Mechanistic Assessment of Norepinephrine Therapy vs. Angiotensin-II in Septic Shock

Inclusion Criteria: \- The presence of septic shock, defined by sepsis-3 criteria: 1-adult patients (18 years or older) with septic shock, defined by SEPSIS-3 criteria: a) suspected or known infection, b) hypotension requiring vasopressors, and c) lactate \>2mmol/L 2-receiving either norepinephrine or phenylephrine with or without additional vasopressor support 3- total norepinephrine equivalent dose (NED) ≥0.1 mcg/kg/min and ≤0.5 mcg/kg/min, to maintain a MAP of at least 65 mmHg, is required for randomization 4-ability to consent and randomize within 24 hrs of first reaching NED threshold and within 48 hrs of hospital arrival Exclusion Criteria: * Age \<18 years * Prisoners * Pregnant women * Patients for whom urgent surgery is anticipated * Leukocyte count \<1,000 cells/μL * Absolute monocyte count \<200 cells/μL * Bone marrow transplant within the past 30 days * Patients that will be withdrawing aggressive resuscitation, including withdraw of vasopressor support * transfer from outside ICU * history of liver cirrhosis with Child-Pugh score ≥6