{"paper_id":"20d160e0-82cb-4dce-9e5b-7ea82e844f75","body_text":"Reliability and Reproducibility of the Venous Excess Ultrasound (VExUS) Score, A Multi-Site Prospective Study Validating a Novel Ultrasound Technique for Comprehensive Assessment of Volume Status | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Reliability and Reproducibility of the Venous Excess Ultrasound (VExUS) Score, A Multi-Site Prospective Study Validating a Novel Ultrasound Technique for Comprehensive Assessment of Volume Status August A Longino, Katharine C Martin, Katarina R Leyba, Gabriel Siegel, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3993434/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Though the novel Venous Excess Ultrasound (VExUS) score is increasingly used as a noninvasive ultrasonographic method to measure venous congestion, the inter-rater reliability (IRR) and inter-user reproducibility (IUR) of this procedure have not been established. For this reason, we conducted a multi-site study of the IRR and IUR of the VExUS score between a wide range of physicians, reporting the Kappa statistic (KS) and Intraclass Correlation Coefficient (ICC) for IRR and IUR. We found that when VExUS images were interpreted by physicians specializing in cardiology, pulmonology, hospital medicine, and emergency medicine, there was substantial IRR, with a KS of 0.71 and ICC of 0.83 for the overall VExUS grade (p < 0.001), and IUR, with a KS 0.63 and ICC of 0.8, suggesting that the VExUS score is likely to be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds. Figures Figure 1 Background Historically, the medical community has focused principally on the arterial side of the circulation. However, pathologic venous congestion is increasingly being recognized an under-appreciated cause of harm in multiple patient populations, especially those with cardiac disease. 1–3 Despite the importance of this clinical parameter, assessment of venous congestion remains challenging, as conventional physical exam findings depend on patient characteristics and provider experience. While ultrasound of the inferior vena cava (IVC) was thought to address these issues, studies have shown a lower-than expected clinical utility. 4 Recognizing these barriers, clinicians often rely on right heart catheterization (RHC), the gold standard for assessment of venous congestion. Unfortunately, RHC is invasive, resource-intensive, and unavailable in many centers. 5 These limitations demonstrate a need for a reliable, cost-effective, noninvasive means of measuring venous congestion. To address this need, Beaubien-Souligny and colleagues developed the novel “Venous Excess Ultrasound (VExUS)” Score. The authors described a noninvasive 4-point exam combining IVC measurement with Doppler ultrasonography of the hepatic vein (HV), portal vein (PV), and renal veins (RV), and reported a positive likelihood ratio of 6.37 for cardiorenal acute kidney injury (AKI). 2, 3 Since that time multiple reviews have been published on the use of VExUS, with a focus on its clinical utility for assessment of volume status. 6–8 Subsequent validation studies found Sthat VExUS correlates with AKI and intracardiac pressures measured by RHC. 9, 10 These preliminary findings have generated considerable interest in the technique, and multiple prospective trials evaluating its utility are currently underway. 11, 12 However, despite its rapid adoption, much remains unknown about the VExUS score, including inter-rater reliability (IRR, consistency of interpretation by multiple different readers), and inter-user reproducibility (IUR, consistency of images acquired from one patient by multiple ultrasonographers), and whether or not a concurrent electrocardiogram (ECG) tracing is necessary for interpretation. Best practices and standardized protocols have not been established, and real-world implementation of VExUS varies widely. To address these gaps in the literature, we conducted a multi-center, multidisciplinary prospective observational study to assess IRR, IUR, and the necessity of a ECG tracing in the interpretation of VExUS images. Methods Patients from two tertiary medical centers in Denver, CO were enrolled. Inclusion criteria were inpatient admission and ability to tolerate a VExUS exam. Exclusion criteria included pregnancy or inability to provide informed consent. Patients with conditions that might confound VExUS(e.g., cirrhosis) were included to increase generalizability of findings. Two sets of VExUS images were acquired per patient by different ultrasonographers, blinded to each other’s exams. VExUS Protocol: Following acquisition of informed consent, VExUS exams were conducted as previously described. 2 Ultrasonographers measured IVC diameter 1–2 cm caudal to the confluence of the HV and IVC. HV pulsatility was assessed in a subxiphoid or lateral view, placing the Doppler gate across any of the hepatic veins. Portal venous pulsatility was assessed by placing the Doppler gate across the PV and observing waveform pulsatility index. Renal vasculature was visualized with the probe in the posterior axillary line, with the Doppler gate placed to detect flow in the interlobar or arcuate vessels in the renal cortex. Exams were conducted using the abdominal probe of the Mindray TE7 (Mindray Bio-Medical Electronics Co). This study had the ethical and institutional approval the local institutional review board (COMIRB Number VExUS Scoring: The VExUS score is composed of evaluations of the IVC, HV, PV, and RV (Fig. 1 ). 2 If a patient’s IVC diameter is < 2 cm, the exam is assigned a score of 0, (no congestion). In the presence of an IVC ≥ 2 cm, the examiner categorizes each vein as either normal, mildly abnormal, or severely abnormal. For study purposes, all views were acquired in all patients. Normal HV Doppler waveforms show a small, retrograde a-wave, followed by anterograde systolic (S) and diastolic (D) waves, with the ratio of the S:D waves being > 1. In increasing states of congestion, the S wave shrinks relative to the D wave before reversing entirely, becoming retrograde. A S:D ratio > 1 is normal, a S:D ratio ≤ 1 is mildly abnormal, and S wave reversal is severely abnormal. A normal PV Doppler waveform shows pulsatility of < 30%. Pulsatility of 30–49% is mildly abnormal, and a pulsatility > 50% is severely abnormal. A normal RV Doppler pattern shows continuous, non-pulsatile anterograde flow. A continuous venous baseline is normal. Biphasic pulsations during systole and diastole are considered mildly abnormal. Monophasic pulsation during diastole is severely abnormal (Fig. 1 ). [Figure 1 ] Any combination of normal or mildly abnormal scores is given a grade of 1. If the patient has one severely abnormal score, they are given a grade of two. Two or more severely abnormal scores results in a grade of 3, reflecting severe congestion. Ultrasonographers were 4 internal medicine residents with extensive remote and in-person training in VExUS. Serial exams took place within a 20-minute window to avoid changes in volume status. Ultrasonographer order was randomized. An ECG tracing was added to the protocol for a subset of 30 patients. Anonymized VExUS images were reviewed by a four-member interpretation team including: a board-certified and currently practicing pulmonologist/intensivist, cardiologist, emergency medicine physician, and hospitalist, all familiar with the VExUS technique. Interpreters provided a grade for each exam component, an overall score, and a holistic assessment of image quality on a scale of 1 (“uninterpretable”) to 5 (“clear, unequivocal”). Data Analysis: Exams with an image quality score of < 3 were excluded. We calculated Light’s Kappa Statistic (KS) and the two-way intraclass correlation coefficients (ICC) 13 to assess IRR between all four interpreters for grades of the overall VExUS exam and grades for each exam component. We then assessed IUR by comparing concordance between the first and second scans on each patient as reported by each interpreter and calculated mean and standard deviation of the ICC and KS of all 4 interpreters. Scores were presented as mean, standard deviation (SD), and highest p-value. Results 56 patients were enrolled in the study. Of these, 42 had quality scores > 2 for both VExUS exams and were included in the final analysis, allowing for comparison of 84 paired scans. Sixty scans had concomitant ECG tracings. Demographics and concordance statistics are presented in Tables 1 and 2 . Table 2 Concordance Statistics [Table 1] Inter-Rater Reliability: The KS and ICC between interpreters was 0.71 and 0.83 for the overall VExUS grade (p < 0.001), suggesting substantial agreement. 13 Kappa statistics and ICCs for the individual VExUS components were lower than for the overall VExUS exam, ranging from fair to moderate; 0.52 and 0.71 for HV, 0.53 and 0.74 for PV, and 0.32 and 0.48 for RV (p < 0.03) (Table 1). There was an increase in concordance with the ECG tracing, with a KS and ICC of 0.75(p < 0.01) and 0.86(p < 0.01) with an ECG lead compared to 0.42(p < 0.01) and 0.59(p < 0.01) without an ECG lead. Inter-User Reproducibility: When comparing images from the same patient, the average ICC was 0.8 for VExUS grade, 0.72 for HV, 0.61 for PV, and 0.56 for RV. The average KS was 0.63 for VExUS grade, 0.57 for HV, 0.41 for PV, and 0.38 for RV (Table 2 ). [Table 2 ] Discussion We found substantial IRR for the VExUS score between multiple readers and IUR between images acquired from the same patient by sequential ultrasonographers. The IRR of the VExUS exam as collected and interpreted by physicians was superior the reported IRR of IVC measurement in a group of emergency department physicians, 14 and similar to the IRR of IVC measurements when collected by professional ultrasonographers. 15 The overall VExUS exam showed higher levels of IRR and IUR than individual components of the exam, suggesting that the redundancy of the VExUS score may compensate for variability of interpretation of individual components. The renal component of the exam had the lowest IRR and IUR, likely due to difficulty of acquiring and interpreting renal images. As VExUS undergoes further refinement, the necessity of the renal view should be critically assessed. The increase in interpreter agreement following introduction of an ECG tracing suggests that ECG integration improves VExUS readability, and should be considered as part of a standardized VExUS protocol. Strengths of the current study include a diverse patient population from different centers, strengthening the generalizability of the findings to a broader population than VExUS is usually applied to, as well as a diverse interpretation team including multiple subspecialities, suggesting that VExUS is interpretable by a wide range of physicians. Weaknesses of the study include a limited sample size, which should be addressed in future studies. While more study is needed, these preliminary results suggest that the VExUS score is likely to be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds when paired with an ECG tracing. Declarations Authors have no conflicts of interest to disclose. Ethical Approval: This study had approval from the local Colorado Multiple Institutional Review Board (#22–2024). Funding Declaration: None of the authors have any competing interests or competing interests to report. No funding was provided for this research. References Messmer AS, Zingg C, Muller M, Gerber JL, Schefold JC, Pfortmueller CA. Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies. Crit Care Med. 2020;48(12):1862-70. Beaubien-Souligny W, Rola P, Haycock K, Bouchard J, Lamarche Y, Spiegel R, Denault AY. Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess ultrasound grading system. Ultrasound J. 2020;12(1):16. Bhardwaj V, Vikneswaran G, Rola P, Raju S, Bhat RS, Jayakumar A, Alva A. Combination of Inferior Vena Cava Diameter, Hepatic Venous Flow, and Portal Vein Pulsatility Index: Venous Excess Ultrasound Score (VEXUS Score) in Predicting Acute Kidney Injury in Patients with Cardiorenal Syndrome: A Prospective Cohort Study. Indian J Crit Care Med. 2020;24(9):783-9. Di Nicolo P, Tavazzi G, Nannoni L, Corradi F. Inferior Vena Cava Ultrasonography for Volume Status Evaluation: An Intriguing Promise Never Fulfilled. J Clin Med. 2023;12(6). Hoeper MM, Lee SH, Voswinckel R, Palazzini M, Jais X, Marinelli A, et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol. 2006;48(12):2546-52. Argaiz ER. VExUS Nexus: Bedside Assessment of Venous Congestion. Adv Chronic Kidney Dis. 2021;28(3):252-61. Gupta S, Tomar DS. VEXUS-The Third Eye for the Intensivist? Indian J Crit Care Med. 2020;24(9):746-7. Koratala A, Reisinger N. Venous Excess Doppler Ultrasound for the Nephrologist: Pearls and Pitfalls. Kidney Med. 2022;4(7):100482. Longino A, Martin K, Leyba K, Siegel G, Thai TN, Riscinti M, et al. Prospective Evaluation of Venous Excess Ultrasound (VExUS) for Estimation of Venous Congestion. Chest. 2023. Longino A, Martin K, Leyba K, Siegel G, Gill E, Douglas IS, Burke J. Correlation between the VExUS score and right atrial pressure: a pilot prospective observational study. Crit Care. 2023;27(1):205. Prager R, Argaiz E, Pratte M, Rola P, Arntfield R, Beaubien-Souligny W, et al. Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS). BMJ Open. 2023;13(7):e074843. Romano M, Viana E, Martins JD, Corga Da Silva R. Evaluation Of Congestion Levels in Septic Patients Admitted to Critical Care Units with a Combined Venous Excess-Lung Ultrasound Score (VExLUS) - a Research Protocol. POCUS J. 2023;8(1):93-8. Mandrekar JN. Measures of interrater agreement. J Thorac Oncol. 2011;6(1):6-7. Fields JM, Lee PA, Jenq KY, Mark DG, Panebianco NL, Dean AJ. The interrater reliability of inferior vena cava ultrasound by bedside clinician sonographers in emergency department patients. Acad Emerg Med. 2011;18(1):98-101. Blanca D, Schwarz EC, Olgers TJ, Ter Avest E, Azizi N, Bouma HR, Ter Maaten JC. Intra-and inter-observer variability of point of care ultrasound measurements to evaluate hemodynamic parameters in healthy volunteers. Ultrasound J. 2023;15(1):22. Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-3993434\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Short Report\",\"associatedPublications\":[],\"authors\":[{\"id\":276551821,\"identity\":\"c2b8a64e-6c1c-4394-93f0-fa47d2efdf93\",\"order_by\":0,\"name\":\"August A Longino\",\"email\":\"data:image/png;base64,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\",\"orcid\":\"\",\"institution\":\"University of Colorado Hospital\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"August\",\"middleName\":\"A\",\"lastName\":\"Longino\",\"suffix\":\"\"},{\"id\":276551822,\"identity\":\"48d07b0a-761a-4f0f-991d-b5915cb07f20\",\"order_by\":1,\"name\":\"Katharine C Martin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Colorado Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Katharine\",\"middleName\":\"C\",\"lastName\":\"Martin\",\"suffix\":\"\"},{\"id\":276551823,\"identity\":\"a81ebe92-6cbc-40ed-be3a-927b3cedafe4\",\"order_by\":2,\"name\":\"Katarina R Leyba\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Colorado Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Katarina\",\"middleName\":\"R\",\"lastName\":\"Leyba\",\"suffix\":\"\"},{\"id\":276551824,\"identity\":\"22fab8a7-4ff5-4dda-9544-ae6de59f4190\",\"order_by\":3,\"name\":\"Gabriel Siegel\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Denver Health Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Gabriel\",\"middleName\":\"\",\"lastName\":\"Siegel\",\"suffix\":\"\"},{\"id\":276551825,\"identity\":\"d730b175-0680-4572-8108-5d4365cc677b\",\"order_by\":4,\"name\":\"Vibhu M Sharma\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Colorado Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Vibhu\",\"middleName\":\"M\",\"lastName\":\"Sharma\",\"suffix\":\"\"},{\"id\":276551826,\"identity\":\"2579272d-bd91-4aec-a0c8-13e0e50861c1\",\"order_by\":5,\"name\":\"Matthew Riscinti\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Colorado Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Matthew\",\"middleName\":\"\",\"lastName\":\"Riscinti\",\"suffix\":\"\"},{\"id\":276551827,\"identity\":\"d3337a96-8d26-4862-a25d-5a2759def7ea\",\"order_by\":6,\"name\":\"Carolina O Lopez\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Colorado Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Carolina\",\"middleName\":\"O\",\"lastName\":\"Lopez\",\"suffix\":\"\"},{\"id\":276551828,\"identity\":\"0810d91e-e18c-4e0a-92e3-ed747aa1ba2a\",\"order_by\":7,\"name\":\"Edward A Gill\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Colorado Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Edward\",\"middleName\":\"A\",\"lastName\":\"Gill\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-02-27 09:15:10\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-3993434/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-3993434/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":52182974,\"identity\":\"0d7a2d87-53fa-4d52-bae7-53ca5809c7cb\",\"added_by\":\"auto\",\"created_at\":\"2024-03-07 18:08:45\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":444006,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cu\\u003e\\u003cstrong\\u003eVenous Excess Ultrasound (VExUS) Image Grading\\u003c/strong\\u003e\\u003c/u\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe Venous Excess Ultrasound (VExUS) grading rubric. Normal hepatic (HD), portal (PD) and Renal (RD) doppler waveforms (I-III). \\u0026nbsp;The HD is considered mildly abnormal when the systolic (S) component is lower in magnitude than the diastolic (D) component (IV), but still toward the liver, and severely abnormal when the S component is reversed (VII). The PD is considered mildly abnormal when a variation in the velocities during the cardiac cycle of 30 to \\u0026lt; 50% are observed (V) and severely abnormal when a variation of ≥ 50% is seen (VIII). The RD is considered mildly abnormal when it is discontinuous with a systolic (S) and diastolic (D) phase (VI), while is it considered severely abnormal when it is discontinuous with only a diastolic phase seen during the cardiac cycle (IX).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3993434/v1/81fd1cc1bfc9ff68b9d6ac4b.png\"},{\"id\":52701323,\"identity\":\"8e73fc3f-f9d9-43e8-92e6-f4697afb6f88\",\"added_by\":\"auto\",\"created_at\":\"2024-03-14 17:29:56\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":674436,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3993434/v1/8598f1e0-6bc3-4cf6-b7a6-98927c321cc0.pdf\"},{\"id\":52182982,\"identity\":\"ee63bcd0-1326-4f3a-a604-6034eb57016f\",\"added_by\":\"auto\",\"created_at\":\"2024-03-07 18:08:50\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":31283,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Tables.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3993434/v1/8114eb5a899230d9fd9a5ff6.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Reliability and Reproducibility of the Venous Excess Ultrasound (VExUS) Score, A Multi-Site Prospective Study Validating a Novel Ultrasound Technique for Comprehensive Assessment of Volume Status\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eHistorically, the medical community has focused principally on the arterial side of the circulation. However, pathologic venous congestion is increasingly being recognized an under-appreciated cause of harm in multiple patient populations, especially those with cardiac disease.\\u003csup\\u003e1\\u0026ndash;3\\u003c/sup\\u003e Despite the importance of this clinical parameter, assessment of venous congestion remains challenging, as conventional physical exam findings depend on patient characteristics and provider experience. While ultrasound of the inferior vena cava (IVC) was thought to address these issues, studies have shown a lower-than expected clinical utility.\\u003csup\\u003e4\\u003c/sup\\u003e Recognizing these barriers, clinicians often rely on right heart catheterization (RHC), the gold standard for assessment of venous congestion. Unfortunately, RHC is invasive, resource-intensive, and unavailable in many centers.\\u003csup\\u003e5\\u003c/sup\\u003e These limitations demonstrate a need for a reliable, cost-effective, noninvasive means of measuring venous congestion.\\u003c/p\\u003e \\u003cp\\u003eTo address this need, Beaubien-Souligny and colleagues developed the novel \\u0026ldquo;Venous Excess Ultrasound (VExUS)\\u0026rdquo; Score. The authors described a noninvasive 4-point exam combining IVC measurement with Doppler ultrasonography of the hepatic vein (HV), portal vein (PV), and renal veins (RV), and reported a positive likelihood ratio of 6.37 for cardiorenal acute kidney injury (AKI).\\u003csup\\u003e2, 3\\u003c/sup\\u003e Since that time multiple reviews have been published on the use of VExUS, with a focus on its clinical utility for assessment of volume status.\\u003csup\\u003e6\\u0026ndash;8\\u003c/sup\\u003e Subsequent validation studies found Sthat VExUS correlates with AKI and intracardiac pressures measured by RHC.\\u003csup\\u003e9, 10\\u003c/sup\\u003e These preliminary findings have generated considerable interest in the technique, and multiple prospective trials evaluating its utility are currently underway.\\u003csup\\u003e11, 12\\u003c/sup\\u003e However, despite its rapid adoption, much remains unknown about the VExUS score, including inter-rater reliability (IRR, consistency of interpretation by multiple different readers), and inter-user reproducibility (IUR, consistency of images acquired from one patient by multiple ultrasonographers), and whether or not a concurrent electrocardiogram (ECG) tracing is necessary for interpretation. Best practices and standardized protocols have not been established, and real-world implementation of VExUS varies widely. To address these gaps in the literature, we conducted a multi-center, multidisciplinary prospective observational study to assess IRR, IUR, and the necessity of a ECG tracing in the interpretation of VExUS images.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003ePatients from two tertiary medical centers in Denver, CO were enrolled. Inclusion criteria were inpatient admission and ability to tolerate a VExUS exam. Exclusion criteria included pregnancy or inability to provide informed consent. Patients with conditions that might confound VExUS(e.g., cirrhosis) were included to increase generalizability of findings. Two sets of VExUS images were acquired per patient by different ultrasonographers, blinded to each other\\u0026rsquo;s exams.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eVExUS Protocol:\\u003c/h2\\u003e \\u003cp\\u003eFollowing acquisition of informed consent, VExUS exams were conducted as previously described.\\u003csup\\u003e2\\u003c/sup\\u003e Ultrasonographers measured IVC diameter 1\\u0026ndash;2 cm caudal to the confluence of the HV and IVC. HV pulsatility was assessed in a subxiphoid or lateral view, placing the Doppler gate across any of the hepatic veins. Portal venous pulsatility was assessed by placing the Doppler gate across the PV and observing waveform pulsatility index. Renal vasculature was visualized with the probe in the posterior axillary line, with the Doppler gate placed to detect flow in the interlobar or arcuate vessels in the renal cortex. Exams were conducted using the abdominal probe of the Mindray TE7 (Mindray Bio-Medical Electronics Co). This study had the ethical and institutional approval the local institutional review board (COMIRB Number\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eVExUS Scoring:\\u003c/h2\\u003e \\u003cp\\u003eThe VExUS score is composed of evaluations of the IVC, HV, PV, and RV (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003csup\\u003e2\\u003c/sup\\u003e If a patient\\u0026rsquo;s IVC diameter is \\u0026lt;\\u0026thinsp;2 cm, the exam is assigned a score of 0, (no congestion). In the presence of an IVC\\u0026thinsp;\\u0026ge;\\u0026thinsp;2 cm, the examiner categorizes each vein as either normal, mildly abnormal, or severely abnormal. For study purposes, all views were acquired in all patients. Normal HV Doppler waveforms show a small, retrograde a-wave, followed by anterograde systolic (S) and diastolic (D) waves, with the ratio of the S:D waves being \\u0026gt;\\u0026thinsp;1. In increasing states of congestion, the S wave shrinks relative to the D wave before reversing entirely, becoming retrograde. A S:D ratio\\u0026thinsp;\\u0026gt;\\u0026thinsp;1 is normal, a S:D ratio\\u0026thinsp;\\u0026le;\\u0026thinsp;1 is mildly abnormal, and S wave reversal is severely abnormal. A normal PV Doppler waveform shows pulsatility of \\u0026lt;\\u0026thinsp;30%. Pulsatility of 30\\u0026ndash;49% is mildly abnormal, and a pulsatility\\u0026thinsp;\\u0026gt;\\u0026thinsp;50% is severely abnormal. A normal RV Doppler pattern shows continuous, non-pulsatile anterograde flow. A continuous venous baseline is normal. Biphasic pulsations during systole and diastole are considered mildly abnormal. Monophasic pulsation during diastole is severely abnormal (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e[Figure \\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/h2\\u003e \\u003cp\\u003eAny combination of normal or mildly abnormal scores is given a grade of 1. If the patient has one severely abnormal score, they are given a grade of two. Two or more severely abnormal scores results in a grade of 3, reflecting severe congestion.\\u003c/p\\u003e \\u003cp\\u003eUltrasonographers were 4 internal medicine residents with extensive remote and in-person training in VExUS. Serial exams took place within a 20-minute window to avoid changes in volume status. Ultrasonographer order was randomized. An ECG tracing was added to the protocol for a subset of 30 patients. Anonymized VExUS images were reviewed by a four-member interpretation team including: a board-certified and currently practicing pulmonologist/intensivist, cardiologist, emergency medicine physician, and hospitalist, all familiar with the VExUS technique. Interpreters provided a grade for each exam component, an overall score, and a holistic assessment of image quality on a scale of 1 (\\u0026ldquo;uninterpretable\\u0026rdquo;) to 5 (\\u0026ldquo;clear, unequivocal\\u0026rdquo;).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eData Analysis:\\u003c/h2\\u003e \\u003cp\\u003eExams with an image quality score of \\u0026lt;\\u0026thinsp;3 were excluded. We calculated Light\\u0026rsquo;s Kappa Statistic (KS) and the two-way intraclass correlation coefficients (ICC)\\u003csup\\u003e13\\u003c/sup\\u003e to assess IRR between all four interpreters for grades of the overall VExUS exam and grades for each exam component. We then assessed IUR by comparing concordance between the first and second scans on each patient as reported by each interpreter and calculated mean and standard deviation of the ICC and KS of all 4 interpreters. Scores were presented as mean, standard deviation (SD), and highest p-value.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003e56 patients were enrolled in the study. Of these, 42 had quality scores\\u0026thinsp;\\u0026gt;\\u0026thinsp;2 for both VExUS exams and were included in the final analysis, allowing for comparison of 84 paired scans. Sixty scans had concomitant ECG tracings. Demographics and concordance statistics are presented in Tables 1 and \\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eConcordance Statistics\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e[Table\\u0026nbsp;1]\\u003c/h2\\u003e \\u003cdiv id=\\\"Sec9\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003eInter-Rater Reliability:\\u003c/h2\\u003e \\u003cp\\u003eThe KS and ICC between interpreters was 0.71 and 0.83 for the overall VExUS grade (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001), suggesting substantial agreement.\\u003csup\\u003e13\\u003c/sup\\u003e Kappa statistics and ICCs for the individual VExUS components were lower than for the overall VExUS exam, ranging from fair to moderate; 0.52 and 0.71 for HV, 0.53 and 0.74 for PV, and 0.32 and 0.48 for RV (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.03) (Table\\u0026nbsp;1). There was an increase in concordance with the ECG tracing, with a KS and ICC of 0.75(p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01) and 0.86(p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01) with an ECG lead compared to 0.42(p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01) and 0.59(p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01) without an ECG lead.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eInter-User Reproducibility:\\u003c/h2\\u003e \\u003cp\\u003eWhen comparing images from the same patient, the average ICC was 0.8 for VExUS grade, 0.72 for HV, 0.61 for PV, and 0.56 for RV. The average KS was 0.63 for VExUS grade, 0.57 for HV, 0.41 for PV, and 0.38 for RV (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e[Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e]\\u003c/h2\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eWe found substantial IRR for the VExUS score between multiple readers and IUR between images acquired from the same patient by sequential ultrasonographers. The IRR of the VExUS exam as collected and interpreted by physicians was superior the reported IRR of IVC measurement in a group of emergency department physicians,\\u003csup\\u003e14\\u003c/sup\\u003e and similar to the IRR of IVC measurements when collected by professional ultrasonographers.\\u003csup\\u003e15\\u003c/sup\\u003e The overall VExUS exam showed higher levels of IRR and IUR than individual components of the exam, suggesting that the redundancy of the VExUS score may compensate for variability of interpretation of individual components. The renal component of the exam had the lowest IRR and IUR, likely due to difficulty of acquiring and interpreting renal images. As VExUS undergoes further refinement, the necessity of the renal view should be critically assessed. The increase in interpreter agreement following introduction of an ECG tracing suggests that ECG integration improves VExUS readability, and should be considered as part of a standardized VExUS protocol.\\u003c/p\\u003e \\u003cp\\u003eStrengths of the current study include a diverse patient population from different centers, strengthening the generalizability of the findings to a broader population than VExUS is usually applied to, as well as a diverse interpretation team including multiple subspecialities, suggesting that VExUS is interpretable by a wide range of physicians. Weaknesses of the study include a limited sample size, which should be addressed in future studies. While more study is needed, these preliminary results suggest that the VExUS score is likely to be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds when paired with an ECG tracing.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003eAuthors have no conflicts of interest to disclose.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eEthical Approval: This study had approval from the local Colorado Multiple Institutional Review Board (#22\\u0026ndash;2024).\\u003c/p\\u003e\\n\\u003cp\\u003eFunding Declaration: None of the authors have any competing interests or competing interests to report. No funding was provided for this research.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eMessmer AS, Zingg C, Muller M, Gerber JL, Schefold JC, Pfortmueller CA. Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies. Crit Care Med. 2020;48(12):1862-70.\\u003c/li\\u003e\\n\\u003cli\\u003eBeaubien-Souligny W, Rola P, Haycock K, Bouchard J, Lamarche Y, Spiegel R, Denault AY. Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess ultrasound grading system. Ultrasound J. 2020;12(1):16.\\u003c/li\\u003e\\n\\u003cli\\u003eBhardwaj V, Vikneswaran G, Rola P, Raju S, Bhat RS, Jayakumar A, Alva A. Combination of Inferior Vena Cava Diameter, Hepatic Venous Flow, and Portal Vein Pulsatility Index: Venous Excess Ultrasound Score (VEXUS Score) in Predicting Acute Kidney Injury in Patients with Cardiorenal Syndrome: A Prospective Cohort Study. Indian J Crit Care Med. 2020;24(9):783-9.\\u003c/li\\u003e\\n\\u003cli\\u003eDi Nicolo P, Tavazzi G, Nannoni L, Corradi F. Inferior Vena Cava Ultrasonography for Volume Status Evaluation: An Intriguing Promise Never Fulfilled. J Clin Med. 2023;12(6).\\u003c/li\\u003e\\n\\u003cli\\u003eHoeper MM, Lee SH, Voswinckel R, Palazzini M, Jais X, Marinelli A, et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol. 2006;48(12):2546-52.\\u003c/li\\u003e\\n\\u003cli\\u003eArgaiz ER. VExUS Nexus: Bedside Assessment of Venous Congestion. Adv Chronic Kidney Dis. 2021;28(3):252-61.\\u003c/li\\u003e\\n\\u003cli\\u003eGupta S, Tomar DS. VEXUS-The Third Eye for the Intensivist? Indian J Crit Care Med. 2020;24(9):746-7.\\u003c/li\\u003e\\n\\u003cli\\u003eKoratala A, Reisinger N. Venous Excess Doppler Ultrasound for the Nephrologist: Pearls and Pitfalls. Kidney Med. 2022;4(7):100482.\\u003c/li\\u003e\\n\\u003cli\\u003eLongino A, Martin K, Leyba K, Siegel G, Thai TN, Riscinti M, et al. Prospective Evaluation of Venous Excess Ultrasound (VExUS) for Estimation of Venous Congestion. Chest. 2023.\\u003c/li\\u003e\\n\\u003cli\\u003eLongino A, Martin K, Leyba K, Siegel G, Gill E, Douglas IS, Burke J. Correlation between the VExUS score and right atrial pressure: a pilot prospective observational study. Crit Care. 2023;27(1):205.\\u003c/li\\u003e\\n\\u003cli\\u003ePrager R, Argaiz E, Pratte M, Rola P, Arntfield R, Beaubien-Souligny W, et al. Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS). BMJ Open. 2023;13(7):e074843.\\u003c/li\\u003e\\n\\u003cli\\u003eRomano M, Viana E, Martins JD, Corga Da Silva R. Evaluation Of Congestion Levels in Septic Patients Admitted to Critical Care Units with a Combined Venous Excess-Lung Ultrasound Score (VExLUS) - a Research Protocol. POCUS J. 2023;8(1):93-8.\\u003c/li\\u003e\\n\\u003cli\\u003eMandrekar JN. Measures of interrater agreement. J Thorac Oncol. 2011;6(1):6-7.\\u003c/li\\u003e\\n\\u003cli\\u003eFields JM, Lee PA, Jenq KY, Mark DG, Panebianco NL, Dean AJ. The interrater reliability of inferior vena cava ultrasound by bedside clinician sonographers in emergency department patients. Acad Emerg Med. 2011;18(1):98-101.\\u003c/li\\u003e\\n\\u003cli\\u003eBlanca D, Schwarz EC, Olgers TJ, Ter Avest E, Azizi N, Bouma HR, Ter Maaten JC. Intra-and inter-observer variability of point of care ultrasound measurements to evaluate hemodynamic parameters in healthy volunteers. Ultrasound J. 2023;15(1):22.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003eTables are available in the Supplementary Files section.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-3993434/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-3993434/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eThough the novel Venous Excess Ultrasound (VExUS) score is increasingly used as a noninvasive ultrasonographic method to measure venous congestion, the inter-rater reliability (IRR) and inter-user reproducibility (IUR) of this procedure have not been established. For this reason, we conducted a multi-site study of the IRR and IUR of the VExUS score between a wide range of physicians, reporting the Kappa statistic (KS) and Intraclass Correlation Coefficient (ICC) for IRR and IUR. We found that when VExUS images were interpreted by physicians specializing in cardiology, pulmonology, hospital medicine, and emergency medicine, there was substantial IRR, with a KS of 0.71 and ICC of 0.83 for the overall VExUS grade (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001), and IUR, with a KS 0.63 and ICC of 0.8, suggesting that the VExUS score is likely to be a reliable and reproducible measure interpretable by clinicians with diverse backgrounds.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Reliability and Reproducibility of the Venous Excess Ultrasound (VExUS) Score, A Multi-Site Prospective Study Validating a Novel Ultrasound Technique for Comprehensive Assessment of Volume Status\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-03-07 18:07:58\",\"doi\":\"10.21203/rs.3.rs-3993434/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":1}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"887fa1a9-b44b-4ed5-a671-5ef6d65df2bd\",\"owner\":[],\"postedDate\":\"March 7th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-04-23T10:54:00+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-03-07 18:07:58\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-3993434\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-3993434\",\"identity\":\"rs-3993434\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}