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A3278 - Esmolol Infusion in Patients with Septic Shock and Tachycardia: A Prospective, Single-Arm Pilot Study
Author Block: S. M. Brown1, S. Beesley2, M. Lanspa3, C. Grissom4, E. Wilson1, S. Parikh5, T. Sarge6, D. Talmor7, V. Banner-Goodspeed6, V. Novack6, B. Thompson8, S. Shahul9; 1Critical Care Medicine, Intermountain Medical Center, Murray, UT, United States, 2Division of Pulmonary Medicine, Salt Lake City, UT, United States, 3Intermountain Medical Center, Salt Lake City, UT, United States, 4Crit Care, Intermountain Med Ctr, Murray, UT, United States, 5Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States, 6Beth Israel Deaconess Medical Center, Boston, MA, United States, 7Beth Israel Deaconess Medical Ctr, Boston, MA, United States, 8Massachusetts General Hosp, Boston, MA, United States, 9Critical Care Medicine, University of Chicago, Chicago, IL, United States.
Background: High adrenergic tone appears to be associated with mortality in septic shock, while adrenergic antagonism may improve survival. In preparation for a randomized trial, we conducted a prospective, single-arm pilot study of esmolol infusion for patients with septic shock and tachycardia that persists after adequate volume expansion. Methods: From April 2016 to March 2017, we enrolled patients admitted to an intensive care unit with sepsis who were receiving vasopressor infusion and were tachycardic despite adequate volume expansion. All patients received a continuous intravenous infusion of esmolol, targeted to heart rate 80-90/min, while receiving vasopressors. The feasibility outcomes were proportion of eligible patients consented, compliance with pre-infusion safety check, and compliance with the titration protocol. The primary clinical outcome was organ-failure-free days (OFFD) at 28 days. Results: We enrolled 7 of 10 eligible patients. Mean age was 46 (+/-19) years and mean admission APACHE II was 28 (+/-8). Median norepinephrine infusion rate at the initiation of esmolol infusion was 0.20 (0.14-0.23) mcg/kg/min. Compliance with the safety check was 100%; compliance with components of the titration protocol was 98-100%. OFFD were 26 (24.5-26); all patients survived to day 90. Median peak esmolol infusion was 50 (25-50) mcg/kg/min. Median peak norepinephrine infusion rate during esmolol infusion was 0.46 (0.13-0.50) mcg/kg/min. Four patients achieved target heart rate. Protocol-defined stop events, suggesting intolerance to a given infusion rate, occurred in three patients, all of whom were receiving at least 50mcg/kg/min of esmolol. Conclusions: In a pilot, single-arm study, we report the first published experience with esmolol infusion in tachycardic patients with septic shock in the United States. These findings support a larger trial of esmolol infusion for septic shock. Lower doses of esmolol infusion may be better tolerated and more feasible than higher doses for such a trial.