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).

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.

Tidal volume challenge to predict preload responsiveness in patients with acute respiratory distress syndrome under prone position.

BACKGROUND: Prone position is frequently used in patients with acute respiratory distress syndrome (ARDS), especially during the Coronavirus disease 2019 pandemic. Our study investigated the ability of pulse pressure variation (PPV) and its changes during a tidal volume challenge (TVC) to assess preload responsiveness in ARDS patients under prone position. METHODS: This was a prospective study conducted in a 25-bed intensive care unit at a university hospital. We included patients with ARDS under prone position, ventilated with 6 mL/kg tidal volume and monitored by a transpulmonary thermodilution device. We measured PPV and its changes during a TVC (ΔPPV TVC6-8) after increasing the tidal volume from 6 to 8 mL/kg for one minute. Changes in cardiac index (CI) during a Trendelenburg maneuver (ΔCITREND) and during end-expiratory occlusion (EEO) at 8 mL/kg tidal volume (ΔCI EEO8) were recorded. Preload responsiveness was defined by both ΔCITREND ≥ 8% and ΔCI EEO8 ≥ 5%. Preload unresponsiveness was defined by both ΔCITREND < 8% and ΔCI EEO8 < 5%. RESULTS: Eighty-four sets of measurements were analyzed in 58 patients. Before prone positioning, the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen was 104 ± 27 mmHg. At the inclusion time, patients were under prone position for 11 (2-14) hours. Norepinephrine was administered in 83% of cases with a dose of 0.25 (0.15-0.42) µg/kg/min. The positive end-expiratory pressure was 14 (11-16) cmH2O. The driving pressure was 12 (10-17) cmH2O, and the respiratory system compliance was 32 (22-40) mL/cmH2O. Preload responsiveness was detected in 42 cases. An absolute change in PPV ≥ 3.5% during a TVC assessed preload responsiveness with an area under the receiver operating characteristics (AUROC) curve of 0.94 ± 0.03 (sensitivity: 98%, specificity: 86%) better than that of baseline PPV (0.85 ± 0.05; p = 0.047). In the 56 cases where baseline PPV was inconclusive (≥ 4% and < 11%), ΔPPV TVC6-8 ≥ 3.5% still enabled to reliably assess preload responsiveness (AUROC: 0.91 ± 0.05, sensitivity: 97%, specificity: 81%; p < 0.01 vs. baseline PPV). CONCLUSION: In patients with ARDS under low tidal volume ventilation during prone position, the changes in PPV during a TVC can reliably assess preload responsiveness without the need for cardiac output measurements. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04457739). Registered 30 June 2020 -Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT04457739.

Changes in peripheral perfusion index during intraoperative end-expiratory occlusion tests do not predict the response to fluid administration in patients undergoing lung protective ventilation.

INTRODUCTION: The end-expiratory occlusion test (EEOT) may predict the response to fluid administration in patients undergoing lung-protective ventilation, but arterial catheter insertion is necessary to evaluate changes in stroke volume (SV). The peripheral perfusion index is a potential noninvasive alternative to evaluate SV. The aim of this study is to investigate whether changes in perfusion index during an intraoperative EEOT can predict the response to fluid administration in patients undergoing lung-protective ventilation (tidal volume 7 ml/kg predicted body weight). METHODS: Forty-one elective surgical patients were enrolled. The SV and perfusion index were recorded before (baseline), during a 40-s EEOT and after volume expansion (250 ml of lactated Ringer's solution over 10 min). Patients with an increase in SV greater than 10% after volume expansion were defined as responders. ΔPI (change in perfusion index between baseline and 20 (ΔPI20) or 40 s (ΔPI40) after the beginning of EEOT were calculated using: ΔPI20 (%) = [(PI at 20 s after EEOT beginning - PIbaseline)/PIbaseline] × 100, ΔPI40 (%) = [(PI at 40 s after EEO beginning - PIbaseline)/PIbaseline] × 100). RESULTS: Sixteen patients were responders, and 25 were non-responders. The area under the receiver operating characteristics curves generated for ΔPI20 and ΔPI40 to predict response to a fluid challenge were 0.561 (95% CI 0.374-0.749) and 0.688 (95% CI 0.523-0.852), respectively. CONCLUSION: Changes in perfusion index during intraoperative EEOT in patients undergoing lung-protective ventilation (7 ml/kg) were unable to predict the response to fluid administration.

Functional hemodynamic tests: a systematic review and a metanalysis on the reliability of the end-expiratory occlusion test and of the mini-fluid challenge in predicting fluid 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 I2 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.

Predictors of fluid responsiveness in critically ill patients mechanically ventilated at low tidal volumes: systematic review and meta-analysis.

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.

A wearable carotid Doppler tracks changes in the descending aorta and stroke volume induced by end-inspiratory and end-expiratory occlusion: A pilot study.

BACKGROUND AND AIMS: To test the feasibility of a novel, wearable carotid Doppler ultrasound to track changes in cardiac output induced by end-inspiratory and end-expiratory occlusion tests. METHODS: We observed the pattern of Doppler change of the common carotid artery during a simulated end-inspiratory and expiratory occlusion test (sEIOT/sEEOT) in 10, nonventilated, healthy subjects. Simultaneously, we measured the Doppler signal of the descending aorta using duplex ultrasound (Xario, Toshiba Medical Systems) and stroke volume (SV) using noninvasive pulse contour analysis (Clearsight, Edwards Lifesciences, Irvine, California). RESULTS: During sEIOT, SV, maximum velocity time integral (VTI) of the descending aorta, and common carotid fell by 25.7% (P = .0131), 26.1% (P < .0001), and 18.5% (P < .0001), respectively. During sEEOT, SV, maximum VTI of the descending aorta, and common carotid rose by: 41.3% (P = .0051), 28.3% (P < .0001), and 41.6% (P < .0001), respectively. There was good correlation between change in aortic VTI and carotid VTI (r 2 = 0.79); SV and aortic VTI (r 2 = 0.82), and SV and carotid VTI (r 2 = 0.95).The coefficient of variation of the VTI measured by the Doppler patch was roughly 60% less than that of the duplex system. CONCLUSIONS: The pattern of SV change induced by a sEIOT/sEEOT in nonmechanically ventilated volunteers is reflected in the common carotid artery and descending aorta. The VTI variability of the Doppler patch was less than that of the traditional, duplex Doppler.

Monitoring volume and fluid responsiveness: from static to dynamic indicators.

Fluid therapy represents, most of the time, the first-line treatment of circulatory failure in critically ill patients. However, after initial resuscitation, fluid administration can be deleterious in patients with sepsis and/or acute respiratory distress syndrome. In this context, several tests have been developed to predict fluid responsiveness and fluid unresponsiveness to identify patients who can be eligible for fluid therapy (fluid respondents) and those who cannot benefit from volume expansion (fluid non-respondents) and in whom fluid loading can even be deleterious. For this purpose, 'static' markers of cardiac preload have been used for many years. However, a large number of studies clearly showed that neither pressure nor volume markers of cardiac preload could predict fluid responsiveness. This is the reason why a 'dynamic approach' has been developed to assess preload responsiveness. The respiratory variation of arterial pulse pressure and of other surrogates of stroke volume has been used first for this purpose and has received a large amount of evidence. However, such indices suffer from several limitations. In such instances, alternative methods such as passive leg raising, end-expiratory occlusion test or 'mini' fluid challenge have been developed.