Differential Cardiac Responses After Passive Leg Raising: A Brief Report

Differential Cardiac Responses After Passive Leg Raising: A Brief Report | 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 Differential Cardiac Responses After Passive Leg Raising: A Brief Report RICARDO CASTRO, Eduardo Kattan, Glenn Hernandez, Jan Bakker This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4063909/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Purpose This study retrospectively examined the hemodynamic effects of passive leg raising (PLR) in mechanically ventilated patients during fluid removal, prior to spontaneous breathing trials. In previous studies, we had noticed varying cardiac responses after PLR completion, particularly in positive tests. Methods Using a bioreactance monitor, we recorded and analyzed hemodynamic parameters, including stroke volume and cardiac index (CI), before and after PLR in post-acute ICU patients. Results We included 27 patients who underwent 60 PLR procedures. In preload-unresponsive patients, no significant CI changes were observed (CIt—6 = 3.5 ± 1.5 vs CIt9 = 2.9 ± 1.2; p =0.361), while in preload-responsive patients, two distinct CI response types to PLR were identified: a transient peak with immediate return to baseline (CIt—6 = 2.7 ± 0.7 vs CIt9 = 3.1 ± 1.1; p = 0.282) and a sustained CI elevation lasting beyond the PLR maneuver (CIt—6 = 2.6 ± 0.7 vs CIt9 = 3.6 ± 0.4; p = 0.002). The latter was particularly noted when ΔCI during PLR exceeded 25%. Conclusion Our findings suggest that in certain preload-responsive patients, PLR can induce a more sustained increase in CI, indicating a possible persistent hemodynamic effect, potentially due to a combination of autotransfusion and sympathetic activation affecting venous return. Further research in larger cohorts and more comprehensive hemodynamic assessments are warranted to validate these observations and to elucidate the possible underlying mechanisms. Bioreactance provides a noninvasive yet effective method for hemodynamic monitoring in the post-resuscitation phase of care. Figures Figure 1 Introduction The understanding of passive leg raising (PLR) and its clinical implications have evolved significantly over time. PLR was originally thought to be a therapeutic maneuver to increase cardiac output (CO) through stroke volume (SV) changes without affecting either heart rate or blood pressure[ 1 ]. However, subsequent studies found that PLR did not induce sustained hemodynamic benefits or autotransfusion effects in normovolemic adults[ 2 ]. Successive research highlighted the probable benefits of PLR in hypovolemic patients[ 3 ] and as a dynamic predictor of preload responsiveness in critically ill patients with acute circulatory failure, especially those with sepsis[ 4 ]. In a landmark study in 2002, the short-term effects of PLR were redefined as a diagnostic tool, allowing the assessment of preload responsiveness and the potential for increasing SV and CO with fluid loading[ 5 ]. The effectiveness of PLR in increasing cardiac preload by testing the dependence of both ventricles on preload was confirmed in further studies[ 6 ] and meta-analyses[ 7 , 8 ], which established the maneuver as a reliable predictor of SV response to volume expansion in adult patients with acute circulatory failure[ 8 ]. PLR also has proven effectiveness in preload-unresponsive patients for guiding fluid de-escalation[ 9 ] and in predicting weaning failure of cardiac origin prior to spontaneous breathing trials (SBT)[ 10 , 11 ]. It has also been acknowledged that there is a lack of a unified physiological model that accounts for the observed variability in PLR responses[ 12 ]. These issues warrant further research on this topic. In this context, bioreactance emerges as a viable non-invasive modality for continuous, real-time monitoring of CO. Bioreactance technology capitalizes on the resistive, capacitive, and inductive electrical properties intrinsic to blood and biological tissues, which induce phase shifts between an applied electrical current and the resultant voltage signal [ 8 , 13 ]. Phase shifts can be quantitatively correlated with systolic volume (SV), and consequently, may be utilized to approximate the CO or cardiac index (CI). This presents a valuable alternative in the post-resuscitative phase of patient care, facilitating the removal of more invasive monitoring devices while still providing critical hemodynamic information. In a cohort of patients with fluid overload, the regular performance of PLR was an integral component of a standardized fluid removal protocol that we applied in preparation for SBT. During these maneuvers, we observed differential cardiac responses, as in some positive tests, there was an unexpected, more sustained increase in CI after PLR completion compared with baseline levels. This observation prompted us to analyze SV and CI behaviors before and after PLR in more detail, with the aim of identifying possible patterns in CI responses to the maneuver. Methods Patient data were obtained from an ancillary study of the FLOW protocol (clinicaltrials.gov NCT04496583), with approval from the local Ethics Committee and Institutional Review Board (ID 201015001-2021). Briefly, the FLOW project studies whether preload responsiveness is a valid endpoint for fluid depletion compared with an empirical negative fluid balance in fluid-overloaded patients before SBT. The FLOW project was funded by FONDECYT grant Nº 1200248, from the Agencia Nacional de Investigación y Desarrollo (ANID), Chile. Patients were prospectively recruited from 2021–2023 after ICU admission to an academic tertiary care center for medical or postoperative management. We enrolled patients aged > 18 years who were mechanically ventilated, fluid overloaded (> 10% increase in baseline weight), in a stabilized critical condition, with normal macrohemodynamics and peripheral perfusion and minimal or no vasopressor support requirement. These patients were under active fluid removal with diuretics or ultrafiltration as part of their preparation for weaning. Patients were consecutively included in this study when the research team was available (business days from 8:00 to 12:00). Bioreactance monitoring We used a noninvasive bioreactance monitor (Cheetah-Starling SV©, Baxter. USA) because of its provision of continuous real-time data on cardiovascular function, non-existent risk of complications, and increased patient comfort. Bioreactance analyses the relative phase shift of an oscillating current passing through the thoracic cavity[ 13 ]. The device outputs a multiparameter spreadsheet including SV, CI, and heart rate in an 8-s refreshing time record. PLR procedure Stable data for baseline SV and CI were obtained after 3 minutes in a semi-recumbent position at 45°. PLR maneuvers were initiated by placing the patient in the supine position with the motorized ICU bed system and simultaneously raising the legs to 45° by two operators. The legs were properly positioned using a rigid cushioned frame and the results were displayed on the device screen after 3 min. After the test, patients were returned to their previous positions. We assessed the absolute and relative changes in SV and CI in a 15 min timelapse (6 min before starting PLR (t—6) and 6 min after its end (t9)). Statistical analyses Data are reported as the mean ± SD. Statistical analyses were conducted using the t-test to compare the CI and HR between time points, as these variables demonstrated a normal distribution. The significance level was set at p < 0.05. Curves were constructed using the advanced median-spline function of the Stata 17 software. Results We enrolled 27 patients (Table 1 ) and performed 60 PLR maneuvers. All patients exhibited stable hemodynamics and normal peripheral perfusion. Twenty-five (42%) PLR maneuvers resulted in ΔCI 10%, indicating preload responsiveness. Table 1 Characteristics of patients. Variable Value Demographics n = 27 Age (years) 63 [52,67] Sex (female) 48% Height (cm) 160 [157,174] Weight (kg) 75 [56,80] Body mass index 24 [22,27] Clinical condition at admission APACHE II 11 [9,21] SOFA 8 [ 6 , 10 ] Norepinephrine (mcg/kg/min) (only 8 pts) 0.1 [0.04,0.13] Fluid balance (mL) 4000 [3595,5500] Diagnosis Postoperative abdominal 14 (52%) Pneumonia 6 (22%) Septic shock (abdominal) 5 (19%) Other 2 7(%) Laboratory Hemoglobin (g/dL) 8.7 [7.9,11.5] Albumin (g/dL) 3.0 [2.4,4.1] Na (mEq/L) 142 (135,146] K (mEq/L) 4.6 [3.5,4.9] BUN (mg/dL) 16 [12,24] Creatinine (mg/dL) 0.9 [0.7,1.3] Lactate (mmol/L) 1.5 [1.1,3.3] Data are reported as median and interquartile range [25,75] APACHE II Acute Physiology and Chronic Health disease Classification System II, SOFA Sequential organ failure assessment, BUN blood urea nitrogen In preload-unresponsive patients, a transient reduction in CI following PLR initiation was observed. However, this decrease was not statistically significant and lasted briefly before reverting to baseline after the patients were returned to their previous position (CI t−6 = 3.48 ± 1.46 | CI t9 = 2.91 ± 1.18; p = 0.361) (Fig. 1 A). In the preload-responsive tests, two types of CI increases were observed after PLR. The first, observed in 20 tests, was characterized by marked CI elevation peaking within 2–3 minutes of leg raising, which returned to baseline upon repositioning the patient semi-recumbently (CI t−6 = 2.74 ± 0.66 | CI t9 = 3.11 ± 1.12; p = 0.282) (Fig. 1 B). This profile was observed in tests in which the ΔCI increased by 10–25%. The second type was noted in 15 maneuvers, where CI persisted elevated longer than the 9 minutes after PLR initiation, relative to baseline values (CI t−6 = 2.62 ± 0.71, CI t9 = 3.55 ± 0.38; p = 0.002) (Fig. 1 C). This pattern was observed when ΔCI with PLR was > 25%. Throughout these assessments, heart rate variations were not statistically significant. Discussion The results of our study suggest that certain patients with preload responsiveness exhibit a longer elevation in CI after completion of a PLR maneuver. This increase lasted for several minutes and was particularly notable in patients whose PLR test elicited a more pronounced increase in CI. Overall, the observed changes in the CI after PLR represent well-known physiological cardiovascular responses. In preload-unresponsive patients, the Starling function had previously reached a plateau, indicating that temporary increases in preload would not increase CI. Interestingly, we observed a transient decrease in the CI during the test, which returned to baseline immediately after the end of the maneuver. In preload-responsive patients, the characteristic transient increase in CI upon PLR was not the only response to the maneuver. In fact, in an important proportion of tests, the increase in CI persisted beyond PLR finalization and was exclusive to tests whose ΔCI increased by > 25% after PLR. As mentioned previously, all patients were under fluid depletion because of fluid overload. We cannot assert that this latter group was more depleted than the others; however, we conjecture that fluid removal led to a gradual reduction in plasma volume, which may not have been completely counterbalanced by fluid redistribution and vascular refilling[ 14 ]. This imbalance potentially induced a steady, low-grade, increased sympathetic tone, which could have triggered a decrease in venous capacitance through the mobilization of unstressed volume that amplified the systemic hemodynamic effects associated with PLR-induced autotransfusion. We acknowledge that this is a preliminary and presumptive elaboration that provides a theoretical physiological mechanism for the observed phenomena. Reversibility of the maneuver was clearly demonstrated in the first type of response described for preload-responsive patients; however, in the second type, immediate reversibility may have been overrun by offsetting mechanisms. Notably, the persistent increase in CI could be attributed solely to an increase in SV, as the heart rate remained stable across all time points. As mentioned, in these patients, PLR was not utilized to tailor fluid therapy but to ascertain the preload responsiveness state in the context of fluid removal[ 9 ] and as a predictor prior to SBT [ 10 ]. The present study has several limitations. First, the small sample size may have introduced bias in the measurements because some patients had more than one PLR. This limitation extends to the described findings, which require validation in larger cohorts. Secondly, the CI behavior observed in preload-responsive patients may not be generalizable to cases with strong vasodilation and capillary leakage, which may respond differently to PLR maneuvers. Third, we did not have additional hemodynamic metrics, such as central venous pressure or direct echocardiography, which could have helped elucidate the mechanisms at play. Fourth, median-spline functions are considered robust for modeling nonlinear relationships but can suffer from overfitting or underfitting, resulting in overly complex or simplistic curves[ 15 ]. Therefore, they sometimes render inaccurate representations of data, particularly at the edges of the generated curves. In summary, our study provides a depiction of some cardiovascular responses elicited by PLR maneuvers during the preload-responsive tests. This behavior was characterized by persistence of increased CI in some patients. If confirmed, our results could imply reconsidering the PLR test not merely as a binary predictor of preload responsiveness but also as a more complex assessment that entails nuanced interpretation. In addition, bioreactance offers a favorable alternative in the post-resuscitative phase of patient care by allowing for the discontinuation of more invasive monitoring, yet it continues to deliver essential hemodynamic data. Declarations Funding This work was supported by FONDECYT grant Nº 1200248-2020, from the Agencia Nacional de Investigación y Desarrollo (ANID), Chile. Competing interests The authors RC, EK, GH and JB declare no financial interests. Authors' contributions RC, EK, GH, and JB contributed to the study conception and design. Material preparation and data collection were performed by Ricardo Castro Data analyses and discussion were performed by Ricardo Castro, Eduardo Kattan, Glenn Hernández and Jan Bakker The first draft of the manuscript was written by Ricardo Castro, and all the authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics approval This study was approved by the Clinical Ethics Committee (ID 201015001-2021) and Institutional Review Board (ID 201015001) of the Pontificia Universidad Católica de Chile. As the present study was an ancillary study of the main FLOW protocol (NCT04496583 clinicaltrials.gov), the requirement for informed consent was waived owing to its observational nature. Consent to participate Informed consent was obtained from all individual participants included in the FLOW study (clinicaltrials.gov NCT04496583). For patient data obtained from an observational ancillary study of the FLOW protocol (Local Ethics Committee and Institutional Review Board approval ID 201015001-2021the requirement for informed consent was waived. Consent to publish Not applicable References Thomas M, Shillingford J. The Circulatory Response To A Standard Postural Change In Ischæmic Heart Disease. Br Hear J. 1965;27:17. Gaffney FA, Bastian BC, Thal ER, Atkins JM, Blomqvist CG. Passive Leg Raising Does Not Produce a Significant or Sustained Autotransfusion Effect. J Trauma: Inj, Infect, Crit Care. 1982;22:190–3. Wong DH, Tremper KK, Zaccari J, Hajduczek J, Konchigeri HN, Hufstedler SM. Acute cardiovascular response to passive leg raising. Crit Care Med. 1988;16:123–5. Michard F, Teboul J-L. Using heart-lung interactions to assess fluid responsiveness during mechanical ventilation. Crit Care. 2000;4:282. Boulain T, Achard J-M, Teboul J-L, Richard C, Perrotin D, Ginies G. Changes in BP Induced by Passive Leg Raising Predict Response to Fluid Loading in Critically Ill Patients. Chest. 2002;121:1245–52. Monnet X, Rienzo M, Osman D, Anguel N, Richard C, Pinsky MR et al. Passive leg raising predicts fluid responsiveness in the critically ill*. Crit Care Med [Internet]. 2006;34:1402–7. https://doi.org/10.1097/01.ccm.0000215453.11735.06 . Cavallaro F, Sandroni C, Marano C, Torre GL, Mannocci A, Waure CD, et al. Diagnostic accuracy of passive leg raising for prediction of fluid responsiveness in adults: systematic review and meta-analysis of clinical studies. Intensiv Care Med. 2010;36:1475–83. Monnet X, Marik P, Teboul J-L. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensiv Care Med. 2016;42:1935–47. Monnet X, Cipriani F, Camous L, Sentenac P, Dres M, Krastinova E, et al. The passive leg raising test to guide fluid removal in critically ill patients. Ann Intensiv Care. 2016;6:46. Dres M, Teboul J-L, Anguel N, Guerin L, Richard C, Monnet X. Passive leg raising performed before a spontaneous breathing trial predicts weaning-induced cardiac dysfunction. Intens Care Med. 2015;41:487–94. Lemaire F, Teboul J-L, Cinotti L, Giotto G, Abrouk SF, Steg G, et al. Acute Left Ventricular Dysfunction during Unsuccessful Weaning from Mechanical Ventilation. Anesthesiology. 1988;69:171–9. Søndergaard S. A critical review of the hemodynamics in assessment of volume responsiveness by using passive leg raising (PLR). Trends Anaesth Crit Care. 2023;53:101292. Keren H, Burkhoff D, Squara P. Evaluation of a noninvasive continuous cardiac output monitoring system based on thoracic bioreactance. Am J Physiol-heart C. 2007;293:H583–9. Mitsides N, Pietribiasi M, Waniewski J, Brenchley P, Mitra S. Transcapillary Refilling Rate and Its Determinants during Haemodialysis with Standard and High Ultrafiltration Rates. Am J Nephrol. 2019;50:133–43. Strasak AM, Umlauf N, Pfeiffer RM, Lang S. Comparing penalized splines and fractional polynomials for flexible modelling of the effects of continuous predictor variables. Comput Stat Data Anal. 2011;55:1540–51. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 02 Apr, 2024 Reviews received at journal 25 Mar, 2024 Reviewers agreed at journal 13 Mar, 2024 Reviewers invited by journal 12 Mar, 2024 Editor assigned by journal 05 Mar, 2024 Submission checks completed at journal 05 Mar, 2024 First submitted to journal 01 Mar, 2024 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. 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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-4063909","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":280950465,"identity":"6a6354e5-c49d-4939-919f-eb2bcbff0f15","order_by":0,"name":"RICARDO CASTRO","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAoUlEQVRIiWNgGAWjYBADGX4wVUCs+gMMDDySDSCWASlaDA4Qq8W8/fDjzx/32PAY30h+wPCDGC0yZ9LMJA48S+Mxu5FmwNhDjBYJCQYzhgMHDgO15DAwE+UwCQn2zx9AWoxnEK+Fx0ACpMVAgmgtPDllEmcOpPFInHlmcJA4v7Af3/yh4oCNHH978sMHPyqI0IICDpCqYRSMglEwCkYBDgAAINwwe3Z2AD4AAAAASUVORK5CYII=","orcid":"","institution":"Pontificia Universidad Católica de Chile","correspondingAuthor":true,"prefix":"","firstName":"RICARDO","middleName":"","lastName":"CASTRO","suffix":""},{"id":280950466,"identity":"9f5ebd80-ccbd-4ebc-b01c-8f7753f11824","order_by":1,"name":"Eduardo Kattan","email":"","orcid":"","institution":"Pontificia Universidad Católica de Chile","correspondingAuthor":false,"prefix":"","firstName":"Eduardo","middleName":"","lastName":"Kattan","suffix":""},{"id":280950467,"identity":"be0dccf6-f517-4854-8853-0e70cdb29ac9","order_by":2,"name":"Glenn Hernandez","email":"","orcid":"","institution":"Pontificia Universidad Católica de Chile","correspondingAuthor":false,"prefix":"","firstName":"Glenn","middleName":"","lastName":"Hernandez","suffix":""},{"id":280950468,"identity":"72b85ccf-f062-4102-8f89-0bd4c2fe2820","order_by":3,"name":"Jan Bakker","email":"","orcid":"","institution":"Pontificia Universidad Católica de Chile","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Bakker","suffix":""}],"badges":[],"createdAt":"2024-03-10 10:00:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4063909/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4063909/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53198814,"identity":"c33c7fbc-71d5-4d6a-b8fa-42c0485cfa4a","added_by":"auto","created_at":"2024-03-21 18:48:43","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":352238,"visible":true,"origin":"","legend":"\u003cp\u003eMedian-spline curves showing the dynamics of the cardiac index (CI) and heart rate before and after the PLR maneuver in (A) preload-unresponsive and (B and C) preload-responsive patients. CI = cardiac index. A. ΔCI \u0026lt;10%; B. ΔCI 10-25%; C. ΔCI \u0026gt;25%. The blue band represents the PLR period.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4063909/v1/dffe0e586f164381c9c028ed.jpeg"},{"id":53199409,"identity":"b63177ba-dc83-4bfc-bd21-b8472274119a","added_by":"auto","created_at":"2024-03-21 18:56:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":217891,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4063909/v1/3fb9b930-9e5a-41b0-b366-271dfab339c3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eDifferential Cardiac Responses After Passive Leg Raising: A Brief Report\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe understanding of passive leg raising (PLR) and its clinical implications have evolved significantly over time. PLR was originally thought to be a therapeutic maneuver to increase cardiac output (CO) through stroke volume (SV) changes without affecting either heart rate or blood pressure[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, subsequent studies found that PLR did not induce sustained hemodynamic benefits or autotransfusion effects in normovolemic adults[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSuccessive research highlighted the probable benefits of PLR in hypovolemic patients[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and as a dynamic predictor of preload responsiveness in critically ill patients with acute circulatory failure, especially those with sepsis[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In a landmark study in 2002, the short-term effects of PLR were redefined as a diagnostic tool, allowing the assessment of preload responsiveness and the potential for increasing SV and CO with fluid loading[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe effectiveness of PLR in increasing cardiac preload by testing the dependence of both ventricles on preload was confirmed in further studies[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and meta-analyses[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], which established the maneuver as a reliable predictor of SV response to volume expansion in adult patients with acute circulatory failure[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePLR also has proven effectiveness in preload-unresponsive patients for guiding fluid de-escalation[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and in predicting weaning failure of cardiac origin prior to spontaneous breathing trials (SBT)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It has also been acknowledged that there is a lack of a unified physiological model that accounts for the observed variability in PLR responses[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These issues warrant further research on this topic.\u003c/p\u003e \u003cp\u003eIn this context, bioreactance emerges as a viable non-invasive modality for continuous, real-time monitoring of CO. Bioreactance technology capitalizes on the resistive, capacitive, and inductive electrical properties intrinsic to blood and biological tissues, which induce phase shifts between an applied electrical current and the resultant voltage signal [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Phase shifts can be quantitatively correlated with systolic volume (SV), and consequently, may be utilized to approximate the CO or cardiac index (CI). This presents a valuable alternative in the post-resuscitative phase of patient care, facilitating the removal of more invasive monitoring devices while still providing critical hemodynamic information.\u003c/p\u003e \u003cp\u003eIn a cohort of patients with fluid overload, the regular performance of PLR was an integral component of a standardized fluid removal protocol that we applied in preparation for SBT. During these maneuvers, we observed differential cardiac responses, as in some positive tests, there was an unexpected, more sustained increase in CI after PLR completion compared with baseline levels. This observation prompted us to analyze SV and CI behaviors before and after PLR in more detail, with the aim of identifying possible patterns in CI responses to the maneuver.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003e Patient data were obtained from an ancillary study of the FLOW protocol (clinicaltrials.gov NCT04496583), with approval from the local Ethics Committee and Institutional Review Board (ID 201015001-2021). Briefly, the FLOW project studies whether preload responsiveness is a valid endpoint for fluid depletion compared with an empirical negative fluid balance in fluid-overloaded patients before SBT. The FLOW project was funded by FONDECYT grant Nº 1200248, from the Agencia Nacional de Investigación y Desarrollo (ANID), Chile.\u003c/p\u003e\u003cp\u003ePatients were prospectively recruited from 2021–2023 after ICU admission to an academic tertiary care center for medical or postoperative management.\u003c/p\u003e\u003cp\u003eWe enrolled patients aged \u0026gt; 18 years who were mechanically ventilated, fluid overloaded (\u0026gt; 10% increase in baseline weight), in a stabilized critical condition, with normal macrohemodynamics and peripheral perfusion and minimal or no vasopressor support requirement. These patients were under active fluid removal with diuretics or ultrafiltration as part of their preparation for weaning. Patients were consecutively included in this study when the research team was available (business days from 8:00 to 12:00).\u003c/p\u003e\u003cp\u003eBioreactance monitoring\u003c/p\u003e\u003cp\u003eWe used a noninvasive bioreactance monitor (Cheetah-Starling SV©, Baxter. USA) because of its provision of continuous real-time data on cardiovascular function, non-existent risk of complications, and increased patient comfort. Bioreactance analyses the relative phase shift of an oscillating current passing through the thoracic cavity[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The device outputs a multiparameter spreadsheet including SV, CI, and heart rate in an 8-s refreshing time record.\u003c/p\u003e\u003cp\u003ePLR procedure\u003c/p\u003e\u003cp\u003eStable data for baseline SV and CI were obtained after 3 minutes in a semi-recumbent position at 45°. PLR maneuvers were initiated by placing the patient in the supine position with the motorized ICU bed system and simultaneously raising the legs to 45° by two operators. The legs were properly positioned using a rigid cushioned frame and the results were displayed on the device screen after 3 min. After the test, patients were returned to their previous positions. We assessed the absolute and relative changes in SV and CI in a 15 min timelapse (6 min before starting PLR (t—6) and 6 min after its end (t9)).\u003c/p\u003e\u003cp\u003eStatistical analyses\u003c/p\u003e\u003cp\u003eData are reported as the mean ± SD. Statistical analyses were conducted using the t-test to compare the CI and HR between time points, as these variables demonstrated a normal distribution. The significance level was set at p \u0026lt; 0.05. Curves were constructed using the advanced median-spline function of the Stata 17 software.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe enrolled 27 patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and performed 60 PLR maneuvers. All patients exhibited stable hemodynamics and normal peripheral perfusion. Twenty-five (42%) PLR maneuvers resulted in ΔCI\u0026thinsp;\u0026lt;\u0026thinsp;10%, indicating preload unresponsiveness, whereas 35 maneuvers (58%) resulted in ΔCI\u0026thinsp;\u0026gt;\u0026thinsp;10%, indicating preload responsiveness.\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 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 [52,67]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160 [157,174]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 [56,80]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 [22,27]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical condition at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACHE II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 [9,21]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNorepinephrine (mcg/kg/min) (only 8 pts)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1 [0.04,0.13]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluid balance (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4000 [3595,5500]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative abdominal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (52%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeptic shock (abdominal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 7(%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.7 [7.9,11.5]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.0 [2.4,4.1]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNa (mEq/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e142 (135,146]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK (mEq/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.6 [3.5,4.9]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBUN (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 [12,24]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9 [0.7,1.3]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 [1.1,3.3]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eData are reported as median and interquartile range [25,75]\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cem\u003eAPACHE\u003c/em\u003e II Acute Physiology and Chronic Health disease Classification System II, \u003cem\u003eSOFA\u003c/em\u003e Sequential organ failure assessment, \u003cem\u003eBUN\u003c/em\u003e blood urea nitrogen\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn preload-unresponsive patients, a transient reduction in CI following PLR initiation was observed. However, this decrease was not statistically significant and lasted briefly before reverting to baseline after the patients were returned to their previous position (CI \u003csub\u003et\u0026minus;6\u003c/sub\u003e = 3.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46 | CI \u003csub\u003et9\u003c/sub\u003e = 2.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18; p\u0026thinsp;=\u0026thinsp;0.361) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003eIn the preload-responsive tests, two types of CI increases were observed after PLR. The first, observed in 20 tests, was characterized by marked CI elevation peaking within 2\u0026ndash;3 minutes of leg raising, which returned to baseline upon repositioning the patient semi-recumbently (CI \u003csub\u003et\u0026minus;6\u003c/sub\u003e = 2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66 | CI \u003csub\u003et9\u003c/sub\u003e = 3.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12; p\u0026thinsp;=\u0026thinsp;0.282) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). This profile was observed in tests in which the ΔCI increased by 10\u0026ndash;25%. The second type was noted in 15 maneuvers, where CI persisted elevated longer than the 9 minutes after PLR initiation, relative to baseline values (CI \u003csub\u003et\u0026minus;6\u003c/sub\u003e = 2.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71, CI \u003csub\u003et9\u003c/sub\u003e = 3.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38; p\u0026thinsp;=\u0026thinsp;0.002) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). This pattern was observed when ΔCI with PLR was \u0026gt;\u0026thinsp;25%. Throughout these assessments, heart rate variations were not statistically significant.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of our study suggest that certain patients with preload responsiveness exhibit a longer elevation in CI after completion of a PLR maneuver. This increase lasted for several minutes and was particularly notable in patients whose PLR test elicited a more pronounced increase in CI.\u003c/p\u003e \u003cp\u003eOverall, the observed changes in the CI after PLR represent well-known physiological cardiovascular responses. In preload-unresponsive patients, the Starling function had previously reached a plateau, indicating that temporary increases in preload would not increase CI. Interestingly, we observed a transient decrease in the CI during the test, which returned to baseline immediately after the end of the maneuver. In preload-responsive patients, the characteristic transient increase in CI upon PLR was not the only response to the maneuver. In fact, in an important proportion of tests, the increase in CI persisted beyond PLR finalization and was exclusive to tests whose ΔCI increased by \u0026gt;\u0026thinsp;25% after PLR.\u003c/p\u003e \u003cp\u003eAs mentioned previously, all patients were under fluid depletion because of fluid overload. We cannot assert that this latter group was more depleted than the others; however, we conjecture that fluid removal led to a gradual reduction in plasma volume, which may not have been completely counterbalanced by fluid redistribution and vascular refilling[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This imbalance potentially induced a steady, low-grade, increased sympathetic tone, which could have triggered a decrease in venous capacitance through the mobilization of unstressed volume that amplified the systemic hemodynamic effects associated with PLR-induced autotransfusion. We acknowledge that this is a preliminary and presumptive elaboration that provides a theoretical physiological mechanism for the observed phenomena.\u003c/p\u003e \u003cp\u003eReversibility of the maneuver was clearly demonstrated in the first type of response described for preload-responsive patients; however, in the second type, immediate reversibility may have been overrun by offsetting mechanisms. Notably, the persistent increase in CI could be attributed solely to an increase in SV, as the heart rate remained stable across all time points. As mentioned, in these patients, PLR was not utilized to tailor fluid therapy but to ascertain the preload responsiveness state in the context of fluid removal[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and as a predictor prior to SBT [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study has several limitations. First, the small sample size may have introduced bias in the measurements because some patients had more than one PLR. This limitation extends to the described findings, which require validation in larger cohorts. Secondly, the CI behavior observed in preload-responsive patients may not be generalizable to cases with strong vasodilation and capillary leakage, which may respond differently to PLR maneuvers. Third, we did not have additional hemodynamic metrics, such as central venous pressure or direct echocardiography, which could have helped elucidate the mechanisms at play. Fourth, median-spline functions are considered robust for modeling nonlinear relationships but can suffer from overfitting or underfitting, resulting in overly complex or simplistic curves[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Therefore, they sometimes render inaccurate representations of data, particularly at the edges of the generated curves.\u003c/p\u003e \u003cp\u003eIn summary, our study provides a depiction of some cardiovascular responses elicited by PLR maneuvers during the preload-responsive tests. This behavior was characterized by persistence of increased CI in some patients. If confirmed, our results could imply reconsidering the PLR test not merely as a binary predictor of preload responsiveness but also as a more complex assessment that entails nuanced interpretation. In addition, bioreactance offers a favorable alternative in the post-resuscitative phase of patient care by allowing for the discontinuation of more invasive monitoring, yet it continues to deliver essential hemodynamic data.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was supported by FONDECYT grant Nº 1200248-2020, from the Agencia Nacional de Investigación y Desarrollo (ANID), Chile.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors RC, EK, GH and JB declare no financial interests.\u003c/p\u003e\n\u003cp\u003eAuthors' contributions\u003c/p\u003e\n\u003cp\u003eRC, EK, GH, and JB contributed to the study conception and design.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMaterial preparation and data collection were performed by Ricardo Castro\u003c/p\u003e\n\u003cp\u003eData analyses and discussion were performed by Ricardo Castro, Eduardo Kattan, Glenn Hernández and Jan Bakker\u003c/p\u003e\n\u003cp\u003eThe first draft of the manuscript was written by Ricardo Castro, and all the authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Clinical Ethics Committee (ID 201015001-2021) and Institutional Review Board (ID 201015001) of the Pontificia Universidad Católica de Chile. As the present study was an ancillary study of the main FLOW protocol (NCT04496583 clinicaltrials.gov), the requirement for informed consent was waived owing to its observational nature.\u003c/p\u003e\n\u003cp\u003eConsent to participate\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the FLOW study\u0026nbsp;(clinicaltrials.gov NCT04496583). For patient\u0026nbsp;data obtained from an\u0026nbsp;observational\u0026nbsp;ancillary study of the FLOW protocol\u0026nbsp;(Local Ethics Committee and Institutional Review Board approval ID 201015001-2021the requirement for informed consent was waived.\u003c/p\u003e\n\u003cp\u003eConsent to publish\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eThomas M, Shillingford J. The Circulatory Response To A Standard Postural Change In Isch\u0026aelig;mic Heart Disease. Br Hear J. 1965;27:17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaffney FA, Bastian BC, Thal ER, Atkins JM, Blomqvist CG. Passive Leg Raising Does Not Produce a Significant or Sustained Autotransfusion Effect. J Trauma: Inj, Infect, Crit Care. 1982;22:190\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWong DH, Tremper KK, Zaccari J, Hajduczek J, Konchigeri HN, Hufstedler SM. Acute cardiovascular response to passive leg raising. Crit Care Med. 1988;16:123\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichard F, Teboul J-L. Using heart-lung interactions to assess fluid responsiveness during mechanical ventilation. Crit Care. 2000;4:282.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoulain T, Achard J-M, Teboul J-L, Richard C, Perrotin D, Ginies G. Changes in BP Induced by Passive Leg Raising Predict Response to Fluid Loading in Critically Ill Patients. Chest. 2002;121:1245\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonnet X, Rienzo M, Osman D, Anguel N, Richard C, Pinsky MR et al. Passive leg raising predicts fluid responsiveness in the critically ill*. Crit Care Med [Internet]. 2006;34:1402\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/01.ccm.0000215453.11735.06\u003c/span\u003e\u003cspan address=\"10.1097/01.ccm.0000215453.11735.06\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavallaro F, Sandroni C, Marano C, Torre GL, Mannocci A, Waure CD, et al. Diagnostic accuracy of passive leg raising for prediction of fluid responsiveness in adults: systematic review and meta-analysis of clinical studies. Intensiv Care Med. 2010;36:1475\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonnet X, Marik P, Teboul J-L. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensiv Care Med. 2016;42:1935\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonnet X, Cipriani F, Camous L, Sentenac P, Dres M, Krastinova E, et al. The passive leg raising test to guide fluid removal in critically ill patients. Ann Intensiv Care. 2016;6:46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDres M, Teboul J-L, Anguel N, Guerin L, Richard C, Monnet X. Passive leg raising performed before a spontaneous breathing trial predicts weaning-induced cardiac dysfunction. Intens Care Med. 2015;41:487\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLemaire F, Teboul J-L, Cinotti L, Giotto G, Abrouk SF, Steg G, et al. Acute Left Ventricular Dysfunction during Unsuccessful Weaning from Mechanical Ventilation. Anesthesiology. 1988;69:171\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026oslash;ndergaard S. A critical review of the hemodynamics in assessment of volume responsiveness by using passive leg raising (PLR). Trends Anaesth Crit Care. 2023;53:101292.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeren H, Burkhoff D, Squara P. Evaluation of a noninvasive continuous cardiac output monitoring system based on thoracic bioreactance. Am J Physiol-heart C. 2007;293:H583\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitsides N, Pietribiasi M, Waniewski J, Brenchley P, Mitra S. Transcapillary Refilling Rate and Its Determinants during Haemodialysis with Standard and High Ultrafiltration Rates. Am J Nephrol. 2019;50:133\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrasak AM, Umlauf N, Pfeiffer RM, Lang S. Comparing penalized splines and fractional polynomials for flexible modelling of the effects of continuous predictor variables. Comput Stat Data Anal. 2011;55:1540\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-clinical-monitoring-and-computing","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Clinical Monitoring and Computing](https://www.springer.com/journal/10877)","snPcode":"10877","submissionUrl":"https://submission.nature.com/new-submission/10877/3","title":"Journal of Clinical Monitoring and Computing","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4063909/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4063909/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose \u003c/strong\u003eThis study retrospectively examined the hemodynamic effects of passive leg raising (PLR) in mechanically ventilated patients during fluid removal, prior to spontaneous breathing trials. In previous studies, we had noticed varying cardiac responses after PLR completion, particularly in positive tests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eUsing a bioreactance monitor, we recorded and analyzed hemodynamic parameters, including stroke volume and cardiac index (CI), before and after PLR in post-acute ICU patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eWe included 27 patients who underwent 60 PLR procedures. In preload-unresponsive patients, no significant CI changes were observed (CIt—6 = 3.5 ± 1.5 vs CIt9 = 2.9 ± 1.2; p =0.361), while in preload-responsive patients, two distinct CI response types to PLR were identified: a transient peak with immediate return to baseline (CIt—6 = 2.7 ± 0.7 vs CIt9 = 3.1 ± 1.1; p = 0.282) and a sustained CI elevation lasting beyond the PLR maneuver (CIt—6 = 2.6 ± 0.7 vs CIt9 = 3.6 ± 0.4; p = 0.002). The latter was particularly noted when ΔCI during PLR exceeded 25%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eOur findings suggest that in certain preload-responsive patients, PLR can induce a more sustained increase in CI, indicating a possible persistent hemodynamic effect, potentially due to a combination of autotransfusion and sympathetic activation affecting venous return. Further research in larger cohorts and more comprehensive hemodynamic assessments are warranted to validate these observations and to elucidate the possible underlying mechanisms. Bioreactance provides a noninvasive yet effective method for hemodynamic monitoring in the post-resuscitation phase of care.\u003c/p\u003e","manuscriptTitle":"Differential Cardiac Responses After Passive Leg Raising: A Brief Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-21 18:48:39","doi":"10.21203/rs.3.rs-4063909/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-02T07:26:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-25T15:51:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"55e1abf7-ee60-4098-9199-74a99597aec2","date":"2024-03-13T14:13:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-12T07:13:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-05T09:30:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-05T09:30:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Clinical Monitoring and Computing","date":"2024-03-01T16:28:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-clinical-monitoring-and-computing","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Clinical Monitoring and Computing](https://www.springer.com/journal/10877)","snPcode":"10877","submissionUrl":"https://submission.nature.com/new-submission/10877/3","title":"Journal of Clinical Monitoring and Computing","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ab86d2e1-ad86-49f9-bb1a-cbd3122ac067","owner":[],"postedDate":"March 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-19T16:08:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-21 18:48:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4063909","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4063909","identity":"rs-4063909","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}