Angiotensin II vs. Vasopressin in Septic Shock

Inclusion Criteria: * 1\. Adult patients ≥18 years-old with vasodilatory shock refractory to norepinephrine monotherapy, defined as those who require ≥0.2 mcg/kg/min to maintain a MAP between 65-70 mmHg. Patients will be screened once they require ≥0.1 mcg/kg/min of norepinephrine and, if eligible, may be consented at this point. Study drug (angiotensin II or vasopressin) will be initiated once norepinephrine dose reaches ≥0.2 mcg/kg/min for at least 30 minutes. * 2\. Patients are required to have central venous and arterial catheters present, and they are expected to remain in place for at least the initial 72 hours of study. * 3\. Patients are required to have an indwelling urinary catheter present, and it is expected to remain in place for at least the 72 hours of study. * 4\. Patients must have received 20-30 mL/kg of crystalloid over the previous 24-hour period, as clinically appropriate, and no longer be fluid responsive as per UNMH protocol. By UNMH protocol, lack of fluid responsiveness is considered a failure to increase stroke volume, stroke volume index, cardiac output, or cardiac index (typically measured by non-calibrated pulse contour analysis using a FloTrac device) by at least 10% after a 500-mL crystalloid bolus or a passive leg raise. Patients for whom the treating physicians feel that 20 mL/kg of crystalloid may be clinically inappropriate can qualify for the study if the reason for withholding further IV fluids is documented. * 5\. Patient or (in patients unable to consent) legal authorized representative (LAR) is willing and able to provide written informed consent and comply with all protocol requirements. * 6\. Approval from the attending physician and clinical pharmacist conducting the study. Exclusion Criteria: * 1\. Patients who are \< 18 years of age. * 2\. Patients diagnosed with acute occlusive coronary syndrome requiring intervention and/or cardiogenic shock. * 3\. Patients with or suspected to have abdominal aortic aneurysm or aortic dissection. * 4\. Acute stroke. * 5\. Patients with acute mesenteric ischemia or those with a history of mesenteric ischemia. * 6\. Patients with known Raynaud's phenomenon, systemic sclerosis, or vasospastic disease. * 7\. Patients on veno-arterial (VA) ECMO. * 8\. Patients with liver failure with a Model for End-Stage Liver Disease (MELD) score of ≥30. * 9\. Patients with burns covering \>20% of total body surface area. * 10\. Patients with a history of asthma or COPD with active acute bronchospasm or (if not mechanically ventilated) with an acute exacerbation of their asthma/COPD requiring the use of inhaled bronchodilators. * 11\. Patients requiring more than 500 mg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose. * 12 Patients with an absolute neutrophil count (ANC) of \< 1,000/mm3. * 13\. Patients with hemorrhagic shock OR active bleeding AND an anticipated need (within 48 hours of initiation of the study) for transfusion of \>4 units of packed red blood cells. * 14\. Patients with active bleeding AND hemoglobin \< 7g/dL or any other condition that would contraindicate serial blood sampling. * 15\. Untreated venous thromboembolism (VTE) or inability to tolerate pharmacologic VTE prophylaxis. * 16\. Patients with a known allergy to mannitol. * 17\. Patients with an expected survival of \<24 hours, SOFA score ≥ 16, or death deemed to be imminent or inevitable during the admission * 18\. Either the attending physician or patient and/or substitute decision-maker are not committed to all active treatment (e.g., DNR status). * 19\. Patients who are known to be pregnant at the time of screening. \[All women ≤50 years-old will need a negative serum pregnancy test (serum quantitative beta-hCG) to enroll.\] * 20\. Prisoner status * 21\. Patients who are current participating in another interventional clinical trial.