The assessment of intravascular volume is challenging in the management of critical patients. Clinical history and physical examination provide the initial information about blood volume. However, even when combined with laboratory tests, chest X-ray, central venous pressure, and cardiac afterload monitoring, these parameters are not sufficiently accurate or reliable for determining a patient’s intravascular volume, particularly in cases of hypovolemia not associated with blood loss.¹

Critically ill patients with hemodynamic instability are managed according to the definition of intravascular volume and based on the improvement or worsening of hemodynamic parameters due to therapeutic test results. The diagnostic methods used for this purpose require safety, receptivity, reproducibility, and continuous monitoring since fluid replacement therapies impact a patient’s systemic perfusion and influence the risk of organ failure.²

Fluid responsiveness is generically defined as a 10%–15% increase in stroke volume after crystalloid infusion. Volume replacement improves the oxygen supply to the tissues by increasing afterload and cardiac output. However, only 50% of critically ill patients are on the ascending portion of the Frank-Starling curve, i.e., cardiac output increases in response to increased preload. Volume overload in heart failure is associated with the need for mechanical ventilation, an increased incidence of acute kidney injury, and an increased mortality rate.^3,4

In recent years, due to these limitations, ultrasound of the inferior vena cava (IVC) has been widely used as a non-invasive diagnostic method for intravascular volume and predicting fluid responsiveness. Most venous return to the heart occurs through the IVC. The correct assessment of its diameter and dynamics during respiratory cycles may provide an approximate ventricular preload estimate and, consequently, demonstrate its relationship with afterload and cardiac output.⁵

In clinical practice, there are no direct methods of assessing preload, which is traditionally estimated through static measurements such as central venous pressure and pulmonary artery occlusion pressure or dynamic measurements such as ejection volume variation and pulse pressure. Most of these diagnostic methods are invasive and risky.⁶

Challenges defining blood volume and fluid management in critically ill patients justify efforts to assess the applicability of IVC ultrasonography as an alternative, safe, and non-invasive method.

This study aimed to describe the applicability of ultrasound indices for assessing intravascular volume and predicting fluid responsiveness in critically ill patients.

This systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines⁷ aimed to answer the following research question: “What is the applicability of IVC ultrasound indices for assessing intravascular volume and predicting fluid responsiveness in critically ill patients?” The PICOS strategy was used to prepare the guiding question (Table 1).

Initially, 130 (81.8%) studies were identified in the PubMed^®, 15 (9.4%) in the Lilacs, and 14 (8.8%) in the SciELO databases. Of these 159 articles, 18 (11.3%) were eliminated as duplicates. Of the 141 resulting reports, 108 (76.6%) were excluded after the title and abstract screening for not meeting the study objective. Thus, a total of 33 articles were subjected to full-text review.

After the full-text review, 21 (63.63%) were excluded, nine (27.27%) for being conducted in environments other than the intensive care unit, nine (27.27%) for being using an unclear method of calculating the evaluated ultrasound index, and three (9.09%) for using animal models. Finally, the final sample included 12 scientific articles, the selection process of which is shown in Figure 1.

The 12 analyzed articles were observational in design. Of them, three (25%) were included children and nine (75%) included adults. A total of 1,047 patients were evaluated. Five studies (41.66%) were performed of mechanically ventilated patients, one (8.33%) of spontaneously ventilated patients receiving ventilatory support, and six (50%) of spontaneously ventilated patients.

There was no significant variation among studies regarding the method of IVC diameter acquisition and its variation during the respiratory cycle. All measurements were performed on M-mode ultrasonography. The objectives of each study were to demonstrate, alone or comparatively, the sensitivity and specificity of the cutoff points of each index used to assess intravascular volume and predict fluid responsiveness (Table 3).

Estimating right ventricular preload is important for defining intravascular volume and predicting fluid responsiveness since the relationship between diastolic filling volume and stroke volume is mainly influenced by the Frank-Starling mechanism. An increased or decreased preload in the right ventricle translates to a change in the left ventricular systolic volume.³ Accordingly, the ultrasonographic evaluation of the IVC is a non-invasive instantaneous method that strongly correlates with ventricular preload and circulating blood volume. Hypovolemic patients are expected to present the image of a depleted or collapsed vessel. However, in conditions that course with hypervolemia, the IVC is dilated or lacks respiratory collapse.⁵ This is because the IVC reaches its maximum and minimum diameters due to interactions between the heart and lung during the respiratory cycle, i.e., in spontaneous breathing, inspiration induces an increased intra-abdominal pressure due to the diaphragmatic movement toward this cavity. Thus, the IVC diameter decreases. On the other hand, a decreased abdominal pressure results in an increased vessel diameter.²¹

Mechanical ventilation with positive pressure substantially increases intrathoracic pressure, which reduces cardiac preload and stroke volume. Consequently, the IVC diameter will maximize during inspiration and minimize during expiration.^22,23 Thus, ultrasound assesses IVC diameter variability (ΔIVC) during a spontaneous or mechanical respiratory cycle to establish intravascular volume and predict fluid responsiveness.^21,24

Spontaneously breathing patients have ΔVCI represented by the IVCci.⁸ The collapsibility index in healthy people during the respiratory cycle varies with a mean of 38%. Values above or below this value were considered abnormal and required further investigation.²⁵ In the studies analyzed in this review, the IVCci cutoff points were 0.25–0.5 to determine hypovolemic states. However, it is important to emphasize that the higher the IVC cutoff point, the lower the ability to distinguish hypervolemic from hypovolemic states.

CVP is one of the best established methods in clinical practice for assessing intravascular volume. A study of 100 patients admitted to an intensive care unit aimed to identify the relationship between CVP and IVC ultrasound measurements. An inversely proportional relationship was found between CVP and IVCci, i.e., the higher the IVCci, the lower the CVP, indicating hypovolemia.² These data corroborate those of the study by Babaie et al. of children aged 1 month to 12 years under mechanical ventilation. On the other hand, Saritas et al. found no negative linear correlation between CVP and IVC in the evaluated scenarios of spontaneous ventilation under ventilatory support.

The ΔIVC in mechanically ventilated patients is represented by IVCdi and IVC distensibility variability (IVCdv).⁸ The use of ΔIVC in mechanically ventilated patients is recommended by the consensus on shock and hemodynamic monitoring of the European Society of Intensive Care Medicine as a dynamic measurement index of fluid responsiveness.²⁶

However, the evaluated studies diverged in the IVCdi cutoff points used for predicting fluid responsiveness. The values were 10.2%–20.5%, with a predominance of cutoff points below 17%. Only Lu et al. reported a higher IVCdi value of (20.5%).¹⁸ A systematic review and meta-analysis of the accuracy of IVCdi for defining intravascular volume in patients under mechanical ventilation reported that in scenarios of a PEEP ≤ 5 cmH₂O at a tidal volume ≥ 8 mL/kg, an IVCdi of 16% accurately predicted fluid responsiveness with 80% sensitivity and 94% specificity. On the other hand, in a patient with a PEEP > 5 cmH₂O and a tidal volume < 8 mL/kg, an IVCdi of 14% had diagnostic limitations with only 66% sensitivity and 68% specificity. Therefore, IVCdi should be cautiously used in certain mechanical ventilation scenarios.²¹

There are significant correlations between IVC diameter and body surface area (BSA). Estimating BSA can be challenging and time-consuming in the emergency and critical care settings. Thus, it is necessary to compare the IVC diameter using an index that does not significantly change with intravascular volume but has a similar relationship with body growth and BSA.²⁷ In turn, use of the aortic diameter (AoD) as a comparative index is justified because it is a vessel whose fetal development occurs simultaneous to that of the IVC. Thus, there is a correlation between age, sex, and BSA with AoD. Due to the anatomical characteristic of this artery, the volumetric status does not significantly change its diameter. As a consequence, the IVC/Ao was proposed to facilitate and accelerate the ultrasonographic diagnosis of intravascular volume.²⁸

The IVC/Ao plays a relevant role in the identification of hypovolemic and hypervolemic states, especially in the pediatric population. The assessment of the impact of individual characteristics with the IVC/Ao in healthy children aged 1–13 years found significant variations in maximum IVC and aorta diameters with individual characteristics. However, they presented no significant variation versus the IVC/Ao. This analysis found that the use of the IVC/Ao with a reference value of 0.68–1.4 was useful for defining pediatric volumetric status.²⁹ In one of the analyzed studies, Babaie et al. reported a sensitivity of only 50.8% and specificity of 87.5% for predicting pediatric hypovolemic states. Furthermore, the IVC/Ao had superior ability to IVCci for predicting hypovolemia in children under spontaneous ventilation.¹⁰

An analysis of the IVC/Ao index variation by individual characteristics in healthy adults showed a significant change since the aorta was observed as the component most susceptible to the influence of individual characteristics in adults. Therefore, the IVC/Ao did not perform better than the other IVC indices at predicting volumetric status and fluid responsiveness.³⁰ However, the studies analyzed here showed the applicability of the IVC/Ao for assessing intravascular volume in adult patients with signs of hemodynamic instability with sensitivity and specificity rates higher than 93% and 42%, respectively. Thus, a mean IVC/Ao of 1.14 was established to identify the initial phase of hypovolemic shock in adults with a standard deviation of 0.18 as a cutoff point and no significant correlation with individual characteristics.³¹

The assessment of intravascular volume and the prediction of fluid responsiveness is a major challenge in the intensive care environment. Traditional diagnostic methods lead to potential complications that worsen hemodynamic instability. Although the results showed significant variations in sensitivity and specificity in critically ill patients, the use of ultrasound in the analysis of IVC indices (IVCci, IVCdi, and IVCdv) is essential for rapid non-invasive diagnosis with good applicability in patient management, especially when integrated with a systemic ultrasound approach. However, value standardization studies are needed due to divergence in the cutoff points for each index.