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BACKGROUND: Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. METHODS: Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80-85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). RESULTS: CRT decreased significantly with both tests (from 5 [3.5-7.6] to 4 [2.4-5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3-5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. CONCLUSIONS: Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.

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INTRODUCTION: Prediction of fluid responsiveness in acutely ill patients might be influenced by a number of clinical and technical factors. We aim to identify variables potentially modifying the operative performance of fluid responsiveness predictors commonly used in clinical practice. METHODS: A sensitive strategy was conducted in the Medline and Embase databases to search for prospective studies assessing the operative performance of pulse pressure variation, stroke volume variation, passive leg raising (PLR), end-expiratory occlusion test (EEOT), mini-fluid challenge, and tidal volume challenge to predict fluid responsiveness in critically ill and acutely ill surgical patients published between January 1999 and February 2023. Adjusted diagnostic odds ratios (DORs) were calculated by subgroup analyses (inverse variance method) and meta-regression (test of moderators). Variables potentially modifying the operative performance of such predictor tests were classified as technical and clinical. RESULTS: A total of 149 studies were included in the analysis. The volume used during fluid loading, the method used to assess variations in macrovascular flow (cardiac output, stroke volume, aortic blood flow, volume‒time integral, etc.) in response to PLR/EEOT, and the apneic time selected during the EEOT were identified as technical variables modifying the operative performance of such fluid responsiveness predictor tests (p < 0.05 for all adjusted vs. unadjusted DORs). In addition, the operative performance of fluid responsiveness predictors was also influenced by clinical variables such as the positive end-expiratory pressure (in the case of EEOT) and the dose of norepinephrine used during the fluid responsiveness assessment for PLR and EEOT (for all adjusted vs. unadjusted DORs). CONCLUSION: Prediction of fluid responsiveness in critically and acutely ill patients is strongly influenced by a number of technical and clinical aspects. Such factors should be considered for individual intervention decisions.

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Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).

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Resuscitative fluid therapy aims to increase stroke volume (SV) and cardiac output (CO) and restore/improve tissue oxygen delivery in patients with circulatory failure. In individualized goal-directed fluid therapy (GDFT), fluids are titrated based on the assessment of responsiveness status (i.e., the ability of an individual to increase SV and CO in response to volume expansion). Fluid administration may increase venous return, SV and CO, but these effects may not be predictable in the clinical setting. The fluid challenge (FC) approach, which consists on the intravenous administration of small aliquots of fluids, over a relatively short period of time, to test if a patient has a preload reserve (i.e., the relative position on the Frank-Starling curve), has been used to guide fluid administration in critically ill humans. In responders to volume expansion (defined as individuals where SV or CO increases ≥10-15% from pre FC values), FC administration is repeated until the individual no longer presents a preload reserve (i.e., until increases in SV or CO are <10-15% from values preceding each FC) or until other signs of shock are resolved (e.g., hypotension). Even with the most recent technological developments, reliable and practical measurement of the response variable (SV or CO changes induced by a FC) has posed a challenge in GDFT. Among the methods used to evaluate fluid responsiveness in the human medical field, measurement of aortic flow velocity time integral by point-of-care echocardiography has been implemented as a surrogate of SV changes induced by a FC and seems a promising non-invasive tool to guide FC administration in animals with signs of circulatory failure. This narrative review discusses the development of GDFT based on the FC approach and the response variables used to assess fluid responsiveness status in humans and animals, aiming to open new perspectives on the application of this concept to the veterinary field.

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INTRODUCTION: Dynamic predictors of fluid responsiveness have shown good performance in mechanically ventilated patients at tidal volumes (Vt) > 8 mL kg-1. Nevertheless, most critically ill conditions demand lower Vt. We sought to evaluate the operative performance of several predictors of fluid responsiveness at Vt ≤ 8 mL kg-1 by using meta-regression and subgroup analyses. METHODS: A sensitive search was conducted in the Embase and MEDLINE databases. We searched for studies prospectively assessing the operative performance of pulse pressure variation (PPV), stroke volume variation (SVV), end-expiratory occlusion test (EEOT), passive leg raising (PLR), inferior vena cava respiratory variability (Δ-IVC), mini-fluid challenge (m-FC), and tidal volume challenge (VtC), to predict fluid responsiveness in adult patients mechanically ventilated at Vt ≤ 8 ml kg-1, without respiratory effort and arrhythmias, published between 1999 and 2020. Operative performance was assessed using hierarchical and bivariate analyses, while subgroup analysis was used to evaluate variations in their operative performance and sources of heterogeneity. A sensitivity analysis based on the methodological quality of the studies included (QUADAS-2) was also performed. RESULTS: A total of 33 studies involving 1,352 patients were included for analysis. Areas under the curve (AUC) values for predictors of fluid responsiveness were: for PPV = 0.82, Δ-IVC = 0.86, SVV = 0.90, m-FC = 0.84, PLR = 0.84, EEOT = 0.92, and VtC = 0.92. According to subgroup analyses, variations in methods to measure cardiac output and in turn, to classify patients as responders or non-responders significantly influence the performance of PPV and SVV (p < 0.05). Operative performance of PPV was also significantly affected by the compliance of the respiratory system (p = 0.05), while type of patient (p < 0.01) and thresholds used to determine responsiveness significantly affected the predictability of SVV (p = 0.05). Similarly, volume of fluids infused to determine variation in cardiac output, significantly affected the performance of SVV (p = 0.01) and PLR (p < 0.01). Sensitivity analysis showed no variations in operative performance of PPV (p = 0.39), SVV (p = 0.23) and EEOT (p = 0.15). CONCLUSION: Most predictors of fluid responsiveness reliably predict the response of cardiac output to volume expansion in adult patients mechanically ventilated at tidal volumes ≤ 8 ml kg-1. Nevertheless, technical and clinical variables might clearly influence on their operative performance.

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BACKGROUND: Arterial blood pressure is the most common variable used to assess the response to a fluid challenge in routine clinical practice. The aim of this study was to evaluate the accuracy of the change in the radial artery pulse pressure (rPP) to detect the change in cardiac output after a fluid challenge in patients with septic shock. METHODS: Prospective observational study including 35 patients with septic shock in which rPP and cardiac output were measured before and after a fluid challenge with 400 mL of crystalloid solution. Cardiac output was measured with intermittent thermodilution technique using a pulmonary artery catheter. Patients were divided between responders (increase >15% of cardiac output after fluid challenge) and nonresponders. The area under the receiver operating characteristic curve (AUROC), Pearson correlation coefficient and paired Student t test were used in statistical analysis. RESULTS: Forty-three percent of the patients were fluid responders. The change in rPP could not neither discriminate between responders and nonresponders (AUROC = 0.52; [95% confidence interval: 0.31-0.72] P = .8) nor correlate (r = .21, P = .1) with the change in cardiac output after the fluid challenge. CONCLUSIONS: The change in rPP neither discriminated between fluid responders and nonresponders nor correlated with the change in cardiac output after a fluid challenge. The change in rPP cannot serve as a surrogate of the change in cardiac output to assess the response to a fluid challenge in patients with septic shock.

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This study investigated the effects of tidal volume (TV) on the diagnostic value of pulse pressure variation (PPV) and the inferior vena cava dispensability index (IVC-DI) for volume responsiveness during mechanical ventilation. In patients undergoing elective surgery with mechanical ventilation, different TVs of 6, 9, and 12 mL/kg were given for two min. The left ventricular outflow tract velocity-time integral (VTI) was measured by transthoracic echocardiography. The IVC-DI was measured at sub-xyphoid transabdominal long axis. The PPV was measured via the radial artery and served as baseline. Index measurements were repeated after fluid challenge. VTI increased by more than 15% after fluid challenge, which was considered as volume responsive. Seventy-nine patients were enrolled, 38 of whom were considered positive volume responsive. Baseline data between the response group and the non-response group were similar. Receiver operating characteristic curve confirmed PPV accuracy in diagnosing an increase in volume responsiveness with increased TV. When TV was 12 mL/kg, the PPV area under the curve (AUC) was 0.93 and the threshold value was 15.5%. IVC-DI had the highest diagnostic accuracy at a TV of 9 mL/kg and an AUC of 0.79, with a threshold value of 15.3%. When TV increased to 12 mL/kg, the IVC-DI value decreased. When the TV was 9 and 12 mL/kg, PPV showed improved performance in diagnosing volume responsiveness than did IVC-DI. PPV diagnostic accuracy in mechanically ventilated patients was higher than IVC-DI. PPV accuracy in predicting volume responsiveness was increased by increasing TV.

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OBJECTIVES: To assess correlations among variations in hemodynamic parameters during fluid volume loading. MATERIAL AND METHODS: Prospective observational study in 2 intensive care units. Sixty patients requiring intravenous fluids underwent challenge tests with 300 mL of crystalloids over a 48-hour period. Percent change in hemodynamic parameters after infusion was measured. We used hierarchical cluster and principal component analyses to explore correlations among changes in hemodynamic responses. RESULTS: The parameters that underwent the greatest median (interquartile range) percent changes were central venous pressure (24% [0.0%-41.7%]), pulse pressure (12.9% [0.0%-22.4%]), shock index (5.8% [2.7%-13.7%]), rate-pressure product (5.8% [3.8%-18.8%]), and systemic pressure difference (5.8% [-3.8%-18.8%]). There were strong correlations between percent changes in the following parameters: systolic blood pressure, pulse pressure, rate-pressure product, shock index, and systemic pressure difference. Central venous pressure was not correlated with any of the other hemodynamic parameters. CONCLUSION: The relationships between changes in hemodynamic parameters after fluid loading are complex and must be taken into account if fluids are infused during resuscitation.

OBJETIVO: Determinar la relación entre los parámetros hemodinámicos durante la expansión del volumen. METODO: Estudio observacional y prospectivo en dos unidades de cuidados intensivos. En las primeras 48 horas se realizó una prueba de volumen con 300 ml de cristaloides en 60 pacientes con indicación de fluidos endovenosos. Se evaluaron los cambios en los parámetros hemodinámicos después de la infusión de volumen, y las relaciones entre las variaciones se exploraron con los análisis de clústeres jerárquicos y de componentes principales. RESULTADOS: Los mayores porcentajes de variación se observaron en la presión venosa central [mediana 24% (rango intercuartil (RIC) 0,0-41,7%)], presión del pulso [mediana 12,9% (RIC 0,0-22,4%)], índice de shock [mediana 5,8% (RIC 2,7-13,7%)], producto presión del pulso-frecuencia cardiaca [mediana 5,8% (RIC ­3,8-18,8%)] y diferencia de presiones sistémicas [mediana 5,8% (RIC ­3,8-18,8%)]. Hubo una fuerte correlación entre las variaciones de la presión arterial sistólica, presión del pulso, producto presión del pulso-frecuencia cardiaca, índice de shock y diferencia de presiones sistémicas. La presión venosa central no se correlacionó con ningún parámetro hemodinámico. CONCLUSIONES: Las relaciones entre las variaciones que se producen en los parámetros hemodinámicas después del aporte de volumen son complejas, lo que se debe tener en cuenta durante la reanimación con volumen.

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BACKGROUND: This study was performed to compare intestinal and sublingual microcirculation and their response to a fluid challenge. METHODS: Twenty-two septic patients in the first postoperative day of an intestinal surgery, in which an ostomy had been constructed, were evaluated both before and 20 min after a challenge of 10 mL/kg of 6% hydroxyethylstarch 130/0.4. We measured systemic hemodynamics and sublingual and intestinal microcirculation. Correlations between variables were determined through the Pearson test. RESULTS: Fluid administration increased the cardiac index (2.6 ± 0.5 vs. 3.3 ± 1.0 L/min/m(2), P < 0.01) and mean arterial blood pressure (68 ± 11 vs. 82 ± 12 mm Hg, P < 0.0001). The sublingual but not the intestinal red blood cell (RBC) velocity increased (912 ± 270 vs. 1,064 ± 200 µm/s, P < 0.002 and 679 ± 379 vs. 747 ± 419 µm/s, P = 0.12, respectively). The sublingual and intestinal perfused vascular density (PVD) did not change significantly (15.2 ± 2.9 vs. 16.1 ± 1.2 mm/mm(2) and 12.3 ± 6.7 vs. 13.0 ± 6.7 mm/mm(2)). We found no correlation between the basal sublingual and intestinal RBC velocities or between their changes in response to the fluid challenge. The individual changes in sublingual RBC velocity correlated with those in cardiac index and basal RBC velocity. Individual changes in intestinal RBC velocity did not correlate with either the cardiac index modifications or the basal RBC velocity. The same pattern was observed with the sublingual and the intestinal PVDs. The sublingual RBC velocities and PVDs were similar between survivors and nonsurvivors. But the intestinal RBC velocities and PVDs were lower in nonsurvivors. CONCLUSIONS: In this series of postoperative septic patients, we found a dissociation between sublingual and intestinal microcirculation. The improvement in the sublingual microcirculation after fluid challenge was dependent on the basal state and the increase in cardiac output. In contrast, the intestinal microcirculation behaved as an isolated territory.

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Si bien los principios básicos para el diagnóstico y la monitorización hemodinámica como los pilares terapéuticos del niño con choque séptico se mantienen en el tiempo, es innegable que en las últimas décadas se han incorporado nuevos y trascendentes conceptos, por lo que es importante que el médico tratante de las unidades de cuidados intensivos tenga conocimiento de ellos a cabalidad. La monitorización hemodinámica es una herramienta que no solamente permite detectar el origen de la inestabilidad hemodinámica sino también guiar el tratamiento y evaluar su efectividad. La resucitación con fluidos debe ser el primer paso en la reanimación del paciente hemodinámicamente inestable. Sin embargo, la determinación clínica del volumen intravascular puede ser, en ocasiones, difícil de establecer en el paciente crítico. Las presiones de llenado cardiaco no son capaces de predecir la respuesta a fluidos. Los indicadores dinámicos de respuesta a fluidos evalúan el cambio en el volumen eyectivo durante la ventilación mecánica; de este modo, se valora la curva de Frank-Starling del paciente. Mediante la prueba de fluido es posible evaluar el grado de la reserva de precarga que se puede utilizar para aumentar el volumen eyectivo. En esta revisión se actualiza la información disponible sobre la monitorización hemodinámica básica y funcional.

In recent decades, new and important concepts have emerged for the diagnosis and management of the pediatric patient with septic shock, although the basic principles have remained similar over time. Attending physicians in the pediatric intensive care unit (PICU) must be fully aware of these concepts in order to improve patient care in the critical care unit. Hemodynamic monitoring is a tool that not only allows detection of the source of hemodynamic instability but also guides treatment and assesses its effectiveness. Fluid loading is considered the first step in the resuscitation of hemodynamically unstable patients. Nevertheless, clinical determination of the intravascular volume can be extremely difficult in a critically ill patient. Studies performed have demonstrated that cardiac filling pressures are unable to predict fluid responsiveness. Dynamic tests of volume responsiveness use the change in stroke volume during mechanical ventilation assessing the patients' Frank-Starling curve. Through fluid challenge the clinician can assess whether the patient has a preload reserve that can be used to increase the stroke volume. In this review we updated the available information on basic and functional hemodynamic monitoring.