We have shown that greater intraoperative short-term blood pressure variability is positively associated with high postoperative serum creatinine concentration and is an independent risk factor for PO-AKI.
The most important findings were that high intraoperative blood pressure variability is positively associated with a perioperative increase in serum creatinine concentration and that this relationship is independent of intraoperative SBP. In the present study, the postoperative serum creatinine concentration increased by a mean 4.9 µmol/L, and previous studies have shown similar increases.24, 25 After adjustment for factors that clearly affected postoperative serum creatinine concentration, such as intraoperative blood pressure, the variabilities in MAP, PP, and SBP positively correlated with the perioperative increase in serum creatinine; and one unit increases in each of MAP_CV, PP_CV, and SBP_CV were associated with increases in serum creatinine of 0.23 µmol/L, 0.17 µmol/L, and 0.30 µmol/L, respectively. Of these, SBP_CV showed the closest correlation. This suggests that the variability in SBP should be monitored and reduced during surgery to protect the kidneys and minimize the perioperative increase in serum creatinine. In addition, generalized linear models for the other parameters (MAP_SD, PP_SD, SBP_VIM, etc.) all yielded similar results, which further supports our conclusion that high intraoperative blood pressure variability is positively associated with higher postoperative serum creatinine concentration.
We also found that high intraoperative short-term blood pressure variability is an independent risk factor for PO-AKI. Compared with the lowest quartile groups, the risk of PO-AKI was 1.98-fold and 2.12-fold higher in the highest quartile groups for MAP_CV and SBP_CV, respectively, after adjustment for factors that have been identified to affect PO-AKI. Previous studies have shown a 1.43-fold higher risk of PO-AKI when MAP ≤ 65 mmHg,17 and we found a 2.12-fold higher risk of PO-AKI in the highest quartile of intraoperative SBP variability, which suggests that high intraoperative BP variability may be more deleterious than intraoperative hypotension. Of the various indices of blood pressure variability, SD is the most intuitive and practical. We found that standard deviation increases in SBP_SD (5.36 mmHg) was associated with a 1.29-fold increase in the risk of PO-AKI, and this was similar to the risk of PO-AKI associated with a MAP ≤ 65 mmHg. In addition, multivariate logistic regression models for the other parameters (SBP_SD, SBP_VIM, PP_SD) and previous studies all yielded similar results,19, 20 further supporting our conclusion that intraoperative blood pressure variability is a risk factor for PO-AKI.
Although we have shown that high intraoperative blood pressure variability is positively associated with high serum creatinine and high postoperative risk of PO-AKI, the mechanisms involved remain unclear, but on the basis of previous findings, we can speculate that the following may be involved. The factors that affect BP, such as anesthesia, blood loss, and the nature of the surgical procedure20, 26 may have direct effects on kidney function. For example, in individuals with hypertension, the use of antihypertensive drugs can cause a reduction in renal blood flow and contraction of renal afferent arterioles, which affects renal function and may lead to AKI.27 AKI may also result from the acute renal tubular injury caused by the reduction in renal blood flow induced by anesthetic use and blood loss, which activates the renin-angiotensin-aldosterone system, renal sympathetic nervous activity, and the glomerular feedback system.28–30 Surgical procedures may also activate these systems, leading to AKI.20 In addition, high intraoperative blood pressure variability may result in intraoperative hemodynamic instability, causing inappropriate renal perfusion19 and the redistribution of blood flow in the kidney, leading to acute or repeated hypoxic injury to the renal medulla, high circulating concentrations of cytokines and reactive oxygen species, dysregulation of the inflammatory response, and further renal parenchymal injury.31, 32 The AKI may be further aggravated by immune activation and inflammation following renal parenchymal injury.
The present findings have implications for clinical practice. First, because of a lack of evidence, the existing clinical guidelines for intraoperative blood pressure management focus on avoiding intraoperative hypotension, to reduce the risk of PO-AKI, while ignoring the potential importance of intraoperative blood pressure fluctuations.23, 33 The present results provide new evidence to facilitate the design of strategies for the control of blood pressure fluctuations. Second, the findings suggest that attention should be paid not only to hypotension, but also to fluctuations in SBP during intraoperative blood pressure management. The intraoperative adjustment of blood pressure should be performed carefully, such that the fluctuations do not exceed 5 mmHg, except in emergencies.
The present study had some limitations. First, PO-AKI was not defined in advance, because this was a retrospective study, resulting in inconsistent timing and standardization of the serum creatinine measurements, which may have caused errors in the identification of PO-AKI. Second, the study sample was selected from the Kailuan study population, and therefore the findings may not be representative of other populations. Further selection bias may have been introduced by the fact that patients for whom invasive blood pressure monitoring is used are frequently at high risk of PO-AKI, thereby potentially causing an overestimation of the strength of the relationship between intraoperative blood pressure variability and PO-AKI. Finally, although we attempted to account for the influence of a number of confounding factors, residual confounding may have been caused by the use of perioperative angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, or intraoperative medication, which may have affected the intraoperative blood pressure variability and pathogenesis of PO-AKI.
In conclusion, short-term intraoperative blood pressure variability is positively associated with a perioperative increase in serum creatinine concentration and PO-AKI in patients undergoing non-cardiac surgery. Therefore, fluctuations in SBP should be monitored and minimized in patients undergoing such surgery.