Combination of Inferior Vena Cava Diameter, Hepatic Venous Flow, and Portal Vein Pulsatility Index: Venous Excess Ultrasound Score (VEXUS Score) in Predicting Acute Kidney Injury in Patients with Cardiorenal Syndrome: A Prospective Cohort Study

BACKGROUND

Fluid overload is deleterious in critically ill patients; apart from increased mortality, it can cause end-organ damage, thereby increasing the incidence of acute kidney injury (AKI), length of stay in ICU, and duration of mechanical ventilation.^1–3 The attributable mortality to AKI is 20% and is an independent predictor of mortality.⁴

Fluid overload leads to venous congestion, thereby increasing venous pressure and theoretically increasing the backpressure and reducing renal blood flow, and since kidneys are encapsulated organs it might make them more sensitive to this effect.

There is no clear consensus to measure renal venous pressure. Clinical signs of fluid overload like peripheral edema and ascites are poor indicators of fluid overload in the ICU setup.⁵ Central venous pressure (CVP), which is routinely used in ICU, has shown to be associated with increased incidence of AKI, but CVP as a single measure reflecting venous pressure is highly questionable as there is no clear consensus on reference value, position of the patients, effect of varying intrathoracic pressure in mechanically ventilated patients, and might not reflect preload directly.^6,7

In view of lack of reliable peripheral signs of venous congestion, objective determination of the same is the need of the hour to aid key clinical decisions like stopping fluids, diuretic administration, and management of AKI, to name a few. The underlying physiological principle has been considered to grade venous congestion bedside.

The inferior vena cava (IVC) is the initial screen for venous congestion. Whether due to increased stressed venous volume or an increased right atrial pressure (for any given reason), the first venous compartment where congestion becomes apparent is the IVC. In an observational trial by Guinot et al., right ventricular systolic dysfunction and venacaval dilatation preceded altered renal function in postoperative cardiac surgery patients serving as a marker of venous congestion.⁸ Dilated inferior vena cava was associated with renal failure but it was found to be inconsistent as a marker for hemodynamic congestion.⁹

When the IVC reaches the flat part of its compliance, the pressure begins to be transmitted in a retrograde fashion and dilation of the hepatic venous tree is seen and so on for the renal veins. The portal system may show abnormalities as the congestion becomes more severe, making it potentially a more specific marker of an injurious level of congestion. This likely takes place because the pressure has to transmit across the hepatic sinusoids, which buffer the hepatic venous pressure. Eventually, the portal venous flow pattern changes, going from a monophasic signal to a progressively more pulsatile pattern that can eventually become interrupted (100% pulsatility). A fairly linear relationship between right atrial pressure and the portal vein pulsatility index has been described in congestive heart failure (CHF) patients in acute exacerbation.¹⁰ A case series published by Denault et al. on post-cardiac surgery patients showed portal vein Doppler assessment to be a promising modality for end-organ venous congestion in post-cardiac surgery patients.¹¹ Portal vein is subjected to variation because of body habitus and intrathoracic pressure.^12,13

Hence, venous congestion leads to distension of IVC followed by hepatic venous flow abnormality along with development of portal vein pulsatility and renal venous Doppler flow abnormalities, which was proposed as the VEXUS scoring system.¹⁰ By utilizing multiple parameters, the negative aspects of individual parameters might get negated and emerge as a reliable tool to assess congestion of kidneys.

There has been a greater emphasis on maintaining the perfusion than identifying venous congestion, which can be an important contributor to AKI; there are no validated tools to objectively identify venous congestion bedside, hence we hypothesize that venous excess ultrasound score (VEXUS), which uses three parameters, i.e., inferior vena cava, hepatic vein waveform, and portal vein pulsatility, correlates with severity of fluid overload. In our study, we have not included renal venous Doppler, which was proposed in the original VEXUS score.

MATERIALS AND METHODS

The single-center prospective study was conducted at medical ICU and recruited patients admitted with provisional diagnosis of cardiorenal syndrome during a period of 6 months from September 2019 to February 2020. Patients aged more than 18 years being admitted to ICU with a provisional diagnosis of cardiorenal syndrome were eligible for the study. Patients were excluded from study if they were known cases of cirrhosis with portal hypertension, not willing for ultrasound examination, inadequate window, and IVC thrombus. Patients enrolled in the study underwent ultrasound examination with serial determination till AKI resolved or patient is initiated on dialysis. The study was approved by the institutional ethics committee. The primary objective was to assess the correlation between serial VEXUS score and AKI in patients with cardiorenal syndrome. The secondary objective was to assess correlation between VEXUS score and fluid balance, right heart function, and clinical signs of fluid overload.

RESULTS

A total of 35 patients were enrolled into the study, and 5 patients were excluded in view of poor visualization of portal and hepatic vein.

Thirty patients with AKI were included for the study with a mean age of 59.53 ± 16.47. Seventy percent of them (21 of 30) were males. Mean SOFA score was 5.03 ± 1.97. Fourteen patients (46.7%) were in AKI stage 1, while eight patients (26.7%) were in AKI stage 2 and stage 3 each. Twenty patients (66.7%) had a VEXUS grade III (Table 1).

Patients were categorized on day 3 based on VEXUS grade as improving, no change, or worsening. Resolution of AKI injury showed significant correlation with improvement in the VEXUS grade (p value 0.003). Similarly, there was significant association between changes in the VEXUS grade and fluid balance (p value 0.006). There was no correlation between CVP, left ventricular function, and right ventricular function with change in VEXUS grade (Table 2). There was a significant difference in fluid balance between the VEXUS score improving group (0.20 ± 1.24) compared to the no change group (1.67 ± 1.03) and the worsening group (1.00 ± 0.00) (p value 0.03).

Figure 1 shows relationship between the VEXUS grade and AKI staging. With improvement in kidney function, there is decline in the VEXUS grade as well.

Patients were assessed for the presence of pulmonary edema, pleural effusion, pedal edema, and ascites and were categorized based on the number of positive signs. Peripheral signs of volume overload were not associated with change in the VEXUS grade (Table 3). There was no association with use of IV fluids, inotropes, diuretics, and dialysis on change in VEXUS grades (Table 4).

DISCUSSION

Acute kidney injury is characterized by a rapid deterioration of kidney function; its occurrence in the ICU is associated with significant mortality and morbidity with an attributable mortality of 40–65%.¹

Acute kidney injury can be caused by multiple factors, i.e., circulatory failure, sepsis, nephrotoxic agents, vasopressors, as well as venous congestion. There has long been an emphasis on forward flow, with a focus on maintaining MAP, avoiding nephrotoxic agents, as well as the aggressive treatment of sepsis. However, the quest to achieve normovolemia and normotension with aggressive fluid therapy and vasopressors may be counterproductive as it can lead to fluid overload and venous congestion leading to a decrease in organ perfusion. Indeed, the focus, traditionally being on managing the inflow pressure (MAP), the outflow pressure, a critical determinant of the organ perfusion pressure, is generally overlooked in clinical practice, with important consequences (Figs 2 to 6).

Our study uses a new scoring system: the VEXUS for the evaluation of venous congestion in a cohort of patients with cardiorenal syndrome. As AKI has many confounding factors, we chose cardiorenal syndrome patients as they are more prone to venous congestion. The study tests the utility of bedside serial ultrasonographic examination of two-dimensional and spectral Doppler imaging of the inferior vena cava, hepatic vein, and portal vein, with a derived scoring system based on hypothesis that the first venous compartment where congestion becomes apparent is the IVC. When the IVC reaches the flat part of its compliance, the pressure begins to be transmitted in a retrograde fashion and dilation of the hepatic venous tree is seen followed by the development of portal vein pulsatility and renal venous Doppler flow abnormalities. This scoring system was first validated by Beaubien-Souligny et al. in postoperative cardiac surgery patients where a significant association was found between an elevated VEXUS score and the development of AKI.¹⁶

Our study results support the hypothesis that serial VEXUS scoring is correlated with AKI staging. Among 30 patients, 20 patients with resolving AKI correlated with the downward/improving trend of VEXUS score accounting for 87% of cases associated with a decreasing trend of fluid balance. Five patients who had worsening of AKI showed either no change or worsening in VEXUS score correlating with the clinical picture. This finding shows that the dynamic trend of VEXUS grading correlated with the improving clinical condition.

Elevated CVP correlated with AKI as corroborated by a meta-analysis done by Chen et al.¹¹ Central venous pressure did not normalize in those patients with AKI resolution showing CVP trend might not truly reflect the clinical picture because of its limitations, and possibly also because different patients may have different levels of tolerance of CVP, whereas Doppler flow markers may better reflect the severity of organ congestion and potential dysfunction. Peripheral signs of fluid overload did not correlate with AKI, which reemphasizes the fact that they might not truly reflect the intravascular volume status.⁵

Right heart dysfunction and VEXUS scoring did not have a statistically significant association suggesting that a high congestion score and its resolution reflecting resolving AKI was associated with venous fluid overload and not necessarily with cardiac dysfunction per se.

This study adds to the growing body of literature underscoring the critical importance of the venous side of the circulation, which, although not a novel concept,¹⁷ has been largely overlooked in favor of the arterial side ever since critical care has existed.

With the growing availability of point-of-care ultrasound (POCUS), dynamic flow parameters of physiology are becoming increasingly available to the clinician, many of which only require basic echographic competence. Along with the increasing prevalence of POCUS training in the core medical curriculum, this should change the landscape of clinical assessment in the next decade.

Given the prevalence of AKI in critically ill patients, fluid therapy is an important question. Unfortunately, clinicians today are confronted with contradictory data in the literature, with fluid resuscitation goals (SCCM reference of 8–12 CVP)¹⁸ and renal dysfunction indicators (Damman et al. up curve at 6–8 CVP of renal) being at odds with each other.¹⁹

Limitations of the study mainly include single-center study, small sample size, and observational design with no randomization of the patient. Additionally, as an observational study, it is hypothesis-generating, and a therapeutic direction cannot be widely implemented solely on its basis. Also, it is conducted in a specific group of patients with AKI that is cardiorenal syndrome.

Future directions: the VEXUS grading may be a useful tool in acute care and can be employed in various critical care scenarios:

• As a fluid stop and/or removal point in any fluid resuscitation (sepsis, hypovolemia)
• As a routine parameter in the evaluation of AKI to aid the clinical decision to add/increase the dose of diuretic and/or inotropic support
• In the critical phase of viral syndromes (severe dengue) to decide on fluids/diuretics

We propose a new flow chart as an initial approach to AKI subject to further testing by interventional clinical trials (Flowchart 1).

CONCLUSION

The above results show that a combined grading of IVC, hepatic vein, and portal vein might reliably demonstrate venous congestion and aid in the clinical decision to perform fluid removal. We conclude that bedside sonographic assessment of dynamic blood flow parameters is of great importance and warrants urgent further interventional trials.

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