This is the first study to assess the predictive value of VIS calculated in the postoperative care of patients suffering from infective endocarditis. The VIS, primarily used in the intensive care treatment of septic patients, has been shown to be a good predictor for poor clinical outcome after cardiac surgery in various patient groups5,6,7,8,11,17. Studies repeatedly described, that an increased requirement for vasoactive and inotropic agents during the first 48 h after cardiac surgery can successfully predict the risk of postoperative complications, including mortality up to one year5,6,11,17.
The principal findings of the present study are as followed: (1) The VIS at 48 h independently predicted mortality after cardiac surgery in IE patients and (2), the VIS is particularly suitable for patients with infective endocarditis due to combined assessment of postoperative cardiovascular dysfunction and IE related inflammatory response.
The present study showed that an increased need for vasoactive and inotropic agents, quantified by the VIS, was significantly associated with non-survival after surgical treatment of IE. The VIS was significantly increased in patients expiring during hospital stay at almost any time within the first 48 h and a score above 4.1 was identified as independent threshold of mortality. When comparing lactate levels, SvO2, and VIS after 48 h, VIS showed the highest predictive value in terms of mortality.
Surgical trauma, cardiopulmonary bypass, ischemia-reperfusion phenomena, and the effects of general anesthesia cause a vasoplegic reaction that can lead to a generalized inflammatory response and multiorgan failure1,2. Acute cardiovascular dysfunction is anticipated in 20% or even more patients in the perioperative period of cardiac surgery18. At the same time variable degrees of left ventricular dysfunction have been observed in 25–50% of septic shock patients18. The combination of all these effects makes the postoperative treatment of IE patients challenging. IE patients are prone to excessive release of cytokines and other inflammatory mediators during surgery as they are exposed to infected material during the removal of vegetations and resection of infected tissue. There is ample evidence that the following increase in cytokine levels correlates with the severity of postoperative organ dysfunction in IE patients19,20,21. In sepsis, high levels of proinflammatory cytokines (i.e., IL-6, IL-8, IL-18, and IL-1β) have been associated with higher mortality, a similar correlation in IE patients can be assumed19,20,21. The present study confirms this correlation. There was a significant association between preoperative as well as POD 1, POD 2 and POD 4 elevated IL6 levels and non-survivors. The combination of cardiovascular dysfunction as well as CPB- and IE-associated inflammation in the postoperative assessment of IE patients is not yet addressed by conventional ICU scoring systems. The analysis of vasoactive and inotropic support using the VIS, which reflects both cardiac dysfunction and inflammation-related vasoplegia, can close this gap.
Patients with critical cardiovascular dysfunction often require a combination of vasoactive and inotropic agents. However, the underlying cause of this dysfunction can vary, particularly in postoperative IE patients. As previously described, the condition may also has an inflammatory or surgical etiology in addition to purely cardiovascular causes. The VIS reflects the extent of hemodynamic support required, with a negative correlation between VIS and clinical outcomes13. In the present study, there was no significant correlation between non-survival and a median cardiac index of > 3 l/min/m2 for all measurements, so therapeutic success in terms of guideline directed postoperative hemodynamic management (MAP > 65mmHg; CI > 2.1 l/min/m2) can be assumed but did not prevent non-survivors from having poor outcome22. Other studies already confirmed that myocardial function is depressed in sepsis despite hemodynamic measurements showing increased cardiac output18. Furthermore, not only macro- but also microcirculatory dysfunction may contribute to poor outcome in septic patients. Even if increased CO initially compensates for vasodilation and fluid shifts, it does not ensure adequate tissue perfusion. Microcirculatory disorders, such as endothelial dysfunction, leukocyte adhesion and microthrombosis, impair blood flow at the capillary level and prevent adequate tissue oxygenation23,24.
Several mechanisms may explain the increased mortality in postoperative patients caused by a high amount of vasoactive support in a vicious circle. This includes increased myocardial oxygen consumption induced by inotropic support and an increased risk for cardiac arrhythmias18,25. In addition, low cardiac output may be a result of cardiac tamponade, so inotropes may mask this by initially improving hemodynamics and therefore delaying early surgical intervention25. In addition, catecholamines are associated with reduced metabolic efficiency as they promote the oxidation of fatty acids over glucose25. This may be a further barrier to optimal cardiac performance. Studies have also found an association with increased bacterial growth, increased bacterial virulence, biofilm formation, insulin resistance and hyperglycemia25,26. If this vicious circle is not broken within the first 48 h, the outcome will be poor.
VIS represents the extent of medical inotropic and vasoactive support as a therapeutic necessity in the complex treatment of postoperative and IE-associated circulatory insufficiency as well as the side effects caused by this amount of support, which explains its particular suitability for this special patient group.
Compared to postoperative lactate levels and ScvO2, which are commonly used in postoperative monitoring of cardiac surgery patients, the VIS showed superiority in predicting mortality after 48 h. In the present study, lactate, which can be elevated postoperatively due to a transient decrease in systemic organ perfusion, e.g. due to high vasopressor demand, consistently showed a significant correlation with mortality, albeit with a pronounced range of variation and is considered a comparatively unspecific outcome parameter11,27,28. ScvO2 levels only showed a significant correlation with non-survival after 48 h and surprisingly they were significantly increased compared to survivors. Studies have shown that ScvO2 levels can be elevated in septic patients due to microcirculatory dysfunction and insufficient tissue oxygen consumption29,30. This confirms, that ScvO2 levels especially in septic patients may not always be a reliable indicator for tissue perfusion or outcome and a comprehensive assessment of macro- and microcirculatory parameters is warranted29,30. In addition, ScvO2 levels are considered susceptible to disturbances caused by circulatory stress and analgosedation, which preferentially redistribute the blood towards the heart muscle and brain31.
EuroSCORE II was significantly associated with non-survival in the univariate analysis. However, evaluating its predictive performance in the ROC analysis revealed only limited discriminatory ability, especially when compared to VIS at 48 h. We therefore decided to include key components of EuroSCORE II such as CKD, IDDM and preoperative mechanical ventilation as individual variables. Including both the composite score and its components would have introduced substantial collinearity and impaired model stability. These findings suggest that the VIS provides superior predictive accuracy in this clinical context.
Unlike traditional outcome-based parameters which are more general and consider different organ systems, the VIS focuses specifically on the severity of circulatory support. The VIS captures changes in circulatory support in real time, may providing an early and specific indicator of adverse outcomes such as mortality, prolonged ICU stay or the need for additional interventions. Further studies comparing the VIS with other outcome markers such as SOFA or SAPS II could provide additional insight into its role as a complementary tool in predicting postoperative outcomes.
