Abstract
Background
Dynamic arterial elastance (Eadyn) has been investigated for its ability to predict hypotension during the weaning of vasopressors. Our study focused on assessing Eadyn’s performance in the context of critically ill adult patients admitted to the intensive care unit, regardless of diagnosis.
Main body
Our study was conducted in accordance with the Preferred Reported Items for Systematic Reviews and Meta-Analysis checklist. The protocol was registered in PROSPERO (CRD42023421462) on May 26, 2023. We included prospective observational studies from the MEDLINE and Embase databases through May 2023. Five studies involving 183 patients were included in the quantitative analysis. We extracted data related to patient clinical characteristics, and information about Eadyn measurement methods, results, and norepinephrine dose. Most patients (76%) were diagnosed with septic shock, while the remaining patients required norepinephrine for other reasons. The average pressure responsiveness rate was 36.20%. The synthesized results yielded an area under the curve of 0.85, with a sensitivity of 0.87 (95% CI 0.74–0.93), specificity of 0.76 (95% CI 0.68–0.83), and diagnostic odds ratio of 19.07 (95% CI 8.47–42.92). Subgroup analyses indicated no variations in the Eadyn based on norepinephrine dosage, the Eadyn measurement device, or the Eadyn diagnostic cutoff to predict cessation of vasopressor support.
Conclusions
Eadyn, evaluated through subgroup analyses, demonstrated good predictive ability for the discontinuation of vasopressor support in critically ill patients.
Introduction
In the intricate realm of circulatory shock management, striking a delicate equilibrium between sustaining mean arterial pressure (MAP) and enhancing cardiac output (CO) after initial fluid loading is pivotal. Traditionally, shock patients are administered vasopressor support and fluid therapy to maintain MAP. However, a nuanced challenge arises during the weaning of patients from vasopressor support, where a lack of clear predictive parameters for hypotension development complicates the clinical landscape. The dynamic arterial elastance (Eadyn), derived from the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV), could bridge this gap. Eadyn has emerged as a predictor of increased MAP after a fluid challenge in hypotensive volume-responsive patients [1, 2], suggesting that multifactorial insight is primarily associated with ventricular-arterial coupling [3,4,5,6]. A previous study delineated its link with left ventricular pulsatile load [3], positioning Eadyn as a predictor of vasopressor weaning without reactive hypotension. Notably, a randomized clinical trial assessing Eadyn clinical efficacy revealed a shortened vasopressor support duration and reduced acute kidney injury risk [7].
This study therefore aimed to evaluate the ability of the operative performance of Eadyn in critically ill adult patients to predict a subsequent reduction in MAP during the weaning of vasopressors. We also examined potential differences in the performance of the Eadyn according to the measurement methods and different clinical conditions.
Methods
Protocol
This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [8] and was registered in PROSPERO (registration number: CRD42023421462) in May 2023.
Search strategy and data extraction
The MEDLINE and Embase databases were searched for all peer-reviewed articles published in May 2023 without publication date or language restrictions. Two independent researchers (J.I.A.S. and S.S.R.) reviewed potential studies according to the inclusion and exclusion criteria and extracted the data. Additionally, reference lists of selected manuscripts were manually scrutinized to identify potential studies that may not have been captured in the initial search. Keywords, index terms, and the detailed search strategy can be found in the protocol submitted to PROSPERO (registration number CRD42023421462, registered 26 May 2023).
Study selection and inclusion criteria
Studies were selected according to the PICO framework as follows:
-
P-Population: Critical care patients without any diagnostic restrictions.
-
I – Index test: We included studies that evaluated the operative performance of Eadyn as a predictor of reactive hypotension during vasopressor weaning.
-
C - Comparison: The analysis exclusively considered studies that included a well-defined criterion—specifically, a decrease in mean arterial pressure (MAP) following a reduction in norepinephrine dose—as the reference standard.
-
O-Outcomes: We included studies that evaluated the operative performance of Eadyn as a predictor of vasopressor weaning support. When studies presented multiple datasets related to operative performance, all relevant information, including sensitivity, specificity, and area under the curve (AUC), was incorporated into the analysis.
Exclusion criteria
Studies involving patients under 18 years of age, pregnant individuals, case reports, abstracts, and animal experiments were excluded.
Study selection and data collection
Two authors (J.I.A.S. and S.S.R.) independently extracted the data in different spreadsheets; subsequently, the two spreadsheets were compared. Disagreements between the two authors were addressed through discussion. If a disagreement persisted, a third author reviewed the data extraction sheet to reach a consensus among all the authors.
Data items
The data extracted from each clinical trial encompassed various parameters, including authors, year of publication, number of patients enrolled, type of patient, age, height, norepinephrine dose, diagnosis, APACHE II score, SOFA score, method used for Eadyn measurement, definition of positive responders, proportion of positive responders, diagnostic test cutoff point, pre- and post-norepinephrine weaning MAP values, mechanical ventilation requirement, tidal volume, lung compliance, positive end respiratory pressure (PEEP), airway driving pressure, diagnosis of acute respiratory distress syndrome (ARDS), presence of arrhythmias, specificity, sensitivity, and the Eadyn AUC.
Risk of bias in individual studies
Two researchers (J.I.A.S. and S.S.R.) independently evaluated the risk of bias in the included studies using the QUADAS-2 tool [9]. Any disagreements between them were resolved through discussion with a third reviewer (J.J.D.F.). Additionally, the quality of evidence or the certainty of evidence was assessed using the GRADE framework [10].
Statistical analysis
Analysis of individual studies
The sensitivity, specificity, and diagnostic odds ratio (DOR) were computed using a contingency table. The DOR provides a metric for assessing the discriminative ability of a diagnostic test, indicating how effectively it can distinguish between individuals with and without a specific condition. It is calculated as the ratio of the odds of true positives to false positives. A higher DOR suggests an increased probability that the test will yield true positive results compared to false positive results.
Analysis of summary measures
Fitted sensitivity, specificity, and AUC data were evaluated through bivariate and hierarchical analyses. Receiver operating characteristic (ROC) curve summaries were calculated using the Rutter and Gatsonis method [11]. The AUC was graded according to Fisher et al. [12]. Heterogeneity among trials was gauged using Cochran’s Q tests, and its impact was quantified by calculating inconsistency (I2). An I2 (> 50%) indicates statistical significance [13]. A random effects model was used for the meta-analysis.
Analysis of risk of bias across studies
Publication bias was assessed through a funnel plot. However, certain statistical tests were deemed inapplicable due to the limited number of included studies, rendering these tests impractical.
Additional analysis
Some studies had several sets of operative performance data [7, 14]. In this situation, we also performed an analysis that included all the operative performance data. Subgroup analyses and random effect model meta-regression analyses were conducted based on various parameters: norepinephrine dose, diagnosis, APACHE II score, SOFA score, device used to measure SVV, device used to measure PPV, pressure responder definition, diagnostic test cutoff point, mechanical ventilation requirement, tidal volume, lung compliance, PEEP, airway driving pressure, diagnosis of acute respiratory distress syndrome (ARDS), and presence of arrhythmia. All operative performance data were included in the subgroup analyses.
Additionally, a sensitivity analysis was performed considering the risk of bias determined by QUADAS-2, the number of patients included in the studies, and the type of patient. The threshold effect was assessed using Spearman’s rank correlation coefficient and the Moses–Shapiro–Littenberg method [15]. R software, version 3.4.3, along with the mada and meta packages, was used for statistical analysis. The results are presented as 95% confidence intervals (CIs) and p values. A p value < 0.05 was considered to indicate statistical significance.
Results
A total of 910 studies were gathered from the MEDLINE and Embase database searches. After applying the inclusion criteria, five studies met all the requirements and were included in the quantitative analysis [7, 14, 16,17,18] (Fig. 1).
Five of the clinical and Eadyn operative performance characteristics were evaluated, and the five studies involved a total of 183 patients (Tables 1 and 2). One hundred thirty-nine (139) patients were diagnosed with septic shock (76%), while the remaining forty-four patients required vasopressor support for other reasons (postoperative, n = 30 [16,4%]; polytrauma, n = 9 [4,9%]; hemorrhagic shock, n = 5 [2,7%]). A total of 183 vasopressor weaning procedures (one per patient) were cumulatively carried out, resulting in an average blood pressure responsiveness rate of 36.20%.
Risk of bias
The five studies included in the study were classified as having a low risk of bias according to the QUADAS-2 tool (Additional file 1a). Funnel plot analysis revealed asymmetry in the included papers (Fig. 2). The GRADE assessment categorizes the certainty of the body of evidence as ‘moderate’ (Additional file 1b).
Synthesis of results
The estimated Eadyn operative performance was as follows: AUC = 0.85 (Fig. 3), sensitivity = 0.87 (95% CI = 0.74–0.93), specificity = 0.76 (95% CI = 0.68–0.83), and cutoff point = 0.89. The DOR was 19.07 (95% CI 8.47–42.92), and the I2 statistic for quantifying inconsistency among the included studies indicated that heterogeneity might not be important (I2 = 0%, Q = 0.20; p = 0.99) (Fig. 4).
Additional analysis
We evaluated all the operative performance data reported by the included studies, encompassing a total of 9 sets of operative performance data. One study presented four sets of operative performance data [7], while another study included two sets [14] (Additional file 2). The Eadyn operative performance as a predictor of hypotension during the weaning of vasopressors was as follows: AUC, 0.85; sensitivity, 0.81 (95% CI, 0.64–0.91); specificity, 0.79 (95% CI, 0.73–0.84); and cutoff point, 0.85. The DOR was 14.46 (95% CI 8.00-26.15), and the I2 statistic suggested that heterogeneity might not be important (I2 = 0%, Q = 3.14; p = 0.92).
According to the evaluation of the 9 operative performance datasets, the operative performance of Eadyn was unaffected by variations in the norepinephrine dose (by meta-regression), the PPV measuring device, the SVV measuring device, the pressure responder definition, or the diagnostic cutoff point (p > 0.05) (Table 3). Subgroup analysis for the remaining variables was omitted due to missing or insufficient data in certain studies. Furthermore, sensitivity analysis based on the number of patients indicated no changes in the operative performance of Eadyn (DOR = 1.12 + 1.03 per number of patients, p > 0.57). A sensitivity analysis based on the QUADAS-2 was not conducted because all the included studies exhibited a low risk of bias. Spearman’s rank correlation test indicated the presence of a threshold effect (r = 0.80, p < 0.05). However, upon conducting a meta-regression between DOR and the cutoff values of each study, no such effect was discerned (Table 3).
Discussion
Our study revealed that Eadyn serves as a good predictor of MAP reduction during vasopressor weaning. Considering our findings, an Eadyn value greater than 0.89 predicts no reduction in mean arterial pressure during the weaning of vasopressor support. Additionally, we observed that different SVV measurement methods employed for Eadyn estimation consistently demonstrated comparable operative performance.
The assessment of arterial load is intricate and involves factors such as pulsatile and steady components, which, in turn, depend on other hemodynamic variables. For instance, systemic vascular resistance and the MAP are associated with the steady component, while arterial variables (impedance, elastance, and compliance) and wave reflection are linked with the pulsatile component [3,4,5,6, 19]. The resultant MAP is contingent upon the interplay between cardiac and arterial elements. Under typical pressure conditions and when preload dependence is present, the SVV aligns with the PPV, causing Eadyn to approach 1. Conversely, in clinical scenarios characterized by low arterial load and preload dependence, Eadyn is < 1, while with increased vasomotor tone, Eadyn is often > 1.5 [3, 4, 6]. This interaction is particularly dependent on arterial compliance because the PPV is primarily altered by arterial compliance [3]. Notably, the operative performance of Eadyn serves as a predictor of an increase in MAP after a fluid challenge in hypotensive critically ill patients, where arterial compliance is fixed and decreases with the use of norepinephrine [1, 20,21,22]. However, the operative performance of Eadyn is poorer in surgical patients in whom norepinephrine is not frequently used and in whom arterial compliance could be high or normal [23,24,25,26]. Additionally, the relationship between Eadyn and arterial compliance has allowed us to assess the use of the Eadyn as a predictor of MAP during the weaning of critically ill adult patients [7, 14, 16, 18].
It is important to emphasize that Eadyn is correlated with vascular waterfall (WV, a pressure essential for maintaining tissue perfusion during periods of low blood flow) and critical closing pressure (CCP, the arterial pressure at which blood flow is halted owing to arteriole occlusion) [27]. The augmentation of VW and CCP, facilitated by the administration of norepinephrine, contributes to an enhancement in tissue perfusion [28]. In alignment with the aforementioned findings, the Eadyn can serve as a variable that elucidates the intricate relationship between cardiac function and arterial load, delineates the effects of hemodynamic treatment on arterial load, and reveals hemodynamic coherence. This assertion was supported by the findings of a clinical trial in which the use of Eadyn as a hemodynamic tool for vasopressor weaning demonstrated a reduction of duration of vasopressor support, the length of hospital stay, and the incidence of renal failure [29, 30].
Our meta-analysis revealed several interesting findings and raised new research questions. First, a consistent and favorable predictive performance was observed in critically ill patients, and these findings are homogeneous, suggesting that the findings can be extrapolated to general clinical settings. Second, the device used to measure the SVV and calculate the Eadyn did not affect the operative performance. We included studies that used calibrated pulse analysis contours [7], transthoracic echocardiography [14], and uncalibrated pulse analysis contours [16, 18]. This is important because the SVV is usually derived from the arterial pressure waveform, so inherent covariance of PPV and SVV changes can occur. Thus, the consistency of Eadyn across measurement methods attests to the robustness of the parameter. Finally, no studies have evaluated the operative efficacy of Eadyn in patients treated with vasopressor drugs other than norepinephrine. However, we would expect that their responses would be similar.
Our study has certain limitations. First, the inclusion of a limited number of studies raises the possibility of publication bias and heterogeneity among the included studies, underscoring the need for additional research. Second, certain clinical scenarios, such as hypovolemic and neurogenic shock, were not assessed. Consequently, the generalizability of our findings to these specific conditions is limited, highlighting the importance of further research addressing the usefulness of Eadyn in such clinical contexts.
Conclusions
Our study concludes that the Eadyn operative performance is good to predict hypotension during the weaning of vasopressors in critically ill adult patients, particularly in septic shock patients. The consistency of the results, given the high methodological quality of the included studies, supports our findings. Despite the need for further evaluation of the Eadyn evaluation in other clinical scenarios, our results suggest that the Eadyn has potential as a predictive tool for optimizing vasopressor weaning strategies. These findings may provide useful insights for improving clinical decision-making and patient outcomes in critical care settings.
Data availability
All the data generated and analyzed during this study are available from the corresponding author upon reasonable request. The studies included in this systematic review are available from their corresponding author and journal.
References
Monge García MI, Gil Cano A, Gracia Romero M. Dynamic arterial elastance to predict arterial pressure response to volume loading in preload-dependent patients. Crit Care. 2011;15:R15.
Pinsky MR. Defining the boundaries of bedside pulse contour analysis: dynamic arterial elastance. Crit Care. 2011;15:120.
Alvarado Sánchez JI, Caicedo Ruiz JD, Diaztagle Fernández JJ et al. Unveiling the Significance of Dynamic Arterial Elastance: An Insightful Approach to Assessing Arterial Load in an Endotoxin Shock Model. Shock 2023.
Monge Garcia MI, Guijo González P, Saludes Orduña P et al. Dynamic arterial elastance during experimental endotoxic septic shock: a potential marker of Cardiovascular Efficiency. Front Physiol 2020; 11.
Monge García MI, Jian Z, Hatib F, et al. Dynamic arterial elastance as a ventriculo-arterial Coupling Index: an experimental animal study. Front Physiol. 2020;11:1–16.
Monge García MI, Guijo González P, Gracia Romero M, et al. Effects of arterial load variations on dynamic arterial elastance: an experimental study. Br J Anaesth. 2017;118:938–46.
Guinot P-G, Bernard E, Levrard M, et al. Dynamic arterial elastance predicts mean arterial pressure decrease associated with decreasing norepinephrine dosage in septic shock. Crit Care. 2015;19:1–7.
McInnes MDF, Moher D, Thombs BD, et al. Preferred reporting items for a systematic review and Meta-analysis of Diagnostic Test Accuracy studies the PRISMA-DTA Statement. JAMA - J Am Med Association. 2018;319:388–96.
Whiting PF, Rutjes AWS, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.
Yang B, Mustafa RA, Bossuyt PM, et al. GRADE Guidance: 31. Assessing the certainty across a body of evidence for comparative test accuracy. J Clin Epidemiol. 2021;136:146–56.
Rutter CM, Gatsonis CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med. 2001;20:2865–84.
Fischer JE, Bachmann LM, Jaeschke R. A readers’ guide to the interpretation of diagnostic test properties: clinical example of sepsis. Intensive Care Med. 2003;29:1043–51.
Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, et al. Assessing heterogeneity in meta-analysis: Q statistic or I 2 index? Psychol Methods. 2006;11:193–206.
Nguyen M, Abou-Arab O, Bar S, et al. Echocardiographic measure of dynamic arterial elastance predict pressure response during norepinephrine weaning: an observational study. Sci Rep. 2021;11:2853.
Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary Roc curve: data-analytic approaches and some additional considerations. Stat Med. 1993;12:1293–316.
Persona P, Tonetti T, Valeri I, et al. Dynamic arterial elastance to Predict Mean arterial pressure decrease after reduction of Vasopressor in septic shock patients. Life. 2022;13:28.
Liang FM, Yang T, Dong L, et al. [The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock]. Zhonghua Nei Ke Za Zhi. 2017;56:344–8.
Bar S, Leviel F, Abou Arab O, et al. Dynamic arterial elastance measured by uncalibrated pulse contour analysis predicts arterial-pressure response to a decrease in norepinephrine. Br J Anaesth. 2018;121:534–40.
Monge García MI, Santos A, Del Diez B, et al. Noradrenaline modifies arterial reflection phenomena and left ventricular efficiency in septic shock patients: a prospective observational study. J Crit Care. 2018;47:280–6.
García MIMIM, Romero MG, Cano AG, et al. Dynamic arterial elastance as a predictor of arterial pressure response to fluid administration: a validation study. Crit Care. 2014;18:626.
Bar S, Leviel F, Abou Arab O, et al. Dynamic arterial elastance measured by uncalibrated pulse contour analysis predicts arterial-pressure response to a decrease in norepinephrine [Internet]. Br J Anaesth. 2018;121:534–40.
Luetrakool P, Morakul S, Tangsujaritvijit V, et al. Dynamic arterial elastance for predicting mean arterial pressure responsiveness after fluid challenges in acute respiratory distress syndrome patients [Internet]. J Med Assoc Thai. 2020;103:646–51.
Zhou X, Pan W, Chen B, et al. Predictive performance of dynamic arterial elastance for arterial pressure response to fluid expansion in mechanically ventilated hypotensive adults: a systematic review and meta-analysis of observational studies. Ann Intensive Care. 2021;11:119.
Lanchon R, Nouette-Gaulain K, Stecken L, et al. Dynamic arterial elastance obtained using arterial signal does not predict an increase in arterial pressure after a volume expansion in the operating room. Anaesth Crit Care Pain Med. 2017;36:377–82.
de Courson H, Boyer P, Grobost R, et al. Changes in dynamic arterial elastance induced by volume expansion and vasopressor in the operating room: a prospective bicentre study. Ann Intensive Care. 2019;9:117.
Seo H, Kong Y-G, ** S-J, et al. Dynamic arterial Elastance in Predicting arterial pressure increase after Fluid Challenge during Robot-assisted laparoscopic prostatectomy. Medicine. 2015;94:e1794.
Bar S, Nguyen M, Abou-Arab O et al. Dynamic arterial elastance is Associated with the Vascular Waterfall in patients treated with norepinephrine: an observational study. Front Physiol 2021; 12.
Andrei S, Bar S, Nguyen M, et al. Effect of norepinephrine on the vascular waterfall and tissue perfusion in vasoplegic hypotensive patients: a prospective, observational, applied physiology study in cardiac surgery. Intensive Care Med Exp. 2023;11:52.
Guinot P-G, Huette P, Bouhemad B, et al. A norepinephrine weaning strategy using dynamic arterial elastance is associated with reduction of acute kidney injury in patients with vasoplegia after cardiac surgery: a post-hoc analysis of the randomized SNEAD study. J Clin Anesth. 2023;88:111124.
Guinot PG, Abou-Arab O, Guilbart M, et al. Monitoring dynamic arterial elastance as a means of decreasing the duration of norepinephrine treatment in vasoplegic syndrome following cardiac surgery: a prospective, randomized trial. Intensive Care Med. 2017;43:643–51.
Acknowledgements
Not applicable.
Funding
The authors received no financial support for the research, authorship, or publication of this article.
Author information
Authors and Affiliations
Contributions
Design: All authors. Performed the literature review: J.I.A.S., S.R.R. Acquisition of the data: J.I.A.S., S.R.R. Statistical analysis: J.I.A.S. Interpretation of the data: All the authors. Manuscript drafting: All the authors. Critical revision of the manuscript: All the authors.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Alvarado-Sánchez, J.I., Salazar-Ruiz, S., Caicedo-Ruiz, J.D. et al. Predictive value of dynamic arterial elastance for vasopressor withdrawal: a systematic review and meta-analysis. Ann. Intensive Care 14, 108 (2024). https://doi.org/10.1186/s13613-024-01345-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s13613-024-01345-8