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. 2025 Dec;38(1):2445603.
doi: 10.1080/08941939.2024.2445603. Epub 2025 Jan 6.

Norepinephrine Infusion and the Central Venous Waveform in a Porcine Model of Endotoxemic Hypotension with Resuscitation: A Large Animal Study

Zachary R Bergman  1 , Roy K Kiberenge  2 , Richard W Bianco  1 , Gregory J Beilman  1 , Colleen M Brophy  3   4 , Kyle M Hocking  3   4 , Bret D Alvis  4   5   6 , Eric S Wise  1
Affiliations

Norepinephrine Infusion and the Central Venous Waveform in a Porcine Model of Endotoxemic Hypotension with Resuscitation: A Large Animal Study

Zachary R Bergman et al. J Invest Surg. 2025 Dec.

Abstract

Background: Venous waveform analysis is an emerging technique to estimate intravascular fluid status by fast Fourier transform deconvolution. Fluid status has been shown proportional to f0, the amplitude of the fundamental frequency of the waveform's cardiac wave upon deconvolution. Using a porcine model of distributive shock and fluid resuscitation, we sought to determine the influence of norepinephrine on f0 of the central venous waveform.

Methods: Eight pigs were anesthetized, catheterized and treated with norepinephrine after precipitation of endotoxemic hypotension, and subsequent fluid resuscitation to mimic sepsis physiology. Hemodynamic parameters and central venous waveforms were continually transduced throughout the protocol for post-hoc analysis. Central venous waveform f0 before, during and after norepinephrine administration were determined using Fourier analysis.

Results: Heart rate increased, while central venous pressure, pulmonary capillary wedge pressure and stroke volume decreased throughout norepinephrine administration (p < 0.05). Mean f0 at pre-norepinephrine, and doses 0.05, 0.10, 0.15, 0.20 and 0.25 mcg/kg/min, were 2.5, 1.4, 1.7, 1.7, 1.6 and 1.4 mmHg2, respectively (repeated measures ANOVA; p < 0.001). On post-hoc comparison to pre-norepinephrine, f0 at 0.05 mcg/kg/min was decreased (p = 0.04).

Conclusions: As the performance of f0 was previously characterized during fluid administration, these data offer novel insight into the performance of f0 during vasopressor delivery. Central venous waveform f0 is a decreased with norepinephrine, in concordance with pulmonary capillary wedge pressure. This allows contextualization of the novel, venous-derived signal f0 during vasopressor administration, a finding that must be understood prior to clinical translation.

Keywords: Central venous pressure; animal models; shock; venous waveform analysis; volume status.

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Conflict of interest statement

Disclosure of Interest:

Dr. Bergman, Dr. Kiberenge, Dr. Bianco, Dr. Beilman and Dr. Wise have no competing interests to disclose.

VoluMetrix is a company that uses venous waveform analysis to assess fluid status in heart failure. Kyle Hocking, PhD, is the Founder, CEO and President of VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to Vanderbilt and licensed to VoluMetrix. Colleen Brophy, MD, is the Founder and CMO of VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to Vanderbilt and licensed to VoluMetrix. Bret Alvis, MD, owns stock in VoluMetrix and an inventor on intellectual property in the field of venous waveform analysis assigned to Vanderbilt and licensed to VoluMetrix and is married to the COO of VoluMetrix.

Additionally, research reported in this publication was supported, in part, by the National Heart Lung and Blood Institute of the National Institutes of Health under Award Number K08HL171885. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

    1. Bergman ZR, Kiberenge RK, Mohammed A, et al. Central Venous Waveform Analysis and Cardiac Output in a Porcine Model of Endotoxemic Hypotension and Resuscitation. J Am Coll Surg 2023;236(2):294–304. - PubMed
    1. Alvis BD, McCallister R, Polcz M, et al. Non-Invasive Venous waveform Analysis (NIVA) for monitoring blood loss in human blood donors and validation in a porcine hemorrhage model. J Clin Anesth 2020;61:109664. - PMC - PubMed
    1. Alvis BD, Polcz M, Miles M, et al. Non-invasive venous waveform analysis (NIVA) for volume assessment in patients undergoing hemodialysis: an observational study. BMC Nephrol 2020;21(1):194. - PMC - PubMed
    1. Alvis BD, Polcz M, Huston JH, et al. Observational Study of Noninvasive Venous Waveform Analysis to Assess Intracardiac Filling Pressures During Right Heart Catheterization. J Card Fail. 2020;26(2):136–141. - PubMed
    1. Alvis B, Huston J, Schmeckpeper J, et al. Noninvasive Venous Waveform Analysis Correlates With Pulmonary Capillary Wedge Pressure and Predicts 30-Day Admission in Patients With Heart Failure Undergoing Right Heart Catheterization. J Card Fail. 2022;28(12):1692–1702. - PMC - PubMed

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