Abstract
Background & Aims
Patients with decompensated cirrhosis are susceptible to iatrogenic hypervolemia. A pilot study using point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) found severe hypervolemia in 20% of patients after intravenous (IV) albumin, despite adherence to current guidelines. CPMX2 is a novel non-invasive device that uses external jugular vein (EJV) compression to assess central venous pressure, but its ability to predict post-albumin hypervolemia has not been studied. We aimed to track changes in intravascular volume status during passive leg raise (PLR) and IV albumin using both methods.
Methods
IVC diameters (IVCmin, IVCmax) and IVC collapsibility index (IVCCI) were measured by POCUS, and EJV compression pressures (EJVmin, EJVmax, EJVmean) were measured by CPMX2, in parallel before and during PLR, as well as before and after IV albumin. Potential intravascular overload was defined as IVCmax >2.1 cm and IVCCI <50%, or EJVmean ≥9 mmHg.
Results
In this prospective cohort of 20 patients (35% women; median age 62 years; mean BMI 25.7 kg/m2; 55% Child-Pugh B; 80% receiving paracentesis), all IVC diameters and EJV compression pressures increased during PLR and after IV albumin. Percentage changes in EJV compression pressures were greater than changes in IVC diameters during PLR (mean EJVmax +88%, EJVmean +65% vs. IVCmax +16%, IVCmin +26%; all p <0.01). After IV albumin, changes were comparable between the methods (mean EJVmax +68%, EJVmin +80%, EJVmean +75% vs IVCmax +58%, IVCmin +79%). Potential post-albumin volume overload occurred in most cases (POCUS 65%, CPMX2 95%).
Conclusions
Both POCUS and CPMX2 detected substantial volume changes during PLR and following IV albumin. CPMX2 appeared more sensitive to dynamic changes during PLR and identified more patients with potential post-albumin volume overload, suggesting it may help individualize fluid management in decompensated cirrhosis.
Impact and implications
Intravascular volume overload after albumin infusion is a major concern in patients with decompensated cirrhosis and was observed in its most severe form in 20% of patients using POCUS-IVC (point-of-care ultrasound of the inferior vena cava). In this pilot study, we detected substantial volume shifts during passive leg raise and after albumin infusion using both POCUS-IVC and a novel external jugular vein compression technique (CPMX2) in parallel. CPMX2 appeared more sensitive to dynamic changes during passive leg raise and identified a larger proportion of patients with intravascular volume overload following intravenous albumin. These findings suggest that CPMX2 could serve as a promising non-invasive tool for early assessment and individualized monitoring of volume status in decompensated cirrhosis.
Keywords: cirrhosis, point of care ultrasound, volume management, inferior vena cava, external jugular vein, compression
Graphical abstract
Highlights
-
•
POCUS and CPMX2 detected significant intravascular volume changes during PLR and after IV albumin.
-
•
Both CPMX2 and POCUS identified a high frequency of potential post-albumin volume overload.
-
•
CPMX2 was more sensitive than POCUS for detecting dynamic volume shifts during PLR.
-
•
CPMX2 may enable individualized fluid management in decompensated cirrhosis after further validation.
Introduction
Patients with decompensated cirrhosis are at risk for iatrogenic volume overload,[1], [2], [3] a significant complication and clinical challenge following intravenous (IV) albumin infusion. IV albumin is commonly used to manage complications of portal hypertension, including large-volume ascites requiring paracentesis, acute kidney injury (AKI) with or without hepatorenal syndrome, and spontaneous bacterial peritonitis. In a prospective cohort of 55 patients and 81 measurements using point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) diameters and collapsibility,4 we identified intravascular overload in nearly half of patients, and severe intravascular volume overload in approximately 20% immediately after IV albumin, even with strict adherence to current albumin dosage recommendations.5,6 Severe volume overload correlated with elevations in NT-proBNP (N-terminal pro-brain natriuretic peptide), suggesting potential clinical relevance. Interestingly, traditional tests for assessing fluid responsiveness, such as passive leg raise (PLR),7 which are validated in intensive care settings, failed to predict impending iatrogenic overload post-infusion as assessed by IVC-POCUS. This may be attributable to variable increases in intra-abdominal pressure caused by large-volume ascites, which can obscure accurate assessment of intravascular volume shifts. Consequently, there is an unmet need for reliable, non-invasive tools to monitor fluid responsiveness and predict volume overload in decompensated cirrhosis. CPMX2 (Compremium AG, Switzerland) is an innovative non-invasive medical device designed to assess central venous pressure by applying controlled compression to the external jugular vein (EJV),8 and has been validated in critically ill patients requiring intensive care, demonstrating promising accuracy, safety and applicability.9,10 However, its predictive accuracy in patients with decompensated cirrhosis, particularly in the context of post-albumin infusion, remains unexplored.
Patients and methods
In this prospective single-center pilot study comparing POCUS of the IVC and the novel compression pressure technique CPMX2, we aimed to track changes in intravascular volume status during PLR and following IV albumin administration. We collected all data in an observational setting during standard medical treatment from July 2024 and April 2025 at the Department of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland. The study protocol had been approved by the local institutional board (BASEC 2024-D0007).
For this pilot project, we included ambulatory and hospitalized adult patients with decompensated cirrhosis and an indication for IV albumin therapy according to current international guidelines (such as therapeutic paracentesis, AKI, AKI-hepatorenal syndrome, spontaneous bacterial peritonitis)5,6 upon informed consent. Cirrhosis was diagnosed following combined histological, biochemical, radiologic and/or clinical information. Patients were excluded if they had a history of liver transplantation, right heart failure, clinical evidence of pulmonary edema, recent hemodynamic shock, current pregnancy, unavailable transthoracic echocardiography within 3 months of study inclusion, admission to intensive or intermediate care at baseline, recent IV albumin within the past 5 days, or contraindications to PLR (e.g. increased intracranial pressure) or IV albumin (e.g. anaphylaxis). Our primary outcomes included absolute and percentage changes in external jugular vein (EJV) occlusion pressures – maximum (EJVmax), minimum (EJVmin), and mean (EJVmean) – as well as inferior vena cava (IVC) diameters –maximum (IVCmax) and minimum (IVCmin) – and collapsibility (IVCCI) measured before and during PLR, and before and after IV albumin (see supplementary materials and methods for measurement details). As secondary outcomes, we assessed potential intravascular volume overload, defined as IVCmax >2.1 cm and IVCCI <50%, using POCUS, and EJVmean ≥9 mmHg for CPMX2. We implemented a rather conservative EJV threshold to increase sensitivity for detecting intravascular volume overload, considering the highly heterogeneous literature on the limit of increased central venous pressure.11
Results
In our prospective cohort of 20 patients with decompensated cirrhosis (35% women, median age 62 years, mean BMI 25.7 kg/m2, 55% Child-Pugh B, median MELD 15, 80% paracentesis as an indication for IV albumin, Table 1), all IVC diameters and EJV compression pressures considerably increased during PLR and after IV albumin infusion (Fig. 1A,B). Percentage changes in most EJV compression pressures were markedly higher than those observed in IVC diameters during PLR (mean EJVmax +88.4%, EJVmean +65.1% vs. IVCmax +16.4%, IVCmin +25.9%; p <0.01, Fig. 1C,D). On the other hand, percentage changes in the parameters obtained by the two techniques were comparable after IV albumin infusion (mean EJVmax +68.3%/EJVmin +80.3%, EJVmean +74.7% vs. IVCmax +57.5%/IVCmin +78.9%, Fig. 1C,D). Intravascular volume overload after IV albumin was very frequent, occurring in the majority of observed cases (POCUS: 65.0%, CPMX2: 95.0%, Fig. 1E). CPMX2 showed a substantially higher agreement for volume overload at PLR and after IV albumin than POCUS (90.0% vs. 23.1%). There was a weak positive correlation between percentage changes in EJVmin post-infusion and previously infused albumin dosages (rho 0.486, p = 0.03), while absolute values or dynamics in other IVC and EJV parameters showed no clear correlation with the amount of albumin infused.
Table 1.
Baseline characteristics of the included population.
| Sex | |
| Male (n, %) | 13 (65%) |
| Female (n, %) | 7 (35%) |
| Age (years, median, IQR) | 62 (55.3-66.8) |
| BMI (kg/m2, median, IQR) | 24.9 (22.0-29.7) |
| Child-Pugh score | |
| B (n, %) | 11 (55%) |
| C (n, %) | 9 (45%) |
| MELD score (median, IQR) | 18 (11-25) |
| Etiology of cirrhosis | |
| ALD (n, %) | 13 (65%) |
| MetALD (n, %) | 1 (5%) |
| MASH (n, %) | 1 (5%) |
| Miscellaneous (n, %) | 5 (25%) |
| Indication for IV albumin infusion | |
| Large volume paracentesis (n, %) | 17 (85%) |
| Acute kidney injury (n, %) | 5 (25%) |
| Spontaneous bacterial peritonitis | 1 (5%) |
| Dosage for albumin infusion (g, median, IQR) | 40 (20-40) |
| Quantity of ascites removed (L, median, IQR) | 5.5 (3.3-7.3) |
ALD, alcohol-related liver disease; IV, intravenous; MASH, metabolic-dysfunction associated steatohepatitis; MELD, model for end-stage liver disease; MetALD, metabolic dysfunction and alcohol-related liver disease.
Fig. 1.
EJV compression pressures and IVC diameters and occurence of any potential volume overload during passive leg raise and albumin infusion .
(A) EJV occlusion pressures (mean, SD) before/after PLR and IV albumin. (B) IVC diameters and collapsibility before/after PLR and IV albumin. (C) Percentage changes in EJV occlusion pressures during PLR and after IV albumin. (D) Percentage changes in IVC parameters during PLR and after IV albumin. (E) Occurrence of any volume overload defined by IVC and EJV criteria. Percentage changes in EJV occlusion pressures and IVC parameters after PLR and albumin infusion were analyzed using paired Wilcoxon signed-rank tests or one-sample t-tests, as appropriate. EJV, external jugular vein; IV, intravenous; IVC, inferior vena cava; IVCCI, IVC collapsibility index; IVCmax, maximum IVC diameter; IVCmin, minimum IVC diameter; PLR, passive leg raise.
Discussion
In this pilot project, we found that both POCUS-based IVC assessment and CPMX2-derived EJV compression pressures detect considerable intravascular volume changes during PLR and following IV albumin infusion in patients with decompensated cirrhosis. CPMX2 appeared more sensitive to dynamic changes during PLR and identified a greater proportion of patients with intravascular volume overload after IV albumin. These findings suggest that CPMX2 could serve as a promising, non-invasive tool for early characterization of volume status and fluid responsiveness, which could help tailor albumin therapy, particularly in the context of large volume paracentesis. This may represent an advantage over IVC-POCUS, which can yield false negatives due to elevated intra-abdominal pressure. Nevertheless, an important limitation of our study is the absence of a direct comparison between CPMX2, POCUS, and invasive measurements of central venous pressure (the current reference standard), which is required to verify the diagnostic accuracy of both non-invasive techniques in detecting volume overload. Furthermore, associations between detected changes in intravascular volume status and cardiopulmonary and liver-related events deserve further investigation. Future studies should compare CPMX2 and POCUS with invasive measurements, and evaluate CPMX2-guided albumin dosing as part of a personalized therapeutic approach in decompensated cirrhosis.
Abbreviations
AKI, acute kidney injury; IV, intravenous; IVC, inferior vena cava; IVCCI, IVC collapsibility index; IVCmax, maximal diameter of the inferior vena cava during an entire respiratory cycle; IVCmin, minimal diameter of the inferior vena cava during an entire respiratory cycle; PLR, passive leg raise; POCUS, point-of-care ultrasound.
Authors’ contributions
Study design: DS, AB, JB, UB. Study set-up: DS, AB, JB, UB; Data collection and analysis: DS, BM; Manuscript writing: DS, AB, JB, BM, UB. Manuscript revision; DS, AB, BM, UB. All authors approved the current version of the manuscript.
Data availability
All datasets generated and/or analyzed during this study can be obtained from the corresponding author upon reasonable request.
Financial support
The work has been supported by Compremium AG, Switzerland. JB was supported by the Swiss Liver Foundation.
Conflicts of interest
DS reports travelling fees from Gilead and Falk. AB is a consultant for Boehringer-Ingelheim and Astra Zeneca; Speakers’ fees from GE Healthcare and Hologic. JB was a consultant for AstraZeneca, NovoNordisk, Boehringer Ingelheim and Resolution Therapeutics. BM has nothing to disclose. UB is chief medical officer and founder of Compremium AG.
Please refer to the accompanying ICMJE disclosure forms for further details.
Acknowledgements
We would like to thank Lilian Smith and Judith Freiburghaus for their support during the whole duration of the project.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jhepr.2025.101712.
Supplementary data
The following are the Supplementary data to this article:
References
- 1.Velez J.C.Q., Petkovich B., Karakala N., et al. Point-of-Care echocardiography Unveils misclassification of acute kidney injury as hepatorenal syndrome. Am J Nephrol. 2019;50(3):204–211. doi: 10.1159/000501299. Epub 20190808. [DOI] [PubMed] [Google Scholar]
- 2.Caraceni P., Riggio O., Angeli P., et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet. 2018;391(10138):2417–2429. doi: 10.1016/S0140-6736(18)30840-7. Epub 20180601. [DOI] [PubMed] [Google Scholar]
- 3.China L., Freemantle N., Forrest E., et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med. 2021;384(9):808–817. doi: 10.1056/NEJMoa2022166. [DOI] [PubMed] [Google Scholar]
- 4.Segna D., Brazerol F., Radu P., et al. Point-of-care ultrasound of the inferior vena cava for intravascular volume assessment during intravenous albumin infusion in patients with cirrhosis. JHEP Rep. 2025 doi: 10.1016/j.jhepr.2025.101559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.de Franchis R., Bosch J., Garcia-Tsao G., et al. Baveno VII - renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–974. doi: 10.1016/j.jhep.2021.12.022. Epub 20211230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.European Association for the Study of the Liver EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–460. doi: 10.1016/j.jhep.2018.03.024. Epub 20180410. [DOI] [PubMed] [Google Scholar]
- 7.Monnet X., Marik P., Teboul J.L. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensive Care Med. 2016;42(12):1935–1947. doi: 10.1007/s00134-015-4134-1. Epub 20160129. [DOI] [PubMed] [Google Scholar]
- 8.Baumann U.A., Marquis C., Stoupis C., et al. Estimation of central venous pressure by ultrasound. Resuscitation. 2005;64(2):193–199. doi: 10.1016/j.resuscitation.2004.08.015. [DOI] [PubMed] [Google Scholar]
- 9.Thalhammer C., Siegemund M., Aschwanden M., et al. Non-invasive central venous pressure measurement by compression ultrasound--a step into real life. Resuscitation. 2009;80(10):1130–1136. doi: 10.1016/j.resuscitation.2009.06.027. Epub 20090725. [DOI] [PubMed] [Google Scholar]
- 10.Uthoff H., Siegemund M., Aschwanden M., et al. Prospective comparison of noninvasive, bedside ultrasound methods for assessing central venous pressure. Ultraschall Med. 2012;33(7) doi: 10.1055/s-0031-1299506. E256-e62. Epub 20120601. [DOI] [PubMed] [Google Scholar]
- 11.Joseph A., Petit M., Vignon P., et al. Fluid responsiveness and venous congestion: unraveling the nuances of fluid status. Crit Care. 2024;28(1):140. doi: 10.1186/s13054-024-04930-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All datasets generated and/or analyzed during this study can be obtained from the corresponding author upon reasonable request.