The presence of IOH was associated with an increased risk of developing postoperative AKI after liver transplantation and this association was independent of potential perioperative confounders. Moreover, the longer a patient spent with a MAP < 65 mmHg during the liver transplantation procedure, the greater the risk he or she had of developing AKI in the immediate postoperative period. These findings confirm that IOH is of real clinical importance and should not be overlooked during the intraoperative period.
Multiple large retrospective studies have shown an association between IOH and postoperative AKI,[13–20, 22] and others have reported an association between the duration of IOH and cardiac, renal and neurological adverse events.[13, 17, 23, 24] However, this association remains poorly defined in the context of liver transplantation. To our knowledge, only one study has assessed the relationship between IOH and the risk of AKI in this patient population. In that study, the authors demonstrated that severe IOH, defined as a MAP < 50 mmHg was strongly related to the development of moderate and severe AKI (stage 2–3). Patients undergoing liver transplant surgery frequently experience IOH as a result of various factors, including, among others, the duration of surgery, the severity of bleeding, the severity of the ischaemic reperfusion syndrome and the severity of the end-stage liver disease, characterised by a hyperdynamic state (high cardiac output and low systemic vascular resistance). However, most studies, that have assessed predisposing factors for AKI after liver transplant surgery, focused mainly on preoperative factors, which are often not modifiable. Perioperative risk factors, such as IOH, are, in contrast, potentially modifiable, and may be minimised by close a collaboration between the surgeon and the anaesthetist. Our results suggest that avoiding or at least minimising the duration of IOH may be a valuable target to reduce the development of postoperative AKI.
Importantly, our hospital has no any strict MAP targets for liver transplant surgery (except to avoid a MAP < 65 mmHg) and MAP management is left to the discretion of the anaesthetist in charge of the patient. Two large randomised controlled trials have demonstrated that targeting a higher arterial pressure during surgery (well above 65 mmHg) was associated with a lower incidence of postoperative AKI.[25, 26] In the first, there was a lower incidence of organ dysfunction in the group of patients managed using a targeted systolic arterial pressure closer to the patient's baseline value compared to the control group in which the same blood pressure target was used for all patients. In the second study, targeting a MAP level between 80–95 mmHg in chronically hypertensive patients reduced the occurrence of postoperative AKI compared to two other MAP targets (65–79 and 96–110 mmHg). French national guidelines recommend maintaining of MAP > 70 mmHg in patients with chronic hypertension (which is the case in 60% of our study cohort) in order to prevent AKI. It naturally follows that targeting a strict MAP goal of 65 mmHg can potentially be flawed as a strict definition of IOH is quite challenging. While some authors use a reduction from baseline value” (e.g. a 20–30% reduction from the patient’s preoperative MAP value), others continue to use the well-known “absolute” threshold value of 65 mmHg to define IOH. We decided in this study to choose the latter as this is the most common practice at our institution. The validity of this threshold can of course be challenged, but Salmasi and colleagues demonstrated that management based on an absolute MAP threshold of 65 mmHg in all patients was equivalent to management targeting relative reductions in MAP from preoperative values in terms of incidence of myocardial and kidney injury. Additionally, although the results of a large randomised controlled study supported the individualization of arterial pressure targets in order to reduce the incidence of organ dysfunction (including a reduction in AKI),[25, 28] it is important to remember that such an approach can be extremely challenging to apply in patients undergoing liver transplant surgery, as higher values may potentially increase bleeding, making surgical conditions more challenging. As always, the risk-benefit ratio should be carefully assessed and future investigation into an optimal definition of IOH is urgently required for liver transplant recipients.
This study has several additional limitations that should be taken into consideration when interpreting our findings. Firstly, it was observational, retrospective, single-centre and included a relatively small sample size. Therefore, a causal relationship cannot be established and our results may not be generalisable to other hospitals with different perioperative haemodynamic and anaesthetic management. Secondly, our findings may be biased by unmeasured confounding parameters at both the patient and hospital levels. Thirdly, as urine output was not taken into account for the classification of AKI, this may have led to a slight “underestimation” of the incidence of postoperative AKI in our study cohort. Fourthly, per KDIGO definitions, we defined AKI as the change in creatinine value between the preoperative value and the highest value during the first postoperative week. This might introduce time-varying confounding or mediating factors, which limit interpretation of the study finding. Fifthly, postoperative hypotension was not taken into account as MAP was less frequently measured in the intensive care unit or on the floor than in the operating room. Sixthly, although all patients had a pulmonary catheter, data on mixed venous oxygen saturation (SvO2) and cardiac index were not linked to our electronic medical records and thus, could not be assessed in the present study. However, it is important to note that a recent manuscript demonstrated that decreased SvO2 was associated with postoperative AKI after liver transplantation. Seventhly, we had no data on the occurrence of post- reperfusion syndrome and its importance on IOH duration. Finally, it is important to note that we reported the odds ratio for a frequent outcome (AKI), and the odds ratio can overestimate the risk in this situation.