Dynamic changes of hepatic vein Doppler velocities predict preload responsiveness in mechanically ventilated critically ill patients.

BACKGROUND: Assessment of dynamic parameters to guide fluid administration is one of the mainstays of current resuscitation strategies. Each test has its own limitations, but passive leg raising (PLR) has emerged as one of the most versatile preload responsiveness tests. However, it requires real-time cardiac output (CO) measurement either through advanced monitoring devices, which are not routinely available, or echocardiography, which is not always feasible. Analysis of the hepatic vein Doppler waveform change, a simpler ultrasound-based assessment, during a dynamic test such as PLR could be useful in predicting preload responsiveness. The objective of this study was to assess the diagnostic accuracy of hepatic vein Doppler S and D-wave velocities during PLR as a predictor of preload responsiveness. METHODS: Prospective observational study conducted in two medical-surgical ICUs in Chile. Patients in circulatory failure and connected to controlled mechanical ventilation were included from August to December 2023. A baseline ultrasound assessment of cardiac function was performed. Then, simultaneously, ultrasound measurements of hepatic vein Doppler S and D waves and cardiac output by continuous pulse contour analysis device were performed during a PLR maneuver. RESULTS: Thirty-seven patients were analyzed. 63% of the patients were preload responsive defined by a 10% increase in CO after passive leg raising. A 20% increase in the maximum S wave velocity after PLR showed the best diagnostic accuracy with a sensitivity of 69.6% (49.1-84.4) and specificity of 92.8 (68.5-99.6) to detect preload responsiveness, with an area under curve of receiving operator characteristic (AUC-ROC) of 0.82 ± 0.07 (p = 0.001 vs. AUC-ROC of 0.5). D-wave velocities showed worse diagnostic accuracy. CONCLUSIONS: Hepatic vein Doppler assessment emerges as a novel complementary technique with adequate predictive capacity to identify preload responsiveness in patients in mechanical ventilation and circulatory failure. This technique could become valuable in scenarios of basic hemodynamic monitoring and when echocardiography is not feasible. Future studies should confirm these results.

Venous Congestion Assessed by Venous Excess Ultrasound (VExUS) and Acute Kidney Injury in Children with Right Ventricular Dysfunction.

Background: Right ventricular dysfunction (RVD) is a complication following congenital cardiac surgery in children and can lead to systemic venous congestion, low cardiac output, and organ dysfunction. Venous congestion can be transmitted backwards and adversely affect encapsulated organs such as the kidneys. Primary objective: To investigate the association between systemic venous congestion, as estimated by Venous Excess Ultrasound (VExUS), and the occurrence of acute kidney injury (AKI) in children with RVD following congenital heart surgery. Secondary objectives included comparing changes in VExUS scores after initiating treatment for RVD and venous congestion. Methods and results: This was a prospective observational study in children with RVD. The VExUS study was performed on day 1, day 2, and day 3 and categorized as VExUS-1, VExUS-2, and VExUS-3. Among 43 patients with RVD and dilated inferior vena cava, 19/43 (44%), 10/43 (23%), and 12/43 (28%) were VExUS-2 and VExUS-3, respectively. There was an association between severe RVD and elevated pulmonary artery systolic pressures and a VExUS score >2. A significant association was observed between central venous pressure (CVP) measurements and VExUS. Among 31 patients with a high VExUS score >2, 18 (58%) had AKI. Additionally, improvement in CVP and fluid balance was associated with improving VExUS scores following targeted treatment for RVD. Conclusion: VExUS serves as a valuable bedside tool for diagnosing and grading venous congestion through ultrasound Doppler. An elevated VExUS score was associated with the occurrence of AKI, and among the components of VExUS, portal vein pulsatility may be useful as a predictor of AKI. How to cite this article: Natraj R, Bhaskaran AK, Rola P, Haycock K, Siuba MTT, Ranjit S. Venous Congestion Assessed by Venous Excess Ultrasound (VExUS) and Acute Kidney Injury in Children with Right Ventricular Dysfunction. Indian J Crit Care Med 2024;28(5):447-452.

Coexistence of a fluid responsive state and venous congestion signals in critically ill patients: a multicenter observational proof-of-concept study.

BACKGROUND: Current recommendations support guiding fluid resuscitation through the assessment of fluid responsiveness. Recently, the concept of fluid tolerance and the prevention of venous congestion (VC) have emerged as relevant aspects to be considered to avoid potentially deleterious side effects of fluid resuscitation. However, there is paucity of data on the relationship of fluid responsiveness and VC. This study aims to compare the prevalence of venous congestion in fluid responsive and fluid unresponsive critically ill patients after intensive care (ICU) admission. METHODS: Multicenter, prospective cross-sectional observational study conducted in three medical-surgical ICUs in Chile. Consecutive mechanically ventilated patients that required vasopressors and admitted < 24 h to ICU were included between November 2022 and June 2023. Patients were assessed simultaneously for fluid responsiveness and VC at a single timepoint. Fluid responsiveness status, VC signals such as central venous pressure, estimation of left ventricular filling pressures, lung, and abdominal ultrasound congestion indexes and relevant clinical data were collected. RESULTS: Ninety patients were included. Median age was 63 [45-71] years old, and median SOFA score was 9 [7-11]. Thirty-eight percent of the patients were fluid responsive (FR+), while 62% were fluid unresponsive (FR-). The most prevalent diagnosis was sepsis (41%) followed by respiratory failure (22%). The prevalence of at least one VC signal was not significantly different between FR+ and FR- groups (53% vs. 57%, p = 0.69), as well as the proportion of patients with 2 or 3 VC signals (15% vs. 21%, p = 0.4). We found no association between fluid balance, CRT status, or diagnostic group and the presence of VC signals. CONCLUSIONS: Venous congestion signals were prevalent in both fluid responsive and unresponsive critically ill patients. The presence of venous congestion was not associated with fluid balance or diagnostic group. Further studies should assess the clinical relevance of these results and their potential impact on resuscitation and monitoring practices.

Simultaneous Venous-Arterial Doppler Ultrasound During Early Fluid Resuscitation to Characterize a Novel Doppler Starling Curve: A Prospective Observational Pilot Study.

Background: The likelihood of a patient being preload responsive-a state where the cardiac output or stroke volume (SV) increases significantly in response to preload-depends on both cardiac filling and function. This relationship is described by the canonical Frank-Starling curve. Research Question: We hypothesize that a novel method for phenotyping hypoperfused patients (ie, the "Doppler Starling curve") using synchronously measured jugular venous Doppler as a marker of central venous pressure (CVP) and corrected flow time of the carotid artery (ccFT) as a surrogate for SV will refine the pretest probability of preload responsiveness/unresponsiveness. Study Design and Methods: We retrospectively analyzed a prospectively collected convenience sample of hypoperfused adult emergency department (ED) patients. Doppler measurements were obtained before and during a preload challenge using a wireless, wearable Doppler ultrasound system. Based on internal jugular and carotid artery Doppler surrogates of CVP and SV, respectively, we placed hemodynamic assessments into quadrants (Qx) prior to preload augmentation: low CVP with normal SV (Q1), high CVP and normal SV (Q2), low CVP and low SV (Q3) and high CVP and low SV (Q4). The proportion of preload responsive and unresponsive assessments in each quadrant was calculated based on the maximal change in ccFT (ccFTΔ) during either a passive leg raise or rapid fluid challenge. Results: We analyzed 41 patients (68 hemodynamic assessments) between February and April 2021. The prevalence of each phenotype was: 15 (22%) in Q1, 8 (12%) in Q2, 39 (57%) in Q3, and 6 (9%) in Q4. Preload unresponsiveness rates were: Q1, 20%; Q2, 50%; Q3, 33%, and Q4, 67%. Interpretation: Even fluid naïve ED patients with sonographic estimates of low CVP have high rates of fluid unresponsiveness, making dynamic testing valuable to prevent ineffective IVF administration.

Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized Open-Label Pilot Trial.

BACKGROUND: Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia. RESEARCH QUESTION: Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2? STUDY DESIGN AND METHODS: The prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care or to standard of care plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle. RESULTS: Twenty-three patients were randomized to the standard of care arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median (interquartile range) duration of respiratory support (6 [3-10] vs 9 [4-12] days; P = .34), median duration of hospitalization (9 [6-12] vs 10 [6-18] days; P = .20), and median time to clinical improvement (4 [3-7] vs 7 [3-11] days; P = .12) for OZA compared with standard of care, respectively. Heart rate was significantly lower with OZA (65 [ 63-67] vs 71 [69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported. INTERPRETATION: To our knowledge, SRL utility in severe pneumonia has never been tested in patients. This study shows for the first time that this new pharmacologic agent may safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04405102; URL: www. CLINICALTRIALS: gov.

What every intensivist should know about the IVC.

Assessment of the IVC by point-of-care ultrasound in the context of resuscitation has been a controversial topic in the last decades. Most of the focus had been on its use as a surrogate marker for fluid responsiveness, with results being equivocal. We review its important anatomical aspects as well as the physiological rationale behind ultrasound assessment and propose a new way to do so, as well as explain its central role in the concept of fluid tolerance.

Inferior Vena Caval Measures Do Not Correlate with Carotid Artery Corrected Flow Time Change Measured Using a Wireless Doppler Patch in Healthy Volunteers.

(1) Background: The inspiratory collapse of the inferior vena cava (IVC), a non-invasive surrogate for right atrial pressure, is often used to predict whether a patient will augment stroke volume (SV) in response to a preload challenge. There is a correlation between changing stroke volume (SV∆) and corrected flow time of the common carotid artery (ccFT∆). (2) Objective: We studied the relationship between IVC collapsibility and ccFT∆ in healthy volunteers during preload challenges. (3) Methods: A prospective, observational, pilot study in euvolemic, healthy volunteers with no cardiovascular history was undertaken in a local physiology lab. Using a tilt-table, we studied two degrees of preload augmentation from (a) supine to 30-degrees head-down and (b) fully-upright to 30-degrees head down. In the supine position, % of IVC collapse with respiration, sphericity index and portal vein pulsatility was calculated. The common carotid artery Doppler pulse was continuously captured using a wireless, wearable ultrasound system. (4) Results: Fourteen subjects were included. IVC % collapse with respiration ranged between 10% and 84% across all subjects. Preload responsiveness was defined as an increase in ccFT∆ of at least 7 milliseconds. A total of 79% (supine baseline) and 100% (head-up baseline) of subjects were preload-responsive. No supine venous measures (including IVC % collapse) were significantly related to ccFT∆. (5) Conclusions: From head-up baseline, 100% of healthy subjects were 'preload-responsive' as per the ccFT∆. Based on the 42% and 25% IVC collapse thresholds in the supine position, only 50% and 71% would have been labeled 'preload-responsive'.

Unifying Fluid Responsiveness and Tolerance With Physiology: A Dynamic Interpretation of the Diamond-Forrester Classification.

Point of care ultrasound (POCUS) is a first-line tool to assess hemodynamically unstable patients, however, there is confusion surrounding intertwined concepts such as: "flow," "congestion," "fluid responsiveness (FR)," and "fluid tolerance." We argue that the Frank-Starling relationship is clarifying because it describes the interplay between "congestion" and "flow" on the x-axis and y-axis, respectively. Nevertheless, a single, simultaneous assessment of congestion and flow via POCUS remains a static approach. To expand this, we propose a two-step process. The first step is to place the patient on an ultrasonographic Diamond-Forrester plot. The second step is a dynamic assessment for FR (e.g., passive leg raise), which individualizes therapy across the arc of critical illness.

Bedside Ultrasound in the Management of Cardiorenal Syndromes: An Updated Review.

BACKGROUND: Cardiorenal syndromes constitute a spectrum of disorders involving heart and kidney dysfunction modulated by a complex interplay of neurohormonal, inflammatory, and hemodynamic derangements. The management of such patients often poses a diagnostic and therapeutic challenge to physicians owing to gaps in understanding of pathophysiology, paucity of objective bedside diagnostic tools, and individual biases. SUMMARY: In this narrative review, we discuss the role of clinician who performed bedside ultrasound in the management of patients with cardiorenal syndromes. Novel sonographic applications such as venous excess ultrasound score (VExUS) are reviewed in addition to the lung and focused cardiac ultrasound. Further, underrecognized causes of heart failure such as high-flow arteriovenous fistula are discussed. KEY MESSAGE: Bedside ultrasound allows a comprehensive hemodynamic characterization of cardiorenal syndromes.

Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS).

INTRODUCTION: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. METHODS AND ANALYSIS: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. ETHICS AND DISSEMINATION: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. TRIAL REGISTRATION NUMBER: NCT05057611.

A Wireless, Wearable Carotid Doppler Ultrasound Aids Diagnosis and Monitoring of Pericardial Tamponade: A Case Report.

Pericardial tamponade can often be diagnosed through clinical findings and echocardiography; however, the diagnosis can be aided by demonstrating the hemodynamic consequences of the effusion. We describe the use of a wearable carotid Doppler device to help diagnose and monitor pericardial tamponade. CASE SUMMARY: A 54-year-old man developed hypotension after an endobronchial biopsy for a lung mass. Echocardiography showed a pericardial effusion with sonographic evidence of tamponade. A wearable carotid Doppler device demonstrated low corrected carotid flow time (CFT) (a surrogate for stroke volume) with significant respiratory variation, supporting the diagnosis of tamponade. The patient underwent pericardiocentesis which revealed purulent pericardial fluid from a mediastinal abscess. After drainage there was increased CFT and reduced respiratory variability in Doppler, surrogates of improved stroke volume. CONCLUSION: A wearable carotid Doppler device is a noninvasive tool that can help determine the hemodynamic impact of a pericardial effusion, and potentially aid in the diagnosis of pericardial tamponade.

The effect of gravity-induced preload change on the venous excess ultrasound (VExUS) score and internal jugular vein Doppler in healthy volunteers.

BACKGROUND: The venous excess ultrasound (VExUS) score is a multi-organ Doppler approach to assess venous congestion. Despite growing use of VExUS in research and clinical practice, other veins can be visualized to assess for venous hypertension, which may overcome acquisition barriers of the VExUS exam. In this pilot, observational study, we used a wearable Doppler ultrasound to assess the relationship between jugular venous Doppler and the VExUS score under different preload conditions. We hypothesized that jugular Doppler morphology would accurately distinguish preload conditions, that it would most closely relate to the hepatic venous Doppler morphology in the fully supine position and that the VExUS score would be influenced by preload condition. RESULTS: We recruited 15 healthy volunteers with no cardiovascular history. Preload change was achieved using a tilt-table with three positions: supine, fully upright, and 30-degree head-down tilt. In each position, a VExUS score was performed; furthermore, inferior vena collapsibility and sphericity index were calculated. At the same time, jugular venous Doppler was captured by a novel, wireless, wearable ultrasound system. A continuous jugular venous Doppler morphology was 96% accurate for detecting the low preload condition. The jugular venous Doppler morphology was highly correlated with the hepatic vein, but only in the supine position. Gravitational position did not significantly affect the sphericity index or the VExUS score. CONCLUSIONS: The jugular vein Doppler morphology was able to accurately distinguish low from high preload conditions in healthy volunteers. Comparisons between VExUS Doppler morphologies and other veins should occur in the supine position when gravitational pressure gradients are minimized; finally, different preload conditions in healthy subjects did not affect the VExUS score.

Multiorgan evaluation of perfusion and congestion using ultrasound in patients with shock.

There is increasing evidence on the role of ultrasound in the evaluation of multiorgan hypoperfusion and congestion in patients with cardiocirculatory shock both to identify the underlying pathophysiological mechanism and to drive and monitor the treatment. The cardiac and lung ultrasound is included as an integrated multiparametric approach to the very early phase of patients with haemodynamic instability/cardiogenic shock. Splanchnic ultrasound has been mainly applied in heart failure and predominant circulatory failure. Although poorly validated in the critically ill, many ultrasound parameters have a strong physiological background to support their use in the acute setting those that apply either for heart/lung and for splanchnic organ evaluation. This review summarizes the ultrasonographic parameters that have shown evidence in literature in the diagnostic/therapeutic pathway to define the congestion/perfusion profile of the organs that are involved in the pathophysiological cascade of cardiocirculatory shock.

Venous Doppler to Assess Congestion: A Comprehensive Review of Current Evidence and Nomenclature.

Organ congestion from venous hypertension is an important pathophysiological mechanism mediating organ injury in several clinical contexts including critical illness, congestive heart failure and end-stage chronic kidney disease. However, the practical evaluation of venous congestion is often challenging at the bedside because of the limitations of traditional methods. Point-of-care ultrasound (POCUS) enables the clinician to assess venous velocity profiles during the cardiac cycle using Doppler modalities. Venous Doppler profile abnormalities at multiple sites are detected when elevated venous pressure results in hemodynamic changes within the systemic venous circulation. The detection of these abnormal Doppler profiles may identify patients with clinically significant systemic venous congestion. These patients have been reported to be at increased risk of medical complications. Improving the evaluation of venous congestion may lead to individualized treatment and improved patient outcomes. In this review, we describe the physiologic principles necessary to understand venous Doppler assessment. We also propose a nomenclature for the description of venous Doppler profiles. Finally, we provide a narrative review of the current clinical evidence related to use of venous Doppler assessment in various clinical contexts.

Fluid management in acute kidney injury: from evaluating fluid responsiveness towards assessment of fluid tolerance.

Despite the widespread use of intravenous fluids in acute kidney injury (AKI), solid evidence is lacking. Intravenous fluids mainly improve AKI due to true hypovolaemia, which is difficult to discern at the bedside unless it is very pronounced. Empiric fluid resuscitation triggered only by elevated serum creatinine levels or oliguria is frequently misguided, especially in the presence of fluid intolerance syndromes such as increased extravascular lung water, capillary leak, intra-abdominal hypertension, and systemic venous congestion. While fluid responsiveness tests clearly identify patients who will not benefit from fluid administration (i.e. those without an increase in cardiac output), the presence of fluid responsiveness does not guarantee that fluid therapy is indicated or even safe. This review calls for more attention to the concept of fluid tolerance, incorporating it into a practical algorithm with systematic venous Doppler ultrasonography assessment to use at the bedside, thereby lowering the risk of detrimental kidney congestion in AKI.

The emerging concept of fluid tolerance: A position paper.

Fluid resuscitation is a core component of emergency and critical care medicine. While the focus of clinicians has largely been on detecting patients who would respond to fluid therapy, relatively little work has been done on assessing patients' tolerance to this therapy. In this article we seek to review the concept of fluid tolerance, propose a working definition, and introduce relevant clinical signals by which physicians can assess fluid tolerance, hopefully becoming a starting point for further research.

Airway Pressure Release Ventilation With Time-Controlled Adaptive Ventilation (TCAV™) in COVID-19: A Community Hospital's Experience.

Santa Cabrini Ospedale, a community hospital in Montreal, Canada, used the airway pressure release ventilation following a time-controlled adaptive ventilation (APRV-TCAV™) approach for several patients in the first wave of the coronavirus disease 2019 (COVID-19) outbreak in the spring of 2021. Based on favorable patient responses, it became the primary mode of invasive mechanical ventilation-from initiation through extubation-during the second and third waves of COVID-19. In this article, we describe our success with APRV-TCAV™ over more conventional modes and protocols and look at three cases that aptly demonstrate our experience. We then outline several risks with our approach and the lessons learned from our experience. While we generally saw improvement in patients' clinical course with APRV-TCAV™, there are inherent risks with this approach that others must prepare for if they attempt to implement it in their practice.