Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Feb;53(2):171-174.
doi: 10.1097/SHK.0000000000001357.

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

Lex M van Loon  1   2   3 , Roeland F Stolk  3   4 , Johannes G van der Hoeven  3   4 , Peter H Veltink  2 , Peter Pickkers  3   4 , Joris Lemson  3 , Matthijs Kox  3   4
Affiliations
Randomized Controlled Trial

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

Lex M van Loon et al. Shock. 2020 Feb.

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT02675868.

PubMed Disclaimer

References

    1. Dubin A, Pozo MO, Casabella CA, Pálizas F, Murias G, Moseinco MC, Kanoore Edul VS, Pálizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 13:R92, 2009.
    1. Krejci V, Hiltebrand LB, Sigurdsson GH. Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis. Crit Care Med 34:1456–1463, 2006.
    1. Vincent J-L, Post EH. Vasopressin: a first-line agent for septic shock? Nat Rev Nephrol 12:718–719, 2016.
    1. Draisma A, Bemelmans R, van der Hoeven JG, Spronk P, Pickkers P. Microcirculation and vascular reactivity during endotoxemia and endotoxin tolerance in humans. Shock 31:581–585, 2009.
    1. Kiers D, Koch RM, Hamers L, Gerretsen J, Thijs EJM, van Ede L, Riksen NP, Kox M, Pickkers P. Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin. Sci Rep 7:40149, 2017.

Publication types

Associated data

LinkOut - more resources