End-tidal to arterial carbon dioxide gradient is associated with increased mortality in patients with traumatic brain injury: a retrospective observational study

Early definitive airway protection and normoventilation are key principles in the treatment of severe traumatic brain injury. These are currently guided by end tidal CO2 as a proxy for PaCO2. We assessed whether the difference between end tidal CO2 and PaCO2 at hospital admission is associated with in-hospital mortality. We conducted a retrospective observational cohort study of consecutive patients with traumatic brain injury who were intubated and transported by Helicopter Emergency Medical Services to a Level 1 trauma center between January 2014 and December 2019. We assessed the association between the CO2 gap-defined as the difference between end tidal CO2 and PaCO2-and in-hospital mortality using multivariate logistic regression models. 105 patients were included in this study. The mean +/- SD CO2 gap at admission was 1.64 +/- 1.09 kPa and significantly greater in non-survivors than survivors (2.26 +/- 1.30 kPa vs. 1.42 +/- 0.92 kPa, p<.001). The correlation between EtCO2 and PaCO2 at admission was low (Pearson's r=.287). The mean CO2 gap after 24 h was only 0.64 +/- 0.82 kPa, and no longer significantly different between non-survivors and survivors. The multivariate logistic regression model showed that the CO2 gap was independently associated with increased mortality in this cohort and associated with a 2.7-fold increased mortality for every 1 kPa increase in the CO2 gap (OR 2.692, 95% CI 1.293 to 5.646, p=.009). This study demonstrates that the difference between EtCO2 and PaCO2 is significantly associated with in-hospital mortality in patients with traumatic brain injury. EtCO2 was significantly lower than PaCO2, making it an unreliable proxy for PaCO2 when aiming for normocapnic ventilation. The CO2 gap can lead to iatrogenic hypoventilation when normocapnic ventilation is aimed and might thereby increase in-hospital mortality.