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Fluid challenge is a common diagnostic method to help the physician detennine fluid responsiveness, which is an important component of fluid management in critically ill patients）H Raising legs of a patient induces the transfer of a variable amount of blood （approximately 200-300 ml） contained in the venous reservoir from the limb to central venous compartment. According to Franck-Starling curve, this transient increase of preload might lead to an increase in cardiac output （CO） in thture responders resulting from their preload-reserve status. Many clinical studies have validated passive leg raising （PLR）, and the advantage of PLR is attractive in Intensive Care Unit （ICU）. Recently, PER has been suggested as a simple and potential method to predict fluid responsiveness, which is similar to an ＂auto-fluid challenge＂ without a drop of fluid. However, one study revealed poor application of PLR in the real world, We acknowledged that the lack of education on PLR would result in the current practice. On the other hand, the application of PLR might be not simple in clinical practice, and the holy grail of fluid responsiveness still needs to be discovered. The standard of PLR has not been established, and some questions of PLR merit discussion.

(1) Background: Right ventricular (RV) strain parameters derived from the analysis of the tricuspid annular displacement (TAD) are emergent two-dimensional speckle tracking echocardiography (2D-STE) parameter used for the quantitative assessment of RV systolic function. Few data are available regarding 2D-STE parameters and their dependency on RV preload. Our aim was to evaluate the effect of an acute change in RV preload on 2D-STE parameters in healthy volunteers. (2) Methods: Acute modification of RV preload was performed by a fluid challenge (FC): an infusion of 500 mL of 0.9% sodium chloride was given over 5 min in supine position. Preload dependency (responder group) was confirmed by a stroke volume increase of at least 10% measured by echocardiography. (3) Results: Among 32 healthy volunteers, 19 (59%) subjects were classified as non-responders and 13 (41%) as responders. In the responder group, the tricuspid annular plane systolic excursion (TAPSE) significantly increased (20 (20–23.5) mm to 24 (20.5–26.5) mm; p = 0.018), while RV strain parameters significantly decreased after FC: −23.5 ((−22.3)–(−27.3))% to −25 ((−24)–(29.6))%; p = 0.03) for RV free wall longitudinal strain and −22.8 ((−20.4)–(−30.7))% to −23.7 ((−21.2)–(−27))%; p = 0.02) for RV four-chamber longitudinal strain. 2D-STE parameters derived from the TAD analysis were not influenced by the FC (all p > 0.05). (4) Conclusions: In young, healthy volunteers, RV strain parameters and TAPSE are preload dependent, while TAD parameters were not. The loading conditions must be accounted for when evaluating RV systolic function by 2D-STE parameters.

Background： Evaluating the hemodynamic status and predicting fluid responsiveness are important in critical ultrasound assessment of shock patients. Transthoracic echocardiography with noninvasive diagnostic parameters allows the assessment of volume responsiveness. This study aimed to assess tile hemodynamic changes in the liver and systemic hemodynamic changes during fluid challenge and during passive leg raising （PLR） by measuring hepatic venous flow （HVF） velocity. Methods： This is an open-label study in a tertiary teaching hospital. Shock patients with hypoperfusion who required fluid challenge were selected for the study. Patients 〈l 8 years old and those with contraindications to PLR were excluded from the study. Baseline values were measured, PLR tests were performed, and 500 ml of saline was infused over 30 rain. Parameters associated with cardiac output （CO） in the left ventricular outflow tract were measured using the Doppler method. In addition, HVF velocity and right ventricular function parameters were determined. Results： Middle hepatic venous （MHV） S-wave velocity was positively correlated in all patients with CO at baseline （r= 0.706, P〈 0.01 ） and after volume expansion （r= 0.524, P = 0.003）. CO was also significantly correlated with MHV S-wave velocity in responders （r = 0.608, P 〈 0.01）. During PLR, however, hepatic venous S-wave velocity did not correlate with CO. For the parameter AMHV D （increase in change in MHV D-wave velocity after volume expansion）, defined as （MHV D - MHV Dtaseline）/MHV DBaseli.,e x 100%, 〉21% indicated no fluid responsiveness, with a sensitivity of 100%, a specificity of 71.2%, and an area under the receiver operating characteristic curve of 0.918. Conclusions： During fluid expansion, hepatic venous S-wave velocity can be used to monitor CO, whether or not it is increasing. AMHV D 〉21% indicated a lack of fluid responsiveness, thus helping to decide when to stop infusions.

Introduction Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000–2010 and 2011–2021. Methods We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold. Results We included 124 studies, 32 (25.8%) published in 2000–2010 and 92 (74.2%) in 2011–2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011–2021 compared to the 2000–2010 period. Conclusions In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000–2010 decade, in 2011–2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.

Although the administration of fluid is the first treatment considered in almost all cases of circulatory failure, this therapeutic option poses two essential problems: the increase in cardiac output induced by a bolus of fluid is inconstant, and the deleterious effects of fluid overload are now clearly demonstrated. This is why many tests and indices have been developed to detect preload dependence and predict fluid responsiveness. In this review, we take stock of the data published in the field over the past three years. Regarding the passive leg raising test, we detail the different stroke volume surrogates that have recently been described to measure its effects using minimally invasive and easily accessible methods. We review the limits of the test, especially in patients with intra-abdominal hypertension. Regarding the end-expiratory occlusion test, we also present recent investigations that have sought to measure its effects without an invasive measurement of cardiac output. Although the limits of interpretation of the respiratory variation of pulse pressure and of the diameter of the vena cava during mechanical ventilation are now well known, several recent studies have shown how changes in pulse pressure variation itself during other tests reflect simultaneous changes in cardiac output, allowing these tests to be carried out without its direct measurement. This is particularly the case during the tidal volume challenge, a relatively recent test whose reliability is increasingly well established. The mini-fluid challenge has the advantage of being easy to perform, but it requires direct measurement of cardiac output, like the classic fluid challenge. Initially described with echocardiography, recent studies have investigated other means of judging its effects. We highlight the problem of their precision, which is necessary to evidence small changes in cardiac output. Finally, we point out other tests that have appeared more recently, such as the Trendelenburg manoeuvre, a potentially interesting alternative for patients in the prone position.

Background The fluid challenge is considered the gold standard for diagnosis of fluid responsiveness. The objective of this study was to describe the fluid challenge techniques reported in fluid responsiveness studies and to assess the difference in the proportion of ‘responders,’ (PR) depending on the type of fluid, volume, duration of infusion and timing of assessment. Methods Searches of MEDLINE and Embase were performed for studies using the fluid challenge as a test of cardiac preload with a description of the technique, a reported definition of fluid responsiveness and PR. The primary outcome was the mean PR, depending on volume of fluid, type of fluids, rate of infusion and time of assessment. Results A total of 85 studies (3601 patients) were included in the analysis. The PR were 54.4% (95% CI 46.9–62.7) where <500 ml was administered, 57.2% (95% CI 52.9–61.0) where 500 ml was administered and 60.5% (95% CI 35.9–79.2) where >500 ml was administered ( p  = 0.71). The PR was not affected by type of fluid. The PR was similar among patients administered a fluid challenge for <15 minutes (59.2%, 95% CI 54.2–64.1) and for 15–30 minutes (57.7%, 95% CI 52.4–62.4, p  = 1). Where the infusion time was ≥30 minutes, there was a lower PR of 49.9% (95% CI 45.6–54, p  = 0.04). Response was assessed at the end of fluid challenge, between 1 and 10 minutes, and >10 minutes after the fluid challenge. The proportions of responders were 53.9%, 57.7% and 52.3%, respectively ( p  = 0.47). Conclusions The PR decreases with a long infusion time. A standard technique for fluid challenge is desirable.

During septic shock, fluid therapy is aimed at increasing cardiac output and improving tissue oxygenation, but it poses two problems: it has inconsistent and transient efficacy, and it has many well-documented deleterious effects. We suggest that there is a place for its personalization according to the patient characteristics and the clinical situation, at all stages of circulatory failure. Regarding the choice of fluid for volume expansion, isotonic saline induces hyperchloremic acidosis, but only for very large volumes administered. We suggest that balanced solutions should be reserved for patients who have already received large volumes and in whom the chloremia is rising. The initial volume expansion, intended to compensate for the constant hypovolaemia in the initial phase of septic shock, cannot be adapted to the patient’s weight only, as suggested by the Surviving Sepsis Campaign, but should also consider potential absolute hypovolemia induced by fluid losses. After the initial fluid infusion, preload responsiveness may rapidly disappear, and it should be assessed. The choice between tests used for this purpose depends on the presence or absence of mechanical ventilation, the monitoring in place and the risk of fluid accumulation. In non-intubated patients, the passive leg raising test and the mini-fluid challenge are suitable. In patients without cardiac output monitoring, tests like the tidal volume challenge, the passive leg raising test and the mini-fluid challenge can be used as they can be performed by measuring changes in pulse pressure variation, assessed through an arterial line. The mini-fluid challenge should not be repeated in patients who already received large volumes of fluids. The variables to assess fluid accumulation depend on the clinical condition. In acute respiratory distress syndrome, pulmonary arterial occlusion pressure, extravascular lung water and pulmonary vascular permeability index assess the risk of worsening alveolar oedema better than arterial oxygenation. In case of abdominal problems, the intra-abdominal pressure should be taken into account. Finally, fluid depletion in the de-escalation phase is considered in patients with significant fluid accumulation. Fluid removal can be guided by preload responsiveness testing, since haemodynamic deterioration is likely to occur in patients with a preload dependent state.

Background In critically ill patients, changes in the velocity-time integral (VTI) of the left ventricular outflow tract, measured by transthoracic echocardiography (TTE), are often used to non-invasively assess the response to fluid administration or for performing tests assessing fluid responsiveness. However, the precision of TTE measurements has not yet been investigated in such patients. First, we aimed at assessing how many measurements should be averaged within one TTE examination to reach a sufficient precision for various variables. Second, we aimed at identifying the least significant change (LSC) of these variables between successive TTE examinations. Methods We prospectively included 100 haemodynamically stable patients in whom TTE examination was planned. Three TTE examinations were performed, the first and the third by one operator and the second by another one. We calculated the precision and LSC (1) within one examination depending on the number of averaged measurements and (2) between measurements performed in two successive examinations. Results In patients in sinus rhythm, averaging three measurements within an examination was enough for obtaining an acceptable precision (interquartile range highest value < 10%) for VTI. In patients with atrial fibrillation, averaging five measurements was necessary. The precision of some other common TTE variables depending on the number of measurements is provided. Between two successive examinations performed by the same operator, the LSC was 11 [5–18]% for VTI. If two operators performed the examinations, the LSC for VTI significantly increased to 14 [8–26]%. The LSC between two examinations for other TTE variables is also provided. Conclusions Averaging three measurements within one TTE examination is enough for obtaining precise measurements for VTI in patients in sinus rhythm but not in patients with atrial fibrillation. Between two TTE examinations performed by the same operator, the LSC of VTI is compatible with the assessment of the effects of a 500-mL fluid infusion but is not precise enough for assessing the effects of some tests predicting preload responsiveness.

Background Bedside functional hemodynamic assessment has gained in popularity in the last years to overcome the limitations of static or dynamic indexes in predicting fluid responsiveness. The aim of this systematic review and metanalysis of studies is to investigate the reliability of the functional hemodynamic tests (FHTs) used to assess fluid responsiveness in adult patients in the intensive care unit (ICU) and operating room (OR). Methods MEDLINE, EMBASE, and Cochrane databases were screened for relevant articles using a FHT, with the exception of the passive leg raising. The QUADAS-2 scale was used to assess the risk of bias of the included studies. In-between study heterogeneity was assessed through the I 2 indicator. Bias assessment graphs were plotted, and Egger’s regression analysis was used to evaluate the publication bias. The metanalysis determined the pooled area under the receiving operating characteristic (ROC) curve, sensitivity, specificity, and threshold for two FHTs: the end-expiratory occlusion test (EEOT) and the mini-fluid challenge (FC). Results After text selection, 21 studies met the inclusion criteria, 7 performed in the OR, and 14 in the ICU between 2005 and 2018. The search included 805 patients and 870 FCs with a median (IQR) of 39 (25–50) patients and 41 (30–52) FCs per study. The median fluid responsiveness was 54% (45–59). Ten studies (47.6%) adopted a gray zone analysis of the ROC curve, and a median (IQR) of 20% (15–51) of the enrolled patients was included in the gray zone. The pooled area under the ROC curve for the end-expiratory occlusion test (EEOT) was 0.96 (95%CI 0.92–1.00). The pooled sensitivity and specificity were 0.86 (95%CI 0.74–0.94) and 0.91 (95%CI 0.85–0.95), respectively, with a best threshold of 5% (4.0–8.0%). The pooled area under the ROC curve for the mini-FC was 0.91 (95%CI 0.85–0.97). The pooled sensitivity and specificity were 0.82 (95%CI 0.76–0.88) and 0.83 (95%CI 0.77–0.89), respectively, with a best threshold of 5% (3.0–7.0%). Conclusions The EEOT and the mini-FC reliably predict fluid responsiveness in the ICU and OR. Other FHTs have been tested insofar in heterogeneous clinical settings and, despite promising results, warrant further investigations.

Background In patients ventilated with tidal volume ( V t) < 8 mL/kg, pulse pressure variation (PPV) and, likely, the variation of distensibility of the inferior vena cava diameter (IVCDV) are unable to detect preload responsiveness. In this condition, passive leg raising (PLR) could be used, but it requires a measurement of cardiac output. The tidal volume (Vt) challenge (PPV changes induced by a 1-min increase in Vt from 6 to 8 mL/kg) is another alternative, but it requires an arterial line. We tested whether, in case of Vt = 6 mL/kg, the effects of PLR could be assessed through changes in PPV (ΔPPV PLR ) or in IVCDV (ΔIVCDV PLR ) rather than changes in cardiac output, and whether the effects of the Vt challenge could be assessed by changes in IVCDV (ΔIVCDV Vt ) rather than changes in PPV (ΔPPV Vt ). Methods In 30 critically ill patients without spontaneous breathing and cardiac arrhythmias, ventilated with Vt = 6 mL/kg, we measured cardiac index (CI) (PiCCO2), IVCDV and PPV before/during a PLR test and before/during a Vt challenge. A PLR-induced increase in CI ≥ 10% defined preload responsiveness. Results At baseline, IVCDV was not different between preload responders ( n  = 15) and non-responders. Compared to non-responders, PPV and IVCDV decreased more during PLR (by − 38 ± 16% and − 26 ± 28%, respectively) and increased more during the Vt challenge (by 64 ± 42% and 91 ± 72%, respectively) in responders. ∆PPV PLR , expressed either as absolute or as percent relative changes, detected preload responsiveness (area under the receiver operating curve, AUROC: 0.98 ± 0.02 for both). ∆IVCDV PLR detected preload responsiveness only when expressed in absolute changes (AUROC: 0.76 ± 0.10), not in relative changes. ∆PPV Vt , expressed as absolute or percent relative changes, detected preload responsiveness (AUROC: 0.98 ± 0.02 and 0.94 ± 0.04, respectively). This was also the case for ∆IVCDV Vt , but the diagnostic threshold (1 point or 4%) was below the least significant change of IVCDV (9[3–18]%). Conclusions During mechanical ventilation with Vt = 6 mL/kg, the effects of PLR can be assessed by changes in PPV. If IVCDV is used, it should be expressed in percent and not absolute changes. The effects of the Vt challenge can be assessed on PPV, but not on IVCDV, since the diagnostic threshold is too small compared to the reproducibility of this variable. Trial registration : Agence Nationale de Sécurité du Médicament et des Produits de santé: ID-RCB: 2016-A00893-48.