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The goals of this study were to determine the incidence and duration of hypotension and hypoxia in the prehospital setting in patients with potentially survivable brain injuries, and to prospectively examine the association of these secondary insults with mortality and disability at hospital discharge.Trauma patients with suspected brain injuries underwent continuous blood pressure and pulse oximetry monitoring during helicopter transport. Postadmission inclusion criteria were (1) diagnosis of acute traumatic brain injury (TBI) confirmed by computed tomography (CT) scan, operative findings, or autopsy findings; and (2) Head Abbreviated Injury Scale (AIS) score of ≥3 or Glasgow Coma Scale (GCS) score of ≤12 within the first 24 hours of admission. Patients were excluded with (1) no abnormal intracranial findings on the patient's CT scan; (2) determination of a nonsurvivable injury (based on an AIS score of 6 for any body region; or, (3) death in less than 12 hours after injury. Primary outcome measures included mortality and Disability Rating Scale score at discharge.We enrolled 150 patients into the study. Fifty-seven patients had at least one secondary insult; 37 had only hypoxic episodes, 14 had only hypotensive episodes, and 6 patients had both. Demographics and injury characteristics did not differ between those with and those without secondary insults. The mortality for patients without secondary insults was 20%, compared with 37% for patients with hypoxic episodes, 8% for patients with hypotensive episodes, and 24% for patients with both. The Disability Rating Scale score at discharge was significantly higher in patients with secondary insults. Using multivariate analysis, the calculated odds ratio of mortality caused by prehospital hypoxia after head injury was 2.66 (p < 0.05).Secondary insults after TBI are common, and these insults are associated with disability. Hypoxia in the prehospital setting significantly increases the odds of mortality after brain injury controlled for multiple variables.