In general, the decision to withdraw medications with cardiovascular effects before surgery depends on the risk balance between the deleterious interaction of the drug with anesthetics and possible morbidity resulting from hemodynamic effects that may occur in the absence of these medications.

Drugs that affect the renin-angiotensin system, such as angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin II receptor subtype 1 antagonists (ARAs), are often used in the management of hypertension, congestive heart failure, and chronic renal failure. These drugs may interfere with the regulation of arterial blood pressure by several different mechanisms, including sympathetic blockade, decrease in responsiveness to α₁-adrenergic agonists, impaired degradation of bradykinin (which promotes vasodilation), and inhibition of the receptor binding of angiotensin II.

Current practice guidelines recommend the perioperative continuation of therapies that have potential for myocardial protection, such as β-adrenoceptor-blocking drugs and calcium-channel blockers. Other drugs that are generally recommended to be continued are those with a potential for rebound hypertension with withdrawal, such as α₂-adrenoceptor agonists.

In the case of perioperative ACEI/ARA therapy, clear guidelines are not available. Severe intraoperative hypotension has been observed in patients treated with preoperative ACEIs and ARAs, and adequate perioperative management of antihypertensive therapy in patients receiving angiotensinsystem blockers has been debated.

Preoperative withdrawal of ACEI/ARA therapy has been proposed on the basis of several reports of intraoperative hypotension, which has been reported to be refractory to common measures such as fluid boluses or intravenous ephedrine and phenylephrine. Several small, controlled, randomized
studies showed an increased frequency of hypotension after the induction of anesthesia when ACEI/ARA therapy was continued through the morning of surgery compared with discontinuation of therapy the night before surgery.

Angiotensin-system inhibition has also been shown to increase vasopressor requirements after cardiopulmonary bypass. Vasopressin or vasopressin analogs such as terlipressin have been advocated in patients on ACEI/ARA therapy to treat hypotension that is refractory to other measures.

Despite reports of intraoperative hypotension, some authors have recommended continued perioperative ACEI/ARA therapy for its potentially beneficial effects. Possible benefits are a decrease in ischemia-related myocardial cell damage in cardiac surgery and improved renal function in patients undergoing cardiopulmonary bypass, as measured by an improvement in urinary excretion of sodium.

In a recent large clinical trial by Comfere et al., the timing of the last ACEI or ARA dose was a major determinant of the frequency of postinduction hypotension. During the first 30 minutes after anesthetic induction, moderate hypotension (systolic blood pressure <85 mm Hg) was more frequent in patients whose most recent ACEI/ARA dose was taken within 10 hours (60%) compared with those whose last dose was taken more than 10 hours before induction (46%).

These findings can be explained by the elimination half-lives of ACEI/ARA drugs (Table 46.1). Specifically, a 10-hour interval between
the last dose and anesthetic induction corresponds to the average half-life of an ACEI or ARA and appears to be sufficient to decrease the incidence of hypotensive episodes after anesthetic induction. In humans, most ACEIs are eliminated renally via glomerular filtration or tubular secretion. Renal insufficiency may have a substantial effect on the half-life of certain ACEIs, and the altered pharmacokinetics of ACEIs in chronic renal failure may be a potential hazard; thus, abstinence for longer than 10 hours before surgery may be considered in patients with renal insufficiency.