Intravenous AII for the Treatment of Severe Hypotension in High Output Shock: A Pilot Study

The investigators propose a dose finding study to determine the feasibility of Angiotensin
II (AII) to increase mean arterial pressure in high-output shock. If AII can be shown to
increase mean arterial pressure, this could lead to future pharmacologic development based
on the AII hormonal pathway. The investigators propose a 20 patient, randomized,
placebo-controlled, blinded study in the treatment of high-output shock. Patients with
high-output shock and a cardiovascular SOFA (sequential organ failure score) score of > 4
will be eligible. In addition, patients must already be receiving cardiac output monitoring
and have a cardiac index > 2.4 L/min/ 1.73 m2. Patients will be randomized to intravenous
AII or saline in a blinded fashion. There will be 10 patients in each arm. This is a safety
and dose finding feasibility study. The investigators are starting with a small cohort
consistent with similar types of studies. The investigators estimate that ten patients in
each arm will generate a basis for determining if there is sufficient signal for AII to
improve blood pressure at the doses outlined. The primary endpoint in the study will be the
effect of AII on the standing dose of norepinephrine which is required to maintain a MAP of
65 mmHg. Secondary endpoints will be the effect of AII on urine output, serum lactate, and
creatinine clearance. 30 day post dose mortality will also be assessed. Subjects discharged
prior to day 30 will be contacted by telephone for this assessment.