Association between prehospital end-tidal carbon dioxide levels and mortality in patients with suspected severe traumatic brain injury

Intensive Care Med. 2023 May;49(5):491-504. doi: 10.1007/s00134-023-07012-z. Epub 2023 Apr 19.


Purpose: Severe traumatic brain injury is a leading cause of mortality and morbidity, and these patients are frequently intubated in the prehospital setting. Cerebral perfusion and intracranial pressure are influenced by the arterial partial pressure of CO2 and derangements might induce further brain damage. We investigated which lower and upper limits of prehospital end-tidal CO2 levels are associated with increased mortality in patients with severe traumatic brain injury.

Methods: The BRAIN-PROTECT study is an observational multicenter study. Patients with severe traumatic brain injury, treated by Dutch Helicopter Emergency Medical Services between February 2012 and December 2017, were included. Follow-up continued for 1 year after inclusion. End-tidal CO2 levels were measured during prehospital care and their association with 30-day mortality was analyzed with multivariable logistic regression.

Results: A total of 1776 patients were eligible for analysis. An L-shaped association between end-tidal CO2 levels and 30-day mortality was observed (p = 0.01), with a sharp increase in mortality with values below 35 mmHg. End-tidal CO2 values between 35 and 45 mmHg were associated with better survival rates compared to < 35 mmHg. No association between hypercapnia and mortality was observed. The odds ratio for the association between hypocapnia (< 35 mmHg) and mortality was 1.89 (95% CI 1.53-2.34, p < 0.001) and for hypercapnia (≥ 45 mmHg) 0.83 (0.62-1.11, p = 0.212).

Conclusion: A safe zone of 35-45 mmHg for end-tidal CO2 guidance seems reasonable during prehospital care. Particularly, end-tidal partial pressures of less than 35 mmHg were associated with a significantly increased mortality.

Keywords: Carbon dioxide; Critical care; Endotracheal intubation; Traumatic brain injury; Ventilation.

Publication types

  • Multicenter Study

MeSH terms

  • Brain Injuries* / complications
  • Brain Injuries, Traumatic* / complications
  • Carbon Dioxide / analysis
  • Emergency Medical Services*
  • Humans
  • Hypercapnia / complications


  • Carbon Dioxide