This is the first retrospective study to explore the relationship between intraoperative MAP and AKI occurrence after RALP. Pneumoperitoneum and the steep Trendelenburg position during RALP cause diverse intraoperative MAP changes. However, we observed no association between these changes (MAP variability, hypotension, and hypertension) and AKI after RALP. Nonetheless, ARV-MAP and TWA-MAP were positively correlated with SCr levels within 7 postoperative days; these SCr elevations did not result in AKI.
Pneumoperitoneum, which is dependent on the amount of intra-abdominal pressure, can induce direct renal vascular and parenchymal compression as well as the release of antidiuretic hormone, renin, and aldosterone, which results in decreased renal blood flow, GFR, and renal excretory function3,4. However, it remains unclear whether compared with open radical prostatectomy, RALP increases the risk of AKI. A study reported that compared with open radical prostatectomy, RALP involves a significantly lower incidence of AKI5. However, in another study, 25 (13.4%) out of 187 patients who underwent RALP showed an acute increase in SCr levels on the operation day, which met the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI; however, none of the patients who underwent open radical prostatectomy met this criteria7. Therefore, AKI after RALP remains a concern; accordingly, there have been clinical trials for mitigating AKI in patients undergoing RALP. Intraoperative infusion of low-dose (0.5 µg/kg/min) nicardipine, which is a calcium channel blocker, has been found to improve renal function on postoperative day 119. Contrastingly, intraoperative infusion of mannitol (0.5 g/kg) did not facilitate the prevention of AKI after RALP6.
Numerous factors, including CO2 gas insufflation and desufflation as well as performing a steep Trendelenburg position and resuming a supine position, induce abrupt changes in BP during RALP9–12. A large-scale study on patients undergoing non-cardiac surgery reported a positive correlation of intraoperative MAP variability with the risk of postoperative AKI, regardless of intraoperative hypotension13. Similarly, systolic BP variability is negatively correlated with renal function in patients with hypertension20,21. Renal perfusion is maintained by neurohormonal responses over time19,22; therefore, abrupt BP fluctuations may exceed the capacity of such adaptations, which may result in kidney damage. We found that an ARV-MAP increase by 15 mmHg was significantly associated with an increase in SCr by 0.21 mg/L even after adjustment of confounding factors (Table 5). However, ARV-MAP could not predict postoperative AKI (Table 4). The median [IQR] ARV-MAP was 7 [6–8] mmHg/min, with the lowest and highest values being 3 and 19 mmHg/min, respectively (Fig. 2). Accordingly, an increase in ARV-MAP by 15 mmHg/min may rarely occur during RALP; additionally, an increase in SCr by 0.21 mg/L is insufficient for inducing AKI, which necessitates an elevation of ≥ 0.3 mg/dL. Therefore, BP variability during RALP may be tolerable with respect to renal function.
There remains no recommended standard measurement for BP variability. We assessed MAP variability using the SD-MAP and ARV-MAP. ARV-MAP may be more appropriate than SD-MAP since ARV represent consecutive changes in MAP, while SD does not consider the timing of measurements13,18. Since we preferred ARV-MAP over SD-MAP, we identified preoperative factors correlated with ARV-MAP (Table 3). BMI was positively correlated with intraoperative ARV-MAP, which is consistent with findings from previous reports that showed that compared with normal-weight patients, overweight and obese patients present higher BP variability during their daily lives23,24. We found that patients with diabetes showed low ARV-MAP, which is inconsistent with the results of a previous report of high intraoperative BP variability in patients with diabetes13. Although hypertension and treatment with ACEI or ARB did not affect ARV-MAP, intraoperative ARV-MAP was positively correlated with preoperative MAP. Additionally, ARV-MAP showed a positive correlation with TWA-MAP and AUT-120 mmHg as well as a negative correlation with AUT-65 mmHg (Fig. 3). These findings suggest a positive correlation of BP with BP variability, which is consistent with a previous finding of high BP variability in patients with uncontrolled hypertension25.
Intraoperative hypotension is known to be strongly correlated with AKI after non-cardiac surgery13–17. Absolute and relative (reduction from baseline) MAP thresholds have been used to define hypotension14,15,26. However, the association of relative and absolute hypotension thresholds with AKI have similar strengths15. Absolute thresholds are easier to use in decision-making without requiring preoperative BP data, with an absolute MAP threshold of < 65 mmHg being the most commonly used14,26. Therefore, we used a MAP threshold of < 65 mmHg and calculated AUT-65 mmHg, which characterizes the hypotension duration and severity (amount of hypotension). However, AUT-65 mmHg was not associated with delta-SCr or AKI, which could be attributed to our low incidence of AKI. A previous study on 138,021 non-cardiac surgeries demonstrated that the relationship of intraoperative hypotension with AKI varied according to the underlying patient and procedural risks. Specifically, intraoperative hypotension was associated with AKI in patients with medium and high but not low risk27. The AKI incidence was 1.7% and ≥ 4.6% in patients with low and medium risk, respectively27. In our study, the AKI incidence was 2.4%, which suggests that patients undergoing RALP had a low risk of AKI and that intraoperative hypotension is not an important determinant of AKI. However, further studies are warranted to elucidate the impact of intraoperative hypotension on AKI after RALP in high-risk patients.
An increase of TWA-MAP by 30 mmHg was significantly associated with an increase of SCr by 0.14 mg/L, even after adjustment for confounding factors (Table 5). This suggests that high BP negatively affects renal function. However, AAT-120 mmHg, which represents the hypertension duration and severity, was not significantly associated with an increase in SCr levels. Moreover, TWA-MAP and AAT-120 mmHg could not predict AKI (Table 4). Therefore, the high BP during RALP might be tolerable and not cause renal damage. Although the association of high BP with increased postoperative morbidity remains unclear, compared with hypotension, elevated intraoperative BP may not be as strongly associated with postoperative morbidity26.
Our findings have strength in terms of the elaborate data quality. Specifically, the MAP values were obtained through invasive arterial monitoring and collected in 10-s intervals; accordingly, 642,336 continuous MAP measurements were included in the analysis. Nevertheless, this study has several limitations. First, this was a single-center retrospective study, which increases the risk of bias and the influence of confounding factors. Although we adjusted for confounding factors based on a previous report28, there could have been unknown and unadjusted confounding factors. Second, we did not consider the use of vasopressors or vasodilators given their dose complexity and inaccuracies. Further studies that consider BP-modifying drugs are warranted to validate our findings. Finally, given the low incidence of AKI (2.4%), there is a need for future large-scale trials.
In conclusion, intraoperative MAP changes, including MAP variability, hypotension, and hypertension, could not predict AKI occurrence after RALP. Although the MAP variability and mean MAP were positively correlated with SCr levels within 7 postoperative days, the increase in SCr levels was not clinically significant. Therefore, dynamic BP changes during RALP may be within the acceptable range for kidney perfusion; accordingly, intraoperative MAP changes may not be an important determinant of postoperative AKI.