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Early intubation is standard for treating severe traumatic brain injury (TBI). Aeromedical crews and select paramedic agencies use rapid sequence intubation (RSI) to facilitate intubation after TBI, with Glasgow Coma Scale (GCS) score commonly used as a screening tool. To explore the association between paramedic GCS and outcome in patients with TBI undergoing prehospital RSI, paramedics prospectively enrolled adult major trauma victims with GCS 3-8 and clinical suspicion for head trauma to undergo succinylcholine-assisted intubation as part of the San Diego Paramedic RSI Trial. The following data were abstracted from paramedic debriefing interviews and the county trauma registry: demographics, mechanism, vital signs including GCS score, clinical evidence of aspiration before RSI, arrival laboratory values, hospital course, and outcome. Paramedic GCS calculations were confirmed during debriefing interviews. Patients were stratified by GCS score, with chi-square and receiver-operator-curve (ROC) analysis used to explore the relationship between GCS and hypoxia, head injury severity, aspiration, intensive care unit (ICU) length of stay, and outcome. Cohort analysis was used to explore potential reasons for early extubation and discharge from the ICU in some patients. A total of 412 patients were included in this analysis. A total of 81 patients (20%) were extubated and discharged from the ICU in 48 h or less; these patients had higher pre-RSI oxygen saturation (SaO(2)) values and higher arrival serum ethanol levels. Paramedic and physician GCS calculations had high agreement (kappa=0.995). A statistically significant relationship was observed between GCS score and Head Abbreviated Injury Score (AIS), survival, and pre-RSI SaO(2) values. However, ROC analysis revealed a limited ability of GCS to predict the presence of severe TBI, injury severity, desaturation, aspiration, ICU length of stay, or ultimate survival. In conclusion, paramedics seem to accurately calculate GCS values before prehospital RSI. Although a relationship between paramedic GCS and outcome exists, the ability to predict the severity of injury, airway-related complications, ICU length of stay, and overall survival is limited using this single variable. Other factors should be considered to screen TBI patients for prehospital RSI.