Should you stop ACE inhibitors prior to major surgery for renoprotection?

I must admit that I have always routinely advised holding ACE/ARB prior to major surgery, given the possibility of hemodynamic instability and assumed risk of AKI due to impaired renal autoregulation when perfusion pressure is low. I’m prepared to accept that I might be biased, as so much of the AKI I see relates to ACEi use, especially in the elderly. But, as it turns out, the question of continuing ACEi pre-operatively is surprisingly controversial. It seems cardiac surgeons are completely split down the middle on the question. Of 167 practicing UK cardiac surgeons who were asked “Do you think it’s beneficial to stop ACEi pre-surgery?” 40% said yes, 40% said no and 20% just grunted. Some even advocate their use for the prevention of AKI. So, you may yet have a friendly tete a tete with your local cardiac surgeon over this issue, and a brief recap of the evidence may stand to you in such an event.

What is immediately striking when you begin read around this issue is the existence of 2 pitched positions, similar to the ongoing debate on renal artery stenting. On the one hand Nephrology journals mostly carry studies supporting ACE avoidance, whereas Anesthetic/Cardiothoracic Surgical journals only seem to have trials that support of ACE continuation. This observation is of itself unsettling, as it suggests to me the existence of publication bias.

Evidence for continuing ACEi:

1. Although small (N=14 CABG patients), this prospective study of 48 hours of iv enalaprilat vs placebo showed that cardiac index, SVR, renal plasma flow (measured by hippurate) and creatinine clearance (measured by timed urine collection) were all significantly improved in the treatment arm and the effects lasted up to post-operative day 7.

2. This small placebo-controlled double blind trial (enalapril vs. placebo) of 40 patients with LVEF < 35% undergoing CABG also showed improved GFR in the treatment arm (GFR increased from 66 to 80; p=0.009 vs no change in placebo).

3. Finally, a prospective multivariate analysis of 536 patients undergoing on-pump CABG, where AKI was defined as a 50% decrease in GFR. The authors observed a reduced rate of AKI associated with pre-op ACEi use (ACE OR 0.48 0.23‐0.77 p = 0.04). The authors tried to reduce selection bias through the use of propensity scores – adjusting for likely group membership (i.e. ACE vs. no ACE) – which are controversial.

Evidence against continuing ACEi:

1. A larger study by Arora et al. (1358, mostly CABG patients), but retrospective and, again, employing propensity scoring to try and mitigate selection bias. Nonetheless, they did observe a 40% increased risk of AKI in multivariate regression analyses.

So where does this leave us? Two small, randomized, prospective studies show a benefit in hemodynamic parameters and GFR. These are consistent with the known vasodilatory effects of ACEi on the systemic and renal circulation, and I have no trouble believing them. However, they do not address the issue of response to a hypotensive insult while on an ACE, which is the crux of the problem in my opinion. Then, we have conflicting evidence from 2 larger observational studies, both of which are concerning for selection bias, with one suggesting the possibility of harm. Based on the above, I would agree with Thomas Berl’s assessment at this years ASN, and invoke Pohl’s rule: “Never trade an unknown benefit for a potential complication.” Given there is no convincing renal benefit to continuing ACE/ARB prior to surgery, and the real possibility of harm, I would hold these drugs for surgeries where post-op hemodynamic instability is likely.