Clinical Research Directory

Inclusion Criteria: * Adult patients ≥18 years-old with persistent vasodilatory shock despite moderate-dose norepinephrine monotherapy, defined as those who require ≥0.1 mcg/kg/min for at least 30 minutes to maintain a MAP between 65-70 mmHg. * 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. * 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. * 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. * 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. * Approval from the attending physician and clinical pharmacist conducting the study. Exclusion Criteria: * Patients who are \< 18 years of age. * Patients diagnosed with acute occlusive coronary syndrome requiring intervention and/or cardiogenic shock. * Patients with or suspected to have abdominal aortic aneurysm or aortic dissection. * Acute stroke. * Patients with acute mesenteric ischemia or those with a history of mesenteric ischemia. * Patients with known Raynaud's phenomenon, systemic sclerosis, or vasospastic disease. * Patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). * Patients with liver failure with a Model for End-Stage Liver Disease (MELD) score of =/\>30. * Patients with burns covering \>20% of total body surface area. * Patients with a history of asthma or chronic obstructive pulmonary disease (COPD) with active acute bronchospasm or (if not mechanically ventilated) with an acute exacerbation of their asthma/COPD requiring the use of inhaled bronchodilators. * Patients requiring more than 500 mg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose. * Patients with an absolute neutrophil count (ANC) of \< 1,000/mm3 * 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. * Patients with active bleeding AND hemoglobin \< 7g/dL or any other condition that would contraindicate serial blood sampling. * Untreated venous thromboembolism (VTE) or inability to tolerate pharmacologic VTE prophylaxis. * Patients with a known allergy to mannitol. * Patients with an expected survival of \<24 hours, SOFA score ≥ 16, or death deemed to be imminent or inevitable during the admission. * Either the attending physician or patient and/or substitute decisionmaker are not committed to all active treatment, e.g., do-not-resuscitate (DNR) status. * 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. * Prisoner status * Patients who are currently participating in another interventional clinical trial.