Norepinephrine Increases Cardiac Preload and Reduces Preload Dependency Assessed By Passive Leg Raising in Septic Shock Patients

This prospective interventional study from France aimed to further characterize the hemodynamic effects of norepinephrine (NE). The authors hypothesized that in addition to its powerful vasoconstrictive arterial effects, NE also exerts an effect on the venous side, increasing venous return, cardiac preload, and cardiac output. This non-blinded single-arm study was conducted in a university hospital in a 15-bed medical intensive care unit and included patients who had a diagnosis of sepsis and circulatory shock (defined as systolic blood pressure < 90 mm Hg plus decreased urine output or heart rate > 100 beats/min or skin mottling), an NE infusion already in place, a diastolic blood pressure < 40 mm Hg, and a positive passive leg raise (PLR). The investigators first recorded baseline hemodynamic measurements including heart rate (HR), systemic mean arterial pressure (MAP), central venous pressure (CVP), left ventricular end-diastolic area (LVEDA), and cardiac index (CI), then recorded these same measurements when the PLR maneuver had its maximum effect to determine whether the patient was preload-dependent. The patient was then returned to a semi-recumbent position and the dose of NE was increased. After hemodynamic variables had time to stabilize on the higher dose of NE, another set of measurements was recorded. Next, another PLR was performed with another set of measurements at the time of the maneuver's maximum effect, followed by a 500-mL saline bolus and one final set of measurements. The study included a total of 25 patients. The authors found that PLR increased MAP, CVP, LVEDA, and CI, as did increasing the dose of NE. They also found that the second PLR (on the higher dose of NE) increased MAP, CVP, LVEDA, and CI but with smaller amplitude than that of the first PLR. The saline bolus also resulted in an increase in MAP, CVP, LVEDA, and CI. The authors concluded that NE increased preload as well as CI. They also concluded that CI increased less with PLR after the dose of NE was increased; however, the PLR still seemed to predict which patients would respond to fluid challenge.