2026 Eastern States Conference

Title: Safety of high dose norepinephrine for the treatment of septic shock in the ICU 
Authors: Kenzie Alexanian, Pharm.D., Martin C. Taylor Jr., Pharm.D., BCPS, Joan Mege, Pharm.D., BCPS 
Objective: Evaluate the safety of high dose norepinephrine when used for the treatment of septic shock 
Self-Assessment Question: It is safe to titrate to doses of NE above 1mcg/kg/min. (True/False) 
Background: There is limited data on the safety of high infusion rates of NE. The objective of this study is to assess the safety of NE when doses exceed 1mcg/kg/min in patients undergoing treatment for septic shock. 
Methods: We conducted a retrospective review of patients, with septic shock, who received doses of norepinephrine exceeding 1mcg/kg/min in the ICU at Sinai Hospital of Baltimore from January 2024 to December 2025. The primary outcome is the incidence of extravasation, tachycardia, and limb necrosis in patients receiving high dose NE. 
Results: Among 38 patients, 15 adverse drug reactions (ADRs) were reported in 11 patients. The most common ADR was tachycardia with eight occurrences. There were two occurrences of digit/limb necrosis. The majority of ADR occurred in patients receiving 1 – 1.9mcg/kg/min. We did not observe a linear relationship in the incidence of ADR with higher doses of NE. Hydrocortisone was administered to 68.4% of patients. The median amount fluid administered during the first six hours of resuscitation was only 13mL/kg. The most common adjunct vasopressor utilized was vasopressin (79%). The overall mortality rate was 76.3% with the greatest mortality rate in patients with NE doses greater than or equal to 3mcg/kg/min (95.65%).
Conclusions: Doses of NE greater than or equal to 3mcg/kg/min were associated with few ADRs (digit/limb necrosis and extravasation).  Mortality was highest with doses greater than or equal to 3mcg/kg/min.  High dose norepinephrine may be safe but has limited efficacy.  Further studies are required to assess the efficacy and safety of high dosed norepinephrine.