Risk factors for mortality in patients undergoing continuous renal replacement therapy after cardiac surgery

Acute kidney injury (AKI) is a common complication after cardiac surgery, with an incidence of approximately 30% [1, 2]. Among patients who experience AKI, 2% to 5% require continuous renal replacement therapy (CRRT) [3, 4], and their mortality rate ranges from 50 to 80% [5, 6].

The identification of risk factors in cardiac surgery patients with AKI requiring CRRT (AKI-CRRT) may help in patient stratification, resulting in more appropriate resource utilization and improving patient prognosis [5, 7]. However, although many studies have investigated the risk factors for AKI in patients after cardiac surgery, few studies have focused on patients with AKI-CRRT [8, 9]. In existing research on the risk factors for AKI-CRRT, the sample size of the experimental group is small [8, 9]. Therefore, the purpose of this study was to assess the risk factors for mortality in patients who underwent AKI-CRRT after cardiac surgery.

This retrospective study included more than 400 patients who required AKI-CRRT after undergoing cardiac surgery, representing approximately 4.9%. We found that a EuroSCORE > 7, massive intraoperative bleeding and prolonged mechanical ventilation time were independent risk factors for mortality in patients with AKI-CRRT, while continuous use of furosemide may be associated with a better outcome.

The EuroSCORE II is widely used to predict mortality after cardiac surgery [14]. Halpin and colleagues reported that the EuroSCORE II had better predictive discrimination for operative mortality than the EuroSCORE I and the Society of Thoracic Surgeons (STS) risk score [15]. Interestingly, David and colleagues also reported that the EuroSCORE could be used to predict postoperative AKI [16]. Moreover, Drosos and colleagues suggested that patients with a higher EuroSCORE II were more likely to require renal replacement therapy after cardiac surgery (7.8 ± 14.4 vs. 1.9 ± 2.1, P = 0.014) [17]. In our study, the EuroSCORE II values of deceased patients were higher, which is in line with previous experiences.

Intraoperative bleeding may be affected by patient- and surgery-related factors, such as the use of anticoagulants, systemic inflammatory responses, the consumption and dilution of clotting factors, and fibrinolysis associated with the use of CPB [18]. Among them, approximately 15%-20% of patients have excessive bleeding during cardiac surgery and consume approximately 80% of blood products used in cardiac surgery procedures [19]. Haemodynamic instability caused by excessive blood loss is an important cause of AKI [20], and the mortality of patients after surgery is also significantly increased [21]. In our centre, Stanford type A aortic dissection patients undergoing emergency surgery account for 15% of all cardiac surgery patients. Therefore, the amount of surgical blood loss and the use of AKI-CRRT in our centre are relatively high.

In addition to the EuroSCORE II, massive intraoperative bleeding was another risk factor for mortality in patients with AKI-CRRT. Bleeding is a determinant of excessive haemodilution during cardiac surgery, and the lowest haematocrit is widely recognized as related to AKI [22‐25]. The main explanation for this association is that first, the increase in renal tubular transport leads to an increase in kidney energy requirements. Second, the reduced oxygen delivery caused by haemodilution can exacerbate renal ischaemic dysfunction, especially in the renal medulla, which is sensitive to oxygen [20, 21, 24]. Unlike intraoperative bleeding, the impact of blood transfusion on AKI after cardiac surgery remains controversial. Some studies contend that blood transfusion worsens CPB-initiated systemic inflammatory response syndrome with a second inflammatory response, thereby increasing the incidence of AKI [26]; in contrast, Ng et al. reported that blood transfusion did not play a role in influencing AKI outcomes [25]. In our study, multivariable regression analysis showed that blood transfusion was not related to the mortality of patients with AKI-CRRT after cardiac surgery. Considering that low haematocrit increases the incidence of AKI and patient mortality, we recommend that blood transfusions be properly used to avoid excessive haemodilution.

Systemic inflammatory response syndrome caused by CPB often leads to AKI and acute lung injury that requires positive-pressure mechanical ventilation (MV) [27, 28]. There is a complicated internal connection between kidney and lung organ dysfunction, broadly categorized as haemodynamic and neurohormonal [27]. Multiple systematic reviews have shown that MV can greatly increase the incidence of AKI in critically ill patients [28, 29]. In addition, Fuhrman et al. reported that AKI was associated with a longer duration of MV after cardiac procedures (OR, 1.47; 95% CI: 1.15–1.89) [30]. Therefore, we suggest that it may be beneficial to withdraw MV as soon as possible for patients undergoing AKI-CRRT, but further research and verification are needed to support this claim.

Multivariable regression analysis showed that continuous use of furosemide after surgery was a protective factor that may reduce the mortality of patients with AKI-CRRT. For AKI-CRRT patients, the value of diuretics remains controversial. A recent large-scale cohort study supports our conclusion, however, suggesting that the difference in evaluation criteria was the cause of the controversy over the value of diuretics. The study authors reported that continuous infusion of furosemide increased urine output and helped with successful CRRT discontinuation [31]. However, a previous systematic review reported that furosemide is not associated with significant clinical benefits on renal outcome, including in-hospital mortality and renal replacement therapy or dialysis [32]. In addition, Vargas et al. suggested that torsemide might show a better dose-dependent diuretic effect in patients after CRRT treatment [33]. In our research, both torsemide (P = 0.038) and the traditional Chinese medicine Jin-Shui Bao capsule (P = 0.070) showed potential value in protecting kidney function, but both need to be verified by specially designed clinical trials.

Some limitations should be considered in this study. First, because of the retrospective study design, some predictors of AKI prognosis, such as fractional excretion of urea, the furosemide stress test and creatinine clearance assessed by 6-h urine, were not included. Second, also related to the retrospective nature of the study, many confounding factors may have affected the reliability of our conclusions, and our research suggests that oral furosemide during AKI-CRRT after cardiac surgery may be beneficial, but further research is necessary. Third, in the multivariable regression analysis, continuous variables were converted to binary variables by upper quartile (> 75th percentile), which may lead to partial loss of information. Finally, the data come from a single centre, and agency-specific variables may have influenced the current results. Future studies will focus on improving the generalization and practicability of the research results.

In summary, the mortality of patients with AKI-CRRT after cardiac surgery remains high. The EuroSCORE, intraoperative bleeding and mechanical ventilation time were independent risk factors for in-hospital mortality. Continuous use of furosemide may be associated with a better outcome.