Prevention of Ischemic Injury in Noncardiac Surgery


Perioperative myocardial infarction (MI) is the most common cause of death in the early postoperative period. Perioperative ischemia can be caused by either acute coronary thrombosis or by a mismatch between myocardial oxygen supply and demand. While the inflammatory response to surgery itself may be responsible for precipitating acute plaque rupture and MI, other hemodynamic disturbances, including hypertension/hypotension, tachycardia, acute blood loss, and anemia, may be also lead to ischemic events in vulnerable patients.

A comprehensive approach to the evaluation and management of patients at risk for major adverse cardiac events (MACE) in the perioperative period is essential to optimize outcomes in this population. In this chapter, we discuss the perioperative management of patients at risk of MI, including preoperative medical optimization, intraoperative management, and anesthetic selection. We also discuss emerging concepts in ischemia prevention. Emphasis is placed on current American College of Cardiology/American Heart Association (ACC/AHA) guidelines for perioperative management and the European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA) guidelines on noncardiac surgery.

Pathophysiology and Natural History of Perioperative Ischemia

The pathophysiology of perioperative MI is complex and variable. Generally, there are two subtypes of perioperative ischemia: acute coronary syndrome from thrombotic occlusion of a coronary artery and demand ischemia. Demand ischemia is far more prevalent than acute coronary syndrome as the etiology of perioperative MI. Perioperative MI typically occurs in the first 4 postoperative days, although it can occur at any point during hospitalization ( Fig. 12.1 ).

Fig. 12.1

Cumulative (gray) and proportional (black) presentation per day of perioperative myocardial infarction.

(With permission from Biccard BM, Rodseth RN. The pathophysiology of peri-operative myocardial infarction. Anaesthesia . 2010;65(7):733–741.)

In contrast to medical patients presenting with MI, who primarily die of thrombotic coronary occlusion, angiographic studies of patients who had a fatal perioperative MI showed a much lower rate of plaque rupture. This suggests that myocardial oxygen supply and demand mismatch play a much more prominent role in perioperative MI. Predictably, patients with a high burden of coronary artery disease preoperatively are at elevated risk for perioperative MI. The number and severity of lesions is correlated with the risk of perioperative mortality in vascular surgery patients, and the presence of a chronic total occlusion of a coronary artery with collateralization is common in patients experiencing perioperative MI.

The incidence of perioperative MI varies, depending on the definition used, but even a minor increase in serum troponin is associated with a significant increase in 30-day mortality, although a cause-and-effect relationship has not been firmly established. Importantly, studies suggest the majority of patients with perioperative MI will not present with symptoms of ischemia, and there should be a low threshold to initiate an ischemic workup in postoperative patients who demonstrate evidence of clinical decompensation. Ultimately, patients who develop perioperative MI are at a significantly increased risk of mortality, with the largest cohort to date examining outcomes in this patient population showing a fivefold increase in 30-day mortality in patients with perioperative MI.

Preoperative Optimization

Screening and Risk Stratification

A detailed discussion of preoperative cardiac assessment can be found in Chapter 5 . In general, risk stratification for noncardiac surgery is performed by assessing functional status and for the presence of comorbidities that predict an increased risk of MACE. Functional status can be determined formally, via exercise testing or a number of existing validated activity indices, or informally, by assessing activities of daily living. Patients who are unable to perform greater than 4 metabolic equivalents of activity are at increased risk of MACE, independent of other comorbidities. Similarly, elderly patients who have significant frailty, as defined by a number of scoring systems, are at increased risk of adverse perioperative events.

Assessment of preexisting comorbidities is also useful for defining perioperative risk, and there are a number of tools that can be used to help assess for risk of MACE. The revised cardiac risk index is a straightforward and easy method of estimating the risk of MACE. Patients are assessed for six criteria: (1) ischemic heart disease, (2) cerebrovascular disease, (3) serum creatinine > 2 mg/dL, (4) congestive heart failure, (5) insulin-dependent diabetes mellitus, and (6) high-risk surgery. Patients with zero or one criterion are at low risk for MACE, and patients who meet two or more criteria are at increased risk. While this algorithm played a central role in directing preoperative cardiac assessment in the 2007 AHA/ACC preoperative testing guidelines, its utility has been deemphasized in the 2014 edition of the guidelines in favor of more sophisticated indices of preoperative risk assessment, such as the American College of Surgeons National Surgical Quality Improvement Program, Myocardial Infarction or Cardiac Arrest, and surgical risk calculators. The current algorithm from the ACC/AHA guidelines for preoperative assessment detailing decision making for preoperative cardiac testing can be found in Fig. 12.2 .

Fig. 12.2

Algorithm for perioperative decision making, risk stratification, and preoperative cardiac evaluation. ACS , Acute coronary syndrome; CAD , coronary artery disease; CPG, clinical practice guidelines; GDMT, guideline-directed medical therapy; HF, heart failure; MACE, major adverse cardiac events; MET, metabolic equivalents; VHD, valvular heart disease.

(With permission from Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol . 2014;64(22):e77-e137.)

Myocardial Revascularization

The role of preoperative myocardial revascularization in the patient with significant coronary artery disease remains controversial, and current literature is conflicting as to its clinical benefit. Most large studies evaluating the utility of preoperative revascularization have been performed in the high-risk vascular surgery population. In 2004, the CARP (Coronary Artery Revascularization Prophylaxis) trial demonstrated no significant mortality benefit and no reduction in 30-day MI in patients who underwent preoperative revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

The management of the patient undergoing preoperative evaluation who is found to have significant coronary artery disease depends on (1) the urgency of the surgery, (2) the anatomic distribution of their coronary artery disease, and (3) their degree of clinical symptoms. The most recent recommendations suggest that patients scheduled for an elevated-risk surgical procedure who are found to have coronary artery disease for which CABG is indicated should undergo CABG prior to proceeding with their originally scheduled procedure if the procedure is not of a time-sensitive nature. The role of PCI is less clear in the perioperative setting and should only be performed in those patients with left main coronary artery disease who are not candidates for CABG or patients with unstable angina or MI.

Importantly, patients presenting for elective surgery with a significant burden of coronary artery disease should be involved in the surgical decision-making process, with consideration for cancelation or delay of surgery if perioperative risk is felt to be high. Perioperative management and decisions regarding preoperative revascularization should be made with input from a multidisciplinary team, including the patient’s cardiologist, surgical team, and anesthesiologist.

Medication Optimization

Preoperative medication optimization has remained a major focus in the anesthetic literature, with numerous major clinical trials attempting to ascertain the potential of various medications to prevent perioperative ischemic events. Although a number of medications have been evaluated, determining the optimal medical regimen for preventing perioperative ischemic events remains under investigation. Here, we review the current evidence for common medications, as well as the current guidelines for perioperative medication management.


The use of beta-adrenergic blocking agents in the perioperative period has been a subject of intense clinical investigation. In general, research into the management of beta-blockers in the perioperative period has focused on the management of patients already taking beta-blockers with examination of the effect of beta-blocker discontinuation and on patients who are not taking beta-blockers preoperatively but are deemed to be at elevated risk of perioperative MACE.

The continuation of beta-blockade in patients previously taking beta-blockers is a core measure in the Surgical Care Improvement Project, with a Class I recommendation in the current ACC/AHA guidelines. Interestingly, despite an extensive body of prospective literature examining initiation of beta-blockade in the perioperative period, the evidence for beta-blocker continuation is still evolving. A 2001 study of 140 vascular surgical patients showed a 50% mortality rate in patients who had beta-blockers discontinued in the early postoperative period, but this group only constituted 8 patients out of a cohort of 140. Hoeks and colleagues examined a similar cohort of 711 vascular surgery patients and found an increase in 1-year mortality in patients who had their beta-blockers discontinued perioperatively. These two studies formed the basis for the initial recommendation for beta-blocker continuation in the 2007 ACC/AHA guidelines. More recent studies examining larger cohorts showed a less dramatic difference but collectively concluded that continuation of beta-blockers was associated with a lower overall risk of cardiovascular events and mortality in patients receiving them preoperatively.

With regard to the initiation of beta-blockade in the perioperative period, the available evidence suggests that initiation on the day of surgery may potentially be detrimental. The largest study to date evaluating perioperative beta-blocker administration was the POISE (PeriOperative ISchemic Evaluation) trial. This trial prospectively randomized over 8000 patients to high-dose, extended-release metoprolol or placebo beginning on the morning of surgery and continuing for 30 days. While the administration of metoprolol was found to be associated with a lower risk of MI, there was an overall increase in the risk of stroke and mortality. In 2014, the ACC/AHA Task Force on Practice Guidelines issued a systematic review specific to perioperative beta-blocker therapy. Consistent with the POISE trial, this systematic review examining over 12,000 patients demonstrated that the initiation of beta-blocker therapy within 1 day of surgery was associated with an overall decrease in the incidence of MI but an increase in stroke, hypotension, and bradycardia. This study also suggested a possible increase in cardiac and all-cause mortality in this population. To date, the effect of initiating beta-blocking medications days to weeks in advance of an operation has not been rigorously evaluated and remains a focus of continued investigation.

Current Recommendations

The 2014 ACC/AHA guidelines for patients undergoing noncardiac surgery suggest that patients receiving beta-blockers preoperatively should be continued on them in the perioperative period (Class I). Patients who are deemed to be at high risk of perioperative MACE may benefit from the initiation of beta-blockers prior to surgery, but there should be adequate time to assess the safety and tolerability of beta-blockade (Class IIB). The guidelines caution against the initiation of beta-blocker therapy on the day of surgery (Class III).

The 2014 ESC/ESA guidelines also emphasize the utility of beta-blocker continuation in patients receiving them preoperatively (Class I) and advocate for the initiation of beta-blockers in patients scheduled for high-risk surgery with at least two clinical risk factors or American Society of Anesthesiologists physical status > 3 or patients with known ischemic heart disease (Class IIB). However, these guidelines advocate for consideration of atenolol or bisoprolol as a first-choice beta-blocker (Class IIB), in contrast to the ACC/AHA guidelines, which do not specify which specific beta-blocker should be used. The guidelines recommend against perioperative initiation of high-dose beta-blockers or initiation in patients having low-risk surgery (Class III).


Until recently, evidence for the perioperative use of statin therapy for prevention of MACE was limited to high-risk patients undergoing vascular or cardiothoracic surgery, with guidelines primarily emphasizing the utility of statin continuation in patients treated with preoperative statin therapy. Recently, London and colleagues performed a large, retrospective, observational review on over 180,000 patients undergoing noncardiac surgery whose information is recorded in the Veterans Affairs (VA) Surgical Quality Improvement Database. They found that exposure to statins on the day of or day after surgery was associated with a significant reduction in 30-day mortality as well as cardiac, respiratory, renal, and infectious complications.

The benefit of initiating statin therapy in patients not previously on a statin is less well defined. A 2015 systematic review examined 16 randomized controlled trials that evaluated preoperative initiation of statin therapy on morbidity and mortality. Of note, 13 of 16 trials looked exclusively at patients having CABG. The authors demonstrated a reduction in mortality, MI, atrial fibrillation, and hospital length of stay, concluding with a recommendation that the initiation of statin therapy should be considered in statin-naïve patients having cardiac surgery, although they were unable to make recommendations based on their subgroup analysis in the noncardiac surgical population. In contrast, a 2013 Cochrane systematic review concluded that statin therapy was not associated in any significant reduction in mortality, cardiovascular-specific mortality, or MI, although it should be noted that the sample reviewed in this analysis was quite small. Unfortunately, as the authors of this analysis noted, the use of statin medications in the population at risk for MACE is already ubiquitous, making large randomized controlled trials difficult to perform.

Current Recommendations

The current ACC/AHA guidelines recommend the continuation of statins during the perioperative period in patients who are already taking them preoperatively (Class I). The guidelines also suggest that preoperative initiation of statins is reasonable in patients who are undergoing vascular surgery (Class IIA) and potentially other elevated-risk procedures, if risk factors for perioperative MACE are present (Class IIB). The ESC/ESA guidelines mirror the ACC/AHA guidelines for statin use.

Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are commonly prescribed medications for the management of hypertension and heart failure. Despite the ubiquity of these medications, they have not been the subject of a large number of randomized controlled trials, as beta-adrenergic blocking drugs have. Instead, investigation of the perioperative management of ACE/ARB medications has proceeded primarily through large retrospective cohort analyses. Current research has focused on (1) whether to continue or stop ACE inhibitors and ARBs in the perioperative period and (2) the benefits of early resumption of therapy following surgery.

Although the current ACC/AHA guidelines recommend continuation of ACE inhibitors or ARBs during the perioperative period, recent evidence suggests that the discontinuation of these medications may actually be associated with a lower risk of death or postoperative vascular complications. This analysis retrospectively analyzed 4802 patients taking an ACE inhibitor or an ARB who underwent noncardiac surgery. The 1245 patients who discontinued their ACE inhibitor/ARB prior to surgery had a lower incidence of death, stroke, and myocardial ischemia, as well as less intraoperative hypotension. This study is in contrast to a 2012 study by Turan and colleagues demonstrating no increase in perioperative morbidity or mortality in patients taking ACE inhibitors and ARBs in the perioperative period.

The utility of early postoperative resumption of ACE inhibitor therapy was investigated in a large retrospective cohort study of VA patients undergoing noncardiac surgery. In this study, the authors demonstrated that failing to resume ACE inhibitor therapy within the first 14 postoperative days is associated with a large increase in 30-day postoperative mortality (hazard ratio, 3.44). Although this retrospective analysis of patients does not establish a causal relationship between failure to resume ACE inhibitors in the postoperative period and eventual mortality, this large study formed the basis for recommendations for early resumption of therapy in the current ACC/AHA guidelines.

Current Recommendations

The current ACC/AHA guidelines suggest that it is appropriate to continue ACE inhibitors and ARBs during the perioperative period (Class IIA). In patients in whom ACE/ARB medications are discontinued, the guidelines recommend early resumption of therapy (Class IIA).

The ESC/ESA guidelines also recommend continuation of ACE inhibitors and ARBs in patients with stable heart failure or left ventricular dysfunction (Class IIA), but they suggest that temporary discontinuation in patients taking ACE inhibitors or ARBs for hypertension may be appropriate (Class IIA). The ESC/ESA guidelines also recommend the initiation of ACE inhibitors or ARBs at least 1 week prior to surgery in patients with heart failure or ventricular dysfunction (Class IIA). However, as discussed above, discontinuation of ACE inhibitors and ARBs in the perioperative period should be considered, given new clinical data.

Alpha-2 Agonists

Alpha-2 agonists are widely used for control of hypertension, and their sympatholytic properties make them potential candidates to prevent perioperative MI. There was initial enthusiasm for the use of alpha-2 agonists for myocardial protection based on early studies showing potential benefit in reducing perioperative morbidity and myocardial ischemia in vascular surgery patients. This conceptually formed the basis for the POISE-2 trial examining the utility of both aspirin and clonidine in preventing perioperative MI. The POISE-2 trial randomized over 10,000 patients to receive either clonidine or placebo with or without aspirin in a 2-by-2 design. Unfortunately, neither clonidine nor aspirin reduced the incidence of MI or death within 30 days of surgery. A subsequent analysis examined the potential ability of clonidine or aspirin to prevent acute kidney injury following noncardiac surgery and again found no benefit.

Current Recommendations

Starting or administering alpha-2 agonists to prevent perioperative MACE is not recommended in the current ACC/AHA guidelines (Class III) or ESC/ESA guidelines.

Aspirin and Antiplatelet Agents

A substantial number of patients at risk for perioperative MI present for surgery taking one of more antiplatelet agents. These patients can be separated into several groups, which will be discussed here: (1) patients who are on aspirin for primary prevention of cardiovascular events, (2) patients with a history of coronary artery disease and prior bare metal stent, (3) patients with a history of coronary artery disease and prior drug-eluting stent, and (4) patients who have undergone recent CABG.

As discussed previously, the initiation or continuation of aspirin therapy to prevent perioperative MI was investigated as part of the POISE-2 trial. This study demonstrated no significant reduction in perioperative ischemic events but did show a significant increase in the risk of major bleeding in patients receiving aspirin compared with placebo. Overall, this trial suggests that the continuation of aspirin in patients without recent coronary artery stenting to prevent perioperative MI is probably not beneficial and may be harmful. There are a number of important patient populations excluded in this trial, most notably patients with recent drug-eluting stent or bare metal stent placement, in whom the management of antiplatelet agents deserves special consideration.

Patients with recent stent placement are at increased risk of in-stent thrombosis, especially with the discontinuation of antiplatelet therapy. However, the optimal approach to the management of dual antiplatelet therapy in these patients in the perioperative period remains unclear. A recent ACC/AHA guideline update on the management of dual antiplatelet therapy advocates a more nuanced approach to antiplatelet therapy in patients with coronary artery disease, with therapy duration based on the type of stent placed, whether the patient presented with stable ischemic heart disease or an acute coronary syndrome, and an assessment of the patient’s overall bleeding risk. In patients who have stable ischemic heart disease and a high bleeding risk, the guidelines suggest that it may be appropriate to discontinue clopidogrel as early as 3 months following drug-eluting stent placement. The association between stent indication and perioperative MACE was recently investigated as part of a large retrospective analysis of VA patients in the United States undergoing noncardiac surgery. In this study, patients who had a stent placed for MI were at significantly increased risk of perioperative MACE, regardless of the type of stent that was placed. Although these data and recommendations have not yet been incorporated into guidelines for perioperative management, it seems likely that a more selective approach to antiplatelet agent discontinuation may be forthcoming. In these recommendations, patients undergoing CABG also have stratified recommendations based on their presentation, with a Class I recommendation for the use of a P2Y 12 inhibitor in patients with acute coronary syndrome who have CABG and a Class IIB recommendation for 12 months of P2Y 12 inhibitor therapy in patients presenting with stable ischemic heart disease.

Ultimately, a patient presenting for noncardiac surgery on antiplatelet therapy should undergo a comprehensive risk assessment with involvement of the patient’s cardiologist, anesthesiologist, and surgical team to discuss the relative risks of surgical bleeding and perioperative cardiac events. Discontinuation of antiplatelet therapy, especially in patients with recent cardiac stent placement, may increase the risk of in-stent thrombosis/stenosis and perioperative MI. Depending on the urgency of the operation, it may be appropriate to delay surgery to attempt to reduce the potential risk of antiplatelet therapy discontinuation.

Current Recommendations

The current ACC/AHA guidelines recommend continuation of dual antiplatelet therapy in any patient undergoing noncardiac surgery in the first 4–6 weeks following either bare metal stent or drug-eluting stent placement. If it is necessary to discontinue the patient’s P2Y 12 inhibitor, aspirin should be continued and the P2Y 12 inhibitor should be restarted as soon as is safe following the surgical procedure (Class I). In patients without prior coronary stenting, clinicians may continue aspirin when the risk of bleeding is outweighed by the risk of cardiac events (Class IIb), but the initiation or continuation of aspirin is not beneficial in elective noncardiac surgery that does not involve carotid artery intervention (Class III) ( Fig. 12.3 ).

Jun 9, 2021 | Posted by in ANESTHESIA | Comments Off on Prevention of Ischemic Injury in Noncardiac Surgery
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