Passive leg raising test versus rapid fluid challenge in critically ill medical patients.

BACKGROUND: The passive leg raising (PLR) test is a simple test to detect preload responsiveness. However, variable fluid doses and infusion times were used in studies evaluating the effect of PLR. Studies showed that the effect of fluid challenge on hemodynamics dissipates in 10 min. This prospective study aimed to compare PLR and a rapid fluid challenge (RFC) with a 300-ml bolus infused within 5 min in adult patients with a hemodynamic compromise. MATERIALS AND METHODS: Critically ill medical patients with signs of systemic hypoperfusion were included if volume expansion was considered. Hemodynamic status was assessed with continuous measurements of cardiac output (CO), when possible, and mean arterial pressure (MAP) at baseline, during PLR, and after RFC. RESULTS: A total of 124 patients with a median age of 65.0 years were included. Their acute physiology and chronic health evaluation (APACHE) II score was 19.7 ± 6.0, with a sequential organ failure assessment (SOFA) score of 9.0 ± 4.4. Sepsis was diagnosed in 73.3%, and 79.8% of the patients were already receiving a norepinephrine infusion. Invasive MAP monitoring was established in all patients, while continuous CO recording was possible in 42 patients (33.9%). Based on CO changes, compared with those with RFC, the false positive and false negative rates with PLR were 21.7 and 36.8%, respectively, with positive and negative predictive values of 70.6 and 72.0%, respectively. Based on MAP changes, compared with those with RFC, the false positive and false negative rates with PLR compared to RFC were 38.2% and 43.3%, respectively, with positive and negative predictive values of 64.4 and 54.0%, respectively. CONCLUSION: This study demonstrated a moderate agreement between PLR and RFC in hemodynamically compromised medical patients, which should be considered when testing preload responsiveness.

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.

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 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).