Background: The hemodynamic effects of the passive leg raising (PLR) test must be assessed through a direct meas‑ urement of cardiac index (CI). We tested whether changes in Doppler common carotid blood flow (CBF) and common femoral artery blood flow (FBF) could detect a positive PLR test (increase in CI ≥ 10%). We also tested whether CBF and FBF changes could track simultaneous changes in CI during PLR and volume expansion. In 51 cases, we measured CI (PiCCO2), CBF and FBF before and during a PLR test (one performed for CBF and another for FBF measurements) and before and after volume expansion, which was performed if PLR was positive. Results: Due to poor echogenicity or insufficient Doppler signal quality, CBF could be measured in 39 cases and FBF in only 14 cases. A positive PLR response could not be detected by changes in CBF, FBF, carotid nor by femoral peak systolic velocities (areas under the receiver operating characteristic curves: 0.58 ± 0.10, 0.57 ± 0.16, 0.56 ± 0.09 and 0.64 ± 10, respectively, all not different from 0.50). The correlations between simultaneous changes in CI and CBF and in CI and FBF during PLR and volume expansion were not significant ( p = 0.41 and p = 0.27, respectively). Conclusion: Doppler measurements of CBF and of FBF, as well as measurements of their peak velocities, are not reli‑ able to assess cardiac output and its changes. Keywords: Volume expansion, Fluid responsiveness, Hemodynamic monitoring, Cardiac output starting from a semi-recumbent position. By transferring Background a consistent amount of venous blood from the legs and Since it has been demonstrated that fluid overload can the splanchnic compartment toward the intrathoracic be deleterious in patients with acute respiratory distress compartment, it increases the mean systemic pressure syndrome  and severe sepsis , it is of paramount , the cardiac preload and consequently cardiac output importance to avoid excessive fluid administration in in the case of preload responsiveness of both ventricles such cases. The decision to give fluids must be guided by . However, it must be coupled with a direct and real- a reliable prediction of fluid responsiveness as only 50% time measurement of cardiac output, which is often inva- of patients respond to fluid administration by increas - sive [6–8]. ing cardiac output . In order to predict the response The Doppler measurement of blood flow and its veloc - of cardiac output to fluid infusion, the passive leg raising ity in the carotid as well as in the femoral arteries may be (PLR) test has been validated. It consists in lifting the legs interesting for estimating the changes in cardiac output passively at 45° and moving the trunk down horizontally, during a PLR test, since changes in arterial blood flow and in cardiac output might be proportional. Neverthe- *Correspondence: firstname.lastname@example.org less, contradictory results have been published regarding Service de Réanimation Médicale, Hôpital de Bicêtre, Hôpitaux this issue [9–14]. Universitaires Paris‑Sud, Insert UMR_999, Université Paris‑Sud, Assistance Publique – Hôpitaux de Paris, Le Kremlin‑Bicêtre, France Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Girotto et al. Ann. Intensive Care (2018) 8:67 Page 2 of 9 Our study had two aims. The first was to test whether the carotid artery was obtained approximately 1–2 cm changes in carotid and femoral Doppler measurements before its bifurcation. We assessed pulsed wave Dop- were able to detect a positive PLR test. The second was pler, the sampling volume being positioned in the middle to investigate the ability of carotid and femoral Doppler of the lumen with caliper parallel to blood flow (Fig. 1). measurements to track the changes in cardiac index, dur- Time average mean velocity (TAMEAN) and peak sys- ing PLR and fluid administration. tolic velocity (PSV) were automatically estimated by the echograph software. Velocity-time integral (VTI) Methods was measured by manually tracing the flow envelope Patients for each image (Fig. 1). We kept an insonation angle of Before starting the study, we obtained the agreement of 60° between Doppler beam and sample. In longitudinal our institutional review board (Comité pour la protection view, the maximal diameter was measured from intima to des personnes Ile-de-France VI, ref # 2016-A00959-42). intima with an angle of 90° to the vessel. All patients or their relatives accepted to participate in To determine carotid blood flow, we used two differ - the study. It took place at a 25-bed medical intensive care ent methods, one based on VTI (cm) and the other on unit of a university hospital between June and November TAMEAN (cm/s): Patients were included in the study if they met the fol- • Carotid blood flow (mL/min) = TAMEAN × π lowing criteria: r × 60. • Carotid blood flow (mL/min) = V TI × π r × Heart • Age ≥ 18 years. rate (beats/min). • A PiCCO2 device (Pulsion Medical Systems, Feld- kirchen, Germany) already in place for clinical pur- where “r” (in cm) represents the radius of the vessel that poses. was assumed to be circular. • Decision to perform a PLR test made by the attend- In addition, we measured TAMEAN with both narrow ing physicians. and large sampling windows within the arterial lumen, in order to compare two different ways of calculating Patients were excluded if the PLR maneuver was con- carotid blood flow. traindicated (intracranial hypertension), if PLR was sup- Measurements were also performed at the level of posed to be unreliable (venous compression stocking and the common femoral artery before the bifurcation into intraabdominal hypertension) or if it was impossible to superficial femoral artery and deep femoral artery. Blood perform vascular Doppler measurements. flow, peak systolic velocity and diameter were measured with the same method and formulas as described before. Hemodynamic measurements Nevertheless, at this level, the only method that was used All patients were equipped with a jugular or subclavian to measure femoral blood flow was the one based on VTI. venous catheter and a thermistor-tipped femoral arterial Indeed, the contour of the femoral velocity that was auto- catheter (PV2024, Pulsion Medical Systems). Hemody- matically traced by the device for measuring time average namic variables were recorded continuously by using a mean velocity included both positive and negative values data acquisition software (HEM 4.2, Notocord, Croissy- of femoral velocities, eventually providing very low values sur-Seine, France). Cardiac Index was recorded by the of TAMEAN. We decided to trace the contour manually, PiCCO Win 4.0 software (Pulsion Medical Systems). For including only the positive values in the measurement of all thermodilution measurements, the results obtained VTI. from three consecutive saline boluses were averaged [15, 16]. Study design At baseline, a first set of transpulmonary thermodilution Doppler measurements and Doppler measurements were recorded (Additional One investigator (VG) performed all ultrasound meas- file 1: Figure S1). Two PLR tests (“PLR1” and “PLR2”) urements. Images were analyzed and measurements were were then consecutively performed because it was not performed offline by two investigators (VG and TG). feasible to simultaneously record carotid and femoral Ultrasound examination was performed with a CX50 Doppler indices during the same PLR test. The PLR posi - (Philips Healthcare, Eindhoven, The Netherlands) by tion was maintained until the maximal value of pulse using a 12–5 MHz flat linear probe. contour analysis-derived cardiac index was reached, At each step of the protocol, we obtained images of what always occurs within 1 min . Between the two the common carotid artery. First, a long-axis view of PLR tests, we waited for approximately 5 min to obtain Girotto et al. Ann. Intensive Care (2018) 8:67 Page 3 of 9 Fig. 1 Example of Doppler measurements performed in a patient stable hemodynamic baseline values. Each PLR test was S1). Catecholamines dosages and ventilation settings performed as previously described . At its maximum were kept constant during the study period. effect, a second set of hemodynamic and Doppler meas - urements was performed (Additional file 1: Figure S1). Data analysis The effects of PLR on cardiac output were measured All data were normally distributed (Kolmogorov– by pulse contour analysis and not by transpulmonary Smirnov test for normality). Date are expressed as thermodilution because these effects must be assessed mean ± standard deviation (SD) or number and fre- by a real-time monitoring technique . In practice, quency (n, %). Comparison between time points of the we observed the continuously changing value of pulse study was performed using paired Student’s t tests. Com- contour analysis-derived cardiac index while perform- parison between PLR responders and non-responders ing the Doppler measurements. As soon as the cardiac was performed using two-tailed Student’s t tests. Pear- index value started to decrease, we considered that it son correlation coefficient was calculated to compare had reached its maximum. At this precise time, we froze carotid/femoral blood flow and cardiac index as well as the image of the echograph and performed the Doppler their relative changes following PLR and fluid infusion. measurements on the values displayed during the previ- A receiving operating characteristics (ROC) curve was ous seconds. If pulse contour analysis-derived cardiac constructed to evaluate the ability of the PLR-induced index increased ≥ 10% during the PLR tests, compared to changes in carotid and femoral blood flows and velocities the baseline value, the patient was regarded as responder to detect responsiveness to PLR. The inter- and intrain - to the tests . In total, the two PLR tests were per- dividual variability of carotid Doppler measurements formed within 15 min. were also calculated. Considering a α-risk of 20% and a After the second PLR, another transpulmonary ther- β-risk of 10%, to evidence an increase in 20% of carotid modilution was performed. Then, according to the deci - and femoral blood flows during PLR [9, 10], we planned sion of the clinicians in charge, only responders to the to include 50 cases in the study. Statistical significance first PLR test were given 500 mL of normal saline over was defined by a p value < 0.05. The statistical analysis 10 min. All echographic and hemodynamic variables was performed using MedCalc 11.6.0 software (MedCalc, were then recorded at the end of fluid infusion, including Mariakerke, Belgium). transpulmonary thermodilution (Additional file 1: Figure Girotto et al. Ann. Intensive Care (2018) 8:67 Page 4 of 9 Table 1 Baseline patient characteristics Results Patient characteristics Gender (male) 22 (67%) Thirty-three patients were included in the study. Patients Age (years) 67 ± 14 could be included more than once at different days, so Weight (kg) 68 ± 12 that we collected 51 cases in total, which were considered Height (cm) 165 ± 9 as individual cases (Fig. 2). Their characteristics are sum - SAPS II 62 ± 19 marized in Table 1. Diagnostic At the time of inclusion, in 48 (94%) cases, patients were Septic shock 16 (49%) intubated and ventilated in the volume-controlled mode. Cardiogenic shock 7 (21%) Patients received catecholamines in 46 (90%) cases (nor- ARDS 6 (18%) epinephrine alone in 41 cases, dobutamine and norepi- Coma 2 (6%) nephrine in three cases, dobutamine alone in two cases). Pancreatitis 1 (3%) Acute renal failure 1 (3%) Feasibility of carotid and femoral Doppler examination LVEF < 50% 8 (24%) Among all carotid Doppler measurements, two cases N = 33 were excluded because of carotid stenosis and 10 because Data are presented as mean ± standard deviation or number (percentage) of poor image quality that prevented to reliably trace the SAPS II simplified acute physiology score, ARDS acute respiratory distress contour of the signal (Fig. 2). Among the remaining 39 syndrome, LVEF left ventricular ejection fraction cases, in one case we could not assess carotid blood flow by TAMEAN (Fig. 2). of a poor 2D echogenicity that prevented to precisely Among all cases, two were excluded because the define the intima edge of the femoral artery and 19 cases femoral site was not accessible for performing Doppler because of poor quality of the Doppler signal (Fig. 2). measurement (obesity), 16 cases were excluded because 33 paents 51 cases Carod bloodﬂow Femoralblood ﬂow Carod stenosis Femoralsite not 2 cases 2 cases accessible Poor Doppler Poor 2D 10 cases 16 cases signal echogenicity 39 cases Poor Doppler 19 cases signal Impossibilityto 1 case measureTAMEAN 38 cases withCBF 39 cases with CBF 14 cases with FBF (TAMEAN method) (VTI method) PLR in 38 cases PLR in 39 cases PLR in 14 cases VE in 21 cases VE in 22 cases VE in 3 cases Fig. 2 Flowchart. CBF carotid blood flow, PLR passive leg raising, TAMEAN time average mean velocity, VE volume expansion, VTI velocity time integral Girotto et al. Ann. Intensive Care (2018) 8:67 Page 5 of 9 An increase in cardiac index ≥ 10% during the first PLR For TAMEAN, the inter-individual variability was predicted fluid responsiveness with a positive predictive 8.9 ± 8.7% and the intraindividual variability was value of 93%. The specificity, sensitivity and negative pre - 12.7 ± 12.2%. For PSV, the inter-individual variability dictive of PLR as a predictor of the response to fluid infu - was 5.0 ± 4.1% and the intraindividual variability was sion value could not be calculated since we performed 2.2 ± 1.7%. No difference was found between values of fluid infusion only in patients with a positive PLR test. An carotid blood flow calculated from TAMEAN sampled in increase in cardiac index ≥ 10% during the second PLR large and narrow sampling windows (p = 0.28). predicted fluid responsiveness with the same positive Considering all measurements at different study steps predictive value because both PLR tests exerted similar (Fig. 2), only weak correlations were found between effects on cardiac index. absolute values of cardiac index and absolutes values of The results of ROC curves analysis are presented in carotid blood flow calculated from TAMEAN (n = 135; Additional file 1: Table S1 and Fig. 3. Neither the changes r = 0.54, p < 0.01) (Additional file 1: Figure S2) and abso- in carotid blood flow measured with the VTI method nor lutes values of carotid PSV (n = 139; r = 0.26, p < 0.01). the carotid blood flow measured the TAMEAN method Absolute values of carotid blood flow calculated with or the carotid PSV could detect a positive response to TAMEAN were almost systematically lower than the cor- the PLR1 test. Neither the changes in femoral blood flow responding values calculated with VTI (data not shown). measured with the VTI method nor the femoral PSV Considering all changes observed during the first PLR could detect a positive response to the PLR2 test (Addi- test (n = 38) and fluid infusion (n = 21) (Fig. 2), we found tional file 1: Table S1, Fig. 3). Results were not different no correlation between changes in cardiac index and when the analysis was performed with only the first case changes in carotid blood flow calculated from TAMEAN measured in each of the patients who had been included (n = 59; r = 0.07, p = 0.61) and between changes in cardiac several times in the study (data not shown). index and changes in carotid blood flow calculated from VTI (n = 61; r = 0.11, p = 0.41). The ability of changes in Relationship between cardiac index and carotid Doppler carotid blood flow calculated from VTI and TAMEAN to measurements in absolute values and relative changes detect changes in cardiac index are illustrated by 4-box Absolute values of carotid blood flow and of PSV as well tables in Additional file 1: Table S2. Results were not dif- as the ratio of carotid blood flow over cardiac index dur - ferent when the analysis was performed with only the ing each study step are reported in Table 2. first case measured in each of the patients who had been included several times in the study (data not shown). Changes in Changes in carod bloodﬂow* femoralblood ﬂow 100 100 60 60 AUC = 0.57±0.16 AUC = 0.58±0.10 (p = 0.62 vs. 0.50) (p = 0.68 vs. 0.50) 20 20 (n = 38) (n = 14) 100-Specificity 100-Specificity Fig. 3 Receiver operating characteristic curves describing the ability of changes in carotid femoral blood flows to detect a positive response of cardiac index to a passive leg raising test (increase ≥ 10%). AUC area under the curve. Asterisks results are provided for carotid blood flow measured by the velocity time integral method Sensitivity Sensitivity Girotto et al. Ann. Intensive Care (2018) 8:67 Page 6 of 9 Table 2 Hemodynamic and Doppler measurements Baseline 1 PLR1 Baseline 2 PLR2 Baseline 3 After fluid infusion Heart rate (beats/min) PLR responders (n = 27) 91 ± 19 92 ± 22 89 ± 17 93 ± 17 92 ± 15 93 ± 15 PLR non‑responders (n = 24) 91 ± 18 91 ± 17 87 ± 14 92 ± 14 89 ± 19 – Systolic arterial pressure (mmHg) # $ PLR responders (n = 27) 117 ± 26 129 ± 32* 115 ± 25 130 ± 34 115 ± 32 129 ± 33 PLR non‑responders (n = 24) 125 ± 21 130 ± 24* 122 ± 18 127 ± 20 125 ± 20 – Diastolic arterial pressure (mmHg) # $ PLR responders (n = 27) 57 ± 13 62 ± 11* 52 ± 16 62 ± 11 57 ± 14 63 ± 18 PLR non‑responders (n = 24) 61 ± 9 64 ± 11* 60 ± 7 64 ± 9 61 ± 10 – Central venous pressure (mmHg) # $ PLR responders (n = 27) 11 ± 4 14 ± 5* 9 ± 4 15 ± 5 11 ± 4 12 ± 4 PLR non‑responders (n = 24) 10 ± 6 14 ± 6* 10 ± 6 13 ± 7 10 ± 6 – Cardiac index (L/min/m ) # $ PLR responders (n = 27) 3.11 ± 1.21 3.62 ± 1.29* 2.98 ± 1.15 3.63 ± 1.27 2.91 ± 0.91 3.53 ± 1.16 PLR non‑responders (n = 24) 3.16 ± 1.07 3.23 ± 1.12 3.14 ± 1.10 3.23 ± 1.24 3.17 ± 1.13 – Carotid artery flow ( TAMEAN) (mL/min) PLR responders (n = 21) 371 ± 138 407 ± 144 – – 335 ± 118 390 ± 141 PLR non‑responders (n = 17) 293 ± 128 344 ± 159 – – 321 ± 130 – Carotid artery flow ( VTI) (mL/min) PLR responders (n = 21) 615 ± 194 674 ± 202 – – 601 ± 214 690 ± 221 PLR non‑responders (n = 17) 593 ± 225 617 ± 218 – – 577 ± 227 – Carotid PSV (cm/s) PLR responders (n = 22) 88 ± 23 82 ± 21 – – 81 ± 22 88 ± 22 PLR non‑responders (n = 17) 83 ± 30 77 ± 28 – – 82 ± 23 – Cardiac index to common carotid artery ( TAMEAN) (%) PLR responders (n = 21) 13 ± 5 12 ± 4 – – 12 ± 3 13 ± 5 PLR non‑responders (n = 17) 9 ± 2 10 ± 3 – – 10 ± 3 – Femoral artery flow ( VTI) (mL/min) PLR responders (n = 3) – – 408 ± 331 404 ± 319 433 ± 400 733 ± 800 PLR non‑responders (n = 11) – – 368 ± 126 386 ± 127 382 ± 78 – PSV femoral (cm/s) # $ PLR responders (n = 17) – – 84 ± 28 111 ± 45 77 ± 28 86 ± 31 PLR non‑responders (n = 18) – – 78 ± 17 89 ± 17 78 ± 20 – Data are presented as mean ± standard deviation. PLR responders: cases with increase in pulse contour analysis-derived cardiac index ≥ 10% during passive leg raising, PLR non-responders: cases with increase in pulse contour analysis-derived cardiac index < 10% during passive leg raising TAMEAN time average mean velocity, PSV peak systolic velocity # $ * p < 0.05 versus Baseline 1; p < 0.05 versus Baseline 2; p < 0.05 versus Baseline 3 Relationship between cardiac index and femoral Doppler Considering all changes observed during the second measurements in absolute values and relative changes PLR test and during fluid infusion (n = 17, Fig. 2), the Considering all measurements at different study steps correlation coefficient between changes in femoral blood (n = 45, Fig. 2), a weak correlation was found between flow and changes in cardiac index was r = 0.28 (p = 0.27). absolute values of femoral blood flow and cardiac index The ability of changes in carotid blood flow calculated (r = 0.21, p = 0.17). Still considering all measurements from VTI and TAMEAN to detect changes in cardiac performed at the femoral level at different study steps index are illustrated by 4-box tables in Additional file 1: (n = 118, Fig. 2), a weak correlation was found between Table S2. Results were not different when the analysis absolute values of PSV and cardiac index (r = 0.32, was performed with only the first case measured in each p < 0.01) (Additional file 1: Figure S3). of the patients who had been included several times in the study (data not shown). Girotto et al. Ann. Intensive Care (2018) 8:67 Page 7 of 9 error . In our study, absolute values of carotid blood Discussion flow measured by TAMEAN were in accordance with The main finding of our study is that carotid and femo - values shown in literature , but they were almost sys- ral blood flow and their peak velocities did not allow the tematically half of the values obtained from VTI. Even in detection of a positive PLR test and that their changes patients that had not been excluded from the study, the were not correlated with the simultaneous changes in echogenicity and the quality of the Doppler signal pre- cardiac index. vented to obtain precise measurements in many cases, The previous results regarding the ability of Doppler especially at the femoral level. This likely led to errors measurements of peripheral arteries to estimate cardiac in the measurement of the vessel diameter and hence to output and its changes are very controversial. Marik et al. even larger miscalculations of blood flow values, as the  have demonstrated an excellent ability of changes in squared value of arterial diameter is taken into account carotid blood flow to detect the PLR effects. Neverthe - for measuring them. The measurement of femoral blood less, the authors used bioreactance as the reference for flow was impeded by the fact that, at this level, the ana - measuring cardiac output, while the accuracy of this tomical landmarks tended to change with PLR. This likely technique has been seriously questioned [17, 18]. In a explained the large intra- and inter-variability, indicat- study by Préau et al. , the variation in femoral artery ing that these techniques are not suitable for the precise peak systolic velocity during PLR could reliably predict measurement of changes of small amplitude. Finally, fluid responsiveness in critically ill patients. Neverthe - access to the femoral site was difficult in obese patients, less, in this study, the carotid blood flow was not inves - such that two of such patients were excluded. Eventually, tigated and, on the femoral site, only the peak systolic we obtained a limited number of Doppler measurements velocity was investigated . Moreover, in this study, for femoral artery. This fact may be enough to conclude the diagnostic threshold that they measured for PLR- that the method is not adapted to current practice in the induced increases in femoral peak velocity was 8%, while ICU setting. the inter-observer variability of this variable was as large as 8.4 ± 9.2%. Limitations In contrast with these results, other studies in cardiac First of all, we obtained only a limited number of meas- surgery patients [11, 12] and healthy volunteers [13, 14] urements of Doppler variables, what has reduced the showed that the correlation between changes in cardiac power of our analysis. Nevertheless, given the poor output and in common carotid blood flow either was results we observed, it is unlikely that including more weak or had wide limits of agreement. Our results cor- patients would have led to better results. Regarding roborate these negative studies. Rohering et al.  found femoral measurements, the fact that it was impossible a strong correlation between absolute values and changes to acquire them in a so large proportion of patients itself of carotid blood flow and cardiac index. However, limits indicates that the technique is not appropriate. Second, of agreement in the Bland–Altman analysis (± 20%) were some patients have been included several times in the so wide that they concluded that carotid Doppler should study. Nevertheless, the analysis performed with only not replace direct cardiac output monitoring, especially the first measurement performed in these patients did for performing the PLR test . In the study by Peatchy not show different results from the main analysis. Third, et al. , changes in carotid diameter were not meas- Doppler measurements were performed on one side only, ured during PLR. We measured this diameter in our while the opposite one may have provided better results. study, but this did not improve the reliability of the esti- Fourth, although we took the precaution to exclude it, it mation of cardiac index by carotid blood flow. is still possible that a mild degree of arterial stenosis may Several reasons may explain these findings. First, have influenced the relationship between cardiac output regarding the carotid Doppler signal, from a physiologi- and arterial flow. Fifth, Doppler examinations were per - cal point of view, the proportion of cardiac output that formed at the bedside in the ICU, while measurements is directed toward the carotid artery may vary depend- performed in an echographic laboratory could provide ing on cerebral blood flow regulation, impairing the cor - more reliable measurements. Nevertheless, our method- relation between carotid blood flow and cardiac output ology reflects the real-life practice. Finally, fluid infusion and controversial results have been reported regarding was not performed in non-responders, so that we could this point [19–24]. Second, another explanation may be not assess the specificity and sensitivity of PLR-induced the lack of reliability of the carotid and femoral Doppler changes in arterial blood flows or velocity to assess fluid measurements themselves. In the literature, we could responsiveness. Nevertheless, given the poor reliability not find a gold standard to calculate femoral and carotid of Doppler measurements obtained in PLR responders, blood flows. Many different methods exist , and they provide discordant results  with numerous sources of Girotto et al. Ann. Intensive Care (2018) 8:67 Page 8 of 9 Ethics approval and consent to participate it is very likely that they did not perform better in PLR We obtained the agreement of our institutional review board (Comité pour la non-responders. protection des personnes Ile‑de‑France VII ref # 2016‑A00959‑42). All patients or their relatives accepted to participate in the study. Conclusions Funding Carotid and femoral blood flows and peak systolic veloci - No funding. ties were not reliable to assess the effects of a PLR test. These methods were not reliable to estimate cardiac out - Publisher’s Note put and its variations in intensive care patients. Many Springer Nature remains neutral with regard to jurisdictional claims in pub‑ lished maps and institutional affiliations. technical and physiological reasons may explain this lack of reliability. Received: 19 October 2017 Accepted: 15 May 2018 Additional file Additional file 1: Table S1. Ability of different Doppler variable to detect a positive passive leg raising test. Table S2. Diagnostic ability of changes References in carotid and femoral blood flows to detect changes in cardiacindex 1. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two ≥ 10% and ≥ 15%. Figure S1. Study design. Figure S2. Correlation fluid‑management strategies in acute lung injury. N Engl J Med. between absolute values of carotid blood flow (measured by TAMEAN) 2006;354:2564–75. and of cardiac index, n = 135 (n = 38 before PLR, 38 during passive leg 2. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: raising (PLR), 38 after PLR and 21 after volume expansion = 135 in total). results of the SOAP study. Crit Care Med. 2006;34:344–53. Figure S3. Correlation between absolute values of femoral blood flow 3. Monnet X, Marik PE, Teboul JL. Prediction of fluid responsiveness: an and of cardiac index, n = 45 ( n = 14 before PLR, 14 during passive leg update. 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Passive leg raising is predictive of and approved the final manuscript. fluid responsiveness in spontaneously breathing patients with severe sepsis or acute pancreatitis. Crit Care Med. 2010;38:819–25. Author details 11. Weber U, Glassford NJ, Eastwood GM, et al. A pilot assessment of carotid Service de Réanimation Médicale, Hôpital de Bicêtre, Hôpitaux Universitaires and brachial artery blood flow estimation using ultrasound Doppler in Paris‑Sud, Insert UMR_999, Université Paris‑Sud, Assistance Publique – Hôpi‑ cardiac surgery patients. J Cardiothorac Vasc Anesth. 2016;30:141–8. taux de Paris, Le Kremlin‑Bicêtre, France. Service de Radiologie, Hôpital de 12. Roehrig C, Govier M, Robinson J, et al. A carotid Doppler flowmetry Bicêtre, Hôpitaux Universitaires Paris‑Sud, Assistance Publique – Hôpitaux de correlates poorly with thermodilution cardiac output following cardiac Paris, Le Kremlin‑Bicêtre, France. surgery. Acta Anaesthesiol Scand. 2017;61:31–8. 13. 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