A Prospective double-blind, randomised controlled trial comparing angiotensin II to norepinephrine to reduce length of hospital stay in cardiac surgery patients (the PORTHOS study protocol).

INTRODUCTION: Cardiac surgery is frequently associated with vasoplegia and vasopressor treatment. Both may be associated with postoperative complications and prolonged length of stay. The most frequently used vasopressor is norepinephrine. However, in a pilot, double-blind, randomised controlled trial (RCT) in cardiac surgery patients, angiotensin II was effective in maintaining blood pressure and was associated with a shorter duration of hospital stay than norepinephrine. Furthermore, hyperreninaemic patients were more sensitive to angiotensin II. These findings support the need for a larger RCT to determine whether angiotensin II is superior to norepinephrine as a first-line treatment for low blood pressure after cardiac surgery.

METHODS AND ANALYSIS: We will conduct a double-blind RCT comparing an infusion of either angiotensin II or norepinephrine intraoperatively and for up to 48 hours after the start of surgery. We will randomly allocate 400 cardiac surgery patients at multiple centres in two countries to either an equipotent angiotensin II or norepinephrine infusion, titrated to a mean arterial pressure of 70-80 mm Hg. The primary outcome will be length of hospital stay. Secondary outcomes will include a composite of renal, cardiovascular and neurological events. A subgroup analysis of patients with elevated baseline renin levels will be undertaken.

ETHICS AND DISSEMINATION: Ethical approval has been granted by the Alfred Human Research Ethics Committee on 14 July 2023 (HREC/97814/Alfred-2023). Results will be published on completion of the trial.

TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry: ACTRN12623000848606.