Does the thoracic fluid content reflect lung water and cardiac preload?

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Daniela ROSALBA, Rui SHI, Chiara BRUSCAGNIN, Christopher LAI, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4803045/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background : Whether the thoracic fluid content (TFC) estimated by bioimpedance actually reflects the thoracic water content and tracks its changes has not been tested yet. We compared TFC changes induced by volume expansion with those of well-established markers of cardiac preload including the global end-diastolic volume indexed (GEDVI) estimated by transpulmonary thermodilution (TPTD) and central venous pressure (CVP). We assessed the relationship between TFC and extravascular lung water indexed (EVLWI) estimated by TPTD in patients with acute respiratory distress syndrome (ARDS). Methods : In 42 patients with a TPTD device (PiCCO2), we measured GEDVI, EVLWI and CVP before and after a 500-mL fluid bolus ( Fluid group ). In 23 patients with ARDS, we measured the day-to-day changes in TFC and EVLWI ( ARDS group ). Results: In the Fluid group (42 measurements) , TFC increased significantly during fluid infusion. There was no correlation between the fluid-induced changes in GEDVI or CVP and the fluid-induced changes in TFC (p=0.71 and p=0.09, respectively). In the ARDS group , 124 measurements were performed, representing 101 changes between timepoints. There was no correlation between the percent changes in GEDVI, EVLWI, the sum of GEDVI+EVLWI and the percent changes in TFC (p=0.52, 0.40 and 0.55, respectively). Considering all 208 pairs of measurements performed, there was no correlation between the absolute values of GEDVI, EVLWI and the sum of GEDVI+EVLWI and those of TFC (p=0.33, 0.04 and 0.39, respectively). Considering all pairs of measurements performed, the percentage of error of cardiac index measured by bioreactance compared to TPTD was 131%. Conclusions : In critically ill patients, TFC measured by bioimpedance does not follow the changes induced by a fluid bolus of well-known markers of cardiac preload. It also does not follow the changes in EVLWI observed in patients with ARDS. It is determined neither by GEDVI, nor by EVLWI or the sum of the two. Figures Figure 1 Figure 2 Background Electrical bioimpedance and bioreactance are two techniques that can be used for hemodynamic monitoring. Both are based on the principle that the electrical conductivity and impedance of the thorax are influenced by its volume [ 1 , 2 ]. The Starling system (Baxter, Deerfield, IL, USA) measures stroke volume (and then cardiac output) through bioreactance, which is the difference in phase between the electrical inward current sent to the thorax by the system and the outward current [ 2 ]. Through bioimpedance, which is the ratio of voltage of the inward and outward electrical currents, the device also measures the mean transthoracic electric impedance (Z0). From it, it derives the thoracic fluid content (TFC), assuming that TFC = 1000 / Z0 [ 3 ]. The TFC is supposed to include the fluid in the lungs (extravascular lung water and pulmonary blood volume), in the large thoracic vessels and in the cardiac cavities [ 2 ]. However, whether it is really the case has not been investigated yet. The first objective of our study was to investigate whether TFC behaves as a marker of cardiac preload by comparing its changes induced by volume expansion with those of well-established markers of cardiac preload, including the global end-diastolic volume indexed for body surface (GEDVI) estimated by transpulmonary thermodilution (TPTD). The second objective was to assess the relationship between TFC and extravascular lung water indexed for ideal body weight (EVLWI) estimated by TPTD during the course of acute respiratory distress syndrome (ARDS). The third objective was to establish the determinants of TFC, among hemodynamic variables including EVLWI and GEDVI estimated by TPTD. Methods This prospective, observational, one-center study was conducted in the intensive care unit (ICU) of a tertiary hospital. Our study was approved by the ethical committee of the French Intensive Care Society (48, avenue Claude Vellefaux, 75010, Paris, France) and was registered on ClinicalTrials (2018-A02825-50/NCT05676723). Consent to participate in the study was obtained from the patients or their next of kin. Patients The inclusion criteria were (i) hospitalization in the ICU, (ii) monitoring by a calibrated TPTD device (PiCCO2, Pulsion Medical Systems, Getinge, Feldkirchen, Germany), (iii) a planned volume expansion as decided by the attending physicians ( Fluid group ) or a diagnosis of ARDS according to the Berlin definition [ 4 ] ( ARDS group ). Exclusion criteria were (i) age < 18 years, (ii) pregnancy, (iii) presence of extracorporeal membrane oxygenation (ECMO) assistance at the time of inclusion, (iv) impossibility to paste bioreactance electrodes properly to the skin of the thorax, (v) large pleural effusions, (vi) in Fluid group , circulatory failure whose treatment could not be postponed for ≥ 5 minutes (time required for setting up the Starling system) and (vii) changes in the catecholamines dose or in the ventilatory settings performed during fluid infusion. Non-inclusion criteria were (i) unavailability of the investigators and (ii) refusal to join the study by the patient or his next of kin. Transpulmonary thermodilution measurements In all patients, a thermistor-tipped femoral artery catheter and a central venous catheter were already in place as part of the patient’s hemodynamic monitoring. After calibrating the PiCCO2 system, the following TPTD variables were collected at baseline: cardiac index (CI), GEDVI, and EVLWI [ 5 ]. The results obtained from three injections of 15-mL cold saline boluses were averaged [ 6 ]. Measurements with the Starling system Once the patient was included, a Starling device was set up by pasting four sensors on the skin surface of the thorax, two sensors above and two below the heart, as recommended by the constructor. This device measures CI through bioreactance and TFC through bioimpedance. Other variables Demographic and other hemodynamic parameters, including heart rate, arterial blood pressure, and central venous pressure (CVP), extracted from the PiCCO2 device, were recorded. The dose of sedatives drugs and catecholamines were also collected. Design of the study Fluid group Immediately after inclusion, the Starling device was set up and automatically self-calibrated. A first set of measurements was collected, including TPTD-derived variables (CI, GEDVI, EVLWI), TFC and bioreactance-derived CI. Volume expansion was then performed, according to the decision of the clinicians in charge, by infusing 500 mL of normal saline intravenously over 10 to 15 minutes. Immediately after the end of fluid infusion, TPTD was performed again and a second set of TPTD- and Starling-derived measurements was collected as before. ARDS group Once inclusion performed and until the PiCCO2 device was removed or the patient was extubated, at each time a TPTD measurement was performed according to current care, TFC and TPTD-derived variables were collected once a day at the same time. When several TPTD measurements were performed in a day, only the first one was considered. Statistical analysis Distribution of variables was assessed visually. Data are expressed as median (interquartile range) or n (%). Comparison of variables between time points of the study was assessed using the paired Student’s t test or the Wilcoxon test, depending on data distribution. Comparisons between different groups of patients was performed using the unpaired Student’s t test or the Mann-Whitney U test, depending on data distribution. For the Fluid group the main analysis consisted in comparing the changes induced by volume expansion in GEDVI, CVP and the sum of GEDVI + EVLWI on the one side and in TFC on the other side. For this purpose, we calculated the Pearson correlation coefficient between simultaneous changes. For the ARDS group the analysis consisted in comparing the relative changes of EVLWI and TFC between two successive measurements. For determining the determinants of TFC, considering all pairs of measurements performed in both groups of patients, we calculated the Pearson correlation coefficient between absolute values of GEDVI, EVLWI, the sum of GEDVI + EVLWI on the one side and of TFC on the other side. In addition, we planned to perform a multiple regression analysis, in which the variable to explain was TFC, and the explaining variables were variables for which the p value of the correlation with TFC was < 0.1, among GEDVI, EVLWI, the sum GEDVI + EVLWI and the bias between CI measured by bioreactance and CI measured by TPTD. We calculated the least significant change in TFC in the first 10 patients included in the study. In these patients, during a period of hemodynamic stability (no change in mean arterial pressure and heart rate ≥ 5% compared to baseline during the last 15 minutes), the values of TFC were collected every 12 seconds for 15 minutes. We calculated the coefficient of variation of TFC as being the standard deviation divided by the mean of the five measurements [ 6 , 7 ]. The precision was calculated as being two times the coefficient of variation, and the least significant change as coefficient of variation x 1.96 x √2 [ 6 , 7 ]. The comparison between absolute values of CI measured by bioreactance and by TPTD measured at different timepoints was performed by using the Bland-Altman analysis. The percentage error was calculated as 2SD divided by the mean of CI measured by TPTD. The changes in CI measured by bioreactance and by TPTD observed in both groups (induced by volume expansion in the Fluid group , between two successive timepoints in the ARDS group ) were assessed by four quadrant analyses (with an exclusion zone of 12% [ 6 ]). The ability of the fluid-induced changes in CI measured by bioreactance to detect an increase in CI measured by TPTD ≥ 15%, defining volume responsiveness [ 8 ], was assessed by a receiving operating characteristic (ROC) curve analysis. Sensitivity, specificity, positive and negative predictive values are expressed as median (95% confidence interval). Considering an α risk at 5% and a β risk at 80%, making the hypothesis of a baseline value of GEDVI of 700 ± 190 mL/m 2 [ 9 ] and of EVLWI of 20 ± 7 mL/kg [ 10 ], and considering a least significant change of both variables of 12% [ 6 ], we calculated that 42 patients should be included in the Fluid group and that 100 changes should be included in the ARDS group . A p value < 0.05 was considered statistically significant. All tests were two-sided. Statistical analysis was performed using Medcalc software (version 20.218) (bvba, Mariakerke, Belgium). Results Patient characteristics We prospectively included 42 patients in the Fluid group and 23 patients in the ARDS group from January to August 2022. No patient was excluded. Patient characteristics are shown in Table 1 . They were included 3 (1–4) days after their admission in the ICU. At inclusion, all patients were mechanically ventilated and sedated with propofol and remifentanil. Septic shock was the main cause for acute circulatory failure in the Fluid group and the only one in the ARDS group (Table 1 ). Among the 23 patients with ARDS, 12 patients (52%) suffered from pneumonia attributed to severe acute respiratory syndrome Coronavirus 2019. Table 1 Patient characteristics in the two study groups Fluid group (n = 42) ARDS group (n = 23) Age (years) 64 [55–71] 66 [58–72] Male sex (n, %) 31 (76%) 21 (91%) Body mass index (kg/m 2 ) 27 [ 23 – 29 ] 26 [ 23 – 28 ] SOFA 10 [ 8 – 12 ] 10 [ 9 – 12 ] SAPS II 50 [39–59] 44 [39–54] Type of shock (n, %) Septic Cardiogenic Hypovolemic 36 (86) 2 (5) 5 (12) 23 (100) 0 (0) 0 (0) Lactate at inclusion (mmol/L) 2.1 [1.6–2.8] 2.3 [1.7–2.9] Acute respiratory distress syndrome (n, %) 23 (55) 23 (100)* ICU length of stay (days) 12 [ 7 – 19 ] 17 [ 11 – 28 ] ICU mortality rate (%) 21 (50) 15 (65) Ventilatory settings Tidal volume (mL/kg PBW) Respiratory rate (breaths/min) FiO 2 (%) Positive end expiratory pressure (cmH 2 O) Plateau pressure (cmH 2 O) 5.4 [5.4–6.1] 25 [ 25 – 28 ] 60 [40–70] 12 [ 8 – 14 ] 25 [ 20 – 29 ] 5.6 [5.1–6.2] 25 [ 25 – 28 ] 60 [40–80] 12 [ 9 – 14 ] 27 [23–31] Drugs and sedation (n, %) Propofol Remifentanil Neuromuscular blocking agents Norepinephrine Dobutamine 42 (100) 42 (100) 18 (43) 40 (95) 7 (17) 23 (100) 23 (100) 17 (74)* 23 (100) 4 (17) Data are expressed as n(%) or median [IQR] * P < 0.05 vs. Fluid group . FiO 2 : inspired fraction of oxygen, ICU: intensive care unit, PBW: predicted body weight, SAPS: Simplified acute physiologic score II at admission, SOFA: Sequential organ failure assessment score at admission Fluid group Hemodynamic variables before and after fluid infusion in these 42 patients are shown in Table 2 . The infusion of the fluid bolus led to an increase in CI ≥ 15% in 23 (55%) volume responders. Simultaneously, GEDVI and TFC significantly increased by 6 [0–13] and 3 [ 2 – 4 ]%, respectively, while EVLWI did not change significantly (Table 2 ). Table 2 Changes in hemodynamic variables induced by volume expansion in volume responders and non-responders in the Fluid group Before volume expansion After volume expansion Heart rate (min − 1 ) Volume responders ( n = 23) 100 [88–111] 96 [88–108] Volume non-responders ( n = 19) 94 [84–109] 89 [82–106] Systolic arterial pressure (mmHg) Volume responders ( n = 23) 111 [88–120] 124 [111–140]* Volume non-responders ( n = 19) 117 [103–137] 134 [116–148]* Diastolic arterial pressure (mmHg) Volume responders ( n = 23) 54 [46–60] 65 [54–70]* Volume non-responders ( n = 19) 55 [50–65] 59 [52–69]* Mean arterial pressure (mmHg) Volume responders ( n = 23) 68 [60–78] 80 [73–90]* Volume non-responders ( n = 19) 75 [70–85] 87 [75–92]* Central venous pressure (mmHg) Volume responders ( n = 23) 8 [ 7 – 9 ] 10 |8–11]* Volume non-responders ( n = 19) 11 [ 8 – 14 ] 12 [ 9 – 15 ]* PiCCO2 cardiac index (L/min/m 2 ) Volume responders ( n = 23) 2.3 [1.9-3.0] 2.9 [2.3–3.4]* Volume non-responders ( n = 19) 2.5 [1.9–3.1] 3.2 [2.7–3.6] Starling cardiac index (L/min/m 2 ) Volume responders ( n = 23) 2.3 [1.9–3.6] 3.0 [2.3–3.7]* Volume non-responders ( n = 19) 2.8 [2.5–3.6] 3.0 [2.5–3.3] Pulse pressure variation (%) Volume responders ( n = 23) 11 [ 6 – 14 ] 5 [ 4 – 8 ] Volume non-responders ( n = 19) 11 [ 6 – 16 ] 7 [ 4 – 11 ]* GEDVI (mL/m 2 ) Volume responders ( n = 23) 635 [545–692] 699 [609–708]* Volume non-responders ( n = 19) 636 [545–692] 684 [619–725]* EVLWI (ml/kg PBW) Volume responders ( n = 23) 12 [ 9 – 13 ] 13 [ 8 – 14 ] Volume non-responders ( n = 19) 12 [ 10 – 14 ] 13 [ 9 – 14 ] Total fluid content Volume responders ( n = 23) 76 [58–100] 80 [59–107]* Volume non-responders (n = 19) 80 [70–99] 82 [74–104]* N = 42. Data are expressed as median [IQR]. * P < 0.05 vs. Before volume expansion EVLWI: extravascular lung water indexed for predicted body weight, GEDVI: global end-diastolic volume indexed for body surface, PBW: predicted body weight. There was no correlation between the fluid-induced changes in GEDVI (Fig. 1 ), in EWLVI, in the sum GEDVI + EVLWI or in CVP on the one side and the fluid-induced changes in TFC on the other (p = 0.71, p = 0.45, p = 0.71 and p = 0.09, respectively). ARDS group In the 23 patients of this group, 124 measurements were performed, representing 101 changes between timepoints. On average, 10 (8–13) changes were measured in each patient. Their characteristics at inclusion are shown in Table 1 , and their hemodynamic variables at inclusion in Supplemental Table 1. Between two timepoints, in absolute value (i.e., non-negative values, without considering the direction of changes), GEDVI, EVLWI, the sum GEDVI + EVLWI and TFC changed by 14 [8–35]%, 15 [6–30]%, 11 [ 4 – 21 ]% and 11 [ 4 – 22 ]%, respectively. There was no correlation between the percent changes in GEDVI, EVLWI, the sum of GEDVI + EVLWI on the one side and the percent changes in TFC on the other side (p = 0.52, 0.40 and 0.55, respectively). When considering only the first measurements performed in each patient (n = 23), there was also no correlation between changes in EVLWI and in TFC between two time points (p = 0.19, 0.38 and 0.21, respectively). Precision of the TFC measurements The coefficient of variation of the TFC was 0.6, the precision was 0.1% and the least significant change was 0.2%. Accuracy of the estimation of cardiac output by bioreactance Considering all pairs of measurements performed during the study (42 in the Fluid group , 124 in the ARDS group ), the bias between CI measured by bioreactance and by TPTD was 0.3 L/min/m 2 and the limits of agreements were 2.0 and − 2.6 L/min/m 2 (Supplemental Fig. 1). The percentage of error was 131%. The coefficient of correlation between the changes in CI measurements (42 induced by volume expansion in the Fluid group , 124 between two successive measurement points in the ARDS group ) was 0.24 (p = 0.001). In the Fluid group , an increase in CI measured by bioreactance ≥ 9% during fluid infusion detected a fluid-induced increase in CI measured by TPTD ≥ 15% with a sensitivity of 83 (63–95)% and a specificity of 89 (65–99)%, with an area under the ROC curve of 0.851 (95% IC: 0.707–0.942) (p < 0.001 vs. 0.5) (Supplemental Fig. 2). The concordance rate outside the exclusion zone was 96% (Supplemental Fig. 3). Determinants of TFC Considering the 208 pairs of measurements performed in both groups (84 in the Fluid group , 124 in the ARDS group ), there was no correlation between the absolute values of GEDVI, EVLWI and the sum of GEDVI + EVLWI (Fig. 2 ) on the one side and those of TFC on the other side (p = 0.33, 0.04 and 0.39, respectively). There was no correlation between the bias in CI measured by bioreactance compared to TPTD on the one side and the difference between TFC and the sum GEDVI + EVLWI on the other side (p = 0.29). Discussion This study conducted in critically ill patients shows that TFC measured by bioimpedance increased during the infusion of a fluid bolus. However, there was no significant correlation between the fluid-induced changes in TFC and those in GEDVI or CVP. In patients with ARDS, the changes in TFC were not correlated with the simultaneous changes in EVLWI over time. There was no correlation between absolute values of TFC and the sum of GEDVI + EVLWI, taken all measurements into account. The bias between TFC measured by bioimpedance and the sum of GEDVI + EVLWI was not correlated with the bias between CI measured by bioreactance and CI measured by TPTD. Bioreactance is one of the non-invasive cardiac output measurement techniques available today [ 11 ]. Alongside the measurement of cardiac output, the Starling system provides the measurement of TFC, estimated by bioimpedance (and not by bioreactance), supposed to estimate the volume of fluid contained in the thorax [ 3 ]. TFC has been demonstrated to predict cardiac events in patients with chronic heart failure [ 12 , 13 , 14 ]. It has also been used to assess the fluid status in children [ 15 ] or adults [ 16 ] especially during hemodialysis [ 17 ], pre-eclampsia [ 16 ] or weaning from mechanical ventilation [ 18 ]. It has been speculated that TFC could be used to guide fluid therapy especially in the peri-operative setting [ 19 ]. Since it should be partly composed of the fluid contained in the lung interstitium and the alveoli, it may also follow the evolution of ARDS severity. Nevertheless, as far as we know, whether TFC actually reflects the thoracic water content and tracks its changes has not been tested yet. Our results all agree to invalidate this hypothesis. First, although TFC significantly increased during standardized volume expansion, these changes did not follow concurrent changes in either GEDVI or CVP, i.e., volumetric and barometric markers of cardiac preload, respectively. This is in agreement with a previous study showing the poor ability of TFC to estimated pulmonary artery occlusion pressure in decompensated chronic heart failure [ 20 ]. Second, in patients with ARDS, day-to-day lung water changes were not tracked by those of TFC. Taking into account all the measurements performed in the study, we found no correlation between the absolute values of TFC, and those of GEDVI, EVLWI or the sum of both. The degree of significance of these correlations prevented us from carrying out the multivariate regression analysis that we had planned to approach the determinants of the TFC. An obvious limitation of our study may be that we compared TFC to GEDVI and EVLWI measured by TPTD, used as references. Indeed, there is no other method available at the bedside to estimate the different volumes of fluid contained in the thorax. Then, our results could be explained by the fact that the TFC includes other volumes than those estimated by the GEDVI and the EVLWI. The pulmonary blood volume, i.e., the volume contained in the pulmonary vessels [ 5 ], was not taken into account, nor the volume of fluid contained in other thoracic spaces (pleural in particular) and tissues (muscles for example). Nevertheless, the fluid volume of the cardiac chambers (estimated by the GEDVI) and of the pulmonary tissue (estimated by the EVLWI) are so predominant in the thoracic total fluid content, that the absence of correlation of TFC with any of them casts doubt on its ability to estimate such volume in the entire thorax. Another explanation for our results could also be that GEDVI and EVLWI do not provide a reliable measurement of the volumes that they are supposed to estimate. This may be the case for GEDVI which, even if it behaves as a preload marker [ 21 ], has been suspected of overestimating the real volume of the four cardiac chambers [ 22 ]. This is probably not the case for EVLWI. Indeed, several studies have shown that this index reliably approximates the actual volume of water contained in the interstitium and the pulmonary alveoli [ 23 , 24 ]. Our study confirms the relative reliability of the measurement of cardiac output by bioreactance [ 25 ]. Even though the percentage error was higher than the 30% considered as the upper bound indicating reliability, Starling-derived CI tracked changes in CI estimated by TPTD, with similar accuracy as previously reported when the last version of the device was compared with TPTD [ 26 ] or echocardiography [ 25 ]. We observed no correlation between the bias of the Starling-derived CI compared to the TPTD-derived CI and the difference between the TFC and the sum GEDVI + EVLWI. This result is however not surprising, the TFC and the CI not being measured by the same method (bioimpedance for the first, bioreactance for the second). Our study has several limitations besides those mentioned above. Firstly, it was carried out in critically ill patients, in whom the Starling system is not best indicated [ 27 , 28 ]. Secondly, we were not able to explain the lack of correlation between the TFC on the one hand and the fluid volumes estimated by TPTD on the other hand. The precise method of TFC calculation is of course kept secret by the manufacturer. We also did not estimate whether these results were due to interferences between the device and the patient's electrical environment, which were suspected to affect the reliability of bioimpedance [ 29 ]. Third, measurements of EVLWI after volume expansion were performed immediately at the end of the fluid bolus infusion, which may have minimized its changes because the increase in EVLWI could theoretically occur later. Finally, in the ARDS group, several changes were measured in the same patient. However, the analysis performed on the first measured change did not provide different results. Conclusion In critically ill patients, the TFC measured by bioimpedance does not follow the changes in well-known markers of cardiac preload induced by a fluid bolus. It also does not follow the changes in EVLWI observed in patients with ARDS. It is determined neither by GEDVI, nor by EVLWI, nor by the sum of the two. Declarations XM and JLT are members of the Medical Advisory Board of Pulsion Medical Systems. XM received fees for lecture for Baxter Healthcare. The other authors have no conflict of interest to declare. Author Contribution D.R. and X.M. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: D.R. and X.M., with advice from all authors. Acquisition of data: D.R., R.S, C.B., G.F., J.H. and C.L. Analysis or interpretation of data: D.R. and X.M. Drafting of the manuscript: D.R. and X.M. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: D.R. and X.M. Administrative, technical, or material support: D.R. and X.M. Supervision: X.M. Data Availability All data supporting the findings of this study are available within the paper and its Supplementary Material. 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Kossari N, Hufnagel G, Squara P. Bioreactance: a new tool for cardiac output and thoracic fluid content monitoring during hemodialysis. Hemodial Int. 2009;13(4):512–7. 10.1111/j.1542-4758.2009.00386.x . Epub 2009 Sep 16. PMID: 19758300. Fathy S, Hasanin AM, Raafat M, Mostafa MMA, Fetouh AM, Elsayed M, Badr EM, Kamal HM, Fouad AZ. Thoracic fluid content: a novel parameter for predicting failed weaning from mechanical ventilation. J Intensive Care. 2020;8:20. 10.1186/s40560-020-00439-2 . PMID: 32161651; PMCID: PMC7059362. Fellahi JL, Fischer MO. Electrical bioimpedance cardiography: an old technology with new hopes for the future. J Cardiothorac Vasc Anesth. 2014;28(3):755 – 60. 10.1053/j.jvca.2013.12.026 . PMID: 24917062. Malfatto G, Blengino S, Perego GB, Branzi G, Villani A, Facchini M, Parati G. Transthoracic impedance accurately estimates pulmonary wedge pressure in patients with decompensated chronic heart failure. Congest Heart Fail. 2012 Jan-Feb;18(1):25–31. 10.1111/j.1751-7133.2011.00248.x . Epub 2011 Sep 14. PMID: 22277174. Michard F, Alaya S, Zarka V, Bahloul M, Richard C, Teboul JL. Global end-diastolic volume as an indicator of cardiac preload in patients with septic shock. Chest. 2003;124(5):1900-8. 10.1378/chest.124.5.1900 . PMID: 14605066. Brivet FG, Jacobs F, Colin P. Calculated global end-diastolic volume does not correspond to the largest heart blood volume: a bias for cardiac function index? Intensive Care Med. 2004;30(11):2133-4; author reply 2135. 10.1007/s00134-004-2432-0 . Epub 2004 Sep 11. PMID: 15368039. Jozwiak M, Teboul JL, Monnet X. Extravascular lung water in critical care: recent advances and clinical applications. Ann Intensive Care. 2015;5(1):38. 10.1186/s13613-015-0081-9 . Epub 2015 Nov 6. PMID: 26546321; PMCID: PMC4636545. Dres M, Teboul JL, Anguel N, Guerin L, Richard C, Monnet X. Extravascular lung water, B-type natriuretic peptide, and blood volume contraction enable diagnosis of weaning-induced pulmonary edema. Crit Care Med. 2014;42(8):1882-9. 10.1097/CCM.0000000000000295 . PMID: 24717458. Li L, Ai Y, Huang L, Ai M, Peng Q, Zhang L. Can bioimpedance cardiography assess hemodynamic response to passive leg raising in critically ill patients: A STROBE-compliant study. Med (Baltim). 2020;99(51):e23764. 10.1097/MD.0000000000023764 . PMID: 33371141; PMCID: PMC7748328. Galarza L, Mercado P, Teboul JL, Girotto V, Beurton A, Richard C, Monnet X. Estimating the rapid haemodynamic effects of passive leg raising in critically ill patients using bioreactance. Br J Anaesth. 2018;121(3):567–573. doi: 10.1016/j.bja.2018.03.013. Epub 2018 Apr 21. PMID: 30115254. Teboul JL, Saugel B, Cecconi M, De Backer D, Hofer CK, Monnet X, Perel A, Pinsky MR, Reuter DA, Rhodes A, Squara P, Vincent JL, Scheeren TW. Less invasive hemodynamic monitoring in critically ill patients. Intensive Care Med. 2016;42(9):1350–9. 10.1007/s00134-016-4375-7 . Epub 2016 May 7. PMID: 27155605. Monnet X, Lai C. Which haemodynamic monitoring should we chose for critically ill patients with acute circulatory failure? Curr Opin Crit Care. 2023;29(3):275–80. 10.1097/MCC.0000000000001048 . Epub 2023 Apr 19. PMID: 37078635. Keren H, Burkhoff D, Squara P. Evaluation of a noninvasive continuous cardiac output monitoring system based on thoracic bioreactance. Am J Physiol Heart Circ Physiol. 2007;293(1):H583–9. 10.1152/ajpheart.00195.2007 . Epub 2007 Mar 23. PMID: 17384132. Additional Declarations Competing interest reported. X.M. and JL.T. are members of the Medical Advisory Board of Pulsion Medical Systems. X.M. received fees for lecture for Baxter Healthcare. The other authors have no conflict of interest to declare. Supplementary Files Supplementarymaterial.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 23 Aug, 2024 Reviews received at journal 13 Aug, 2024 Reviewers agreed at journal 08 Aug, 2024 Reviewers agreed at journal 06 Aug, 2024 Reviewers invited by journal 05 Aug, 2024 Editor assigned by journal 26 Jul, 2024 Submission checks completed at journal 26 Jul, 2024 First submitted to journal 25 Jul, 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. We do this by developing innovative software and high quality services for the global research community. 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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-4803045","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":341303919,"identity":"fa5bbde8-33c4-41d3-8fbe-06950c30e513","order_by":0,"name":"Daniela ROSALBA","email":"data:image/png;base64,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","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":true,"prefix":"","firstName":"Daniela","middleName":"","lastName":"ROSALBA","suffix":""},{"id":341303920,"identity":"a1a38561-eeb7-4476-b487-4a578c74f26f","order_by":1,"name":"Rui SHI","email":"","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"SHI","suffix":""},{"id":341303921,"identity":"e18e5854-d8cd-4975-be01-c35da7f0a167","order_by":2,"name":"Chiara BRUSCAGNIN","email":"","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":false,"prefix":"","firstName":"Chiara","middleName":"","lastName":"BRUSCAGNIN","suffix":""},{"id":341303922,"identity":"085fb128-f3b5-438d-aa0a-198033a233ba","order_by":3,"name":"Christopher LAI","email":"","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":false,"prefix":"","firstName":"Christopher","middleName":"","lastName":"LAI","suffix":""},{"id":341303923,"identity":"c00f9a47-fdb1-4bc8-92e3-103cc4160bdf","order_by":4,"name":"Gaëlle FOUQUE","email":"","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":false,"prefix":"","firstName":"Gaëlle","middleName":"","lastName":"FOUQUE","suffix":""},{"id":341303924,"identity":"daf78408-0ea3-4362-8f6d-cac68ea36bfb","order_by":5,"name":"Julien HAGRY","email":"","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":false,"prefix":"","firstName":"Julien","middleName":"","lastName":"HAGRY","suffix":""},{"id":341303925,"identity":"c9d908df-8748-4076-b172-e1ef3b528e30","order_by":6,"name":"Rosanna VASCHETTO","email":"","orcid":"","institution":"Università del Piemonte Orientale","correspondingAuthor":false,"prefix":"","firstName":"Rosanna","middleName":"","lastName":"VASCHETTO","suffix":""},{"id":341303926,"identity":"df9e3f9e-f607-47b0-a290-3190f3073e3d","order_by":7,"name":"Jean-Louis TEBOUL","email":"","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":false,"prefix":"","firstName":"Jean-Louis","middleName":"","lastName":"TEBOUL","suffix":""},{"id":341303931,"identity":"7a4cf390-f986-4349-8dee-3caef7609f05","order_by":8,"name":"Xavier MONNET","email":"","orcid":"","institution":"Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS","correspondingAuthor":false,"prefix":"","firstName":"Xavier","middleName":"","lastName":"MONNET","suffix":""}],"badges":[],"createdAt":"2024-07-25 15:44:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4803045/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4803045/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63417409,"identity":"f76ff67d-5ac5-452e-91cd-0b15995ff2af","added_by":"auto","created_at":"2024-08-28 02:04:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":515332,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between the changes in thoracic fluid content (TFC) and in global end-diastolic volume indexed (GEDVI) induced by fluid infusion in the Fluid group\u003c/p\u003e\n\u003cp\u003eN = 42, p = 0.71\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4803045/v1/9f70a7f4955689b9e111e6dc.png"},{"id":63417410,"identity":"7a2525de-91d2-43bd-be71-32a914aacd0d","added_by":"auto","created_at":"2024-08-28 02:04:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":541351,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between the absolute values of thoracic fluid content (TFC) and the sum of global end-diastolic volume indexed (GEDVI) and extravascular lung water indexed (EVLWI) considering all pairs pf measurements performed in the study\u003c/p\u003e\n\u003cp\u003eN = 208, p = 0.39\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4803045/v1/91df58c7eaa8508021e833eb.png"},{"id":63417412,"identity":"91a3cf13-325c-4779-8c41-09a207f29790","added_by":"auto","created_at":"2024-08-28 02:04:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1497862,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4803045/v1/a84e12ce-27c6-4906-96b0-93baa13e6fd8.pdf"},{"id":63417411,"identity":"0862950c-a148-4799-a010-e9189dc776bd","added_by":"auto","created_at":"2024-08-28 02:04:02","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":139643,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4803045/v1/fd85eeb0de30fc5a9f6b634e.pdf"}],"financialInterests":"Competing interest reported. X.M. and JL.T. are members of the Medical Advisory Board of Pulsion Medical Systems. \nX.M. received fees for lecture for Baxter Healthcare. \nThe other authors have no conflict of interest to declare.","formattedTitle":"Does the thoracic fluid content reflect lung water and cardiac preload?","fulltext":[{"header":"Background","content":"\u003cp\u003eElectrical bioimpedance and bioreactance are two techniques that can be used for hemodynamic monitoring. Both are based on the principle that the electrical conductivity and impedance of the thorax are influenced by its volume [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The Starling system (Baxter, Deerfield, IL, USA) measures stroke volume (and then cardiac output) through bioreactance, which is the difference in phase between the electrical inward current sent to the thorax by the system and the outward current [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Through bioimpedance, which is the ratio of voltage of the inward and outward electrical currents, the device also measures the mean transthoracic electric impedance (Z0). From it, it derives the thoracic fluid content (TFC), assuming that TFC\u0026thinsp;=\u0026thinsp;1000 / Z0 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The TFC is supposed to include the fluid in the lungs (extravascular lung water and pulmonary blood volume), in the large thoracic vessels and in the cardiac cavities [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, whether it is really the case has not been investigated yet.\u003c/p\u003e \u003cp\u003eThe first objective of our study was to investigate whether TFC behaves as a marker of cardiac preload by comparing its changes induced by volume expansion with those of well-established markers of cardiac preload, including the global end-diastolic volume indexed for body surface (GEDVI) estimated by transpulmonary thermodilution (TPTD). The second objective was to assess the relationship between TFC and extravascular lung water indexed for ideal body weight (EVLWI) estimated by TPTD during the course of acute respiratory distress syndrome (ARDS). The third objective was to establish the determinants of TFC, among hemodynamic variables including EVLWI and GEDVI estimated by TPTD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis prospective, observational, one-center study was conducted in the intensive care unit (ICU) of a tertiary hospital. Our study was approved by the ethical committee of the French Intensive Care Society (48, avenue Claude Vellefaux, 75010, Paris, France) and was registered on ClinicalTrials (2018-A02825-50/NCT05676723). Consent to participate in the study was obtained from the patients or their next of kin.\u003c/p\u003e \u003cp\u003ePatients\u003c/p\u003e \u003cp\u003eThe inclusion criteria were (i) hospitalization in the ICU, (ii) monitoring by a calibrated TPTD device (PiCCO2, Pulsion Medical Systems, Getinge, Feldkirchen, Germany), (iii) a planned volume expansion as decided by the attending physicians (\u003cem\u003eFluid group\u003c/em\u003e) or a diagnosis of ARDS according to the Berlin definition [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] (\u003cem\u003eARDS group\u003c/em\u003e). Exclusion criteria were (i) age\u0026thinsp;\u0026lt;\u0026thinsp;18 years, (ii) pregnancy, (iii) presence of extracorporeal membrane oxygenation (ECMO) assistance at the time of inclusion, (iv) impossibility to paste bioreactance electrodes properly to the skin of the thorax, (v) large pleural effusions, (vi) in \u003cem\u003eFluid group\u003c/em\u003e, circulatory failure whose treatment could not be postponed for \u0026ge;\u0026thinsp;5 minutes (time required for setting up the Starling system) and (vii) changes in the catecholamines dose or in the ventilatory settings performed during fluid infusion. Non-inclusion criteria were (i) unavailability of the investigators and (ii) refusal to join the study by the patient or his next of kin.\u003c/p\u003e \u003cp\u003eTranspulmonary thermodilution measurements\u003c/p\u003e \u003cp\u003eIn all patients, a thermistor-tipped femoral artery catheter and a central venous catheter were already in place as part of the patient\u0026rsquo;s hemodynamic monitoring. After calibrating the PiCCO2 system, the following TPTD variables were collected at baseline: cardiac index (CI), GEDVI, and EVLWI [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The results obtained from three injections of 15-mL cold saline boluses were averaged [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMeasurements with the Starling system\u003c/p\u003e \u003cp\u003eOnce the patient was included, a Starling device was set up by pasting four sensors on the skin surface of the thorax, two sensors above and two below the heart, as recommended by the constructor. This device measures CI through bioreactance and TFC through bioimpedance.\u003c/p\u003e \u003cp\u003eOther variables\u003c/p\u003e \u003cp\u003eDemographic and other hemodynamic parameters, including heart rate, arterial blood pressure, and central venous pressure (CVP), extracted from the PiCCO2 device, were recorded. The dose of sedatives drugs and catecholamines were also collected.\u003c/p\u003e \u003cp\u003eDesign of the study\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eFluid group\u003c/h2\u003e \u003cp\u003eImmediately after inclusion, the Starling device was set up and automatically self-calibrated. A first set of measurements was collected, including TPTD-derived variables (CI, GEDVI, EVLWI), TFC and bioreactance-derived CI. Volume expansion was then performed, according to the decision of the clinicians in charge, by infusing 500 mL of normal saline intravenously over 10 to 15 minutes. Immediately after the end of fluid infusion, TPTD was performed again and a second set of TPTD- and Starling-derived measurements was collected as before.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eARDS group\u003c/h2\u003e \u003cp\u003eOnce inclusion performed and until the PiCCO2 device was removed or the patient was extubated, at each time a TPTD measurement was performed according to current care, TFC and TPTD-derived variables were collected once a day at the same time. When several TPTD measurements were performed in a day, only the first one was considered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDistribution of variables was assessed visually. Data are expressed as median (interquartile range) or n (%). Comparison of variables between time points of the study was assessed using the paired Student\u0026rsquo;s t test or the Wilcoxon test, depending on data distribution. Comparisons between different groups of patients was performed using the unpaired Student\u0026rsquo;s t test or the Mann-Whitney U test, depending on data distribution.\u003c/p\u003e \u003cp\u003eFor the \u003cem\u003eFluid\u003c/em\u003e group the main analysis consisted in comparing the changes induced by volume expansion in GEDVI, CVP and the sum of GEDVI\u0026thinsp;+\u0026thinsp;EVLWI on the one side and in TFC on the other side. For this purpose, we calculated the Pearson correlation coefficient between simultaneous changes. For the \u003cem\u003eARDS\u003c/em\u003e group the analysis consisted in comparing the relative changes of EVLWI and TFC between two successive measurements. For determining the determinants of TFC, considering all pairs of measurements performed in both groups of patients, we calculated the Pearson correlation coefficient between absolute values of GEDVI, EVLWI, the sum of GEDVI\u0026thinsp;+\u0026thinsp;EVLWI on the one side and of TFC on the other side. In addition, we planned to perform a multiple regression analysis, in which the variable to explain was TFC, and the explaining variables were variables for which the p value of the correlation with TFC was \u0026lt;\u0026thinsp;0.1, among GEDVI, EVLWI, the sum GEDVI\u0026thinsp;+\u0026thinsp;EVLWI and the bias between CI measured by bioreactance and CI measured by TPTD.\u003c/p\u003e \u003cp\u003eWe calculated the least significant change in TFC in the first 10 patients included in the study. In these patients, during a period of hemodynamic stability (no change in mean arterial pressure and heart rate\u0026thinsp;\u0026ge;\u0026thinsp;5% compared to baseline during the last 15 minutes), the values of TFC were collected every 12 seconds for 15 minutes. We calculated the coefficient of variation of TFC as being the standard deviation divided by the mean of the five measurements [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The precision was calculated as being two times the coefficient of variation, and the least significant change as coefficient of variation x 1.96 x \u0026radic;2 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe comparison between absolute values of CI measured by bioreactance and by TPTD measured at different timepoints was performed by using the Bland-Altman analysis. The percentage error was calculated as 2SD divided by the mean of CI measured by TPTD. The changes in CI measured by bioreactance and by TPTD observed in both groups (induced by volume expansion in the \u003cem\u003eFluid group\u003c/em\u003e, between two successive timepoints in the \u003cem\u003eARDS group\u003c/em\u003e) were assessed by four quadrant analyses (with an exclusion zone of 12% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]). The ability of the fluid-induced changes in CI measured by bioreactance to detect an increase in CI measured by TPTD\u0026thinsp;\u0026ge;\u0026thinsp;15%, defining volume responsiveness [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], was assessed by a receiving operating characteristic (ROC) curve analysis. Sensitivity, specificity, positive and negative predictive values are expressed as median (95% confidence interval).\u003c/p\u003e \u003cp\u003eConsidering an α risk at 5% and a β risk at 80%, making the hypothesis of a baseline value of GEDVI of 700\u0026thinsp;\u0026plusmn;\u0026thinsp;190 mL/m\u003csup\u003e2\u003c/sup\u003e [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and of EVLWI of 20\u0026thinsp;\u0026plusmn;\u0026thinsp;7 mL/kg [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and considering a least significant change of both variables of 12% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], we calculated that 42 patients should be included in the \u003cem\u003eFluid group\u003c/em\u003e and that 100 changes should be included in the \u003cem\u003eARDS group\u003c/em\u003e. A p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All tests were two-sided. Statistical analysis was performed using Medcalc software (version 20.218) (bvba, Mariakerke, Belgium).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003ePatient characteristics\u003c/p\u003e \u003cp\u003eWe prospectively included 42 patients in the \u003cem\u003eFluid group\u003c/em\u003e and 23 patients in the \u003cem\u003eARDS group\u003c/em\u003e from January to August 2022. No patient was excluded. Patient characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. They were included 3 (1\u0026ndash;4) days after their admission in the ICU. At inclusion, all patients were mechanically ventilated and sedated with propofol and remifentanil. Septic shock was the main cause for acute circulatory failure in the \u003cem\u003eFluid group\u003c/em\u003e and the only one in the \u003cem\u003eARDS group\u003c/em\u003e (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among the 23 patients with ARDS, 12 patients (52%) suffered from pneumonia attributed to severe acute respiratory syndrome Coronavirus 2019.\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\u003ePatient characteristics in the two study groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFluid group (n\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eARDS group (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\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\u003e64 [55\u0026ndash;71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 [58\u0026ndash;72]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (91%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 [\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27 CR28\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 [\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\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\u003e10 [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAPS II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 [39\u0026ndash;59]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 [39\u0026ndash;54]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eType of shock (n, %)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeptic\u003c/p\u003e \u003cp\u003eCardiogenic\u003c/p\u003e \u003cp\u003eHypovolemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (86)\u003c/p\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003cp\u003e5 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (100)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate at inclusion (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1 [1.6\u0026ndash;2.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3 [1.7\u0026ndash;2.9]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute respiratory distress syndrome (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (100)*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU length of stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 [\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU mortality rate (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilatory settings\u003c/p\u003e \u003cp\u003eTidal volume (mL/kg PBW)\u003c/p\u003e \u003cp\u003eRespiratory rate (breaths/min)\u003c/p\u003e \u003cp\u003eFiO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e \u003cp\u003ePositive end expiratory pressure (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e \u003cp\u003ePlateau pressure (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.4 [5.4\u0026ndash;6.1]\u003c/p\u003e \u003cp\u003e25 [\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e60 [40\u0026ndash;70]\u003c/p\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e25 [\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.6 [5.1\u0026ndash;6.2]\u003c/p\u003e \u003cp\u003e25 [\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e60 [40\u0026ndash;80]\u003c/p\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e27 [23\u0026ndash;31]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrugs and sedation (n, %)\u003c/p\u003e \u003cp\u003ePropofol\u003c/p\u003e \u003cp\u003eRemifentanil\u003c/p\u003e \u003cp\u003eNeuromuscular blocking agents\u003c/p\u003e \u003cp\u003eNorepinephrine\u003c/p\u003e \u003cp\u003eDobutamine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (100)\u003c/p\u003e \u003cp\u003e42 (100)\u003c/p\u003e \u003cp\u003e18 (43)\u003c/p\u003e \u003cp\u003e40 (95)\u003c/p\u003e \u003cp\u003e7 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (100)\u003c/p\u003e \u003cp\u003e23 (100)\u003c/p\u003e \u003cp\u003e17 (74)*\u003c/p\u003e \u003cp\u003e23 (100)\u003c/p\u003e \u003cp\u003e4 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eData are expressed as n(%) or median [IQR]\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e* P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. \u003cem\u003eFluid group\u003c/em\u003e.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eFiO\u003csub\u003e2\u003c/sub\u003e: inspired fraction of oxygen, ICU: intensive care unit, PBW: predicted body weight, SAPS: Simplified acute physiologic score II at admission, SOFA: Sequential organ failure assessment score at admission\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFluid group\u003c/p\u003e \u003cp\u003eHemodynamic variables before and after fluid infusion in these 42 patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The infusion of the fluid bolus led to an increase in CI\u0026thinsp;\u0026ge;\u0026thinsp;15% in 23 (55%) volume responders. Simultaneously, GEDVI and TFC significantly increased by 6 [0\u0026ndash;13] and 3 [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]%, respectively, while EVLWI did not change significantly (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in hemodynamic variables induced by volume expansion in volume responders and non-responders in the \u003cem\u003eFluid group\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBefore volume expansion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAfter volume expansion\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eHeart rate (min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 [88\u0026ndash;111]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96 [88\u0026ndash;108]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 [84\u0026ndash;109]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89 [82\u0026ndash;106]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eSystolic arterial pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111\u0026thinsp;[88\u0026ndash;120]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124\u0026thinsp;[111\u0026ndash;140]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117 [103\u0026ndash;137]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e134 [116\u0026ndash;148]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eDiastolic arterial pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 [46\u0026ndash;60]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 [54\u0026ndash;70]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 [50\u0026ndash;65]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 [52\u0026ndash;69]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eMean arterial pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 [60\u0026ndash;78]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 [73\u0026ndash;90]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 [70\u0026ndash;85]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 [75\u0026ndash;92]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eCentral venous pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 |8\u0026ndash;11]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePiCCO2 cardiac index (L/min/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3 [1.9-3.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9 [2.3\u0026ndash;3.4]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.5 [1.9\u0026ndash;3.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2 [2.7\u0026ndash;3.6]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eStarling cardiac index (L/min/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3 [1.9\u0026ndash;3.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0 [2.3\u0026ndash;3.7]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8 [2.5\u0026ndash;3.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0 [2.5\u0026ndash;3.3]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePulse pressure variation (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u0026thinsp;[\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eGEDVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e635 [545\u0026ndash;692]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e699 [609\u0026ndash;708]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e636 [545\u0026ndash;692]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e684 [619\u0026ndash;725]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eEVLWI (ml/kg PBW)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eTotal fluid content\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume responders (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 [58\u0026ndash;100]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 [59\u0026ndash;107]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume non-responders \u003cem\u003e(n\u0026thinsp;=\u0026thinsp;19)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 [70\u0026ndash;99]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82 [74\u0026ndash;104]*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eN\u0026thinsp;=\u0026thinsp;42. Data are expressed as median [IQR].\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e* P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. Before volume expansion\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eEVLWI: extravascular lung water indexed for predicted body weight, GEDVI: global end-diastolic volume indexed for body surface, PBW: predicted body weight.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThere was no correlation between the fluid-induced changes in GEDVI (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), in EWLVI, in the sum GEDVI\u0026thinsp;+\u0026thinsp;EVLWI or in CVP on the one side and the fluid-induced changes in TFC on the other (p\u0026thinsp;=\u0026thinsp;0.71, p\u0026thinsp;=\u0026thinsp;0.45, p\u0026thinsp;=\u0026thinsp;0.71 and p\u0026thinsp;=\u0026thinsp;0.09, respectively).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eARDS group\u003c/p\u003e \u003cp\u003eIn the 23 patients of this group, 124 measurements were performed, representing 101 changes between timepoints. On average, 10 (8\u0026ndash;13) changes were measured in each patient. Their characteristics at inclusion are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and their hemodynamic variables at inclusion in Supplemental Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eBetween two timepoints, in absolute value (i.e., non-negative values, without considering the direction of changes), GEDVI, EVLWI, the sum GEDVI\u0026thinsp;+\u0026thinsp;EVLWI and TFC changed by 14 [8\u0026ndash;35]%, 15 [6\u0026ndash;30]%, 11 [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]% and 11 [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]%, respectively. There was no correlation between the percent changes in GEDVI, EVLWI, the sum of GEDVI\u0026thinsp;+\u0026thinsp;EVLWI on the one side and the percent changes in TFC on the other side (p\u0026thinsp;=\u0026thinsp;0.52, 0.40 and 0.55, respectively). When considering only the first measurements performed in each patient (n\u0026thinsp;=\u0026thinsp;23), there was also no correlation between changes in EVLWI and in TFC between two time points (p\u0026thinsp;=\u0026thinsp;0.19, 0.38 and 0.21, respectively).\u003c/p\u003e \u003cp\u003ePrecision of the TFC measurements\u003c/p\u003e \u003cp\u003eThe coefficient of variation of the TFC was 0.6, the precision was 0.1% and the least significant change was 0.2%.\u003c/p\u003e \u003cp\u003eAccuracy of the estimation of cardiac output by bioreactance\u003c/p\u003e \u003cp\u003eConsidering all pairs of measurements performed during the study (42 in the \u003cem\u003eFluid group\u003c/em\u003e, 124 in the \u003cem\u003eARDS group\u003c/em\u003e), the bias between CI measured by bioreactance and by TPTD was 0.3 L/min/m\u003csup\u003e2\u003c/sup\u003e and the limits of agreements were 2.0 and \u0026minus;\u0026thinsp;2.6 L/min/m\u003csup\u003e2\u003c/sup\u003e (Supplemental Fig.\u0026nbsp;1). The percentage of error was 131%. The coefficient of correlation between the changes in CI measurements (42 induced by volume expansion in the \u003cem\u003eFluid group\u003c/em\u003e, 124 between two successive measurement points in the \u003cem\u003eARDS group\u003c/em\u003e) was 0.24 (p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIn the \u003cem\u003eFluid group\u003c/em\u003e, an increase in CI measured by bioreactance\u0026thinsp;\u0026ge;\u0026thinsp;9% during fluid infusion detected a fluid-induced increase in CI measured by TPTD\u0026thinsp;\u0026ge;\u0026thinsp;15% with a sensitivity of 83 (63\u0026ndash;95)% and a specificity of 89 (65\u0026ndash;99)%, with an area under the ROC curve of 0.851 (95% IC: 0.707\u0026ndash;0.942) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 vs. 0.5) (Supplemental Fig.\u0026nbsp;2). The concordance rate outside the exclusion zone was 96% (Supplemental Fig.\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eDeterminants of TFC\u003c/p\u003e \u003cp\u003eConsidering the 208 pairs of measurements performed in both groups (84 in the \u003cem\u003eFluid group\u003c/em\u003e, 124 in the \u003cem\u003eARDS group\u003c/em\u003e), there was no correlation between the absolute values of GEDVI, EVLWI and the sum of GEDVI\u0026thinsp;+\u0026thinsp;EVLWI (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) on the one side and those of TFC on the other side (p\u0026thinsp;=\u0026thinsp;0.33, 0.04 and 0.39, respectively).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere was no correlation between the bias in CI measured by bioreactance compared to TPTD on the one side and the difference between TFC and the sum GEDVI\u0026thinsp;+\u0026thinsp;EVLWI on the other side (p\u0026thinsp;=\u0026thinsp;0.29).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study conducted in critically ill patients shows that TFC measured by bioimpedance increased during the infusion of a fluid bolus. However, there was no significant correlation between the fluid-induced changes in TFC and those in GEDVI or CVP. In patients with ARDS, the changes in TFC were not correlated with the simultaneous changes in EVLWI over time. There was no correlation between absolute values of TFC and the sum of GEDVI\u0026thinsp;+\u0026thinsp;EVLWI, taken all measurements into account. The bias between TFC measured by bioimpedance and the sum of GEDVI\u0026thinsp;+\u0026thinsp;EVLWI was not correlated with the bias between CI measured by bioreactance and CI measured by TPTD.\u003c/p\u003e \u003cp\u003eBioreactance is one of the non-invasive cardiac output measurement techniques available today [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Alongside the measurement of cardiac output, the Starling system provides the measurement of TFC, estimated by bioimpedance (and not by bioreactance), supposed to estimate the volume of fluid contained in the thorax [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. TFC has been demonstrated to predict cardiac events in patients with chronic heart failure [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. It has also been used to assess the fluid status in children [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] or adults [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] especially during hemodialysis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], pre-eclampsia [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] or weaning from mechanical ventilation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. It has been speculated that TFC could be used to guide fluid therapy especially in the peri-operative setting [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Since it should be partly composed of the fluid contained in the lung interstitium and the alveoli, it may also follow the evolution of ARDS severity. Nevertheless, as far as we know, whether TFC actually reflects the thoracic water content and tracks its changes has not been tested yet.\u003c/p\u003e \u003cp\u003eOur results all agree to invalidate this hypothesis. First, although TFC significantly increased during standardized volume expansion, these changes did not follow concurrent changes in either GEDVI or CVP, i.e., volumetric and barometric markers of cardiac preload, respectively. This is in agreement with a previous study showing the poor ability of TFC to estimated pulmonary artery occlusion pressure in decompensated chronic heart failure [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Second, in patients with ARDS, day-to-day lung water changes were not tracked by those of TFC. Taking into account all the measurements performed in the study, we found no correlation between the absolute values of TFC, and those of GEDVI, EVLWI or the sum of both. The degree of significance of these correlations prevented us from carrying out the multivariate regression analysis that we had planned to approach the determinants of the TFC.\u003c/p\u003e \u003cp\u003eAn obvious limitation of our study may be that we compared TFC to GEDVI and EVLWI measured by TPTD, used as references. Indeed, there is no other method available at the bedside to estimate the different volumes of fluid contained in the thorax. Then, our results could be explained by the fact that the TFC includes other volumes than those estimated by the GEDVI and the EVLWI. The pulmonary blood volume, i.e., the volume contained in the pulmonary vessels [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], was not taken into account, nor the volume of fluid contained in other thoracic spaces (pleural in particular) and tissues (muscles for example). Nevertheless, the fluid volume of the cardiac chambers (estimated by the GEDVI) and of the pulmonary tissue (estimated by the EVLWI) are so predominant in the thoracic total fluid content, that the absence of correlation of TFC with any of them casts doubt on its ability to estimate such volume in the entire thorax.\u003c/p\u003e \u003cp\u003eAnother explanation for our results could also be that GEDVI and EVLWI do not provide a reliable measurement of the volumes that they are supposed to estimate. This may be the case for GEDVI which, even if it behaves as a preload marker [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], has been suspected of overestimating the real volume of the four cardiac chambers [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This is probably not the case for EVLWI. Indeed, several studies have shown that this index reliably approximates the actual volume of water contained in the interstitium and the pulmonary alveoli [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study confirms the relative reliability of the measurement of cardiac output by bioreactance [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Even though the percentage error was higher than the 30% considered as the upper bound indicating reliability, Starling-derived CI tracked changes in CI estimated by TPTD, with similar accuracy as previously reported when the last version of the device was compared with TPTD [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] or echocardiography [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. We observed no correlation between the bias of the Starling-derived CI compared to the TPTD-derived CI and the difference between the TFC and the sum GEDVI\u0026thinsp;+\u0026thinsp;EVLWI. This result is however not surprising, the TFC and the CI not being measured by the same method (bioimpedance for the first, bioreactance for the second).\u003c/p\u003e \u003cp\u003eOur study has several limitations besides those mentioned above. Firstly, it was carried out in critically ill patients, in whom the Starling system is not best indicated [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Secondly, we were not able to explain the lack of correlation between the TFC on the one hand and the fluid volumes estimated by TPTD on the other hand. The precise method of TFC calculation is of course kept secret by the manufacturer. We also did not estimate whether these results were due to interferences between the device and the patient's electrical environment, which were suspected to affect the reliability of bioimpedance [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Third, measurements of EVLWI after volume expansion were performed immediately at the end of the fluid bolus infusion, which may have minimized its changes because the increase in EVLWI could theoretically occur later. Finally, in the ARDS group, several changes were measured in the same patient. However, the analysis performed on the first measured change did not provide different results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn critically ill patients, the TFC measured by bioimpedance does not follow the changes in well-known markers of cardiac preload induced by a fluid bolus. It also does not follow the changes in EVLWI observed in patients with ARDS. It is determined neither by GEDVI, nor by EVLWI, nor by the sum of the two.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003eXM and JLT are members of the Medical Advisory Board of Pulsion Medical Systems. XM received fees for lecture for Baxter Healthcare. The other authors have no conflict of interest to declare.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eD.R. and X.M. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: D.R. and X.M., with advice from all authors. Acquisition of data: D.R., R.S, C.B., G.F., J.H. and C.L. Analysis or interpretation of data: D.R. and X.M. Drafting of the manuscript: D.R. and X.M. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: D.R. and X.M. Administrative, technical, or material support: D.R. and X.M. Supervision: X.M.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data supporting the findings of this study are available within the paper and its Supplementary Material.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCouture EJ, Laferri\u0026egrave;re-Langlois P, Denault A. New Developments in Continuous Hemodynamic Monitoring of the Critically Ill Patient. Can J Cardiol. 2023;39(4):432\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cjca.2023.01.012\u003c/span\u003e\u003cspan address=\"10.1016/j.cjca.2023.01.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2023 Jan 18. PMID: 36669685.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaugel B, Cecconi M, Hajjar LA. Noninvasive Cardiac Output Monitoring in Cardiothoracic Surgery Patients: Available Methods and Future Directions. 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PMID: 17384132.\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-4803045/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4803045/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Whether the thoracic fluid content (TFC) estimated by bioimpedance actually reflects the thoracic water content and tracks its changes has not been tested yet. We compared TFC changes induced by volume expansion with those of well-established markers of cardiac preload including the global end-diastolic volume indexed (GEDVI) estimated by transpulmonary thermodilution (TPTD) and central venous pressure (CVP). We assessed the relationship between TFC and extravascular lung water indexed (EVLWI) estimated by TPTD in patients with acute respiratory distress syndrome (ARDS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: In 42 patients with a TPTD device (PiCCO2), we measured GEDVI, EVLWI and CVP before and after a 500-mL fluid bolus (\u003cem\u003eFluid group\u003c/em\u003e). In 23 patients with ARDS, we measured the day-to-day changes in TFC and EVLWI (\u003cem\u003eARDS group\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn the \u003cem\u003eFluid group (42 measurements)\u003c/em\u003e, TFC increased significantly during fluid infusion. There was no correlation between the fluid-induced changes in GEDVI or CVP and the fluid-induced changes in TFC (p=0.71 and p=0.09, respectively).\u003cstrong\u003e \u003c/strong\u003eIn the \u003cem\u003eARDS group\u003c/em\u003e, 124 measurements were performed, representing 101 changes between timepoints. There was no correlation between the percent changes in GEDVI, EVLWI, the sum of GEDVI+EVLWI and the percent changes in TFC (p=0.52, 0.40 and 0.55, respectively). Considering all 208 pairs of measurements performed, there was no correlation between the absolute values of GEDVI, EVLWI and the sum of GEDVI+EVLWI and those of TFC (p=0.33, 0.04 and 0.39, respectively). Considering all pairs of measurements performed, the percentage of error of cardiac index measured by bioreactance compared to TPTD was 131%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: In critically ill patients, TFC measured by bioimpedance does not follow the changes induced by a fluid bolus of well-known markers of cardiac preload. It also does not follow the changes in EVLWI observed in patients with ARDS. It is determined neither by GEDVI, nor by EVLWI or the sum of the two.\u003c/p\u003e","manuscriptTitle":"Does the thoracic fluid content reflect lung water and cardiac preload?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-28 02:03:57","doi":"10.21203/rs.3.rs-4803045/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-23T16:28:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-13T14:09:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"335374467304057137968924461689891972713","date":"2024-08-08T07:36:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"224898410254499766225632276250208881119","date":"2024-08-06T10:47:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-05T08:53:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-26T09:20:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-26T09:19:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Clinical Monitoring and Computing","date":"2024-07-25T15:41:58+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":"9b39a249-caef-448d-94c3-23f4f85e1e44","owner":[],"postedDate":"August 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-21T08:23:10+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-28 02:03:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4803045","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4803045","identity":"rs-4803045","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}