Withold ACE inhibitors for surgery? Think Again

Anecdotally, the majority of anesthetists withhold ACE inhibitors (angiotensin converting enzyme inhibitors ACEI)  on the day of surgery because of concerns regarding hypotension, particularly in operations that may involve sympathectomy (spinal anesthesia) or blood loss. This appears to be a particular problem with angiotensin receptor blockers (here). We already know that withholding beta blockers and statins preoperatively is associated with an increase in the risk of myocardial ischaemia (reviewed here). ACEI were the wonder drugs of the 1980s: 1. use of ACE inhibitors provide long-term cardiovascular protection and reduce ischemic events and complications; 2. early ACE inhibitor therapy has been demonstrated to produce improved survival and heart function benefits in patients with acute myocardial infarction; 3. they are remarkably effective drugs in the treatment of heart failure and hypertension; 4.  ACEI delays the progression of diabetic nephropathy. So, is it wise to withhold these drugs in the preoperative period?

The following is a quote from a review on this topic in the Postgraduate Medical Journal: “The use of these agents before surgery has been associated with a variable incidence of hypotension during the initial 30 min after induction of anaesthesia; however, these hypotensive episodes have not been conclusively linked to any significant postoperative complications…” (here).

The following is a quote from an excellent review of the topic of drug withholding in preoperative patients: ACEI “intensify the hypotensive effects of anesthesia induction. Because angiotensin II plays a key role in maintaining circulating volume in response to stressors, volume deficits can occur in ACE inhibitor-treated patients as angiotensin II cannot compensate for venous pooling of blood, resulting in diminished cardiac output and arterial hypotension. However, continued renin-angiotensin system suppression may protect regional circulation, as has been demonstrated by reduced release of cardiac enzymes with ACE inhibitor continuation (compared with interruption) in cardiac surgery patients. ACE inhibitors also have a renal protective effect, preserving glomerular filtration rate in patients undergoing aortic abdominal aneurysm repair or coronary artery bypass graft surgery. Hypotension with ACE inhibition is treatable with sympathomimetics, alpha-agonists, and intravenous fluids.” (here). Essentially the author is referring to phenylephrine and vasopressin.

So, it may surprise you to discover that there are emerging data to support the continuation of ACEI in the preoperative setting, particularly in cardiac surgery patients. A recent article in circulation (here – subscription required – the HSE has a 1 year embargo – cheapskates!) suggests that withholding ACEI after cardiac surgery is associated with increased incidence of non fatal cardiac events:

This was a “prospective observational study of 4224 patients undergoing coronary artery bypass graft surgery (CABG). The cohort included 1838 patients receiving ACEI therapy before surgery and 2386 (56.5%) without ACEI exposure. Postoperatively, the pattern of ACEI use yielded 4 groups: continuation, 915 (21.7%); withdrawal, 923 (21.8%); addition, 343 (8.1%); and no ACEI, 2043 (48.4%). Continuous treatment with ACEI versus no ACEI was associated with substantive reductions of risk of nonfatal events (adjusted odds ratio for the composite outcome, 0.69; 95% confidence interval, 0.52–0.91;P=0.009) and a cardiovascular event (odds ratio, 0.64; 95% confidence interval, 0.46–0.88; P=0.006). Addition of ACEI de novo postoperatively compared with no ACEI therapy was also associated with a significant reduction of risk of composite outcome (odds ratio, 0.56; 95% confidence interval, 0.38–0.84; P=0.004) and a cardiovascular event (odds ratio, 0.63; 95% confidence interval, 0.40–0.97;P=0.04). On the other hand, continuous treatment of ACEI versus withdrawal of ACEI was associated with decreased risk of the composite outcome (odds ratio, 0.50; 95% confidence interval, 0.38–0.66; P<0.001), as well as a decrease in cardiac and renal events (P<0.001 and P=0.005, respectively).”

There are some unpublished data that continuing ACCEI up to surgery (and presumably afterwards) is associated with lower 30 day mortality (here). Preoperative use appears to be associated with fewer major adverse events after cardiac surgery (here), and even when no benefit has been demonstrated the agents appear to be safe (here).

So, think twice before you stop the ACEI in your preoperative visit. Nevertheless, I am still going to avoid these agents when anesthetizing patients in the beach chair position (here).

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