Hold the ACE inhibitors during surgery?

Major finding: Among patients randomized to continue ACE inhibitor therapy during surgery, 16 of 21 patients developed hypotension, compared with only 6 of 30 patients who discontinued their ACE inhibitors the day before.

Data source: Review of evidence on the perioperative management of patients with hypertension treated with ACE inhibitors or angiotensin II receptor blockers.

Disclosures: Dr. Grant reported having no financial disclosures.

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Larger trial needed

Dr. Vera DePalo

The findings of the studies presented by Dr. Grant have important implications for understanding the significant issue of hypotension that the postoperative patient may face. However, the studies are relatively small, and in some cases the results are conflicting. A larger randomized, controlled trial would help shed light on how we can better identify the patients who can benefit from these therapeutic choices.

Dr. Vera A. DePalo is associate professor of medicine at Brown University, Providence, R.I. She is the deputy medical editor of CHEST Physician.



SCOTTSDALE, ARIZ. – When it comes to holding or continuing with ACE inhibitors before surgery, all bets are off, a perioperative medicine consultant suggested.

Patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) have about a 50% risk of developing hypotension during surgery, and a significant proportion of those episodes could be severe, said Dr. Paul Grant, of the University of Michigan Health System in Ann Arbor.

Dr. Paul Grant

"I recommend having some sort of standard approach [to perioperative ACE inhibitor use] at your institution if that’s at all possible, either for a certain surgery type or across the board," he said at a meeting on perioperative medicine sponsored by the University of Miami.

Evidence from a small number of randomized trials and observational studies suggests that continuing ACE inhibitors during cardiac surgery may result in less cardiac enzyme release, less kidney injury, and a lower incidence of atrial fibrillation. In vascular surgery, evidence suggests that patients on ACE inhibitors who are undergoing surgery have less of a drop in cardiac output and may have improved creatinine clearance.

On the other hand, patients who remain on ACE inhibitors during surgery can experience a "profound" drop in blood pressure requiring immediate intervention, he said.

Data to support the continue vs. hold debate are sparse, but include a trial of 51 patients randomized to continue ACE inhibitors on the day of surgery or to have the drugs held for 12-24 hours before surgery. In all, 33 of the patients were on captopril (Capoten), and 18 were on enalapril (Vasotec).

The investigators found that among patients randomized to continue ACE inhibitor therapy, 7 of 7 on captopril and 9 of 14 on enalapril developed hypotension, defined as a systolic blood pressure (SBP) less than 90 mm Hg. In contrast, among patients assigned to the ACE-inhibitor hold protocol, only 2 of 11 on captopril and 4 of 19 on enalapril developed hypotension during surgery.

In a second randomized trial, investigators looked at 37 patients on an ARB who were randomly assigned to either discontinue ARB on the day before surgery (18 patients), or to receive their ARB 1 hour before anesthesia induction (19 patients).

The authors defined hypotension for their study as an SBP less than 80 mm Hg for more than 1 minute. They found that all 19 patients who continued on ARB had hypotension during surgery, compared with 12 of 18 who discontinued their ARB the day before. Patients who received their ARB on the day of surgery used significantly more vasoactive drugs. Despite the discontinuation of the ARB, there were no differences in hypertension between the groups in the recovery period. Postoperative cardiac complications occurred in 1 patient in each group.

In the final randomized study that Dr. Grant cited, 40 patients on an ACE inhibitor with good left-ventricular function were scheduled to undergo coronary artery bypass graft (CABG). They were randomly assigned to hold or continue on ACE inhibitors on the day of surgery.

Patients in whom the ACE inhibitors were held before CABG had higher mean blood pressures than patients who continued on the drugs, and they used less vasopressor during the surgery. In contrast, patients who continued on ACE inhibitors needed more vasodilators after CABG and in the recovery period. The authors of this trial did not study other clinical endpoints, Dr. Grant noted.

Evidence from two observational studies was more equivocal, however.

In a retrospective observational study, investigators studied the relationship between the timing of discontinuing ACE inhibitors and angiotensin II receptor subtype 1 antagonists (ARA) and the onset of hypotension in 267 patients scheduled for general surgery.

They found that patients exposed to an ACE inhibitor or ARA within 10 hours of anesthesia had an adjusted odds ratio of 1.74 for moderate hypotension (SBP 85 mm Hg or less; P = .04), but there was no difference in severe hypotension between these patients and those who discontinued the drugs more than 10 hours before surgery. There were no differences in either vasopressor use or postoperative complications, including unplanned intensive care unit stay, myocardial infarction, stroke, renal impairment, or death.

A second, smaller study compared 12 vascular surgery patients on ARB the day of surgery with matched cohorts of patients taking beta-blockers and/or calcium channel blockers the day of surgery, or ACE inhibitors held on the day of surgery.

Hypotension (SBP less than 90 mm Hg in this study) occurred in all of the patients on ARB but in only 60% (27 of 45) patients on the beta-blocker/calcium channel blockers, and in 67% (18 of 27) in the ACE-inhibitor hold cohort. The ARB patients were also less responsive to ephedrine and phenylephrine than other patients, and in some cases responded only to a vasopressin system agonist, Dr. Grant noted.

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