Figure 94.1. Cardiac Evaluation and Care Algorithm for Noncardiac Surgery. From ACC/AHA 2007 Guidelines. Source: Reprinted with permission from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. Circulation. 2007;116(17):e418–499.

    After it has been determined whether there are active cardiac conditions that require treatment prior to surgery, the risk of the surgery and the functional capacity of the patient need to be considered. The ACC/AHA Guidelines use a different definition of what constitutes high-risk surgery than was used in the RCRI derivation. High-risk surgery, as defined in the ACC/AHA Guidelines, is vascular surgery, including aortic or other major vascular procedures, as well as peripheral vascular surgery. Surgeries such as orthopedic surgery, nonvascular intraperitoneal and intrathoracic surgery, and head and neck surgery are all considered intermediate risk. Procedures such as breast surgery and endoscopic surgery are considered low risk.

    Patients undergoing low-risk procedures can generally go to the OR without further testing regardless of their functional capacity. For patients undergoing procedures that are not low risk, the ACC/AHA Guidelines recommend that the patients’ functional capacity be determined based on the history. The current threshold is defined as being able to achieve ≥4 METs (metabolic equivalents) of activity without cardiac symptoms. A functional capacity of 4 METs corresponds to climbing a flight of stairs with a bag of groceries, walking 3.5 mph briskly on a level surface, or sweeping the sidewalk. Patients with a functional capacity of ≥4 METs can go to the OR without the need for additional testing.

    Among patients with a functional capacity of <4 METs, further management is determined by the patient’s risk factors as well as the risk of the procedure. The clinical risk factors in the current ACC/AHA Guidelines generally mirror the RCRI risk factors discussed above (history of ischemic heart disease, heart failure, cerebrovascular disease, diabetes mellitus, and renal insufficiency). An exception is high-risk surgery, which is integrated into the algorithm separately rather than considered a risk factor.

    The ACC/AHA Guidelines state that, among patients who have a functional status of <4 METs, those with no risk factors can proceed directly to surgery. Those with one or two risk factors will generally proceed to surgery without additional testing unless noninvasive testing would alter management of the patient. The Guidelines suggest that patients with three or more risk factors undergoing vascular surgery be seriously considered for noninvasive testing prior to surgery. However, even in these patients, noninvasive testing should be obtained only if it will change management, which will depend on the assessed risk of the patient, the risk of the procedure, and the urgency of the procedure. In general in the absence of ongoing active cardiac conditions, the vast majority of patients will not require noninvasive testing prior to surgery, because trials of noninvasive testing and/or revascularization versus medical management prior to surgery have not shown a benefit to an interventional preoperative strategy. Patients with risk factors for cardiac disease should generally have their heart rates controlled with beta blockers (see discussion on beta blockers several sections below).

STUDIES OF PREOPERATIVE TESTING AND REVASCULARIZATION

Three key trials of preoperative strategies are the DECREASE-II trial, the CARP trial, and the DECREASE-V pilot study.

THE DECREASE-II TRIAL

This trial by Poldermans et al. included about 1500 patients who were undergoing vascular surgery. Patients categorized as intermediate risk were randomized to either a preoperative stress test or no stress test. Patients whose stress tests showed extensive ischemia were considered for revascularization, if feasible. All patients received beta blockers, with a goal heart rate of 60–65 beats per minute (bpm).

Results

Based on a composite endpoint of cardiac death and nonfatal MI at 30 days, the intermediate-risk patients who got stress tests prior to surgery did no better than those who did not get stress tests. The rate of the composite endpoint among the patients who got stress tests was 2.3%, compared to 1.8% among the patients who did not receive stress tests (p = 0.62). Revascularization of the intermediate-risk patients with extensive ischemia also did not appear beneficial, although the number of patients in this group was too small to draw firm conclusions. In addition, those patients with lower heart rates had fewer cardiac events. Thus, the results of this trial suggest that it is not advantageous to have intermediate-risk patients undergo preoperative stress tests in patients who are receiving beta blockers.

THE CARP TRIAL

This trial by McFalls et al. (2004) examined whether revascularization prior to surgery is beneficial in a population of patients undergoing vascular surgery. In this trial 510 patients who were considered at elevated cardiac risk, and who therefore had already undergone diagnostic cardiac catheterization, were eligible for enrollment only if their cardiac catheterization showed ≥70% coronary stenosis. Exclusion criteria included stenosis of the left main coronary artery, left ventricular ejection fraction (LVEF) <20%, or severe aortic stenosis. Enrolled patients were randomized to revascularization or no revascularization prior to surgery, with the rate of perioperative beta-blocker use similar in both groups, at around 85%. Among the patients who were revascularized, 59% underwent percutaneous coronary intervention (PCI), and 41% underwent coronary artery bypass graft (CABG).

Results

There was no significant difference in the outcomes between the revascularization and no-revascularization groups, who had similar MI rates at 30 days (11.6% in the revascularization group vs. 14.3% in the no revascularization group; p = 0.37). The two groups also had similar 30-day death rates and long-term outcomes. In this group of patients undergoing vascular surgery, all of whom had angiographically proven coronary artery disease (CAD), preoperative revascularization did not improve outcomes.

THE DECREASE-V PILOT STUDY

This trial by Poldermans and colleagues sought to study a group at higher risk than the population enrolled in the CARP trial. This pilot study included 101 patients undergoing major vascular surgery, who had at least three cardiac risk factors and whose stress tests showed extensive stress-induced ischemia. These patients were then randomized to either revascularization or no revascularization prior to surgery. Of the patients who were revascularized, 65% underwent PCI, while 35% underwent CABG. All patients received beta blockers, which were titrated to a goal resting heart rate of 60–65 bpm. Among those patients randomized to revascularization, 67% had three-vessel CAD (compared with 35% in the CARP trial).

Results

There was no significant difference in the incidence of the primary outcome—which was a composite of 30-day all-cause death and nonfatal MI—between the two groups, at 42.9% in the revascularization group versus 32.7% in the no revascularization group (p = 0.30). Although this was a pilot study, and so may have been underpowered, it corroborates the findings in the CARP study that, even among patients with documented CAD, preoperative revascularization does not appear to offer significant benefit. Pathophysiologically, the failure of preoperative revascularization to confer benefit in patients with known CAD undergoing vascular surgery raises the possibility that coronary lesions other than the flow-limiting ones that are addressed with revascularization may be causing perioperative events in these patients.

    The results of these three studies helped shape the current ACC/AHA Guidelines, in which it is recommended that, in the absence of an active cardiac condition, patients be considered for preoperative noninvasive testing primarily under the narrow circumstances of high-risk patients undergoing high-risk (vascular) surgery—and then only when the results of the noninvasive testing would alter management.

REVASCULARIZATION PRIOR TO SURGERY AND MANAGEMENT AFTER REVASCULARIZATION

Revascularization prior to surgery requires careful management of the time period between revascularization and surgery and of patients’ antiplatelet therapy. For patients who undergo balloon angioplasty without a stent, at least 2–4 weeks should elapse prior to surgery so that the vessel may heal. In patients who receive bare-metal stents, surgery should be delayed 4–6 weeks to allow for some endothelialization of the stent, but it should ideally occur before 12 weeks, which is the point at which the risk of restenosis is higher. Dual antiplatelet therapy (aspirin and clopidogrel) should be continued for at least 4 weeks after implantation of bare-metal stents. Even after 4 weeks, when clopidogrel may be stopped, aspirin should ideally be continued perioperatively subject to the surgeon’s assessment of the bleeding risk.

    With drug-eluting stents, the risk of stent thrombosis persists for a longer period than with bare-metal stents, and so a longer duration of dual antiplatelet therapy is indicated. Aspirin and clopidogrel should be continued for at least 12 months after implantation of a drug-eluting stent. Increasingly, some cardiologists are recommending dual antiplatelet therapy be continued beyond 12 months in patients with drug-eluting stents. Aspirin should be continued perioperatively, even after the 12-month period during which clopidogrel is required. Of course, the surgeon’s assessment of the bleeding risk from aspirin, or aspirin and clopidogrel, needs to be considered in weighing whether to continue these agents perioperatively after revascularization. However, given the potentially severe consequences of stent thrombosis, premature discontinuation of aspirin and clopidogrel should be avoided if at all possible. If it is felt to be absolutely necessary to prematurely discontinue clopidogrel due to the surgical bleeding risk, then aspirin should be continued perioperatively, and the clopidogrel should be restarted as soon as possible.

    These same time frames dictate which preoperative revascularization technique should be used. If the surgical bleeding risk is such that the surgery cannot be done with aspirin and clopidogrel, then if the surgery needs to happen in 14–29 days, balloon angioplasty should be used; if the surgery needs to happen in 30–365 days, then a bare-metal stent should be used; if the surgery needs to happen in >365 days, then a drug-eluting stent should be used. Aspirin should be continued perioperatively, if at all possible, even after the period is reached when clopidogrel may be stopped.

BETA BLOCKERS

Perioperative beta blockade appears to be of benefit among selected patients who are at elevated risk of perioperative cardiac events. The strongest indications for perioperative beta blockers are in patients who are already on them for an appropriate indication, especially patients with ischemia, as beta-blocker withdrawal perioperatively can be harmful. Patients in whom preoperative testing has demonstrated ischemia and who are undergoing vascular surgery also have a clear indication for beta blockers.

    Lindenauer et al. performed a retrospective cohort study that examined the benefit of perioperative beta blockade, stratifying patients based on the RCRI risk factors. The primary outcome used was in-hospital death. This study found that beta blockade was helpful only among patients at elevated cardiac risk. Patients with zero RCRI risk factors showed harm from beta blockers. Clear benefit was seen among patients with three or more RCRI risk factors, and there was a trend toward benefit among patients with two RCRI risk factors.

    Included among the recommendations regarding perioperative beta blockade from the ACC/AHA Guidelines are that beta blockers are “probably recommended” in patients with coronary heart disease, or those with two or more clinical risk factors who are undergoing intermediate-risk or vascular surgery. Vascular surgery is considered the highest-risk surgery by the ACC/AHA Guidelines, and so beta blockers are also reasonable in patients undergoing vascular surgery with one or more risk factors. When giving beta blockers perioperatively, it is not enough that they be “on board,” as the benefit is greatest with a relatively low resting heart rate (Figure 94.2) as long as hypotension is avoided. Thus, patients should have their beta blockers titrated to try to achieve a low-normal heart rate (i.e., in the 60 bpm range).

THE POISE TRIAL

Designed to address the lack of a large randomized controlled trial (RCT) of perioperative beta blockers, the PeriOperative ISchemic Evaluation (POISE) Trial enrolled 8351 patients undergoing noncardiac surgery with at least one cardiac risk factor. Patients were randomized to either placebo or controlled-release metoprolol (CR metoprolol), 100 mg orally 2–4 hours prior to surgery, a postoperative dose of CR metoprolol based on heart rate and blood pressure, and then 200 mg of CR metoprolol orally daily for the next 30 days. Medication doses were omitted for hypotension or bradycardia, but there was no dose titration.

Results

The patients who received the CR metoprolol had a lower rate of the primary outcome—a composite of cardiovascular death, nonfatal MI, and nonfatal cardiac arrest—than the placebo group (5.8% in the CR metoprolol group vs. 6.9% in the placebo group; p = 0.04). However, the total mortality was higher in the CR metoprolol group (3.1%) than in the placebo group (2.3%) (p = 0.03). This higher mortality in the CR metoprolol group appears to have been driven by a higher rate of stroke in the CR metoprolol group (1.0%) than in the placebo group (0.5%) (p = 0.005).

    There is controversy over what lessons should be drawn from the POISE trial. It is very possible that the unfavorable total mortality outcome in the beta-blocker group in the POISE trial was due to the large dose of beta blockers being given so close to the beginning of the surgery. In response to the POISE trial, in 2009, a focused update to the 2007 ACC/AHA Guidelines was issued, suggesting that perioperative beta blockers ideally should be started days or weeks rather than hours before surgery and urging that close attention be paid to beta-blocker dose titration so as to achieve heart rate control while avoiding hypotension or bradycardia.

THE DECREASE-IV TRIAL

This trial by Dunkelgrun et al. (2009) examined the effect of beta blockers in patients at intermediate cardiovascular risk undergoing noncardiovascular surgery. Patients, all of whom were beta-blocker naive, were randomized to receive placebo (n = 533) or the beta blocker bisoprolol (n = 533), started a median of 34 days prior to surgery and titrated to a heart rate of 50–70 bpm.

Results

The primary endpoint, a composite of 30-day cardiac death and nonfatal MI, was reached in 2.1% of patients in the beta-blocker group versus 6.0% in the placebo group (p = 0.002). This trial also included a statin arm, which did not show a significant benefit, and a combined beta blocker and statin arm, which did not appear significantly better than beta blockers alone. Thus, this trial, unlike the POISE trial, was able to show a clear benefit to perioperative beta blockers started about a month prior to surgery and titrated to a goal heart rate of 50–70 bpm.

    To summarize some conclusions that can be drawn about the use of beta blockers perioperatively:

• In patients who are taking beta blockers as outpatients for an appropriate indication, the beta blocker should be continued perioperatively, as beta-blocker withdrawal can be detrimental.

• In patients with known cardiac ischemia, such as has been demonstrated in preoperative stress testing, beta blockers should be used perioperatively in patients undergoing intermediate- and high-risk surgery.

• In patients with at least three cardiac risk factors, and probably in those with at least two cardiac risk factors, especially if they are undergoing intermediate- and high-risk surgery, it is reasonable to use perioperative beta blockers.

• In patients in whom perioperative beta blockers are indicated it is important to achieve a low-normal heart rate, but care needs to be taken to avoid hypotension that could lead to stroke or other adverse event. It is preferable to start beta blockers weeks to months prior to surgery, if possible.

OTHER MEDICATIONS TO DECREASE PERIOPERATIVE CARDIOVASCULAR RISK

STATINS

Statins have been shown in a number of retrospective studies to decrease perioperative cardiac events. The population examined in many of these studies was vascular surgery patients, so it is in this patient population that the data favoring a benefit from statins perioperatively are greatest. An RCT of statins in vascular surgery patients found a significant benefit from the perioperative use of statins (begun a mean of 37 days prior to surgery). Patients receiving statins (n = 250) had a postoperative cardiac ischemia rate of 10.8%, compared to 19.0% in the placebo group (n = 247) (p = 0.01). The statin group also had a significant reduction in death from cardiac causes or MI. Therefore, consistent with ACC/AHA Guidelines, statins should be continued in patients who are already taking them, and it is reasonable to use them in patients undergoing vascular surgery as well. Recent data from a retrospective study has suggested statins may also be associated with a decreased risk of clinically significant postoperative atrial fibrillation.

ALPHA-2 AGONISTS

The data on the perioperative use of alpha-2 agonists, such as clonidine, are limited. In one RCT involving 190 patients at elevated cardiac risk who received clonidine (orally and transdermally) perioperatively, there was a decrease in the incidence of myocardial ischemia in the clonidine group (14%) versus the placebo group (31%) (p = 0.01). However, at this time, clonidine should be considered a second-line agent, to be used only when other agents are either ineffective or contraindicated, in which case it may be considered in patients at elevated cardiac risk.

CALCIUM CHANNEL BLOCKERS

Perioperative calcium channel blockers have only been tested in small trials. A meta-analysis of these trials concluded that calcium channel blockers, especially diltiazem, reduced ischemia and supraventricular tachycardias. However, the ACC/AHA Guidelines make no recommendations regarding their use.

PULMONARY RISK FACTORS AND RISK REDUCTION

Although less studied in the literature than perioperative cardiac complications, perioperative pulmonary complications can be a significant cause of morbidity. In one series, postoperative pulmonary complications developed in 3.4% of patients undergoing noncardiac surgery at Veterans Affairs hospitals. Postoperative pulmonary complications that contribute to this morbidity include pneumonia, respiratory failure requiring mechanical ventilation, bronchospasm, and atelectasis. A clinical guideline by Smetana et al. evaluated the literature on pulmonary risk factors for noncardiothoracic surgery and identified a number of risk factors for which there was good evidence. These risk factors fall into the three categories of patient-related risk factors, procedure-related risk factors, and laboratory tests (table 94.2). In one risk prediction model the most important risk factor was the type of surgery, with those surgeries that were closest to the diaphragm generally conferring the highest pulmonary risk.

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