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Purpose: Septic patients are at risk for hypotension, and this risk may increase during rapid sequence intubation (RSI). Sedatives such as propofol must be used carefully due to its ability to reduce vascular sympathetic tone. Since the safety of propofol for RSI is not well described in sepsis, this was a study evaluating propofol and its effects on hemodynamics when used for RSI in a septic population. Materials and methods: We conducted a multicenter, retrospective, cohort study of patients with sepsis or severe sepsis requiring sedation for RSI. Patients receiving a propofol bolus for RSI were compared to patients undergoing RSI without a propofol bolus. The safety profile of propofol was evaluated according to the rates of post-intubation hypotension and vasopressor utilization between groups. Results: A total of 179 patients (79 propofol, 100 non-propofol) were evaluated. There were no differences in hypotension (81% vs 78%; P =.62) or vasopressor utilization between the propofol and non-propofol groups (43% vs 49%; P =.43). Patients in the non-propofol group had increased APACHE II scores and healthcare-associated infections. Conclusions: In this cohort study, administration of propofol for RSI in patients with sepsis and severe sepsis did not increase incidence of hypotension or vasopressor use, but acute illness may have introduced provider selection bias causing less propofol use in the non-propofol group. Larger prospective studies are needed to better characterize the adverse hemodynamic effects of propofol, before propofol bolus doses for RSI can be considered for safe use in this population. [ABSTRACT FROM AUTHOR]