Bedside estimates of dead space using end-tidal CO 2 are independently associated with mortality in ARDS

Crit Care. 2021 Sep 15;25(1):333. doi: 10.1186/s13054-021-03751-x.


Purpose: In acute respiratory distress syndrome (ARDS), dead space fraction has been independently associated with mortality. We hypothesized that early measurement of the difference between arterial and end-tidal CO2 (arterial-ET difference), a surrogate for dead space fraction, would predict mortality in mechanically ventilated patients with ARDS.

Methods: We performed two separate exploratory analyses. We first used publicly available databases from the ALTA, EDEN, and OMEGA ARDS Network trials (N = 124) as a derivation cohort to test our hypothesis. We then performed a separate retrospective analysis of patients with ARDS using University of Chicago patients (N = 302) as a validation cohort.

Results: The ARDS Network derivation cohort demonstrated arterial-ET difference, vasopressor requirement, age, and APACHE III to be associated with mortality by univariable analysis. By multivariable analysis, only the arterial-ET difference remained significant (P = 0.047). In a separate analysis, the modified Enghoff equation ((PaCO2-PETCO2)/PaCO2) was used in place of the arterial-ET difference and did not alter the results. The University of Chicago cohort found arterial-ET difference, age, ventilator mode, vasopressor requirement, and APACHE II to be associated with mortality in a univariate analysis. By multivariable analysis, the arterial-ET difference continued to be predictive of mortality (P = 0.031). In the validation cohort, substitution of the arterial-ET difference for the modified Enghoff equation showed similar results.

Conclusion: Arterial to end-tidal CO2 (ETCO2) difference is an independent predictor of mortality in patients with ARDS.

Keywords: ARDS; Blood gas analysis; End-tidal CO2; Mortality.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Carbon Dioxide / analysis*
  • Chicago
  • Cohort Studies
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • ROC Curve
  • Respiratory Dead Space*
  • Respiratory Distress Syndrome / diagnostic imaging*
  • Statistics as Topic / instrumentation
  • Statistics as Topic / methods*
  • Statistics as Topic / trends
  • Validation Studies as Topic


  • Carbon Dioxide