Evaluating the efficacy of a standardized 4 mL/kg fluid bolus technique in critically ill patients with elevated PvaCO2: secondary analysis of two prospective studies.

Background: Limiting the fluid bolus (FB) volume may attenuate side effects, including hemodilution and increased filling pressures, but it may also reduce hemodynamic responsiveness. The minimum volume to create hemodynamic effects is considered to be 4 mL/kg. In critically ill patients, the hemodynamic effects of FB with this volume have not been adequately investigated and compared to higher quantities. We hypothesized that a standardized FB approach using 4 mL/kg has comparable hemodynamic and metabolic effects to the common practice of physician-determined FB in critically ill patients. Methods: We conducted post hoc analysis of two trials in non-selected critically ill patients with central venous-to-arterial CO2 tension (PvaCO2) >6 mmHg and no acute bleeding. All patients received crystalloids either at a physician-determined volume and rate or at 4 mL/kg pump-administered at 1.2 L/h. Cardiac index (CI) was calculated with transthoracic echocardiogram, and arterial and venous blood gas samples were assessed before and after FB. Endpoints were changes in CI and oxygen delivery (DO2) >15%. Results: A total of 47 patients were eligible for the study, 15 of whom received physician-determined FB and 32 of whom received standardized FB. Patients in the physician-determined FB group received 16 (12-19) mL/kg at a fluid rate of 1.5 (1.5-1.9) L/h, compared to 4.1 (3.7-4.4) mL/kg at a fluid rate of 1.2 (1.2-1.2) L/h (p < 0.01) in the standardized FB group. The difference in CI elevations between the two groups was not statistically significant (8.8% [-0.1-19.9%] vs. 8.4% [0.3-23.2%], p = 0.76). Compared to physician-determined FB, the standardized FB technique had similar probabilities of increasing CI or DO2 by >15% (odds ratios: 1.3 [95% CI: 0.37-5.18], p = 0.66 and 1.83 [95% CI: 0.49-7.85], p = 0.38). Conclusion: A standardized FB protocol (4 mL/kg at 1.2 L/h) effectively reduced the volume of fluid administered to critically ill patients without compromising hemodynamic or metabolic effects.

Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study.

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.

Capillary refill time assessment after fluid challenge in patients on venoarterial extracorporeal membrane oxygenation: A retrospective study.

BACKGROUND: Monitoring fluid therapy is challenging in patients assisted with Veno-arterial ECMO. The aim of our study was to evaluate the usefulness of capillary refill time to assess the response to fluid challenge in patients assisted with VA-ECMO. METHODS: Retrospective monocentric study in a cardiac surgery ICU. We assess fluid responsiveness after a fluid challenge in patients on VA-ECMO. We recorded capillary refill time before and after fluid challenge and the evolution of global hemodynamic parameters. RESULTS: A total of 27 patients were included. The main indications for VA-ECMO were post-cardiotomy cardiogenic shock (44%). Thirteen patients (42%) were responders and 14 non-responders (58%). In the responder group, the index CRT decreased significantly (1.7 [1.5; 2.1] vs. 1.2 [1; 1.3] s; p = 0.01), whereas it remained stable in the non-responder group (1.4 [1.1; 2.5] vs. 1.6 [0.9; 1.9] s; p = 0.22). Diagnosis performance of CRT variation to assess response after fluid challenge shows an AUC of 0.68 (p = 0.10) with a sensitivity of 79% [95% CI, 52-92] and a specificity of 69% [95% CI, 42-87], with a threshold at 23%. CONCLUSION: In patients treated with VA-ECMO index capillary refill time is a reliable tool to assesses fluid responsiveness. SPECIALTY: Critical care, Cardiac surgery, ECMO.

Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

Assessing fluid responsiveness with ultrasound in the neonatal intensive care setting: the mini-fluid challenge.

The mini-fluid challenge (MFC) can guide individualised fluid therapy and prevent fluid overload and associated morbidity in adult intensive care patients. This ultrasound test is based on the Frank-Starling principles to assess dynamic fluid responsiveness, but limited MFC data exists for newborns. This brief report describes the feasibility of the MFC in 12 preterm infants with late onset sepsis and 5 newborns with other pathophysiology. Apical views were used to determine the changes in left ventricular stroke volume before and after a 3 ml/kg fluid bolus was given over 5 min. Four out of the 17 infants were fluid responsive, defined as a post-bolus increase in stroke volume of 15% or more.  Conclusion: The MFC was feasible and followed the physiological principles of stroke volume and extravascular lung water changes and 24% were fluid responsive. The MFC could enable future studies to examine whether adding fluid responsiveness to guide fluid therapy in newborns can reduce the risk of fluid overload. What is Known: • Fluid overload is associated with morbidity and mortality. • The mini-fluid challenge (MFC) provides a personalised approach to fluid therapy. What is New: • The MFC is feasible in newborns. • The MFC followed the physiological principles of stroke volume and extravascular lung water changes.

Passive leg raising test induced changes in plethysmographic variability index to assess fluid responsiveness in critically ill mechanically ventilated patients with acute circulatory failure.

BACKGROUND: Passive leg raising (PLR) reliably predicts fluid responsiveness but requires a real-time cardiac index (CI) measurement or the presence of an invasive arterial line to achieve this effect. The plethysmographic variability index (PVI), an automatic measurement of the respiratory variation of the perfusion index, is non-invasive and continuously displayed on the pulse oximeter device. We tested whether PLR-induced changes in PVI (ΔPVIPLR) could accurately predict fluid responsiveness in mechanically ventilated patients with acute circulatory failure. METHODS: This was a secondary analysis of an observational prospective study. We included 29 mechanically ventilated patients with acute circulatory failure in this study. We measured PVI (Radical-7 device; Masimo Corp., Irvine, CA) and CI (Echocardiography) before and during a PLR test and before and after volume expansion of 500 mL of crystalloid solution. A volume expansion-induced increase in CI of >15% defined fluid responsiveness. To investigate whether ΔPVIPLR can predict fluid responsiveness, we determined areas under the receiver operating characteristic curves (AUROCs) and gray zones for ΔPVIPLR. RESULTS: Of the 29 patients, 27 (93.1%) received norepinephrine. The median tidal volume was 7.0 [IQR: 6.6-7.6] mL/kg ideal body weight. Nineteen patients (65.5%) were classified as fluid responders (increase in CI > 15% after volume expansion). Relative ΔPVIPLR accurately predicted fluid responsiveness with an AUROC of 0.89 (95%CI: 0.72-0.98, p < 0.001). A decrease in PVI ≤ -24.1% induced by PLR detected fluid responsiveness with a sensitivity of 95% (95%CI: 74-100%) and a specificity of 80% (95%CI: 44-97%). Gray zone was acceptable, including 13.8% of patients. The correlations between the relative ΔPVIPLR and changes in CI induced by PLR and by volume expansion were significant (r = -0.58, p < 0.001, and r = -0.65, p < 0.001; respectively). CONCLUSIONS: In sedated and mechanically ventilated ICU patients with acute circulatory failure, PLR-induced changes in PVI accurately predict fluid responsiveness with an acceptable gray zone. TRIAL REGISTRATION: ClinicalTrials.govNCT03225378.

Variables influencing the prediction of fluid responsiveness: a systematic review and meta-analysis.

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.

End-tidal carbon dioxide's change to fluid challenge versus internal jugular vein dispensability index for predicting fluid responsiveness in septic patients: A prospective, observational study.

Background and Aims: The prediction of fluid responsiveness is crucial for the fluid management of septic shock patients. This prospective, observational study was conducted to compare end-tidal carbon dioxide (ETCO2) change due to fluid challenge (FC-induced ΔETCO2) versus internal jugular vein distensibility index (IJVDI) as predictors of fluid responsiveness in such patients. Methods: Septic hypoperfused mechanically ventilated patients were classified as fluid responders (Rs) and non-responders (NRs) according to the improvement of left ventricular outflow tract-velocity time integral (ΔLVOT-VTI) after fluid challenge (FC). The receiver operating characteristic (ROC) curves of FC-induced ΔETCO2, pre-(FC) IJVDI and their combination for prediction of fluid responsiveness were compared to that of ΔLVOT-VTI% as a gold standard. Results: Of 140 patients who completed the study, 51 (36.4%) patients were classified as Rs and 89 (63.6%) patients as NRs. With regard to the prediction of fluid responsiveness, no significant difference (P. 0. 384) was found between the diagnostic accuracy of FC-induced ΔETCO2 >2 mmHg (area under the ROC curve [AUC] 0.908, P < 0.001) and that of pre-(FC) IJVDI >18% (AUC 0.938, P < 0.001), but a prediction model combining both markers, ΔETCO2 ≥3 mmHg and IJVDI ≥16%, achieved significantly higher accuracy (AUC 0.982, P < 0.001) than each independent one (P < 0.05). Conclusion: Under stable ventilatory and metabolic conditions, the predictivity of FC-induced ΔETCO2 >2 mmHg can be comparable to that of pre-(FC) IJVDI >18%. A predictive model combining both FC-induced ΔETCO2 ≥3 mmHg and IJVDI ≥16% can provide higher accuracy than that recorded for each one independently.

Can carotid artery Doppler variations induced by the end-expiratory occlusion maneuver predict fluid responsiveness in septic shock patients?

BACKGROUND: An increase in cardiac index (CI) during an end-expiratory occlusion test (EEOt) predicts fluid responsiveness in ventilated patients. However, if CI monitoring is unavailable or the echocardiographic window is difficult, using the carotid Doppler (CD) could be a feasible alternative to track CI changes. This study investigates whether changes in CD peak velocity (CDPV) and corrected flow time (cFT) during an EEOt were correlated with CI changes and if CDPV and cFT changes predicted fluid responsiveness in patients with septic shock. METHODS: Prospective, single-center study in adults with hemodynamic instability. The CDPV and cFT on carotid artery Doppler and hemodynamic variables from the pulse contour analysis EV1000™ were recorded at baseline, during a 20-s EEOt, and after fluid challenge (500 mL). We defined responders as those who increased CI ≥ 15% after a fluid challenge. RESULTS: We performed 44 measurements in 18 mechanically ventilated patients with septic shock and without arrhythmias. The fluid responsiveness rate was 43.2%. The changes in CDPV were significantly correlated with changes in CI during EEOt (r = 0.51 [0.26-0.71]). A significant, albeit lower correlation, was found for cFT (r = 0.35 [0.1-0.58]). An increase in CI ≥ 5.35% during EEOt predicted fluid responsiveness with 78.9% sensitivity and 91.7% specificity, with an area under the ROC curve (AUROC) of 0.85. An increase in CDPV ≥ 10.5% during an EEOt predicted fluid responsiveness with 96.2% specificity and 53.0% sensitivity with an AUROC of 0.74. Sixty-one percent of CDPV measurements (from - 13.5 to 9.5 cm/s) fell within the gray zone. The cFT changes during EEOt did not accurately predict fluid responsiveness. CONCLUSIONS: In septic shock patients without arrhythmias, an increase in CDPV greater than 10.5% during a 20-s EEOt predicted fluid responsiveness with > 95% specificity. Carotid Doppler combined with EEOt may help optimize preload when invasive hemodynamic monitoring is unavailable. However, the 61% gray zone is a major limitation (retrospectively registered on Clinicaltrials.gov NCT04470856 on July 14, 2020).

How I personalize fluid therapy in septic shock?

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.

Ratio of carbon dioxide veno-arterial difference to oxygen arterial-venous difference is not associated with lactate decrease after fluid bolus in critically ill patients with hyperlactatemia: results from a prospective observational study.

BACKGROUND: High ratio of the carbon dioxide veno-arterial difference to the oxygen arterial-venous difference (PvaCO2/CavO2) is associated with fluid bolus (FB) induced increase in oxygen consumption (VO2). This study investigated whether PvaCO2/CavO2 was associated with decreases in blood-lactate levels FB in critically ill patients with hyperlactatemia. METHODS: This prospective observational study examined adult patients in the intensive care unit (ICU) with lactate levels > 1.5 mmol/L who received FBs. Blood-lactate levels were measured before and after FB under unchanged metabolic, respiratory, and hemodynamic conditions. The primary outcome was blood-lactate levels after FB. Significant decreases in blood-lactate levels were considered as blood-lactate levels < 1.5 mmol/L or a decrease of more than 10% compared to baseline. RESULTS: The study enrolled 40 critically ill patients, and their median concentration of blood lactate was 2.6 [IQR:1.9 - 3.8] mmol/L. There were 27 (68%) patients with PvaCO2/CavO2 ≥ 1.4 mmHg/ml, and 10 of them had an increase in oxygen consumption (dVO2) ≥ 15% after FB, while 13 (32%) patients had PvaCO2/CavO2 < 1.4 mmHg/ml before FB, and none of them had dVO2 ≥ 15% after FB. FB increased the cardiac index in patients with high and low preinfusion PvaCO2/CavO2 (13.4% [IQR: 8.3 - 20.2] vs. 8.8% [IQR: 2.9 - 17.4], p = 0.34). Baseline PvaCO2/CavO2 was not found to be associated with a decrease in blood lactate after FB (OR: 0.88 [95% CI: 0.39 - 1.98], p = 0.76). A positive correlation was observed between changes in blood lactate and baseline PvaCO2/CavO2 (r = 0.35, p = 0.02). CONCLUSIONS: In critically ill patients with hyperlactatemia, PvaCO2/CavO2 before FB cannot be used to predict decreases in blood-lactate levels after FB. Increased PvaCO2/CavO2 is associated with less decrease in blood-lactate levels.

Pressure response to fluid challenge administration in hypotensive surgical patients: a post-hoc pharmacodynamic analysis of five datasets.

In this study we evaluated the effect of fluid challenge (FC) administration in elective surgical patients with low or normal blood pressure. Secondarily, we appraised the pharmacodynamic effect of FC in normotensive and hypotensive patients. We assessed five merged datasets of patients with a baseline mean arterial pressure (MAP) above or below 65 mmHg and assessed the changes of systolic, diastolic, mean and dicrotic arterial pressures, dynamic indexes of fluid responsiveness and arterial elastance over a 10-min infusion. The hemodynamic effect was assessed by considering the net area under the curve (AUC), the maximal percentage difference from baseline (dmax), the time when the maximal value was observed (tmax) and change from baseline at 5-min (d5) after FC end. A stroke volume index increase > 10% with respect to the baseline value after FC administration indicated fluid response. Two hundred-seventeen patients were analysed [102 (47.0%) fluid responders]. On average, FC restored a MAP [Formula: see text] 65 mmHg after 5 min. The AUCs and the dmax of pressure variables and arterial elastance of hypotensive patients were all significantly greater than normotensive patients. Pressure variables and arterial elastance changes in the hypotensive group were all significantly higher at d5 as compared to the normotensive group. In hypotensive patients, FC restores a MAP [Formula: see text] 65 mmHg after 5 min from infusion start. The hemodynamic profile of FC in hypotensive and normotensive patients is different; both the magnitude of pressure augmentation and duration is greater in the hypotensive group.

Mixed venous to arterial CO 2 gap as a marker to identify fluid responsiveness in septic shock patients / 中华急诊医学杂志

Objective:To investigate the value of the venous-to-arterial CO 2 gap (Δ CO 2 gap) before and after the fluid challenge (FC) in determining the fluid responsivenessin septic shock patients. Methods:A total of 104 septic shock patients admitted to the Medical Intensive Care Unit (MICU) of Peking Union Medical College Hospital were included in the retrospective study. All patients were monitored by Swan Ganz floating catheter during the FC. Hemodynamics and blood gas indices were collected before FC (T0) and immediately (T1), 10 min (T2), 30 min (T3) and 60 min (T4) after FC. Responders were defined as patients with a > 10% increase in cardiac output (CO) after FC. Spearman correlation analysis was used to evaluate the correlation between CO 2 gap and CO. The value of ΔCO2 gap were calculated by the area under the receiver operating characteristic (AUROC) curve in the whole population. Results:Among 104 patients, the effective rates of FC at T1, T2, T3 and T4 were 59% (61/104), 72% (75/104), 73% (76/104), and 77% (80/104), respectively. CO of patients in the reactive group was lower than that in the non-reactive group at T2 [6.0 (4.7, 7.5) vs. 7.2 (6.4, 8.5) L/min, P=0.019], and there was no significant difference in CO 2 gap between the two groups before FC. Spearman correlation analysis showed that CO 2 gap was negatively correlated with CO, and the correlations between CO 2 content gap and CO was -0.34, and -0.33 of CO 2 pressure gap and CO, respectively (both P <0.05). ROC curve analysis showed that the ΔCO 2 gap at T1 could weakly judge the reactivity at T2, T3 and T4, but could not judge the reactivity at T1. The AUROC at T2 was 0.669 of ΔCO 2 content gap and 0.684 of ΔCO 2 pressure gap (both P <0.05). Conclusions:The evaluate time judging the effect of FC should be appropriately extended. The change value of CO 2 gap before and immediately after volume expansion in septic shock patients can judge the fluid responsiveness within 10 min after FC.

Effects of rapid fluid infusion on hemoglobin concentration: a systematic review and meta-analysis.

BACKGROUND: Rapid fluid administration may decrease hemoglobin concentration (Hb) by a diluting effect, which could limit the increase in oxygen delivery (DO2) expected with a positive response to fluid challenge in critically ill patients. Our aim was to quantify the decrease in Hb after rapid fluid administration. METHODS: Our protocol was registered in PROSPERO (CRD42020165146). We searched PubMed, the Cochrane Database, and Embase from inception until February 15, 2022. We selected studies that reported Hb before and after rapid fluid administration (bolus fluid given over less than 120 min) with crystalloids and/or colloids in adults. Exclusion criteria were studies that included bleeding patients, or used transfusions or extracorporeal circulation procedures. Studies were divided according to whether they involved non-acutely ill or acutely ill (surgical/trauma, sepsis, circulatory shock or severe hypovolemia, and mixed conditions) subjects. The mean Hb difference and, where reported, the DO2 difference before and after fluid administration were extracted. Meta-analyses were conducted to assess differences in Hb before and after rapid fluid administration in all subjects and across subgroups. Random-effect models, meta-regressions and subgroup analyses were performed for meta-analyses. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. RESULTS: Sixty-five studies met our inclusion criteria (40 in non-acutely ill and 25 in acutely ill subjects), with a total of 2794 participants. Risk of bias was assessed as "low" for randomized controlled trials (RCTs) and 'low to moderate' for non-RCTs. Across 63 studies suitable for meta-analysis, the Hb decreased significantly by a mean of 1.33 g/dL [95% CI - 1.45 to - 1.12; p < 0.001; I2 = 96.88] after fluid administration: in non-acutely ill subjects, the mean decrease was 1.56 g/dL [95% CI - 1.69 to - 1.42; p < 0.001; I2 = 96.71] and in acutely ill patients 0.84 g/dL [95% CI - 1.03 to - 0.64; p = 0.033; I2 = 92.91]. The decrease in Hb was less marked in patients with sepsis than in other acutely ill patients. The DO2 decreased significantly in fluid non-responders with a significant decrease in Hb. CONCLUSIONS: Hb decreased consistently after rapid fluid administration with moderate certainty of evidence. This effect may limit the positive effects of fluid challenges on DO2 and thus on tissue oxygenation.

Response of internal carotid artery blood flow velocity to fluid challenge under general anesthesia in pediatric patients with moyamoya disease: A prospective observational study.

BACKGROUND: Maintaining cerebral blood flow is important in intraoperative management of moyamoya disease patients. AIMS: To access changes in the carotid artery blood flow velocity in response to fluid challenge, blood pressure, and cardiac output under general anesthesia in pediatric patients with moyamoya disease. METHODS: This observational study included pediatric patients with moyamoya disease undergoing general anesthesia for encephaloduroarteriosynangiosis. Each patient underwent an ultrasound assessment thrice as follows: after anesthetic induction (T1), after fluid challenge (10 ml/kg, T2), and at the end of surgery (T3). The primary outcome was the change in the internal carotid artery blood flow velocity after fluid challenge and was assessed using a paired t-test. The secondary outcomes comprised changes in the internal, external, and common carotid artery blood flow peak velocities after fluid challenge and the factors influencing these changes. RESULTS: We enrolled and analyzed 30 patients with a mean age of 7.2 years. After fluid challenge, the systolic (p = .003) and mean blood pressure (p = .017), stroke volume index (p = .008), and cardiac index (p = .140) were higher than those at T1. However, both internal carotid artery blood flow velocities did not change after fluid challenge (p = .798, mean difference and 95% confidence interval [CI], -1.1 and -10.3 to 8.0 for right, p = .164, mean difference and 95% CI, -5.2 and -12.7 to 2.2 for left). The internal carotid artery blood flow velocity was correlated with the cardiac index, stroke volume index, and mean and diastolic blood pressure, with low significance. CONCLUSIONS: The internal carotid artery blood flow velocity did not increase in pediatric patients with moyamoya disease under general anesthesia, despite fluid challenge and corresponding changes in the blood pressure and cardiac output. Intraoperative hemodynamic management to improve the cerebral blood flow in these patients requires further investigation.

Optimising fluid requirements after initial resuscitation: A pilot study evaluating mini-fluid challenge and passive leg raising test in patients with predicted severe acute pancreatitis.

BACKGROUND: The goals and approaches to fluid therapy vary through different stages of resuscitation. This pilot study was designed to test the safety and feasibility of a fluid therapy protocol for the second or optimisation stage of resuscitation in patients with predicted severe acute pancreatitis (SAP). METHODS: Spontaneously breathing patients with predicted SAP were admitted after initial resuscitation and studied over a 24-h period in a tertiary hospital ward. Objective clinical assessment (OCA; heart rate, mean arterial pressure, urine output, and haematocrit) was done at 0, 4, 8, 12, 18-20, and 24 h. All patients had mini-fluid challenge (MFC; 250 ml intravenous normal saline within 10 min) at 0 h and repeated at 4 and 8 h if OCA score ≥2. Patients who were fluid responsive (>10% change in stroke volume after MFC) received 5-10 ml/kg/h, otherwise 1-3 ml/kg/h until the next time point. Passive leg raising test (PLRT) was done at each time point and compared with OCA for assessing volume status and predicting fluid responsiveness. RESULTS: This fluid therapy protocol based on OCA, MFC, and PLRT and designed for the second stage of resuscitation was safe and feasible in spontaneously breathing predicted SAP patients. The PLRT was superior to OCA (at 0 and 8 h) for predicting fluid responsiveness and guiding fluid therapy. CONCLUSIONS: This pilot study found that a protocol for intravenous fluid therapy specifically for the second stage of resuscitation in patients with predicted SAP was safe, feasible, and warrants further investigation.

Kinetics of capillary refill time after fluid challenge.

BACKGROUND: Capillary refill time (CRT) is a valuable tool for triage and to guide resuscitation. However, little is known about CRT kinetics after fluid infusion. METHODS: We conducted a prospective observational study in a tertiary teaching hospital. First, we analyzed the intra-observer variability of CRT. Next, we monitored fingertip CRT in sepsis patients during volume expansion within the first 24 h of ICU admission. Fingertip CRT was measured every 2 min during 30 min following crystalloid infusion (500 mL over 15 min). RESULTS: First, the accuracy of repetitive fingertip CRT measurements was evaluated on 40 critically ill patients. Reproducibility was excellent, with an intra-class correlation coefficient of 99.5% (CI 95% [99.3, 99.8]). A CRT variation larger than 0.2 s was considered as significant. Next, variations of CRT during volume expansion were evaluated on 29 septic patients; median SOFA score was 7 [5-9], median SAPS II was 57 [45-72], and ICU mortality rate was 24%. Twenty-three patients were responders as defined by a CRT decrease > 0.2 s at 30 min after volume expansion, and 6 were non-responders. Among responders, we observed that fingertip CRT quickly improved with a significant decrease at 6-8 min after start of crystalloid infusion, the maximal improvement being observed after 10-12 min (-0.7 [-0.3;-0.9] s) and maintained at 30 min. CRT variations significantly correlated with baseline CRT measurements (R = 0.39, P = 0.05). CONCLUSIONS: CRT quickly improved during volume expansion with a significant decrease 6-8 min after start of fluid infusion and a maximal drop at 10-12 min.

Passive leg raising-induced changes in pulse pressure variation to assess fluid responsiveness in mechanically ventilated patients: a multicentre prospective observational study.

BACKGROUND: Passive leg raising-induced changes in cardiac index can be used to predict fluid responsiveness. We investigated whether passive leg raising-induced changes in pulse pressure variation (ΔPPVPLR) can also predict fluid responsiveness in mechanically ventilated patients. METHODS: In this multicentre prospective observational study, we included 270 critically ill patients on mechanical ventilation in whom volume expansion was indicated because of acute circulatory failure. We did not include patients with cardiac arrythmias. Cardiac index and PPV were measured before/during a passive leg raising test and before/after volume expansion. A volume expansion-induced increase in cardiac index of >15% defined fluid responsiveness. To investigate whether ΔPPVPLR can predict fluid responsiveness, we determined areas under the receiver operating characteristic curves (AUROCs) and grey zones for relative and absolute ΔPPVPLR. RESULTS: Of the 270 patients, 238 (88%) were on controlled mechanical ventilation with no spontaneous breathing activity and 32 (12%) were on pressure support ventilation. The median tidal volume was 7.1 (inter-quartile range [IQR], 6.6-7.6) ml kg-1 ideal body weight. One hundred sixty-four patients (61%) were fluid responders. Relative and absolute ΔPPVPLR predicted fluid responsiveness with an AUROC of 0.92 (95% confidence interval [95% CI], 0.88-0.95; P<0.001) each. The grey zone for relative and absolute ΔPPVPLR included 4.8% and 22.6% of patients, respectively. These results were not affected by ventilatory mode and baseline characteristics (type of shock, centre, vasoactive treatment). CONCLUSIONS: Passive leg raising-induced changes in pulse pressure variation accurately predict fluid responsiveness with a small grey zone in critically ill patients on mechanical ventilation. CLINICAL TRIAL REGISTRATION: NCT03225378.

Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades.

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.

Portal Vein Pulsatility Index as a Potential Risk of Venous Congestion Assessed by Magnetic Resonance Imaging: A Prospective Study on Healthy Volunteers.

High values of the portal vein pulsatility index (PI) have been associated with adverse outcomes in perioperative or critically ill patients. However, data on dynamic changes of PI related to fluid infusion are scarce. We aimed to determine if dynamic changes in PI are associated with the fluid challenge (FC). To address this challenge, we conducted a prospective single-center study. The population study included healthy subjects. FC consisted in the administration of 500 ml of Ringer lactate infusion over 5 min. The portal blood flow and PI were assessed by magnetic resonance imaging. The responsiveness to FC was defined as an increase in the cardiac stroke volume of at least 10% as assessed by echocardiography. We included 24 healthy volunteers. A total of fourteen (58%) subjects were responders, and 10 (42%) were non-responders. In the responder group, FC induced a significant increase in portal blood flow from 881 (762-1,001) at the baseline to 1,010 (778-1,106) ml min-1 (p = 0.005), whilst PI remained stable (from 31 [25-41] to 35 (25-42) %; p = 0.12). In the non-responder group, portal blood flow remained stable after FC (from 1,042 to 1,034 ml min-1; p = 0.084), whereas PI significantly increased from 32 (22-40) to 48% *(25-85) after FC (p = 0.027). PI was negatively correlated to portal blood flow (Rho coefficient = -0.611; p = 0.002). To conclude, PI might be a sensitive marker of early congestion in healthy subjects that did not respond to FC. This finding requires further validation in clinical settings with a larger sample size.