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Introduction: Complications associated with rapid sequence intubation (RSI) medications include hypotension, hemodynamic instability, and hypoventilation. Current guidelines recommend RSI weight-based dosing. The emergent environment of RSI often requires dose calculations based on previous or estimated weight as well as considerations for hemodynamic presentation, which may lead to underdosing. It is unknown if lower RSI medication dosing results in different rates of first pass success or medication related complications. Methods: This multicenter, single health system, retrospective cohort study enrolled patients between June 2022 to July 2024. Adult patients in the medical intensive care unit who underwent RSI and were administered an induction sedative agent and a neuromuscular blocking agent (NMBA) were included. The low-dose cohort was defined as patients who received lower than guideline-recommended doses of sedation based on actual body weight (i.e. etomidate < 0.3 mg/kg, ketamine < 1 mg/kg) in combination with a NMBA. The primary outcome was first pass success rates between cohorts. Secondary outcomes included incidence of hypotension, hypoxemia, and hemodynamic instability. Results: One hundred patients were included in the low-dose and standard-dose cohorts, with a total enrollment of 200 patients. The low-dose cohort had higher median weight (kg, 89 [IQR, 75-113] vs 63 [55-76]; p< 0.001) and BMI (kg/m2, 31[26-36] vs 23[20-27], p< 0.001). The majority of patients received sedation with etomidate at mean doses of 0.21 mg/kg and 0.35 mg/kg in each cohort. Mean doses of rocuronium (0.75 mg/kg vs 1.01 mg/kg) and succinylcholine (1.19 mg/kg vs 1.83 mg/kg) were higher in the standard-dose cohort. Rocuronium was used more frequently in the low-dose cohort (84 vs 72, p = 0.041). Rates of first pass success were not different between cohorts (89% vs. 96%; p=0.06). Low-dose sedation in RSI had less incidences of hemodynamic instability compared to standard-dose group (63% vs. 73%, p=0.046), defined as 20% change in systolic blood pressure or tachycardia within 30 minutes after intubation. Conclusions: Utilizing lower doses of sedation induction during RSI in combination with NMBA did not result in a different rate of first pass success but did result in a lower incidence of hemodynamic instability.