In the steady state, venous return is equal to cardiac output [13]; thus, right ventricular function is essential for venous return[14, 15]. The challenge of fluid management is to find the ideal preload to avoid the negative effect of ventricular interdependence on LV function and cardiac output. The right half of the heart behaves very differently from the left. Tyberg et al. [11] measured pericardial pressure and right atrial pressure in patients with acute excessive fluid loading before cardiopulmonary bypass. They found that these two types of pressure increased at the same rate, while the right atrial transmural pressure was unchanged. Previous studies have reported no relationship between right transmural pressure and right ventricular end-diastolic volume and stroke volume[16-18]. The healthy human RV fills at or below its unstressed volume, such that RV end-diastolic volume changes occur without any changes in RV diastolic wall stretch. Presumably, conformational changes in RV shape rather than stretch allow such volume changes to occur without measurable changes in the transmural right atrial pressure. With increased volume loading of the RV, right ventricular end-diastolic pressure and SV both increased. The relation of SV to venous return has a plateau: once this plateau is reached, any further increases in filling pressure will not augment cardiac output[19]. As a result, when RV reaches the flat part of the pressure-volume curve, the left heart no longer determines cardiac output. If the RV further increases in size and the right ventricular end-diastolic pressure rapidly increases, this can cause leftward ventricular septal (VS) shift. VS shift can result in decreased SV, leading to a phenomenon colloquially termed “falling off the Starling curve”[14]14141414[14][14][14].
The present study is a prospective study about the relationship between hemodynamic parameters during negative fluid management. The intervention was performed in a short period of time (39±17 minutes), while other factors affecting CVP were unchanged. Notably, 56.3% of our patients showed increased VTI after negative fluid balance, which is not exactly the same as the comment cognition. As the Starling curve does not have descending branches, it cannot explain the increase in SV after reducing the intravascular volume. Thus, we assume that patients experienced RV volume overload. A negative fluid balance can reduce RV volume, resulting in a rightward VS shift, an increase in left ventricular end-diastolic volume, and an increase in CO. However, it remains unclear if determining RV volume overload is key to therapy. In terms of the hemodynamic and echo parameters in our cohort, CVP, GAP, ScVO2, RV/LV diastolic area ratio, LVOT VTI, and DIVC differed significantly between the two groups. A high RVD/LVD ratio and CVP value were identified as risk factors for RV volume overload. Due to its geometrical complexity, assessment of RV volume is a very difficult task. Although quantitative validation is lacking, the correlation of RV linear dimensions with RV end-diastolic volumes appears to worsen with increased preload[20-22]. RVD/LVD ratio has been shown to be an indicator of RV size, and can thus provide reliable information about RV shape and size. A ratio ≥0.6, regardless of whether RV is within the normal reference limits, may relate to certain conditions such as RV volume overload[20]. In our study, we found that a R/V ratio ≥0.6 was a risk factor for VTI increase after negative fluid balance. Our results are similar to those of previous studies[23]. However, our measurement method is more clinically operable and repeatable. Wiesenack et al. measured RV volume in patients with mechanical ventilation to help guide fluid resuscitation. However, in patients with pulmonary embolism and chronic pulmonary hypertension, only RVEDA/LVEDA>1 indicates RV volume overload[24, 25]. When R/V ratio is applied clinically, it should be considered in combination with the patient’s underlying disease and ventricular septal morphology.
We also identified high CVP as a significant risk factor for RV volume overload. The gold standard for evaluating RV filling pressure is invasive monitoring using a centrally placed venous catheter[26]. CVP can be used as a surrogate of intravascular volume, and is often applied at the bedside to guide fluid administration in critically ill patients. Since the filling pressure and SV of the RV do not have a linear relationship, it has recently been acknowledged that CVP is ineffective for evaluating a patient’s fluid responsiveness[27-29]. While the absolute value of CVP alone cannot predict fluid responsiveness, it is necessary to understand that CVP is a marker of pressure and a regulating factor of venous return. Thus, an increase in CVP can be used as a clinical safety mechanism to avoid fluid overload and high RV filling pressure. We consider CVP to be a safety-related indicator rather than a cardiac preload indicator in clinical settings [30]. In the present study, we found that a high CVP may reflect that the RV volume load has exceeded the normal range; failure to appreciate this limit may result in a VS rightward shift and reduced SV. It has been proposed that, once CVP has exceeded 10–14 mm Hg in non-intubated patients with acute RV myocardial infarction, further volume loading is detrimental. A mean CVP > 14 mmHg is almost always associated with a reduced RVSWI[31, 32]. Garcia-Montilla et al. [33] reported that the optimal RV filling pressure in patients with acute respiratory distress syndrome (ARDS) is 13±2 mm Hg. Furthermore, they demonstrated that once CVP reaches 15 mmHg, further increments in filling pressure did not increase RVSPG; rather, due to overstretching of myocardial fibers, RVSPG decreased. These values may be considered the optimal RV filling pressure in patients with acute RV infarction or ARDS. Our results suggest that CVP > 10.5 mmHg can predict whether VTI increases after a negative fluid balance in patients without underlying cardiac disease with high sensitivity but low specificity. When we combined the two risk factors, the predictive ability improved.
Notably, none of our patients experienced CO and tissue perfusion insufficiency after negative fluid management. However, the oxygenation index improved in both groups—especially Group 1. It is well known that fluid overload may lead to pulmonary edema and failure of weaning from mechanical ventilation. A milestone study by Wiederman et al.[34] showed that a conservative fluid management protocol aimed to lower CVP resulted in a major reduction in net fluid balance, improving lung function and shortening the duration of mechanical ventilation. Clinicians should be alert to high CVP as it may indicate increased RV tension and leftward VS, potentially leading to increased left ventricular filling pressure and pulmonary edema. Accurate fluid therapy for patients with high CVP will not lead to hypoperfusion, but will be beneficial for other organs.
Lastly, this study is subject to several limitations. Firstly, our study included a convenience sample of participants from a single institution, and may have thus systematically excluded some participant groups. As a pragmatic study, this population had similar characteristics to previous clinical audits using the same inclusion criteria. Nevertheless, additional clinical research is needed to confirm our findings. Secondly, although we excluded patients with any pre-existing heart disease based on clinical records or echocardiography, some patients might have developed subclinical heart disease after their last echocardiography. Thirdly, the determination of RV volume load may be imperfect. In our experience, estimation of RV/LV size ratio is fairly accurate, even when assessed by trainees relative to an experienced clinicians.