analyses compared ventilated versus nonventilated and pulmonary versus nonpulmonary sepsis patients. Results: We analyzed 84,819 arterial carbon dioxide pressure measurements in 3,153 patients (57.6% male; median age was 62.5 years). After adjustment for key confounders, both in mechanically ventilated and nonventilated patients and in patients with pulmonary or nonpulmonary sepsis, there was no independent association of hypercapnia with hospital mortality. In contrast, in ventilated patients, the presence of prolonged exposure to both hypercapnia and acidemia was associated with increased mortality (highest odds ratio of 16.5 for ⩾120 hours of potential exposure; P = 0.007). Conclusions: After adjustment, isolated hypercapnia was not associated with increased mortality in patients with sepsis, whereas prolonged hypercapnic acidemia was associated with increased risk of mortality. These hypothesis-generating observations suggest that as hypercapnia is not an independent risk factor for mortality, trials of permissive hypercapnia avoiding or minimizing acidemia in sepsis may be safe.

Original languageEnglish
Pages (from-to)245-254
Number of pages10
JournalAnnals of the American Thoracic Society
Issue number2
Publication statusPublished - Feb 2022


  • critically ill
  • hypercapnia
  • respiratory acidosis
  • respiratory failure
  • sepsis

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