OBJECTIVES: In the UK, 20% of patients with severe traumatic brain injury (TBI) receive prehospital emergency anaesthesia (PHEA). Current guidance recommends an end-tidal carbon dioxide (ETCO2) of 4.0-4.5 kPa (30.0-33.8 mm Hg) to achieve a low-normal arterial partial pressure of CO2 (PaCO2), and reduce secondary brain injury. This recommendation assumes a 0.5 kPa (3.8 mm Hg) ETCO2-PaCO2 gradient. However, the gradient in the acute phase of TBI is unknown. The primary aim was to report the ETCO2-PaCO2 gradient of TBI patients at hospital arrival. METHODS: A retrospective cohort study of adult patients with serious TBI, who received a PHEA by a prehospital critical care team in the East of England between 1 April 2015 and 31 December 2017. Linear regression was performed to test for correlation and reported as R-squared (R2). A Bland-Altman plot was used to test for paired ETCO2 and PaCO2 agreement and reported with 95% CI. ETCO2-PaCO2 gradient data were compared with a two-tailed, unpaired, t-test. RESULTS: 107 patients were eligible for inclusion. Sixty-seven patients did not receive a PaCO2 sample within 30 min of hospital arrival and were therefore excluded. Forty patients had complete data and were included in the final analysis; per protocol. The mean ETCO2-PaCO2 gradient was 1.7 (±1.0) kPa (12.8 mm Hg), with moderate correlation (R2=0.23, p=0.002). The Bland-Altman bias was 1.7 (95% CI 1.4 to 2.0) kPa with upper and lower limits of agreement of 3.6 (95% CI 3.0 to 4.1) kPa and -0.2 (95% CI -0.8 to 0.3) kPa, respectively. There was no evidence of a larger gradient in more severe TBI (p=0.29). There was no significant gradient correlation in patients with a coexisting serious thoracic injury (R2=0.13, p=0.10), and this cohort had a larger ETCO2-PaCO2 gradient, 2.0 (±1.1) kPa (15.1 mm Hg), p=0.01. Patients who underwent prehospital arterial blood sampling had an arrival PaCO2 of 4.7 (±0.2) kPa (35.1 mm Hg). CONCLUSION: There is only moderate correlation of ETCO2 and PaCO2 at hospital arrival in patients with serious TBI. The mean ETCO2-PaCO2 gradient was 1.7 (±1.0) kPa (12.8 mm Hg). Lower ETCO2 targets than previously recommended may be safe and appropriate, and there may be a role for prehospital PaCO2 measurement.