Withholding or continuing angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers on acute kidney injury after non-cardiac surgery

We read with interest the article by Choi et al., which examines the association between acute kidney injury in patients who have had their angiotensin-converting enzyme inhibitors or angiotensin receptor-blocking drugs withheld or continued, respectively, pre-operatively [1]. We commend them on a well-designed study that paid great attention to relevant propensity matching.

We want to comment on the difference between statistical significance and clinical relevance [2]. While we agree that an increase of 26.4 μmol.l^-1 in < 48 h is the definition of acute kidney injury as set out by the Acute Kidney Injury Network, both groups show increased serum creatinine values in the postoperative period [1, 3]. The actual difference in increased serum creatinine values is relatively small between the two groups, which would lead us to question the clinical significance. In contrast, the statistical significance of those who breach the threshold of 26.4 μmol.l^-1 is clear and undeniable. As discussed in the article, a recent meta-analysis by Hollmann et al. failed to show an association between peri-operative administration of angiotensin-converting enzyme inhibitors or angiotensin receptor-blocking drugs and mortality or major adverse cardiac events in patients undergoing non-cardiac surgery [3].

While we agree that the article by Choi et al. supports the routine withholding of angiotensin-converting enzyme inhibitors and angiotensin receptor-blocking drugs pre-operatively, we think the more interesting question is whether we can identify specific subsets of patients who are more significantly impacted by the continuation of these drugs in the peri-operative period. This is addressed in the supplementary material where we see that the odds ratio of developing an acute kidney injury appears to be much greater in those patients who present for surgery with an elevated baseline creatinine, low baseline haemoglobin, low BMI and those requiring pre-operative red blood cell transfusion. We are interested if the authors, knowing the data in detail, have any opinion on whether they see a need to cancel surgery in the higher-risk cohort of patients who erroneously continue these drugs peri-operatively.

The authors report that continuation of these drugs was associated with a mean reduction in intra-operative mean arterial pressure of 1.3 mmHg. While this has reached statistical significance, again, we question its clinical relevance. The patients who had these medications withheld also had a relatively large increase in baseline creatinine levels in the postoperative period. The difference in mean arterial pressure, fluid boluses and vasopressor administration between the groups was statistically significant but, again, we question the clinical significance.

The authors highlight that the type of maintenance of anaesthesia (volatile, total intravenous or even neuraxial techniques), sex of the patient and the type of surgery could potentially contribute to postoperative renal dysfunction. However, there were more male patients enrolled in the study (58%), more patients received volatile anaesthetic maintenance (75%) and there was no difference between the two groups. Oh et. al. performed a retrospective propensity score analysis showing no significant difference in postoperative acute kidney injuries between patients who received total intravenous anaesthesia and those who received sevoflurane-based inhalational anaesthesia [4]. This raises the question of whether these variables were clinically and statistically significant enough to be mentioned in this study.

While the primary outcome of the study by Choi et al. is relevant and an important addition to the literature, the supplementary material poses more interesting questions. Is the key to showing the actual effect of withholding these medications not seen because we are including cohorts of patients with greater renal functional reserve? If the data were further dissected to look at the impact of baseline values, we may find where the true clinical significance of this study lies.