Effect of Vasopressors on the Macro- and Microcirculation During Systemic Inflammation in Humans In Vivo

Abstract

Comparing the effects of different vasopressors in septic shock patients is hampered by high heterogeneity and the fact that current guidelines dictate the use of norepinephrine. Herein, we studied the effects of three vasopressor agents, norepinephrine, phenylephrine, and vasopressin, on the macro- and microcirculation during experimental human endotoxemia, a standardized, controlled model of systemic inflammation in humans in vivo. We performed a randomized controlled study in which 40 healthy male volunteers were assigned to a 5-h infusion of either 0.05 μg/kg/min norepinephrine (n = 10), 0.5 μg/kg/min phenylephrine (n = 10), 0.04 IU/min vasopressin (n = 10), or saline (n = 10), starting 1 h before intravenous administration of 2 ng/kg lipopolysaccharide (LPS). The macrocirculation was monitored using arterial catheter-derived parameters with additional blood pressure waveform contour analysis (PCA) until 4.5 h following LPS administration. Sublingual microcirculatory density and flow were assessed using a handheld video microscope until 6 h post-LPS. LPS administration affected all macrocirculatory and microcirculatory parameters. The LPS-induced decrease in blood pressure and systemic vascular resistance (SVR) was refractory to low-dose norepinephrine and phenylephrine, and to a lesser extent, to vasopressin. Only vasopressin exerted effects on PCA parameters compared with placebo, by mitigating the LPS-induced decrease in diastolic blood pressure by stabilizing SVR and cardiac output. The endotoxemia-induced decreased indices of microvascular flow and density were not influenced by vasopressor therapy. In a highly controlled model of systemic inflammation in humans in vivo, a 5-h infusion of various vasopressors revealed distinctive effects on macrohemodynamic variables without affecting the sublingual microcirculation.