Section 3: Perioperative Risk Assessment and Management

INTRODUCTION

Medical consultation has become an important component of Hospital Medicine. These consultations include preoperative evaluation, perioperative management, and medical care of patients on various nonmedical services. Previous surveys found that many primary care physicians and hospitalists felt inadequately trained in perioperative medicine, and as a result, this area received additional emphasis as part of the core competencies for Hospital Medicine. With the growth of the hospitalist movement, the role of the consultant has evolved from providing evaluation and advice to include comanagement of the patient in certain settings. The goal of this chapter is to review the role and responsibilities of the medical consultant, focusing on the principles of consultation and techniques to improve effectiveness.

GENERAL PRINCIPLES OF CONSULTATION

More than 25 years ago, Goldman and colleagues described the concepts for performing medical consultations. His “Ten Commandments” for effective consultation included the following:

1. Determine the question.

2. Establish urgency.

3. Look for yourself.

4. Be as brief as appropriate.

5. Be specific and concise.

6. Provide contingency plans.

7. Honor thy turf.

8. Teach with tact.

9. Talk is cheap and effective.

10. Follow-up.

These concepts, which incorporated many of the ethical principles described by the American Medical Association (AMA), are important and remain valid for the traditional consultation. However, some modifications are necessary to cover the new role of hospitalists as comanagers.

TYPES OF CONSULTATION

The traditional or standard medical consultation consisted of a formal request from the requesting physician to evaluate a patient and answer a specific question (Table 49-1). The consultant was expected to address the question and to provide advice and recommendations, but not to write orders or bring in other consultants; the requesting physician remained in control and responsible for the patient’s overall care and treatment. The consultant also focused on the specific problem rather than looking for and addressing other issues. Consultations were requested only when necessary and not for routine management. The follow-up period was usually brief and did not involve daily visits for the duration of hospitalization.

This traditional role of the consultant has been changing over the past 5 to 10 years. A survey by Salerno and colleagues revealed that many surgeons wanted the medical consultant to assume more of a comanagement role. Specifically, they wanted the consultant to address all medical issues as necessary as well as to write orders and continue to follow the patient. Comanagement arrangements have most often been with orthopedic surgeons and more recently with neurosurgeons. Comanagement has potential advantages of decreasing length of stay and reducing complications. Surgeons and nurses often prefer comanagement; however, one possible disadvantage is that the comanaging consultant may feel subservient to the surgeon and may be asked to assume responsibilities outside his area of training.

Yet another type of consultation is the so-called curbside or informal consult in which the consultant is asked to provide an opinion or advice without personally seeing the patient. Although these should be avoided from a medicolegal standpoint, they occur frequently. Ideally the consultant should offer to perform a formal consult but if any advice is given, it should be generic and simple. The requesting physician should not refer to the consultant in the medical record if he has not seen the patient, and if he has had any contact with the patient, the consultant should write a note in the chart.

DETERMINING THE QUESTION

In view of the multiple types of consultations, it is imperative that the requesting physician specify exactly what is being requested, and if there is any uncertainty, the consultant should clarify this question by communicating directly with the requesting physician. In addition to specifying the role of the consultant, the requesting physician should be specific as to the question being asked of the consultant. For example, a request for preoperative consultation may be for surgical risk assessment, a “green light” to proceed with anesthesia and surgery, a diagnostic or management issue, reassurance, or documentation for medicolegal purposes. As obvious as this may be, disagreement regarding the primary purpose for the consult still occurs between the requesting physician and the consultant. Several studies noted that the consult requests were vague and nonspecific (eg, clearance or evaluation), or did not even ask a question. Without clarifying the reason for the consult, the consultant may respond in a manner that fails to answer the question being asked by the requesting physician.

ANSWERING THE QUESTION

Traditionally, the consultant restricted his or her advice to the specific problem or question. However, more frequently the consultant is addressing other issues noted during the evaluations. Assuming these other findings and recommendations are relevant and important, most surgeons are in favor of this approach. What the requesting physician does not want is a laundry list of things to do for minor problems or issues that do not need to be addressed during the current hospitalization.

If the consultation is for preoperative evaluation, the consultant needs to:

1. Assess the severity and degree of control of the patient’s medical problems.

2. Estimate surgical risk.

3. Determine if the patient is in his or her optimal medical condition for surgery.

4. Decide whether further tests or interventions are indicated.

5. Make recommendations regarding the patient’s medications and any necessary prophylaxis.

The consultant should avoid making recommendations about the type of anesthesia and other areas outside his or her area of expertise. Also, the consultant should refrain from using the term “cleared for surgery,” even if consulted for that reason, as this implies a guarantee that the patient will not have a complication.

OPTIMIZING EFFECTIVENESS

Factors influencing or improving compliance

Various studies found a number of factors that have been associated with improved compliance with the consultant’s recommendations (Table 49-2). In general, following Goldman’s Ten Commandments or Salerno’s modification (see Salerno SM, Hurst FP, Halvorson S, Mercado DL. Principles of effective consultation: an update for the 21st-century consultant. Arch Intern Med. 2007;167(3):271-275) will result in effective consultation.

Determine and clarify the question: As noted, the reason for the consultation needs to be clearly defined by the requesting physician and understood and addressed by the consultant.

Punctual response: The consultant should be available to respond in a timely fashion, depending on the urgency of the consultation. Truly “stat” consults should be answered in less than 30 minutes, and in general, elective consults should be answered within 24 hours, preferably the same day they were requested.

Recommendations:

1. Prioritize and limit: The consultant should make specific, precise recommendations that should be listed in order of importance. Crucial or critical recommendations are more likely to be followed, as are those at the top of the list. For this reason, it was previously felt that the number of recommendations should be limited to no more than five, but more recently the feeling is to leave as many recommendations as needed to answer the consult and offer to help with writing and implementing them (comanagement). Therapeutic recommendations are more likely to be followed than diagnostic ones.

2. Language: The consultant should use definitive language, be specific with his recommendations, and provide contingency plans. For example, recommendations for medications should specify the drug name, dose, frequency, route of administration, and duration of therapy. The requesting physician should be told what response to expect, how long it will take, as well as how and when to adjust the medication dose if necessary.

3. Communication: Direct verbal communication with the requesting physician is crucial and preferable to just leaving a note in the chart. A quick call to the requesting physician will let him know that the consult has been answered, what the recommendations are, and what needs to be done so the orders can be written and the process expedited. It is also important to communicate with other members of the health care team to coordinate care.

4. Follow-up: Appropriate follow-up visits will reassess the patient’s condition and ensure that recommendations were followed. The consultant should clearly document his findings and update recommendations in the medical record. There is no standard regarding how often the consultant needs to see the patient, but this should be determined by the patient’s medical condition, type of surgery, and whether the requesting physician wants comanagement or not. When the patient is medically stable and there is no longer a need for the medical consultant, he should sign off and document this in the chart. Recommendations and arrangements for long-term follow-up can also be noted at this time.

CONCLUSION

The ideal medical consultant will “render a report that informs without patronizing, educates without lecturing, directs without ordering, and solves the problem without making the referring physician appear to be stupid.” It is hoped that by following these principles, the medical consultant will be effective in providing useful information and recommendations to the requesting physician who will then implement them in an attempt to improve patient outcome.

SUGGESTED READINGS

INTRODUCTION

Hospitalists and internists are frequently called upon to perform preoperative medical consultations, and cardiac risk assessment is what is most often requested. Preoperative evaluation is now part of the core curriculum for Hospital Medicine, but when surveyed a number of years ago, many hospitalists felt inadequately trained to do this.

Preoperative cardiac risk assessment has evolved over the past 40 years from a simple global assessment of a patient’s physical status (the ASA classification) to multivariate risk analyses (Goldman, Detsky) to a simplified scoring system (Lee RCRI) to guidelines from the American College of Cardiology/American Heart Association, American College of Physicians (ACC/AHA, ACP). The most current of these is the 2014 ACC/AHA guidelines for perioperative cardiac evaluation and management, which was originally published in 1996 and incorporated the RCRI factors in the 2007 update. Using these guidelines and selective cardiac testing (pharmacologic stress tests), physicians are now better able to provide a more accurate assessment of perioperative risk, and the focus has turned to risk reduction strategies. These include revascularization by coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), medical therapy (β-blockers, α-agonists, statins), and other intraoperative measures (normothermia, anesthetic technique). Although surgical and anesthetic techniques have improved and perioperative cardiac events have decreased, operative mortality and cardiac morbidity remain significant, especially among high-risk patients or high-risk procedures.

This chapter reviews the current state of the art for perioperative risk assessment and risk reduction in patients with cardiac disease.

PREOPERATIVE RISK INDICES

Goldman and colleagues published the first large prospective multivariate analysis of preoperative cardiac risk. They identified nine independent predictors of death or major postoperative cardiac complications. These risk factors were assigned points based on their relative importance, and the event rates were correlated with the point total in this risk index. Detsky and colleagues modified this risk index by expanding the list of risk factors and combining this with the pretest probability of complications based on the risk of the surgery itself. Eagle and colleagues identified five factors—age, diabetes mellitus (DM), angina, myocardial infarction (MI), and heart failure—associated with perioperative cardiac events and used these to stratify risk and decide when to do further cardiac testing.

Lee and colleagues identified and validated six factors associated with increased risk of perioperative complications. These factors were high-risk surgery, coronary artery disease (CAD), heart failure, cerebrovascular disease (stroke or transient ischemic attack), DM requiring insulin, and renal insufficiency (creatinine >2.0 mg/dL). These studies, using simple clinical evaluation (history, physical examination, and basic laboratory studies) found many similar factors predicting increased risk of perioperative cardiac complications and helped refine preoperative risk stratification.

The newest risk calculators were derived from the National Surgical Quality Improvement Program (NSQIP) database. The Gupta calculator (http://www.surgicalriskcalculator.com/miorcardiacarrest) was derived from over 200,000 patients and validated on another 250,000 patients in the database. It estimates risk of MI or cardiac arrest based on five independent predictors: type of surgery, dependent functional status, abnormal creatinine, American Society of Anesthesiologists (ASA) class, and increasing age. The American College of Surgeons (ACS) surgical risk calculator (http://riskcalculator.facs.org) was derived from over 1.4 million patients in the NSQIP database. It is more comprehensive and is based on the CPT code for the surgical procedure and an additional 20 variables. It predicts mortality, serious complication, cardiac complications, and several others and states whether these risks are average, above average, or below average.

CLINICAL RISK FACTORS

A detailed history and focused physical examination are key in clinical risk assessment, and a few basic diagnostic tests may also be helpful. Current risk assessment is usually based on the ACC/AHA guidelines which now include the Lee RCRI and the NSQIP risk calculators.

The 2014 ACC/AHA guideline algorithm is now specifically for evaluation of patients with CAD and therefore removed heart failure, arrhythmias, and valvular disease, recommending that those conditions be evaluated and managed based on current guideline directed medical therapy (GDMT). Of the previous “active cardiac conditions,” only the presence of an acute coronary syndrome (ACS) remains in the algorithm.

PROCEDURAL RISK

Independent of the patient’s clinical risk factors, the type of surgery has its own inherent risk that needs to be taken into account. This concept was used in Detsky’s modified cardiac risk index and is also considered in the ACC algorithm. For example, a patient undergoing cataract surgery, a low-risk operation, is unlikely to have a complication even if the patient’s clinical risk is high. Conversely a patient with no clinical risk factors undergoing high-risk surgery, such as a Whipple procedure, is more likely to have a postoperative complication than would have been predicted based on clinical pretest probability alone. Therefore, the risk of the surgery itself may alter management and influence the decision to do further testing. The 2014 ACC guidelines now define surgical risk as either low risk (<1% MACE) or elevated risk (>1% MACE) based on a combined procedural and clinical risk. The 2007 ACC guidelines defined three groups for surgical risk—vascular, intermediate, and low. The previous designation of high risk was changed to vascular surgery to reflect that the preponderance of evidence for cardiac testing was done for patients undergoing aortic and major vascular surgery, and the approach to these patients may be somewhat different than that for nonvascular surgery. The intermediate risk category includes most intrathoracic, intra-abdominal, head and neck, orthopedic, and urologic procedures as well as some lower-risk vascular procedures such as carotid endarterectomy and endovascular abdominal aortic aneurysm repair. Low-risk surgery includes procedures not invading the chest or abdomen such as endoscopic or superficial procedures, eye surgery, and breast surgery. The risk indices recommended by the new ACC/AHA guidelines incorporate the type of surgery and those using the NSQIP database include even more specific data based on procedural risk.

FUNCTIONAL CAPACITY

Goldman and colleagues noted that patients with good exercise capacity, even with mild, stable angina, tend to do well. This follows the concept of the ischemic threshold in which a patient developing ischemia on a stress test at a lower exercise level and with a lower rate-pressure product is at higher risk than someone who can perform 8 to 10 metabolic equivalents (METS) before developing symptoms. Reilly and colleagues found that a patient’s self-reported exercise capacity correlated with the risk of postoperative complications, and the ACC guidelines use this in their risk assessment algorithm.

LABORATORY TESTS

Many preoperative screening blood tests are performed unnecessarily, but a few may be helpful in assessing cardiac risk. These include measures of renal function, blood urea nitrogen (BUN) and creatinine, and glucose (as a screen for diabetes). Unless serum potassium is significantly abnormal (<3.0 or >5.5 mEq), it is unlikely to increase risk or alter management. Anemia has been noted as a risk factor in some studies, but there is no evidence that treating it with transfusions alters risk. An electrocardiogram (ECG) looking for evidence of CAD or conduction defects may be of value in at-risk patients. Other findings can either be identified by clinical exam (arrhythmias) or do not change management (left ventricular hypertrophy [LVH], nonspecific ST-T changes).

2014 ACC/AHA ALGORITHM

The new ACC guidelines use a stepwise approach to preoperative cardiac risk evaluation for patients with CAD or risk factors for it using the information obtained from the history, physical examination, and laboratory tests (Figure 50-1). The underlying theme is to minimize testing and not to order a test if the result will not change management. The approach is as follows:

1. Is the surgery emergent (or urgent, meaning within 24 hours)?

   If it is, time does not permit diagnostic testing or revascularization and the patient will proceed to surgery. In the short time period available, the physician can try to medically optimize the patient’s problems.

2. Assuming surgery is not emergent, has the patient had an acute coronary syndrome (ACS) (as opposed to any of the active cardiac conditions in the 2007 guidelines)?

   If so, elective surgery should be delayed for further diagnostic workup and therapy. Most patients do not have these conditions.

3. Is the estimated perioperative risk of MACE based on combined clinical/surgical risk low (<1%)?

   If it is, the patient should proceed to surgery without any further testing or intervention because we cannot further reduce risk that is already low (<1%).

4. If elevated risk, does the patient have moderate or greater functional capacity (≥4 METS)?

   If so, for the most part, these patients will do well and do not need to undergo further cardiac testing.

5. If the patient has poor or unknown exercise capacity, the next question is whether or not further testing will impact decision making or perioperative care. This decision should be based on a discussion with the physician, patient, and perioperative team.

   If the answer is yes, then pharmacologic stress testing is indicated. If the stress test is abnormal, coronary angiography and revascularization may be indicated based on the degree of abnormality, and after that, the patient can proceed to surgery following GDMT. Other alternatives include changing to a lesser surgical procedure, a nonsurgical treatment, or palliation. If the test is normal, proceed to surgery according to GDMT.

6. If further testing will not impact decision making or management, then proceed to surgery according to GDMT or consider alternative as previously mentioned.

These last two steps allow for individualizing management, but are somewhat vague and may lead to significant differences in opinion and approach.

DIAGNOSTIC TESTS

Stress tests were designed to diagnose CAD and myocardial ischemia and not to predict short-term events. Because the pathophysiology of perioperative MIs includes unstable plaque rupture or coronary thrombosis as well as myocardial ischemia related to coronary stenosis and an imbalance of oxygen supply and demand, stress tests are poor at predicting which patients are at increased risk for surgery. Although they are good at identifying a patient with CAD, they have a low positive predictive value (PPV), usually between 15% and 20% for perioperative MI, and most patients, even with an abnormal test, will not have a postoperative cardiac complication. On the other hand, a normal or negative stress test is usually associated with a high negative predictive value (NPV), ranging from 95% to 99%, indicating that there is a low likelihood that these patients will have a perioperative event.

Because many patients with cardiac disease undergoing surgery have suboptimal exercise capacity and would be unable to achieve 85% of their target heart rate on an exercise test, pharmacologic stress testing is usually used. Furthermore, if these patients had adequate exercise capacity, they probably would not be candidates for stress testing in the first place. The tests most commonly used are dobutamine stress echocardiography (DSE) and dipyridamole, adenosine, or regadenoson nuclear imaging (either thallium or technetium). These tests are effective in identifying CAD, but as noted earlier, are poor at identifying patients who will develop postoperative cardiac events and should be used selectively in conjunction with the patient’s pretest probability for the results to be meaningful. The test characteristics are influenced by patient selection and pretest probability. In general, results are similar with DSE and dipyridamole thallium (DPT), and test selection should be based on the local expertise available; however, DSE tends to have fewer false-positives except in the case of left bundle branch block (LBBB) where DPT is preferred. On the other hand, DSE is preferred for patients with asthma or chronic obstructive pulmonary disease (COPD) because DPT can cause bronchospasm. The role of cardiac CT or MRI angiography in the perioperative setting is unclear. Resting two-dimensional (2D) echocardiography is not recommended to predict perioperative ischemic complications and should only be used to evaluate valvular heart disease or heart failure.

WHO NEEDS STRESS TESTING BEFORE SURGERY?

The goal of NIT is to further refine clinical judgment and identify patients at significantly increased risk. Bayes theorem can be applied to preoperative evaluation to decide which patients might benefit from stress testing. A patient with a low pretest probability will usually remain at low risk for perioperative complications even if the NIT is positive. Similarly, a patient with high pretest probability will remain at relatively high risk even if the stress test is negative (may represent a false-negative). Therefore, NIT should probably be restricted to intermediate-risk patients where a positive test can move a patient into a higher-risk category and a negative test can reclassify a patient as being at lower risk. The utility of this theoretical approach was supported by L’Italien and colleagues who showed that clinical assessment correlated with outcomes for low- and high-risk patients, and stress test results only changed the probability of complications (confirmed by outcomes) for intermediate-risk patients. Boersma and colleagues also demonstrated that the clinical risk score correlated with outcomes and was rarely changed by stress testing. However, a study by Poldermans and colleagues randomized intermediate risk patients, all of whom were treated with bisoprolol (titrated to a target heart rate of 60 to 65 beats per minute), to preoperative stress testing or no testing. They found no difference in perioperative MI or cardiac death regardless of whether they had a preoperative stress test assuming they were adequately β-blocked. The results of this study beg the question of whether anyone needs NIT if they can be optimally treated medically. However, questions have been raised about the scientific integrity and results of this and other β-blocker studies (DECREASE trials) by the Poldermans group.

WHEN IS PREOPERATIVE CORONARY ANGIOGRAPHY INDICATED?

The ultimate goal of the preoperative evaluation process is to identify the high-risk patient and intervene in some manner to reduce risk of postoperative complications. Assuming stress testing identifies a patient at high risk for postoperative complications, the next step should be to further define risk using cardiac catheterization with a goal of possible revascularization. Otherwise, if the patient is to be treated medically, the stress test was probably unnecessary as it did not change management. Potential candidates for coronary angiography are those high-risk patients with demonstrated ischemia on stress testing or those with unstable coronary syndromes (recent MI, severe angina, or unstable angina) whose clinical risk is high enough to bypass stress testing and who have independent criteria for coronary angiography independent of their need for noncardiac surgery. If coronary angiography demonstrates significant anatomic lesions, a decision must be made regarding revascularization options—PCI or CABG.

RISK REDUCTION STRATEGIES

Once a patient has been identified as being at high risk, either by clinical evaluation or after stress testing or coronary angiography, the next step is to take measures to reduce that risk. The two main options include revascularization or medical therapy or both. The question is whether these therapies are effective.

CORONARY REVASCULARIZATION

Results from the Coronary Artery Surgery Study (CASS) showed that patients who underwent CABG, were symptom free, and then went on to have noncardiac surgery had a lower risk of postoperative mortality and nonfatal MI than similar study patients treated medically. This benefit was only for high-risk surgery, and the protective effect of CABG appeared to last for 4 to 6 years. However, the morbidity and mortality after CABG were not taken into account, and these patients did not have prophylactic CABG in preparation for noncardiac surgery.

These results differ from those of the Coronary Artery Revascularization Prophylaxis (CARP) trial in which patients with stable cardiac symptoms scheduled to undergo elective major vascular surgery were evaluated by NIT, and those with abnormal tests went on to coronary angiography. Patients with suitable anatomy for revascularization were then randomized to medical therapy with or without revascularization (CABG or PCI). Exclusion criteria included >50% stenosis of the left main coronary artery, significant aortic stenosis, or left ventricular ejection fraction (LVEF) less than 20%. Prophylactic revascularization was associated with a mortality of 1.7%, perioperative MI of 5.8%, and reoperation rate of 2.5%. In this particular study, there were no perioperative strokes, but typically this occurs in up to 2%. A subgroup analysis of this study, as well as a recent meta-analysis showed that CABG appeared to be more protective than PCI, possibly because of a more complete revascularization.

Because of the associated morbidity and mortality, prophylactic revascularization would only be expected to benefit patients at high risk undergoing high-risk surgery. However, DECREASE V, a small study of these very high-risk patients (three or more risk factors and extensive stress-induced ischemia on DSE undergoing major vascular surgery) in whom a previous study showed no benefit from perioperative β-blockers, failed to demonstrate improved short- or long-term outcomes with revascularization in addition to optimal medical therapy. Criticisms of these studies raised concerns that the CARP trial patients did not have severe enough CAD, whereas the DECREASE V patients were too sick.

Another trial found a benefit to routine versus selective cardiac catheterization for screening patients before elective aortic surgery. Intention-to-treat analysis showed decreased cardiac mortality and a similar trend in major adverse cardiac events (MACE) in the routine cardiac catheterization group at 30 days and at follow-up 4 years later.

It was felt that prophylactic PCI, with its lower risk for adverse events related to the procedure than CABG, might be better, but there are no studies to confirm this. On the other hand, numerous studies and a meta-analysis reported an increased risk associated with noncardiac surgery soon after PCI. This is related to stent thrombosis in patients who have prematurely discontinued the recommended course of dual antiplatelet therapy (DAPT) and, to a lesser degree, bleeding in patients who were taking aspirin and clopidogrel. The ACC/AHA guidelines recommend delaying elective surgery for at least 2 weeks after balloon angioplasty, 4 to 6 weeks after placement of a bare metal stent (BMS), and 12 months after a drug-eluting stent (DES) in order to complete the course of DAPT. Should surgery be required before these time intervals in a patient who had PCI, the recommended options, in priority order, are to try to perform the surgery on dual antiplatelet therapy if possible, to continue aspirin but discontinue the second antiplatelet agent (discontinue clopidogrel 5 to 7 days before surgery, prasugrel 7 days before, and ticagrelor 5 days before), or to discontinue both antiplatelet drugs 5 to 7 days before surgery. However, the 2014 ACC/AHA guidelines now state that elective noncardiac surgery may be considered with DES after 180 days of DAPT if the risk of surgical delay is greater than the expected risks of ischemia and stent thrombosis (IIb). The antiplatelet therapy should be resumed as soon as possible after surgery, assuming adequate hemostasis has been assured.

MEDICAL THERAPY

Beta-blockers

Note: The scientific integrity of the DECREASE trials from the Poldermans group has been questioned but they will be mentioned in the text that follows to illustrate the controversy.

Early studies with prophylactic β-blockers demonstrated beneficial effects. Mangano and colleagues randomized 200 patients undergoing various operations to placebo or atenolol, started immediately preoperatively, titrated to a heart rate of 55 to 65 beats per minute and continued for less than 7 days postoperatively. There was less ischemia in the atenolol-treated group but no reduction in short-term outcomes of death or nonfatal MI. However, surviving patients in the β-blocker group went on to have fewer cardiovascular events by 2 years. Poldermans and colleagues randomized 112 patients with abnormal DSEs undergoing major vascular surgery to placebo or bisoprolol, started at least 7 days preoperatively, titrated to a heart rate between 55 and 65 beats per minute, and continued for at least 30 days postoperatively. The trial was stopped early because the bisoprolol-treated group had a significant reduction in postoperative MI and cardiac death (3% vs 34%). Despite the small numbers of patients in these trials and methodologic criticisms, various agencies and society guidelines began recommending prophylactic β-blockers.

Three subsequent studies involving approximately 1500 patients (POBBLE, DIPOM, MaVS) using metoprolol, started at most 1 day before surgery and not titrated to a specific heart rate, showed no benefit in various cardiovascular outcomes. Lindenauer and colleagues using an administrative database of over 600,000 patients, reported that being on a β-blocker within 2 days of surgery was associated with decreased in-hospital mortality in high- but not low-risk patients (stratified by RCRI score).

The POISE trial was expected to resolve this controversy but instead raised more questions. In this study over 8000 patients with atherosclerotic heart disease (ASHD) or risk factors for it who were scheduled for various surgical procedures were randomized to metoprolol controlled release (CR) or placebo. Patients received the first dose (metoprolol CR 100 mg or placebo) 2 to 6 hours before surgery followed by a second dose (100 mg) within 6 hours after the end of surgery, and then a maintenance dose of 200 mg daily started 12 hours after the postoperative dose. The drug was withheld for heart rate less than 45 beats per minute or systolic blood pressure (BP) less than 100 mm Hg and then restarted at half the dose 12 hours later if BP and pulse improved. Primary outcome, a composite of cardiac death, nonfatal MI, and cardiac arrest, was significantly better in the metoprolol-treated group (see Figure 50-1) but was primarily due to a reduction in nonfatal MIs. However, this benefit came at the expense of a significant increase in stroke and total mortality (two of the secondary outcomes) in the treatment group, in part due to more episodes of hypotension and bradycardia. Mortality was increased in patients with sepsis, and stroke risk appeared to be increased in patients with prior strokes and intraoperative hypotension. This study generated significant commentary and criticism, mainly related to the high dose of metoprolol that was started shortly before surgery in β-blocker-naïve patients, many of whom underwent emergency surgery or had sepsis. This tempered the enthusiasm for prophylactic β-blockers.

The DECREASE IV trial using bisoprolol, started well in advance (median 34 days) of surgery and titrated to a heart rate between 50 and 70 beats per minute reduced cardiac death and nonfatal MI in intermediate risk patients. If β-blockers are to be beneficial based on the positive although controversial trials, it appears that they need to be started more than 1 and probably at least 7 days before surgery and potentially titrated to a heart rate somewhere in the range of 55 to 70 beats per minute to minimize the risk of significant hypotension or bradycardia (although most patients remained on their initial β-blocker dose). Higher-risk patients or those undergoing vascular or higher-risk surgical procedures would be most likely to benefit.

Multiple meta-analyses have come to different conclusions based on the studies included or excluded in the analysis. Although the final answer is not in, the ACC/AHA published a systematic review of randomized controlled trials with perioperative β-blockers analyzing the results with and without inclusion of the DECREASE and POISE trials. Their recommendations were to continue β-blockers in patients taking them chronically, that it may be reasonable to begin them before surgery in patients with ischemia on stress testing or with three or more RCRI factors, and that initiating β-blockers in patients with other indications but no RCRI factors was of uncertain benefit. If initiating β-blockers preoperatively, they should be started far enough in advance to assess safety and tolerability. This should be done more than 1 day before surgery and not started on the day of surgery, which was found to be harmful. Although not specifically recommended in the ACC/AHA guidelines, a cardioselective β-blocker (bisoprolol or atenolol) was recommended over metoprolol by the ESC guidelines.

Alpha-2 agonists and aspirin

Although some earlier studies suggested that clonidine might be beneficial in reducing postoperative cardiac complications, the POISE-2 trial, which randomized 10,010 patients to clonidine, aspirin, both, or neither before noncardiac surgery, demonstrated that prophylactic clonidine did not reduce MI or cardiac death but was associated with an increase in nonfatal cardiac arrest and hypotension. The ACC/AHA guidelines state that clonidine is not recommended to prevent perioperative cardiac events. However, in patients already taking clonidine it should be continued to prevent rebound hypertension.

The two aspirin groups—patients already on it and those who were aspirin naïve—also showed no benefit in terms of reducing MI or death but did have an increased risk of bleeding. The earlier the aspirin was started postoperatively, the higher the bleeding risk. Patients with cardiac stents who had not completed their course of antiplatelet therapy, recent strokes, and patients undergoing carotid endarterectomy were excluded. Some controversy exists because there was no subgroup analysis of patients on aspirin for primary versus secondary prevention or for higher versus lower bleeding risk procedures. The ACC/AHA guidelines state that the risk of a cardiovascular event needs to be weighed against the risk of a bleeding event in determining whether or not to continue aspirin in patients already on it (for secondary prevention).

Statins

In addition to lowering cholesterol, statins have a number of so-called pleotropic effects. These include reduced platelet aggregation, improved endothelial function, and reduced inflammation. It is thought that this latter effect in particular may help stabilize plaques and prevent plaque rupture, which might lead to an MI.

Most observational studies report that perioperative statin use is beneficial in reducing postoperative cardiac complications and death in both cardiac and noncardiac surgery. A meta-analysis by Kapoor and colleagues confirmed this benefit; however, there are few randomized controlled trials. The first of these, a small study of 100 patients using atorvastatin 20 mg started 30 days before surgery, demonstrated a beneficial effect on a composite outcome including some weaker end points.

The DECREASE III trial randomized 497 patients to fluvastatin 80 mg extended release or placebo started approximately 1 month before vascular surgery and showed that the statin-treated group had less ischemia and a statistically significant reduction in the composite end point of cardiac death and nonfatal MI. It also demonstrated that statins reduced LDL and total cholesterol, multiple inflammatory markers including C-reactive protein (CRP) and interleukin (IL)-6, but also were safe in that there were no cases of rhabdomyolysis or significant hepatic injury. Although no safety issues were found in a review of statin use in vascular surgery patients, the drug manufacturers still recommend discontinuing statins before major surgery due to these potential safety concerns. However, the ACC/AHA recommends continuing them perioperatively as the potential benefit outweighs the theoretical risk. Based on the DECREASE III trial it appears that patients who are not on a statin but are scheduled for vascular surgery would benefit from starting a statin preoperatively. However, the fluvastatin arm of the DECREASE IV trial in intermediate risk patients only showed a trend toward decreased MI and death that was not statistically significant. The ACC/AHA also states that preoperative initiation of statin therapy is reasonable in patients undergoing vascular surgery and may be considered in patients with clinical indications (CAD, DM, peripheral arterial disease (PAD), hyperlipidemia) undergoing elevated risk surgery. Unanswered questions regarding perioperative statin use are whether this is a class effect, what dose should be used, how long in advance to start it prophylactically for it to be effective, and which patients are most likely to benefit from them.

OTHER CARDIOVASCULAR CONDITIONS

HYPERTENSION

Hypertension is at best a minor risk factor. Although various recommendations mention blood pressures (diastolic BP > 110 mm Hg or systolic BP > 180 mm Hg) when cancellation of elective surgery should be considered or which might be associated with increased risk, there is no hard evidence to support them. Hypertensive patients are more likely to have more labile blood pressure perioperatively and intraoperative hypotension. The etiology of the hypertension, and presence of end organ damage are more likely to be associated with any cardiac morbidity than the preoperative blood pressure itself.

Most antihypertensive medications should be continued, including on the morning of surgery, with the possible exceptions of diuretics and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Of note, the 2014 ACC/AHA guidelines state that continuation of ACEIs or ARBs is reasonable perioperatively although many anesthesiologists recommend stopping them at least 10 hours before surgery due to concerns for potential hypotension with induction of anesthesia. If they are stopped, they should be restarted as soon as safe postoperatively.

ARRHYTHMIAS

Hemodynamically significant arrhythmias including tachyarrhythmias (rapid atrial fibrillation (AF), supraventricular tachycardia (SVT), ventricular tachycardia (VT)) as well as bradyarrhythmias (symptomatic sinus bradycardia, high-degree atrioventricular (AV) block) should be evaluated and treated as per GDMT before elective surgery.

HEART FAILURE

Heart failure is a predictor of postoperative MACE. Systolic and symptomatic heart failure carry a greater risk than diastolic or asymptomatic dysfunction. Decompensated heart failure requires further evaluation and treatment as per GDMT before proceeding with elective surgery. Beta-blockers should not be started preoperatively in these patients, and in a subgroup analysis of the CIBIS II study, patients with heart failure had little benefit from β-blockers.

VALVULAR HEART DISEASE

Patients with valvular heart disease should be evaluated and treated as per GDMT. The lesion most likely to be associated with perioperative cardiac complications is symptomatic, severe aortic stenosis (AS). Patients with a systolic murmur suggestive of AS, particularly if they have chest pain, dyspnea, or syncope, should have a 2D echocardiogram performed. If they have symptomatic severe AS and the planned noncardiac surgery is elective, the recommendation is for valve replacement. Should the patient refuse or if the surgery is more urgent, it has been possible to get most of these patients through surgery successfully using medical therapy and intraoperative monitoring. Patients with asymptomatic aortic stenosis tend to tolerate surgery much better than those with symptoms and comparable severity of stenosis. Mitral stenosis, when associated with atrial fibrillation and heart failure, may also increase risk, but most of the other valvular lesions do not require surgical intervention before noncardiac surgery. The ACC/AHA guidelines state that it is reasonable to perform elevated risk elective noncardiac surgery in patients with asymptomatic valvular disease (even if severe) with appropriate intraoperative and postoperative monitoring. Pulmonary hypertension is now being recognized as a risk factor as well, but studies are limited.

Endocarditis prophylaxis is only indicated for patients undergoing dental and upper respiratory procedures who have a prosthetic valve, previous endocarditis, complex congenital heart disease that has not been repaired (or was repaired in the past 6 months), or valvular disease in a transplanted heart.

BIOMARKERS

Elevated natriuretic peptides (BNP, NT-proBNP) preoperatively and postoperatively have been associated with MACE. These tests have been used in conjunction with the RCRI and may provide incremental value in risk assessment. However, which test to use, when to obtain it, what cutoff is best, and what to do with the results are not known, and at this time their role, if any, in preoperative risk assessment is unclear.

Most postoperative myocardial infarctions are not associated with chest pain, which raises the question of whether patients should be screened postoperatively with troponins or EKGs. An entity termed MINS—myocardial injury after noncardiac surgery—defined as an elevated troponin presumed to be of ischemic etiology but not requiring diagnostic criteria for an MI, is associated with adverse outcomes. However, it is unclear what to do in these situations and whether or not any treatment is beneficial or harmful. For these reasons the ACC/AHA did not recommend routine postoperative screening in patients without signs or symptoms of myocardial ischemia.

CONCLUSION

Using the ACC guidelines and risk calculators, the patient can be classified as low versus elevated risk based on combined clinical and surgical risk. The physician can then decide not only whether further testing is indicated but also whether it is likely to change management. Prophylactic revascularization is rarely necessary just to get a patient through surgery, and the majority of the patients will be managed medically. It is important for future studies to determine optimal use of β-blockers, statins, and other therapies in order to have patients in their optimal medical condition prior to elective noncardiac surgery to reduce postoperative complications.

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INTRODUCTION

A comprehensive preoperative evaluation must include assessment of the risk of postoperative pulmonary complications. While few would argue this point, pulmonary risk is often underappreciated as clinicians typically focus the majority of their energy on the preoperative cardiac evaluation and preventing venous thromboembolic complications. Highlighting the risk of this approach, postoperative respiratory problems occur with similar frequency and greater morbidity than cardiovascular complications.

Pulmonary complications following anesthesia and surgery result from central nervous system suppression and altered respiratory dynamics. Administration of sedating agents and neuromuscular blockade exposes the patient to the risk of aspiration. Furthermore, regardless of the type of anesthetic technique utilized, patients will experience a reduction in lung volumes perioperatively. Reduction in lung volumes is the primary mechanism that may lead to atelectasis and predispose a patient to the additional complications of pneumonia and respiratory failure. This reduction in lung volumes is greatest for patients undergoing thoracic and upper abdominal surgery. Table 51-1 lists specific postoperative pulmonary complications and diagnostic considerations for each.

RISK STRATIFICATION

Clinicians intuitively recognize several risk factors for pulmonary complications, but some predictors of postoperative respiratory problems are not obvious. Additionally, clinicians may struggle with the appropriate utilization of preoperative pulmonary diagnostic testing. Recently published risk indices and practice guidelines provide valuable assistance in the identification of risk factors and the performance of evidence-based preoperative evaluation.

PATIENT-SPECIFIC RISK FACTORS

Several different patient characteristics increase postoperative pulmonary risk (Table 51-2). While most of these patient-specific factors are nonmodifiable, their identification is important for providing patients, surgeons and anesthesiologists with an accurate assessment of perioperative risk and to identify patients for whom one should employ risk reduction strategies.

Chronic lung disease

Multiple studies have identified chronic obstructive pulmonary disease (COPD) as a significant risk factor for postoperative respiratory problems. However, the risk attributable to COPD is lower than several other patient-related risk factors, including total functional dependence, obstructive sleep apnea and age 70 years or greater. The impact of other forms of chronic lung disease on perioperative pulmonary risk has been much less studied, but at least one retrospective review of interstitial lung disease patients found them to have rates of postoperative pneumonia higher than the general population. Additionally, pulmonary hypertension has recently been shown to increase the risk of postoperative pulmonary complications as well as perioperative mortality and cardiac complications.

Advanced age

Advanced age is a major independent predictor of pulmonary complications. Contrary to previous belief, this risk is not a result of the cumulative morbidities associated with aging. Elevated risk begins at age 50 and is especially high in patients aged 70 years and older (adjusted odds ratio of 3). Recognition that age, even in the absence of other comorbidities, is an important source of pulmonary risk is critical as the population ages and more elderly patients undergo surgical procedures. The consequence of these observations is that even healthy older patients are at risk for postoperative pulmonary complications.

Smoking

Cigarette smoking is associated with increased postoperative pulmonary complications, but the degree of risk elevation is actually less than that from most other patient-specific factors including COPD. The adjusted odds ratio (OR) for pulmonary complications in smokers is 1.3, and the risk is greatest among active smokers and recent (<4 weeks) quitters. Patients who have abstained from smoking for at least 2 months have similar rates of postoperative pulmonary complications as nonsmokers. Clinicians should consider a recent history of cigarette smoking to be a moderate predictor of pulmonary complications.

Medical comorbidities

As the number of comorbid illnesses increases, so does the risk of perioperative complications. The American Society of Anesthesiologists (ASA) classification system is easy-to-use and predicts the risk of postoperative respiratory problems, as well as overall morbidity and mortality. Compared to ASA class I patients (no comorbidities), patients with an ASA class of II or greater have a nearly five-fold increase in the rate of postoperative pulmonary complications. The risk increases with each higher ASA class.

Functional status

Large multivariate studies have also identified dependence on others for assistance with activities of daily living as a significant risk factor for postoperative pulmonary complications. The contribution of functional dependence to perioperative pulmonary risk is greater than cigarette smoking and chronic lung disease. For patients with a completely dependent functional status, the adjusted OR for respiratory complications is greater than 4, and for partial functional dependence the adjusted OR is approximately 2.

Congestive heart failure

Congestive heart failure (CHF) is not only an obvious risk factor for perioperative cardiac complications but also a predictor of postoperative respiratory failure. Although the cause of respiratory failure may be CHF-related pulmonary edema, a history of heart failure is nonetheless an independent risk factor for pulmonary complications that confers a relative risk of approximately 6 in the geriatric population.

Obstructive sleep apnea

For years, clinicians have presumed that obstructive sleep apnea (OSA) increases the risk of postoperative complications. Only recently have high-quality studies established this to be true. In several studies OSA patients have increased rates of postoperative pulmonary complications as well as statistically significant increases in cardiac complications and unplanned ICU admissions. This risk extends not only to airway compromise in the immediate postoperative period, but also traditional postoperative pulmonary complications including pneumonia and respiratory failure. Other recent studies also suggest that patients who screen positive for OSA but do not yet carry the diagnosis have an increased risk of postoperative complications. For example, patients with at least two clinical features of OSA (snoring, crowded oropharynx, daytime somnolence, or witnessed apneas) who have abnormal overnight oximetry are more likely to develop postoperative hypoxemia or airway management problems than patients without these features. Whether formally diagnosed or suspected based on clinical features, OSA should be considered at least a moderate risk factor for perioperative respiratory problems.

Other risk factors

In addition to the previously described risk factors, several other patient characteristics have been less consistently linked to postoperative pulmonary complications. For instance, one large study found consumption of more than two alcoholic drinks per day within 2 weeks of surgery, recent weight loss exceeding 10% of total body weight, chronic corticosteroid use, preoperative transfusion of more than 4 units of blood, acute alteration of mental status, and a history of stroke to be modest risk factors for postoperative pneumonia. More recent risk models have not identified these as independent predictors but demonstrated that respiratory infection within a month prior to surgery as well as preoperative sepsis, hypoxemia and anemia significantly contribute to the risk of postoperative pulmonary complications.

Factors not associated with increased pulmonary risk

Notably absent from the described risk factors are four conditions often mistaken as predictors of postoperative pulmonary complications: well-controlled asthma, obesity, diabetes mellitus and immunosuppression. Although a potential relationship between perioperative pulmonary risk and morbid obesity and/or asthma has been assumed by some clinicians, multivariate investigations have consistently found no such correlation. The current literature provides little data on the contributions of immunosuppression and diabetes mellitus to pulmonary surgical complications.

PROCEDURE-SPECIFIC RISK FACTORS

Patient characteristics impact perioperative pulmonary risk significantly, but procedure-specific factors are even greater predictors of postoperative pneumonia and respiratory failure (Table 51-3). Unlike the majority of patient-specific risk factors, some of these surgery-related factors may be modifiable.

Surgery type

The type of surgery is the most important determinant of postsurgical pulmonary risk. As expected, intrathoracic procedures and surgeries in close proximity to the diaphragm carry the highest risk of postoperative pulmonary complications. Head and neck operations are high-risk procedures due in part to impairment of the upper airway. Restriction of diaphragmatic motion by pain from abdominal procedures leads to reduced lung volumes, the precursor of pulmonary complications. Particularly high risks are esophageal and aortic surgeries.

Anesthetic technique

Several studies have identified general endotracheal anesthesia (GETA) as an independent predictor of postoperative pulmonary complications. In some analyses, neuraxial blockade (spinal and epidural anesthesia), either alone or in combination with GETA, has been associated with lower rates of postoperative morbidity and mortality compared to GETA alone. However, randomized controlled trials (RCTs) have not consistently identified GETA as a risk factor. While these data suggest general anesthesia may contribute to pulmonary risk, selection of anesthetic technique is the primary responsibility of the anesthesiologist and is dependent on multiple other factors outside the purview of the hospitalist. The medical consultant should share his or her risk assessment with the anesthesiologist so they can incorporate this into anesthesia planning, but in general should defer the selection of anesthetic type to the anesthesiologist.

Other risk factors

Regardless of the surgical site or anesthetic technique, procedures performed on an emergent basis carry a higher risk of respiratory complications. Surgeries with duration greater than 2 to 3 hours are also associated with an increased risk for postoperative pneumonia and respiratory failure. There is probably no difference in risk between laparoscopic versus open surgeries; decisions regarding the surgical approach should be made by the surgeon based on other factors.

DIAGNOSTIC STUDIES

A thorough history and physical examination are the cornerstones of the preoperative evaluation. In most instances, diagnostic testing adds little to the risk assessment as established by clinical evaluation. Testing has a role when the risk is uncertain after history and physical examination.

Chest radiography

Chest radiography is part of many clinicians’ routine preoperative evaluation despite evidence that chest x-ray results rarely change perioperative management. Abnormalities on preoperative chest radiography are relatively common, occurring on 10% to 20% of x-rays. However, a minority of these findings are unexpected based on the clinician’s physical assessment and history, and an even smaller number influence perioperative care. Clinicians should reserve chest imaging for the same indications as in the nonoperative setting: evaluation of new or changed cardiopulmonary symptoms. As part of the American Board of Internal Medicine’s Choosing Wisely initiative, three different professional societies have specifically recommended not obtaining preoperative chest radiographs in patients without clinical findings suggestive of pulmonary abnormalities.

Arterial blood gas analysis

Early studies of preoperative arterial blood gas (ABG) analysis suggested that hypercarbia and hypoxemia predicted postoperative pulmonary complications. Subsequent reviews concluded that clinical assessment was equally accurate in predicting postsurgical respiratory problems. Taking into account that no arterial CO₂ or O₂ value is an absolute contraindication to surgery, clinicians should perform ABG analysis only if the results will significantly influence perioperative management (eg, excluding hypercarbia and respiratory acidosis in a patient with COPD and increased shortness of breath).

Pulmonary function testing

Formal pulmonary function testing has an established role in the preoperative evaluation of patients before lung resection, but its role in nonthoracic surgery is questionable. Analogous to ABG analysis, initial studies of preoperative spirometry suggested it was useful for predicting postoperative morbidity, but later data comparing spirometry to history and physical examination showed no clear incremental benefit from pulmonary function testing. Further, no spirometric values are a prohibitory threshold for noncardiothoracic surgery. Indications for pulmonary function testing are the same as in the general setting: evaluation of unexplained respiratory symptoms and characterization of lung disease when it is unclear if a patient’s airflow obstruction is optimally reduced.

RISK ASSESSMENT TOOLS

In recent years, the scientific community has paid more attention to the importance of postoperative pulmonary complications. The result has been the generation of practical risk assessment tools.

In 2006, the American College of Physicians developed clinical guidelines for perioperative pulmonary risk assessment and reduction for patients undergoing noncardiothoracic surgery. This systematic review provides a valuable resource for performing an evidence-based preoperative evaluation. Several perioperative pulmonary risk prediction models have also been developed to assist clinical risk stratification. Most of these are restricted to either specific types of surgery or unique respiratory complications (eg, acute respiratory distress syndrome), but three recent models show promise for being fairly generalizable.

Using data from the American College of Surgeons National Surgical Quality Improvement Program, Gupta and colleagues developed separate models for prediction of postoperative respiratory failure and pneumonia. Predictive risk factors for postoperative respiratory failure were: site of surgery, emergency surgery, ASA classification, sepsis and functional status (ie, ability to perform activities of daily living). The pneumonia risk model used the same variables except that age, COPD and smoking were included and emergent surgery was not. Both models were incorporated into risk calculators that are freely available online (www.surgicalriskcalculator.com). The Gupta postoperative pulmonary risk calculators performed very well in their initial study but have not been externally validated.

In 2010, Canet and colleagues developed the ARISCAT index for predicting postsurgical pulmonary complications. This model uses seven predictive factors, each with a weighted score based on its risk contribution (Table 51-4). Tallying the score in this model the clinician can determine which of three different risk classes a patient fits into. The ARISCAT index was originally derived and validated from a geographically localized population but has subsequently been validated in a sample of patients from across Europe.

Although the above risk indices are helpful for estimating risk in the general population, they do not account for risks associated with obstructive sleep apnea. The ASA recommends screening all surgical patients for OSA. Several tools for this purpose are available, including the STOP-BANG, Berlin and Flemons surveys. The STOP-BANG questionnaire accurately identifies patients at risk for moderate to severe OSA and postoperative complications (Table 51-5). A score of 5 or higher (of eight possible points) increases the likelihood of moderate to severe OSA, as well as rates of perioperative complications.

RISK REDUCTION STRATEGIES

Many pulmonary risk factors are nonmodifiable, but for patients with elevated perioperative risk several evidence-based risk reduction methods exist. Although some of these strategies are outside the scope of hospitalists, medical consultants should be aware of all potential risk reduction interventions. For all patients with increased pulmonary risk, special consideration should be given to the patient’s postoperative triage (home vs general hospital admission vs intensive care unit placement), and the hospitalist should incorporate the patient’s preoperative pulmonary risk assessment into postoperative care decision making. For instance, more aggressive work-up of postoperative fever or hypoxia may be initiated in the patient who was preoperatively assessed to be at increased risk for respiratory failure or pneumonia.

PREOPERATIVE SMOKING CESSATION

The role of smoking cessation in perioperative risk reduction remains an area of debate. Some studies have shown that preoperative smoking cessation decreases the risk of postsurgical respiratory complications, while others have demonstrated similar pulmonary morbidity between smokers and nonsmokers. An older study actually suggested an increase in postoperative pulmonary complications if smoking cessation occurred shortly before surgery. Recent meta-analyses of preoperative smoking cessation have identified no statistically significant increase in risk for patients who quit smoking less than 4 to 8 weeks before surgery. Patients who stop smoking more than 4 weeks prior to surgery have a significant decrease in postoperative pulmonary complications. Randomized controlled trials have confirmed that smoking cessation interventions started at least 1 month before surgery lower the incidence of overall complications. The greatest benefit occurs with durations of cessation of at least 8 weeks before surgery. Preoperative smoking cessation interventions (including the use of tobacco cessation pharmacotherapy) cause no harm, and increase rates of long-term abstinence. For any hospitalized surgical patient, clinicians should advise smoking cessation.

ANESTHETIC TECHNIQUES

Anesthesia considerations are the responsibility of the anesthesiologist, but it is important for hospital medicine practitioners to understand potential risk reduction strategies related to anesthetic techniques. Previous studies have shown that avoidance of long-acting neuromuscular blockade medications (pancuronium) can reduce the risk of postoperative pulmonary complications. This results from less residual neuromuscular blockade and resultant hypoventilation after surgery. Data supporting the use of neuraxial (epidural or spinal) anesthesia as a risk reduction modality has been mixed as well. However, a 2012 Cochrane review determined that neuraxial (spinal or epidural) anesthesia either alone or when added to general anesthesia significantly reduced the risk of postoperative pneumonia.

ANALGESIC TECHNIQUES

Sedating analgesics (including opioids and some adjunctive agents) increase the risk of hypoventilation which can lead to atelectasis and other respiratory complications. Thus, limitation of systemic opioids through epidural or regional analgesia or patient-controlled analgesia (PCA) offers the potential for pulmonary risk reduction. Neuraxial analgesia offers more risk reduction than PCA. In addition to less potential for hypoventilation, these strategies reduce postoperative pain, and increase the ability to take deep breaths and increase lung volumes after surgery. Meta-analyses of abdominal aortic and cardiac surgery patients have demonstrated reduced postsurgical respiratory problems with the use of thoracic epidural analgesia. However, evidence of benefit from other regional analgesia is scant. Administration of intravenous opioids through PCA reduces the risk of pulmonary complications when compared to intermittent intravenous administration on a PRN basis.

LUNG EXPANSION TECHNIQUES

The largest body of evidence for a perioperative pulmonary risk reduction strategy is for lung expansion techniques. Incentive spirometry, intermittent positive pressure breathing, deep breathing exercises and continuous positive airway pressure each reduce the risk of postoperative pulmonary complications. None of these strategies has been shown to be superior to another. Given the minimal risk associated with these techniques, the American College of Physicians recommends that incentive spirometry or deep breathing exercises be used for all patients at risk for pulmonary complications. Furthermore, a number of studies have demonstrated the value of lung expansion techniques or cardiopulmonary conditioning therapy started 1 to 2 weeks prior to surgery. This strategy reduces rates of pneumonia and all pulmonary complications by approximately one-half. Preoperative initiation of lung expansion or cardiopulmonary physiotherapy should be considered for patients with elevated pulmonary risk.

SELECTIVE NASOGASTRIC DECOMPRESSION

The American College of Physicians also recommends use of nasogastric tubes only as needed for postoperative nausea or vomiting, oral intake intolerance or symptomatic abdominal distention. This recommendation results from observations that routine, rather than selective, nasogastric decompression following abdominal surgery led to increased rates of pneumonia and atelectasis.

LUNG-PROTECTIVE VENTILATION

A growing body of evidence also supports the use of lung-protective ventilation (lower tidal volume, higher levels of positive end-expiratory pressure [PEEP] and lung recruitment maneuvers) in patients who require perioperative mechanical ventilation. This approach has long been utilized in patients with acute respiratory distress syndrome to reduce ventilator-associated lung injury. More recently, studies and meta-analyses have also shown reduced postoperative pulmonary complications in patients ventilated with tidal volumes of 6 to 8 cc/kg and PEEP of 5 to 10 cm of water pressure (cwp). Data from a 2014 randomized controlled trial indicates that use of lower tidal volume (8 cc/kg) with PEEP levels more than 10 cwp results in an increased risk of hypotension. Therefore, multiple factors influence the selection of an optimal postoperative ventilation strategy (eg, risk of hypotension).

OBSTRUCTIVE SLEEP APNEA MANAGEMENT

As the impact of OSA on perioperative risk is now well established, experts have developed a number of strategies to reduce the risk of sleep apnea-related postoperative complications. Most of these interventions were not derived from RCTs, but prospective studies of patients screened as high risk for OSA provide some evidence of their efficacy. High-risk patients in whom such OSA-targeted interventions were employed have complication rates similar to patients at low risk for OSA. The 2014 ASA practice advisory for perioperative OSA management suggests several strategies for mitigating sleep apnea-related risks (Table 51-6). For patients likely to have severe OSA, empiric use of positive airway pressure (PAP) ventilation is recommended if signs of severe hypoxia or airway obstruction are evident. At least one recent RCT demonstrated no reduction in postoperative pulmonary complications from empiric PAP initiation postoperatively (ie, without signs or symptoms of hypoxemia or airway obstruction). When possible, surgery should be delayed for preoperative evaluation and management of OSA for patients likely to have severe sleep apnea and are undergoing major surgery. Retrospective studies suggest that patients who are formally diagnosed and started on appropriate PAP therapy preoperatively have lower rates of postoperative complications compared to those who were diagnosed and treated after surgery.

CONCLUSION

Postoperative pulmonary complications are an under-recognized source of significant surgical morbidity and mortality. Estimation of pulmonary risk is an essential part of the preoperative evaluation and includes assessment of both patient- and procedure-related risk factors. Most risk factors are not modifiable, but the preoperative pulmonary evaluation provides an accurate estimation of risk for patients and physicians that improves informed decision making. Moreover, identification of high-risk patients can heighten postoperative vigilance for respiratory failure and pneumonia and lead to the use of those strategies proven to reduce risk.

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INTRODUCTION

About 21 million adults have diabetes in the United States, and 5.5 million hospital discharges include diabetes as one of the listed diagnoses. Annual inpatient health care costs directly related to diabetes were estimated at $76 billion in 2012. People with diabetes have a higher lifetime probability of requiring surgery compared to the general population due to increased cardiovascular, ophthalmic, renal, and neuropathic complications from their disease. Diabetes mellitus itself may complicate surgical wound healing and recovery. Surgical site infections may be twice as high in patients with diabetes, potentially from small vessel disease impairing oxygen and nutrient delivery to tissues, impaired leukocyte and monocyte function due to hyperglycemia, and decreased release of neuropeptides in those with peripheral neuropathy. Patients with diabetes also have higher postoperative in-hospital mortality compared to those without diabetes. Patients with higher postoperative blood sugars after coronary bypass surgery have an increased rate of complications. Surgery and anesthesia provoke release of counter-regulatory hormones, which cause hyperglycemia and increased catabolism. Care for the surgical patient with diabetes should focus on avoidance of marked hyperglycemia, which can alter wound healing and disrupt fluid balance, while also avoiding hypoglycemia, which can cause cardiac stress. Perioperative evaluation for patients with diabetes allows for the development of an individualized plan to reduce perioperative complications and to determine a safe and effective diabetes discharge plan.

PREOPERATIVE EVALUATION

A thorough history remains a key component in the preoperative evaluation of the patient with diabetes. A history of comorbidities and complications associated with diabetes may provide additional insight into surgical risk, and therefore perioperative management. For example, elective surgery should be delayed in patients with diabetes after a recent cardiac event (see Chapter 50: Preoperative Cardiac Risk Assessment and Perioperative Management). Patients with concomitant renal disease need to be monitored carefully, with precautions to avoid contrast materials and other nephrotoxic agents. Diabetic autonomic neuropathy may predispose patients to perioperative hypotension. Gastroparesis with impaired gastric emptying may predispose patients to aspiration during intubation and extubation.

Clarification of the patient’s home diabetes regimen and assessment of their home glycemic control and adherence will help guide perioperative management. Ideally, patients will have good glycemic control prior to undergoing elective surgery, but this will not always be possible. Some experts advocate delaying elective surgery if the patients HbA1C is >8.5%, but there is no good literature to support or negate this practice. In addition, the management plan should take into consideration the patients’ typical diet and activity, which may change drastically in the perioperative period. The type and duration of surgery is also important to consider, as longer surgeries and recovery times (including ICU admission or prolonged NPO status) will affect the perioperative glycemic management plan.

Specific physical exam components for patients with diabetes should include inspection of injection sites or insulin pump infusion sites (if applicable) for evidence of lipohypertrophy, which may affect insulin absorption. Evaluation for signs and symptoms of peripheral neuropathy will help plan for fall prevention tactics during the hospital stay. Inspection for associated wounds will help plan for wound prevention and care during the stay. In addition, obtaining orthostatic blood pressures may identify patients who may have a component of autonomic neuropathy, which should be taken into account for blood pressure management during and after surgery.

An inpatient HbA1C measurement is recommended if not obtained within the last 3 months. The HbA1C correlates with the risk for complications, perioperative hyperglycemia, and increased length of stay. More importantly, it may guide both perioperative and discharge diabetes management. Clinicians must be aware of the limitations of HbA1C accuracy, such as in the settings of recent transfusion, anemia, and hemoglobin variants.

Immediate preoperative glucose values predict postoperative glucose and may lead to an alteration of management plan in cases of extreme hyperglycemia or hypoglycemia. A comprehensive chemistry should be checked preoperatively, and will provide information on renal function, liver function, electrolytes, and bicarbonate status; impaired renal function reduces insulin clearance and increases a patient’s risk for hypoglycemia, and impaired liver function increases the risk of hypoglycemia. Correcting hypokalemia is important for patients receiving insulin, as insulin treatment lowers plasma potassium levels. Patients in diabetic ketoacidosis will have an increased anion gap with decreased bicarbonate and hyperglycemia; this should be corrected prior to any surgical procedure.

PREOPERATIVE RECOMMENDATIONS FOR PATIENTS

In addition to receiving recommendations from their surgical team, patients need guidance as to what to do with their home diabetes regimen prior to surgery. In general, oral diabetic agents and other noninsulin diabetic medications should be held prior to surgery (Table 52-1). However, some controversy in the literature exists for certain medications.

• Metformin: It is generally recommended that metformin be held up to 48 hours before surgery and restarted 48 hours after surgery, due to risk of lactic acidosis; however, in diabetic cardiac surgery patients, one study showed better outcomes in patients who inadvertently took metformin. These patients had a lower incidence of prolonged intubation, lower risk of infections, and lower overall morbidity compared to matched patients not taking metformin. While these findings are interesting, routine use of preoperative metformin is not recommended, but this information is reassuring should metformin inadvertently be taken preoperatively.

• Glucagon-like receptor 1 (GLP-1) agonists: These agents are generally held prior to surgery due to the gastric emptying delays and nausea seen with these agents; however, some studies have shown better glucose control with (compared to without) these agents in cardiac and noncardiac surgery patients. A current study may help clarify the potential role for these agents in perioperative management in patients undergoing noncardiac surgery. Several formulations of GLP-1 agonists are dosed once weekly; therefore, it may not be possible to effectively hold these medications given their long half-lives.

• Dipeptidyl peptidase-4 (DPP- IV) inhibitors: These agents are often held perioperatively, though one study of sitagliptan showed it was safe and effective in selective medical-surgical hospitalized patients (without significant renal disease, liver disease or high degree of insulin resistance).

For patients on insulin, basal insulin in many cases can be given at the regular dose or slightly reduced doses for short procedures. In patients with Type 1 diabetes, basal insulin should not be held due to the risk of diabetic ketoacidosis. A reduction in basal insulin may be needed if the patient gives a history of frequent snacking in his or her normal routine, or if they endorse fasting hypoglycemia on their home regimen. In one study, use of 80% of the basal dose was safe and effective in patients with both Type 1 and Type 2 diabetes undergoing noncardiac surgery. Table 52-2 lists commonly used insulin formulations, approach to preoperative dosing, and recommendations for when and how to resume insulin regimens postoperatively and at the time of discharge.

PREOPERATIVE RECOMMENDATIONS FOR THE CARE TEAM

Once a preoperative diabetes plan has been devised and communicated with the patient, the plan should be relayed to the rest of the patient care team, including the surgical team and anesthesiologists. Type of diabetes, duration of diabetes, and complications related to diabetes should also be relayed to the surgical care team, and well documented in the medical record.

Given the limitations of oral diabetic agents in the perioperative setting, insulin management is preferred. Patients with Type 1 diabetes must continue with some form of basal insulin to prevent diabetic ketoacidosis. Basal insulin may be in the form of long acting insulins such as once a day glargine, detemir, or twice daily NPH. Rapid acting insulin analogs (lispro, aspart, and glulisine) act over several hours and are used for prandial insulin and for supplemental (correction) insulin. Regular insulin given subcutaneously can also be used for prandial and supplemental insulin.

Basal bolus regimens have been recommended for the majority of noncritically ill-diabetic patients. This consists of basal insulin + prandial insulin + supplemental insulin. Basal bolus regimens are superior to sliding scale insulin alone (which is not recommended). Basal bolus regimens confer better glycemic control and reduced complications such as wound infection, renal failure, pneumonia, respiratory failure, and bacteremia. In patients with Type 2 diabetes on home oral agents and/or relatively low insulin, basal insulin + supplemental insulin only is comparable to basal bolus insulin, and is a reasonable regimen for these patients.

MONITORING AND GLYCEMIC TARGETS FOR NONCRITICALLY ILL

During surgery, glucose should be monitored hourly for procedures lasting >60 minutes. Glycemic targets for noncritically ill patients on insulin should be <140 mg/dL before a meal and <180 mg/dL randomly. Dose reductions should be considered for any blood glucose levels of <100 mg/dL to prevent hypoglycemia, and dose reductions should be mandatory for any blood glucose levels of <70 mg/dL (unless the event is easily explained by an identified preventable factors). In-patient point-of-care monitoring should be performed four or more times a day, including before meals and at bedtime. For patients who are not eating, monitoring should occur every 4 to 6 hours (around the clock). A plan for preventing hypoglycemia, and a protocol for treating hypoglycemia, should be in place; any episode of hypoglycemia should be documented in the medical record.

INSULIN PUMP THERAPY

Continuous subcutaneous insulin infusion (CSII, eg, insulin pump therapy) has become much more commonly used among patients with diabetes. It provides flexibility, convenience, and ease of adjustments in insulin-treated patients. Often it is associated with less glycemic variability and improved glycemic control. It is often recommended that CSII be discontinued during inpatient hospital stays if the patient is not able to self-manage their pump; however, use during surgery has been less clear. For patients admitted for same day surgery for procedures of <120 minutes, CSII appears to be safe when used with a protocol that allows for the addition of IV insulin by anesthesiology for glucose >250 mg/dL or any extension of surgery beyond 2 hours. Patients with insulin pumps should be instructed to place a fresh infusion set in an area not affected by surgery. A retrospective review of CSII patients found similar control between perioperative CSII versus conversion to perioperative IV insulin drip.

MONITORING AND GLYCEMIC TARGETS FOR CRITICALLY ILL

The American College of Physicians endorses a blood glucose target of 140 to 200 mg/dL in surgical and medical intensive care unit (ICU) patients. The American Diabetes Association and American Association of Clinical Endocrinologists endorse a blood glucose target of 140 to 180 mg/dL for most ICU patients. A target of <110 mg/dL is never recommended, due to increased hypoglycemia and mortality seen with the NICE-Sugar trial. See Table 52-3 for further recommendations for glycemic targets for critically ill.

In a review of patients undergoing cardiac surgery treated with IV insulin infusion postoperatively with a lower glycemic target (80-110 mg/dL) compared with those treated using a higher target (110-140 mg/dL), patients in the higher target group experienced similar mean glucose values, no significant differences in 30-day morbidity and mortality (with the possible exception of increased reintubation), and less hypoglycemia than the lower target group. Similarly, in a study of cardiac patients treated with IV insulin infusion to a target of 110 to 140 versus 140 to 180, there were no significant differences in morbidity or mortality between the groups. Therefore lower targets have been essentially abandoned for ICU patients.

IV INSULIN INFUSION THERAPY

In critically ill patients, glycemic management with an IV insulin infusion is recommended for the majority of patients; it should be initiated at a threshold of 180, with target blood sugars between 140 and 180. The use of insulin protocols are highly recommended, to reduce variability and increase the amount of time within target.

DISCHARGE PLANNING

Discharge planning should begin shortly after admission, so that very clear instructions are provided to the patient at time of discharge. Preoperative HbA1C can be a valuable tool in devising a discharge diabetes regimen. Umpierrez et al demonstrated improved HbA1C at 4 and 12 weeks postdischarge with the use of a discharge protocol based on initial HbA1C in surgical and medical patients with Type 2 diabetes. Follow-up included nursing phone calls every 2 weeks for the first 2 months and visits at 1 and 3 months:

• Patients with HbA1C <7% were discharged on their home regimen (oral agents or insulin).

• Patients with HbA1C between 7% and 9% were discharged on their home oral agents as well as basal insulin at 50% of the inpatient hospital regimen.

• Patients with HbA1C >9% were discharged on their home oral agents as well as 80% of inpatient basal insulin or basal bolus therapy (using 80% basal insulin and 80% prandial insulin used in the hospital).

CONCLUSION

High-quality perioperative care of diabetic patients can reduce morbidity, mortality, and cost. A thorough preoperative diabetes evaluation along with clear communication with all members of the surgical care team remains necessary for the development and implementation of an individualized perioperative care plan. Hospitalists have the opportunity to collaborate and coordinate care for these patients throughout the perioperative process. Hospitalists can play a key role in identifying areas of need and collaborating with surgical teams and diabetologists in improving perioperative and inpatient care.

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INTRODUCTION

Many hospitalists will be asked to assess the operative risk of patients who have acute or chronic liver disease. The following chapter outlines an assessment plan and a basis for predicting operative morbidity and mortality. Evaluation of patients with liver disease prior to surgery is crucial to estimate perioperative morbidity and mortality. The operative risk of liver disease can be related to the rapid changes in liver function that can occur in acute hepatitis, or can be related to chronic complications of portal hypertension and parenchymal liver disease in patients with cirrhosis. Therefore, establishment of a risk profile should be based on the etiology of the underlying liver disease, the degree of hepatic decompensation associated with the presence of cirrhosis and portal hypertension, and the type of surgery the patient is undergoing.

FACTORS THAT AFFECT PERIOPERATIVE OUTCOMES IN LIVER DISEASE PATIENTS

CHANGES IN HEPATIC BLOOD FLOW

The liver receives dual blood supply from the portal vein and the hepatic artery. Unlike most other organs, the majority of hepatic oxygen supply in normal individuals is venous, via the portal vein. Administration of anesthesia and surgery influences both portal and hepatic blood flow; usually, when flow through the portal vein is reduced, the hepatic artery vasodilates to increase oxygen supply to the liver. This compensatory vasodilatation is reduced in patients with altered hepatic architecture (such as fibrosis and nodular formation associated with cirrhosis). Due to intraoperative decreases in blood pressure and cardiac output, blood flow in patients with cirrhosis is decreased in the portal vein, splanchnic vessels, and hepatic artery; anesthetics also reduce the hepatic artery’s ability to vasodilate in response to these changes in portal blood flow.

These changes in hepatic blood flow may lead to hepatic ischemia and necrosis. The release of inflammatory mediators may result in multiorgan system failure. In a study of 733 cirrhosis patients undergoing surgery, Ziser et al found an 11.6% mortality rate. Intraoperative hypotension correlated strongly with perioperative complications and decreased survival.

TYPE OF SURGERY

Postoperative morbidity and mortality in patients with cirrhosis is also influenced by the type of surgery.

Abdominal surgery

During abdominal surgery, direct trauma due to surgical retraction can lead to hepatic injury. Manipulation of the splachnic and portal vasculature may also reduce portal or hepatic flow leading to ischemic injury. In particular, patients with Child-Pugh class C cirrhosis who undergo abdominal surgery have a 75% perioperative mortality.

Cardiovascular surgery

Cardiovascular surgery, due to effects on portal and hepatic artery blood flow, is also associated with high perioperative morbidity and mortality. The need for perioperative pressor support and prolonged cardiopulmonary bypass are factors that strongly correlate with hepatic injury.

Emergency Surgery

Many patients who require emergency surgery may be hemodynamically unstable from systemic vasodilation (eg, sepsis) or hypotensive due to hemorrhage (eg, trauma, abdominal surgery), and their outcome is often poor regardless of underlying conditions. In a study by Demetriades and colleagues of 46 patients with cirrhosis who underwent emergency laparotomy, the postoperative mortality rate was 45%, which was significantly greater than noncirrhotic control patients.

Orthopedic surgery

There is little information in the literature regarding specific operative risks for patients with cirrhosis who undergo orthopedic surgery. Hsieh et al reviewed 38 patients who underwent hip arthroplasty over a 20-year period and found the 30-day complication rate was 27%. Advanced cirrhosis, age, elevated serum creatinine, low serum albumin, low platelet count, ascites, hepatic encephalopathy, and high operative blood loss correlated with the high complication rate.

TYPE OF ANESTHETIC

Anesthetic agents may reduce hepatic blood flow by reducing cardiac output. Even spinal and epidural anesthesia, by reducing the mean arterial pressure, may affect hepatic blood flow. In patients with liver disease, effects on hepatic metabolism may lead to prolonged action of anesthetic agents or production of toxic radicals resulting in increased morbidity and mortality.

CAUSE AND SEVERITY OF LIVER DISEASE

Perioperative morbidity and mortality is highly influenced by the etiology and severity of the patient’s liver disease. The presence of cirrhosis or acute hepatitis at the time of surgery adversely influences surgical outcomes. Generally, patients with chronic hepatitis from any etiology, without features of hepatic decompensation, do very well with surgery and specific precautions are not necessary. However, in patients with acute liver disease or cirrhosis, it is critical to assess their perioperative risk as part of informed consent. Acute hepatitis, especially alcoholic hepatitis, or decompensated cirrhosis are relative contraindications to elective surgery. A number of scoring and staging systems are useful in assessing the perioperative risk, the most common of which are the Child Pugh Score and the MELD score. Measurement of the hepatic venous pressure gradient (HVPG) has excellent prognostic value but its use is confined to a limited number of medical centers. A recent study showed that patients with compensated cirrhosis with clinically significant portal hypertension, defined by a HVPG ≥10 mm Hg, were at significant risk of developing clinical decompensation defined as the occurrence of jaundice, ascites, variceal bleeding, or hepatic encephalopathy.

Child Pugh Score

The Child-Pugh Score combines a subjective and objective assessment of liver function (Table 53-1). In a recent study of 33 patients with cirrhosis, compared to 31 age- and sex-matched control patients, the Child-Pugh score accurately predicted morbidity after cholecystectomy. In another study of 44 patients with cirrhosis who underwent cardiac surgery, a preoperative Child-Pugh score ≥8 was predictive of postoperative mortality. Table 53-2 summarizes the operative mortality risk of patients with different Child-Pugh scores who undergo abdominal surgery.

MELD score

The Model for End Stage Liver Disease (MELD) score predicts short term mortality in patients with cirrhosis. The scoring system uses serum bilirubin, creatinine, and prothrombin time (international normalized ratio) to assess hepatic function. Recent data also suggests the presence of hyponatremia further increases the risk of mortality.

Teh et al assessed 772 patients with cirrhosis who underwent major digestive, cardiac or orthopedic surgery. They found that the 30-day mortality ranged from 5.7% for MELD score <8 to 50% for a MELD score >20. Table 53-3 summarizes the mortality risk for surgical patients with different preoperative MELD scores.

PREOPERATIVE MANAGEMENT

The preoperative management of patients with cirrhosis should involve aggressive treatment of portal hypertension and hepatic insufficiency to reduce operative morbidity and mortality. Depending on the specific etiology of the liver disease, certain preoperative changes in management may be considered (more below).

DIAGNOSTIC STUDIES

Table 53-4 lists laboratory and radiology studies that should be considered in the preoperative assessment of a patient with liver disease to ascertain their perioperative risk.

COAGULOPATHY

Hepatic insufficiency leads to inadequate production of factors II, V, VII, and IX resulting in the development of coagulopathy with an increased risk of perioperative bleeding. Thrombocytopenia in liver disease is multifactorial, including portal hypertension-induced sequestration of platelets, which further increases the risk of bleeding. Administration of platelets, fresh frozen plasma and cryoprecipitate should be administered prior to surgery to reduce the risk of bleeding during and after surgery. There has been interest in the use of recombinant factor VIIa in situations of emergency uncontrollable bleeding in cirrhotic patients. However, studies have not shown any improved outcomes with the use of this factor in patients undergoing hepatic resection, liver transplantation, and upper gastrointestinal bleeding. This agent should be used with caution due to an increased risk of arteriothromboembolic events including myocardial ischemia, myocardial infarction, cerebral ischemia, and cerebral infarction.

VARICES

The risk of bleeding in patients with cirrhosis who have esophageal varices is approximately 8% per year. Once variceal bleeding occurs, there is a 20% mortality associated with the bleeding event. Preventive therapies include the use of nonselective beta blockers and endoscopic variceal ligation. There are no specific treatments to reduce the risk of perioperative variceal bleeding. Preventing “over transfusion” with a target hematocrit of no more than 25 is recommended. In patients who do experience postoperative gastrointestinal bleeding, the use of antibiotics is recommended to reduce the risk of mortality from spontaneous bacterial peritonitis (SBP).

ASCITES AND SPONTANEOUS BACTERIAL PERITONITIS

Ascites is the most frequent and generally the first event to occur in patients with cirrhosis and hepatic decompensation. Treatment includes salt restriction, the use of diuretics (including furosemide and spironolactone) and paracentesis. Transjugular intrahepatic portosystemic shunting (TIPS) in the management of ascites prior to surgery is not recommended except for patients who may be undergoing liver transplantation. For patients with hypoalbuminemia, ascites or edema, perioperative fluid management should include the use of colloids such as albumin. In patients without third space accumulation of fluids, crystalloids (ie, saline) are appropriate.

TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT PRIOR TO SURGERY

Transjugular intrahepatic portosystemic shunts are effective in reducing the complications of portal hypertension (such as variceal hemorrhage and ascites). Preoperative placement of a TIPS may reduce the risk of portal hypertensive complications in patients with cirrhosis, but data regarding its effectiveness is limited.

BILIARY OBSTRUCTION

Biliary obstruction preoperatively is associated with increased morbidity and mortality and should be treated with decompression prior to surgery. Specific factors that increase operative risk are noted in Table 53-5.

HEPATIC ENCEPHALOPATHY

Hepatic encephalopathy is provoked by a number of factors listed in Table 53-3. The risk of hepatic encephalopathy after surgery can be reduced by avoiding specific precipitants (Table 53-6).

ADRENAL INSUFFICIENCY

Adrenal insufficiency can be found in 33% of patients with fulminant hepatic failure and 66% of patients with cirrhosis. In patients with decompensated cirrhosis or acute liver failure who develop signs of adrenal insufficiency (including hypotension and hypoglycemia after surgery), treatment with stress dose steroids should be considered.

ETIOLOGY-SPECIFIC MANAGEMENT

Perioperative management by liver disease etiology is outlined in Table 53-7.

CONCLUSION

It is important to identify the operative risk of patients with liver disease based on the acuity, etiology and severity of the liver disease and the urgency and type of surgery. Generally, patients with mild liver enzyme abnormalities (without cirrhosis) and most compensated Child-Pugh Class A patients can safely undergo surgery. For all other patients, a careful assessment of the benefits of surgical intervention must be weighed against the risk of hepatic decompensation and mortality. These risks should be enumerated as part of the informed consent process.

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INTRODUCTION

Hematologic disorders are diseases of circulating blood cells and plasma proteins that play a role in oxygen delivery, inflammation, infection control, hemostasis, and thrombosis. Given that surgery can result in bleeding and induce hemostatic changes that promote thrombosis, it is not surprising that patients with hematologic disorders present serious preoperative management challenges. The ability of hospitalists to manage diseases associated with blood disorders, and hemostatic and thrombotic risks associated with surgery is vital to the welfare of these patients. This chapter will discuss preoperative assessment of patients with hematologic disorders, and review the risk of perioperative hematologic complications and specific management strategies to reduce perioperative risks in this vulnerable patient population.

PREOPERATIVE ASSESSMENT OF PATIENTS WITH HEMATOLOGIC DISORDERS

HISTORY AND PHYSICAL EXAMINATION

The most important aspect in the preoperative assessment of patients with a hematologic disorder is a thorough history. This is especially true for patients with hemostatic disorders (Table 54-1). Though the patient may have a known hemostatic diagnosis, the clinical phenotype of these patients may vary considerably. Occasionally, a patient may report an unexpected personal and/or family history of bleeding or thrombosis, or a hematologic diagnosis as a child with no subsequent follow-up. Depending on the severity of the presumed diagnosis, these subjective accounts may need to be confirmed objectively. The physical examination is rarely helpful in such situations. However, the presence of petechiae, purpura, ecchymoses, jaundice, ascites, and splenomegaly may alert one to the presence of potential hematologic disorder.

Similarly, given the high perioperative complications in patients with sickle cell disease (SCD), a careful history is critical to ensure optimal surgical outcomes. Specific questions include recent cough, wheezing, dyspnea on exertion, fever, ankle edema, right upper quadrant pain, change in stool or urine color, hematuria, or dysuria. In addition, details on past SCD-related complications should be documented, including acute chest syndrome, frequency of pain episodes, strokes, hyperhemolytic crisis, pulmonary hypertension, aplastic crisis, transfusion reactions, and alloimmunization.

In addition to the specific questions above, all patients with hematologic disorders should have the following documented: alcohol use, smoking history, past anesthesia history, current medications (including vitamins, supplements, and herbal preparations), and allergies. Herbal remedies are often self-administered by patients and can modify hemostasis. These medications should be stopped prior to surgery.

DIAGNOSTIC STUDIES

It has been established by multiple prospective studies that the use of routine preoperative coagulation testing is not helpful in the absence of a bleeding history. In contrast, a preoperative complete blood count and coagulation testing is essential in patients with known hematologic disorders. Table 54-2 list laboratory and radiology studies that should be considered in the preoperative assessment of these patients.

PERIOPERATIVE RISK ASSESSMENT AND MANAGEMENT FOR HEMATOLOGIC DISORDERS

Patients with hematologic disorders are at increased risk for complications related to changes in blood cells and plasma factors initiated by surgery. The magnitude of the risk may vary considerably with the underlying hematologic disorder, nature of the surgery, age of the patient and other comorbidities. These disorders may require specific treatment and consultation with hematologists to ensure an accurate assessment of risk of perioperative complications and to improve outcomes. This involves understanding the nature and severity of the hematologic disorders with the goal to minimize the risk of intraoperative bleeding and postoperative complications including bleeding, infection, thrombosis, and abnormal wound healing. This section discusses several common hematologic disorders that hospitalists may encounter, the nature of the perioperative risk and specific perioperative management.

DISORDERS OF RED BLOOD CELLS

Anemia is a very common abnormality in patients undergoing surgery and is even more common in patients with active hematologic disorders due to treatment, marrow involvement by the disease, bleeding, renal failure, inflammation, or advanced age. Adequate red cell mass is needed to promote tissue oxygen delivery and is a vital factor to aide wound healing and prevent myocardial and central nervous system injury in surgical patients. Red cells can also promote hemostasis and play an important role in postoperative recovery.

Given the importance of red cells, the presence of anemia needs to be recognized preoperatively and corrected if surgery is not emergent. Previously, transfusion of red cells was considered a desirable intervention. However, the administration of red cells was discovered to adversely affect the morbidity and mortality of hospitalized patients in a wide variety of clinical settings. Preoperative anemia has to some extent been a silent risk factor for adverse clinical outcomes due to unnecessary transfusion of red cells that can increase perioperative complications. On the other hand, excess number of red cells may cause hyperviscosity and lead to thrombosis. For instance, patients with polycythemia may need preoperative phlebotomy to reduce the risk, especially when it is caused by polycythemia vera. Common hematologic disorders that can cause anemia and polycythemia will be reviewed.

Nutritional anemias

Patients with iron deficiency anemia should have their anemia corrected preoperatively with oral iron if there is sufficient time, or with intravenous iron if a more urgent response is required. The cause of iron malabsorption or loss should be identified and any possible source of bleeding identified. Folic acid and vitamin B12 are nutrients required to promote proliferation of marrow cells to produce red cells, as well as white cells and platelets. Once these nutrients are replete, it may take several days to start to see a reticulocyte response and several weeks to restore the blood count to normal.

More commonly, some patients do not have a single factor contributing to anemia and correction is often difficult due to diseases associated with renal insufficiency and chronic inflammation that can adversely affect iron utilization, resulting in reduced red cell production. In such circumstances, red cell transfusion may be required to maintain adequate tissue oxygen delivery during surgery.

Hemolytic anemias

Anemia due to production of IgG or IgM autoantibodies is challenging and may require pre- and postoperative interventions. Patients with autoimmune-mediated hemolytic anemia (AIHA) usually have positive Coombs tests, with pan-agglutination of their plasma with donor red cells. The presence of warm IgG autoantibodies results in hemolysis of both the native and transfused red cells making it difficult to provide “crossmatch” compatible blood for surgery. Despite this, when medically necessary, serologically incompatible but type-specific red cells should be transfused if the patient’s hemoglobin levels are causing hypotension and organ dysfunction. Acutely decompensating patients with AIHA who received serologically incompatible blood transfusion do not experience transfusion-related alloimmunization or an increase in hemolysis. Thus, life-saving red cell transfusion should not be denied due to serologically incompatible blood.

Patients with cold agglutinin disease produce IgM antibodies that react in the cold and fix complement to the red cells, promoting extravascular clearance by the reticuloendothelial system. Cold agglutinin disease can occur in response to mycoplasma infection, autoimmune disease and in lymphoproliferative disorders, such as Waldenstrom’s macroglobulinemia. These antibodies can be detected with a positive Coombs test that is complement-mediated. Blood transfusion in patients with cold agglutinin disease should be infused via a blood warmer. If the antibodies are actively promoting hemolysis at room temperature, the patient should be kept warm to prevent hemolysis by increasing the room thermostat.

Many patients with antibody-mediated hemolytic anemia may have had a surgical splenectomy as treatment for their hematologic disorder. Splenectomized patients are at increased risk for both bacterial infection and thromboembolism, both of which can affect perioperative morbidity and mortality. All splenectomized patients should receive immunization against the following organisms: Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis. These vaccinations should be given at least 14 days prior to elective splenectomy or immediately after an emergent splenectomy. In addition, splenectomized patients are at increased risk for venous thromboembolism (VTE) and should receive adequate VTE prophylaxis in the immediate postoperative period.

Patients with atypical hemolytic-uremic syndrome (aHUS) or paroxysmal nocturnal hemoglobinuria (PNH) experience hemolysis due to defects in complement regulation. These patients may be receiving treatment with the complement inhibitor, eculizumab. Since this drug inhibits complement activation, a major mechanism to fight infection, these patients are prone to meningococcemia. A raised awareness of the possibility of meningococcal infection is warranted in these patients.

Patients with hemolytic disorders should receive folic acid, vitamin B12 and iron supplementation to promote hemoglobin synthesis and red cell production. These nutrients should be replete prior to any elective surgery. Patients with coexisting renal failure or chronic inflammation may not produce adequate erythropoietin to promote accelerated erythropoiesis in response to anemia. These patients typically have red cell half-lives that are reduced at least 8-fold and require reticulocyte levels >10% to maintain normal levels of red blood cells. Exogenous erythropoietin injections may be required to compensate for the shortened red cell survival.

Sickle cell disease and other hemoglobinopathies

There exists a substantial degree of variability in the clinical severity of all molecular forms of sickle cell disease. This is due to a wide variety of abnormalities in the hemoglobin molecule. The most common form of sickle cell disease is due to a homozygous point mutation in the beta chain of hemoglobin that leads to the intracellular polymerization of soluble hemoglobin. The cells undergo a change in their shape and forms cells that can be seen on blood smears as irreversible sickle cells. Sickle cell disease presents major challenges to the hospitalist during the pre- and perioperative care.

There can be variable degrees of anemia and end organ damage in sickle cell disease. Some patients experience mild anemia and limited pain crisis while others can have severe hemolytic anemia complicated by pulmonary hypertension, liver disease, renal insufficiency and osteonecrosis of hip and other bones. Strategies for risk reduction require a multidisciplinary approach with surgery, anesthesia and medicine developing a customized care plan for the patient based on surgical risk and severity of sickle cell disease. During the perioperative period, patients with sickle cell disease are at increased risk of painful crisis, acute chest syndrome, and cerebrovascular accidents as surgical procedures may be complicated by hypoxia, hypothermia or acidosis; all of which promotes red cell sickling. The surgical and anesthesia team need to pay special attention to perioperative hydration, oxygenation status and underlying pulmonary, and cardiovascular disease. If the surgery involves general anesthesia, it is strongly recommended that red blood cells be transfused (either through simple or exchange transfusion) in patients with sickle cell anemia (Hb SS) to bring the hemoglobin level to 10 g/dL as this has been shown to reduce perioperative mortality and complications. In patients who already have a hemoglobin level higher than 8.5 g/dL without transfusion, are on chronic hydroxyurea therapy or require high-risk surgery (eg, neurosurgery, prolonged anesthesia, cardiac bypass), a hematologist with experience in sickle cell disease management should be consulted for guidance on appropriate transfusion methods.

As these patients are at high-risk for red blood cell (RBC) alloimmunization, a presurgery type and screen is sent to Blood Bank ahead of time to identify and characterize RBC antibodies (if any), which can be a laborious effort. If no antibodies are found, typically leukocyte-reduced RBC units, which are phenotypically matched for C, E, and Kell as well as ABO and D antigens, are transfused. If antibodies are present, finding compatible phenotypically match units can be time-consuming, hence the need to plan ahead.

Postoperatively, if the patient has a history of acute chest syndrome, admission to the intensive care unit should be considered for close respiratory monitoring. Regardless of location, the primary team should pay particular attention to hydration and oxygenation status. Dehydration and low oxygen levels can precipitate erythrocyte sickling, leading to vaso-occlusive crisis. For management of postoperative surgical pain, patients with chronic pain may have opioid tolerance and require higher doses of narcotics. Reports of pain should be treated accordingly and narcotics should not be withheld for fear of addiction as stress from acute pain can trigger the onset of a vaso-occlusive crisis. On the other hand, overhydration and excessive narcotic use can lead to pulmonary edema and respiratory depression, respectively. Hence, these patients require strict monitoring of hydration and oxygenation status. An incentive spirometer should be prescribed to all patients with sickle cell disease postoperatively as this has been shown to reduce pulmonary complications. Patients with sickle cell disease are also at increased risk of venous thromboembolism (VTE). Given that surgery is a known transient risk factor for VTE, appropriate VTE prophylaxis (either mechanical and/or pharmacological) should be prescribed.

Hemolytic anemia can also occur due to metabolic defects in red cells. Red cell membrane proteins are prone to oxidative damage. The red cells must be capable of reducing oxidatively damaged cells or they will be removed from the body, resulting in hemolysis. Glucose-6-phoshate dehydrogenase deficiency is a common X-linked metabolic disorder that can lead to hemolytic anemia. Patients with this disorder are usually well compensated but will become symptomatic when exposed to drugs that lead to oxidative stress. These patients must not be exposed to specific drugs that can lead to a major hemolytic crisis. The list of drugs that causes hemolysis is published online at: http://g6pd.org/en/G6PDDeficiency/SafeUnsafe/DaEvitare_ISS-it and should be reviewed to minimize the hemolytic risk to these patients preoperatively.

DISORDERS OF STEM CELLS: MYELODYSPLASTIC SYNDROME AND MYELOPROLIFERATIVE DISORDERS

There are several hematologic disorders that can alter white blood cell counts and qualitative function that may lead to serious complication for patients should they require surgical intervention. There are a growing number of individuals over 60 years of age with myelodysplastic syndrome (MDS). This disease syndrome represents a wide variety of defects in the bone marrow stem cells that can cause abnormalities in the production of red cells, white cells and/or platelets. These patients may have varying degrees of blood cell production abnormalities and be at risk for bleeding, infection or thrombosis and cardiopulmonary compromise due to anemia. They may require support with red cells because they are severely anemic and have a low reticulocyte count. Some patients with MDS are responsive to exogenous erythropoietin but others require transfusion support. The hematologist caring for these patients should assist in providing guidance regarding marrow function.

In patients with myeloproliferative disorders, such as polycythemia vera (PV) and essential thrombocythemia (ET), there is an increased perioperative thrombohemorrhagic risk. A high proportion of these surgeries are complicated by vascular occlusion or by major hemorrhage. Uncontrolled PV leads to marked increase in blood viscosity and stasis, reduced capillary blood flow, and subsequently tissue hypoxia. The risk of cardiovascular death and major thrombosis is reduced in patients with PV when the hematocrit is maintained at less than 45% with the use of phlebotomy, with or without cytotoxic chemotherapy. However, it is unclear if an acute reduction in hematocrit results in a decrease in perioperative thrombohemorrhagic risk. A large retrospective study of patients with myeloproliferative disorders undergoing surgery found that despite adequate control of blood count with phlebotomy and administration of standard VTE prophylaxis, these patients had increased bleeding risk (7.3%) and high rates of symptomatic VTE (7.7%) after surgery.

In patients with ET, the uncontrolled production of platelets and megakaryocyte proliferation can often lead to a dramatic increase in platelet count over one million. Platelet function may also be abnormal with defects in both adhesion and/or aggregation responses. The bleeding risk seen in patients with ET can be attributable to either dysfunctional platelets or acquired von Willebrand disease. Patients with acquired von Willebrand disease and ET are more likely to suffer from hemorrhagic events than thrombotic events. The risk of both thrombosis and hemorrhage is higher in older patients and in those who have had prior events. Lowering of hematocrit and platelet count should ideally be done over several weeks to months. Elective surgery should be delayed to allow the hematologist to treat the elevated platelet count or increased red cell mass. If surgery is imminent, repetitive phlebotomy in PV patients to lower the red cell count or platelet pheresis to rapidly lower platelet count in ET are also therapeutic options.

DISORDERS OF WHITE BLOOD CELLS: BENIGN AND HEMATOLOGIC MALIGNANCIES

Hospitalists sometimes encounter a patient that has a low neutrophil count but is not symptomatic and no history of recurrent infections. Benign ethnic neutropenia is due to a polymorphism seen in several ethnic groups of African and Middle East descent. These patients usually do not have an increased risk of infection and no specific intervention is required perioperatively. In contrast, patients with severe congenital neutropenia are prone to infections and have a much lower absolute neutrophil count, usually <500/mm³. About half of all cases of severe congenital neutropenia are caused by mutations in the ELANE gene. These patients may require granulocyte-colony stimulating factor (G-CSF), which increases the neutrophil count and decreases the severity and frequency of infections.

Patients with acute hematologic malignancies (acute myeloid or lymphocytic leukemia) are often anemic, leukopenic and/or thrombocytopenic. They are at a high perioperative risk for bleeding and infection risk. These cytopenias can occur as a clinical manifestation of the underlying hematologic disorder or from bone marrow suppression from treatment with antineoplastic agents. If a patient receiving treatment for a hematologic malignancy requires surgery, the cytopenias secondary to antineoplastic agents or radiation therapy usually recovers 14 to 21 days after exposure to these marrow suppressive agents. It may be prudent to delay elective surgery to allow for bone marrow recovery to minimize both bleeding and infection risk. If surgery is imminent, red cells and platelet transfusion may be required along with aggressive antimicrobial therapy. The use of G-CSF may also be considered to promote leukocyte recovery.

In addition, these patients are often deconditioned with poor functional status from the effects of chemotherapy and prolonged hospitalization, placing them at higher risk for postoperative complications. Antineoplastic agents can also result in poor wound healing. Postoperatively, careful attention should be paid to their nutritional status and rehabilitation to minimize these risks.

DISORDERS OF PLATELETS: CONGENITAL PLATELET DISORDERS AND THROMBOCYTOPENIA

For patients with congenital platelet disorders with a known bleeding history, transfusion of single-donor platelets is usually recommended prior to surgery. The most common platelet disorder is storage pool disease, but there are several other abnormalities that affect platelet aggregation. Postoperatively, depending on the type of surgery, additional platelet transfusion maybe recommended prophylactically or if clinically indicated to manage postoperative bleeding. In patients in whom platelet transfusion is ineffective due to alloantibody development, recombinant factor VIIa (rFVII) has also been used with some success. In certain individuals with mild bleeding phenotype, the consulting hematologist may recommend the use of desmopressin (DDAVP). This is given daily or twice daily for about 3 days before it becomes ineffective due to tachyphylaxis. DDAVP is known to cause fluid retention leading to hyponatremia, thus strict fluid balance is required to avoid electrolyte imbalances postsurgery.

Another common acquired hemostatic disorder is thrombocytopenia, which can be due to decreased production (eg, bone marrow suppression from hematologic malignancies) or increased platelet destruction (eg, immune thrombocytopenia). With the availability of platelet transfusion, even high-risk surgeries can be performed in the severely thrombocytopenic patients. A platelet count of >100,000/μL is usually adequate for all surgical procedures, including high-risk procedures (eg, neurosurgical or spinal surgery). For low- to moderate-risk surgical procedures, transfusion to increase the platelet count to >50,000/μL is usually recommended. Serial monitoring of the platelet count is important during the postoperative period as platelet survival is usually shortened and additional platelet support may be needed. In cases of coexisting liver disease due to cirrhosis or other disease process, the patient may have an enlarged spleen that will sequester platelets, resulting in variable degrees of thrombocytopenia. Furthermore, patients with hepatitis C and cirrhosis may have low thrombopoietin (TPO) levels. These patients may respond to TPO-mimetic agents (romiplostim and eltrombopag) and can be treated for a short duration if needed to optimize management. There is a thrombotic risk with the use of TPO-mimetic agents and this treatment should only be considered when other approaches have failed and bleeding risk is high.

In patients with immune thrombocytopenia (ITP), prophylactic platelet transfusion prior to surgery is usually ineffective. Instead, glucocorticoids and/or intravenous γ-globulin are prescribed to increase the platelet count. Since prednisone and other glucocorticoids can interfere with wound healing, other regimens are preferred in the patient that needs surgery. Other options include RhoGAM (anti-Rh therapy if the patient is Rh antigen positive) and TPO-mimetic agents to increase the platelet count. This can take several days to weeks to observe a response.

DISORDERS OF HEMOSTASIS

Patients with inherited disorders of coagulation (eg, hemophilia A, hemophilia B) are at increased risk of intra and postoperative bleeding. These patients often have an established outpatient hematologist that can define the severity of the patient’s disease and risk for bleeding. The risk should not be underestimated as bleeding into deep tissues, vital organs or along tissue planes can lead to severe hypotension, organ damage and death. A wide variety of hemostatic agents are available to reduce bleeding risk. Issues that assist in defining the dose of hemostatic agent depend upon baseline clotting factor level, nature of surgery and prior clinical response to treatments.

Specific guidelines have been published for management of defects in coagulation factors. All patients should have a treatment plan defining the nature of the product to be used to correct the defect, how the treatment should be monitored and the duration of therapy. Elective surgery should not be performed at an institution that does not have the availability to monitor and infuse the recommended coagulation factor replacement. Perioperative recommendations should be detailed in the medical chart prior to surgery. In the event of an emergent surgery where no recommendations are available, a hematologist should be consulted. In cases of an emergency, it is recommended to infuse either fresh frozen plasma (FFP) or cryoprecipitate to stabilize the patient and transfer to a tertiary center that can manage these patients. FFP can be used in cases of factor IX or XI deficiency. Cryoprecipitate is enriched in vWF, factor VIII, and fibrinogen and can be used in cases of hemophilia A or von Willebrand disease.

Generally, in patients with hemophilia A, B, or von Willebrand disease, specific factor levels should be maintained as high and for as long as clinically indicated based on published guidelines and clinical response to surgery. The prescribed factor is usually infused as a bolus in the morning prior to surgery, with specific factor levels measured before anesthesia induction to confirm that the factor has been administered and the appropriate factor level achieved. Failure to achieve an adequate factor level may be a sign of an inhibitor or inadequate dosing which may require that the surgery be postponed. If the patient has developed an inhibitor the patient may need to be transferred to a center with significant experience in managing inhibitor patients.

Postoperatively, the duration of maintenance therapy depends on the type of surgery performed, ranging from a few days for fairly minor surgical procedures (dental work, simple biopsies) to 2 weeks for more invasive surgery such as abdominal or orthopedic surgery. Factor levels are monitored daily for the first few days and can usually be lowered once surgical hemostasis is achieved (usually by the fourth or fifth day). Once the patient is safe to discharge from a surgical standpoint, it is important to ensure that these patients have an adequate care plan in place for home factor infusion (central line placement, factor delivered to home, self-infusion vs home health nurse infusion) as they will likely require additional days of factor infusion. If a care plan is not in place or not feasible, the patient should remain in the hospital until completion of factor maintenance therapy. Inadequate factor replacement therapy is one of the main risk factor for surgical readmissions due to postoperative bleeding and wound dehiscence in these patients.

Similar principles apply for patients with rare factor deficiencies (fibrinogen, factor II, factor V, factor VII, factor X, factor XI, and factor XIII). Table 54-3 lists the type of factor deficiencies and their treatment options.

The wound healing process is dependent upon a provisional matrix composed of fibrin. Hemostatic defects that limit the formation of a fibrin matrix may lead to wound healing defects resulting in delayed bleeding or reduced rate of wound closure. Patients with hemophilia or other congenital bleeding disorders display delayed bleeding after trauma or surgery if the initial clot that forms is not stable and resistant to breakdown. Furthermore, wound healing is a dynamic process. The initial clot is subsequently remodeled and the ability to reform fibrin must be maintained until the initial fibrin matrix is replaced by the synthesis of extracellular matrix.

Antifibrinolytics such as aminocaproic acid and tranexamic acid are often prescribed as adjunct therapy postsurgery in patients with congenital hemostatic disorders. These agents inhibit tissue fibrinolysis, leading to clot stabilization. The prophylactic use of antifibrinolytics has been shown to reduce postoperative bleeding in cardiac, orthopedic and liver transplant surgery. In patients with hematuria of upper urinary tract origin, antifibrinolytics are not recommended as it can cause intrarenal or ureteral obstruction through clot formation. Of note, there have been case reports of thrombotic complications associated with the use of antifibrinolytics in patients that have chronic DIC syndrome and cancer. Judicious use of these agents is recommended in patients who are known to be prothrombotic (eg, recent thrombotic events, known coronary artery disease, or cancer patients).

The lupus anticoagulant represents a common preoperative issue that generates significant confusion and often leads to delays in surgery. These patients will have an abnormal aPTT and no history of bleeding, assuming there is no other defect reported. The lupus anticoagulant is a misnomer because patients that have this laboratory abnormality do not bleed and are in fact at an increased risk of thrombosis. Lupus anticoagulants are likely to be detected in routine pre-op screening of patients that do not have any bleeding history. Laboratory testing will often document a prolongation of the aPTT. A mixing study of the patient’s plasma with normal plasma will not correct the defect after incubating the plasma for 60 minutes. The only caveat that warrants further consideration is the lupus anticoagulant patient that has a bleeding history or a very prolonged PT. These patients may have a coexisting factor inhibitor or very low prothrombin levels due to the presence of antiprothrombin antibodies that promote the clearance of prothrombin. Consultation with a hematologist will be needed to further define the lab abnormality and provide medical clearance for surgery.

Factors that Increase Risk of Hematologic Complications

There are several patient-specific and procedure-specific risk factors that are known to increase hematologic complications with surgery (Table 54-4).

PATIENT-SPECIFIC RISK FACTORS

Advanced age

Hematologic complications are greatly influenced by advanced age. The incidence of venous thromboembolism increases sharply with age. In individuals in the 25 to 30 years age group, the incidence is approximately 1 per 10,000 person-years. In contrast, the incidence increases about 80-fold with nearly 8 per 1000 person-year in the 85 years and older age group. Advanced age is also a risk factor for bleeding. The IMPROVE bleeding risk model which provides an estimate of in-hospital bleeding from the time of admission up to 14 days following admission for an acute medical illness demonstrated that the probability of major in-hospital bleeding for men was 0.1% in the <40 years, 0.2% in the 40 to 84 years, and 0.5% in the ≥85 years. The probability of a clinically important in-hospital bleeding was 0.5%, 1.1%, and 2.2%, respectively.

The prevalence of anemia, a known risk factor for postoperative mortality, also increases with advancing age, especially after the fifth decade of life and exceeds 20% in those 85 years and older. Anemia in the elderly may be due to decreased red cell production from age-related decline in normal bone marrow function, nutritional deficiencies (iron, B12 or folate) from poor dietary intake or decreased erythropoietin production from chronic kidney disease. Inflammatory response related to chronic disease conditions can also causes anemia of chronic inflammation, a disorder mediated by an increase in hepcidin production. Preoperative anemia can result in increased morbidity and mortality, particularly in elderly patients, as the surgery itself stresses the cardiovascular system, resulting in tissue hypoxia from reduced cardiac output and underlying atherosclerosis. This risk can be minimized through the correction of anemia using iron to correct the anemia or through exogenous erythropoietin injection. However, many elderly patients may have a primary marrow defect and not be responsive to such therapy. Underlying MDS or other changes that influence marrow response may affect the elderly and the threshold for providing transfusion support is dependent on the magnitude and extend of other organ dysfunction such as pulmonary, cardiac, vascular, or neurologic problems.

Other comorbidities

The presence of other comorbidities such as liver and kidney disease also increases the risk of perioperative hematologic complications.

Patients with liver disease are often coagulopathic from decreased hepatic synthesis of procoagulant and anticoagulant clotting factors, impaired hepatic clearance of fibrinolytics, malabsorption of vitamin K from impaired bile salt recirculation, dysfibrinogenemia, thrombocytopenia from hypersplenism and impaired thrombopoietin production, and platelet dysfunction. As both procoagulant and anticoagulant activities are affected, these patients are not “autoanticoagulated.” Instead, these patients remain in a balanced hemostatic state, albeit a more tenuous state, which is easily disturbed by any external stressors, such as surgery. As a result, patients with liver disease are at increased perioperative risk of bleeding and thrombosis.

For patients with mild liver disease (prolongation of INR <2.0) undergoing low- or moderate risk surgery, prophylactic intervention is usually not required. For high-risk surgery or severe liver disease, the correction of factors that are severely depressed may aide hemostasis. However, aggressive therapy with FFP to correct the INR is not feasible and will lead to volume overload in these patients. Recent studies using thromboelastograms to guide therapy have demonstrated that correction of the INR can be replaced by an approach that attempts to correct low fibrinogen, low platelet count and low coagulation factor levels. These patients are often undernourished or exposed to antibiotics. As these patients may be vitamin K deficient, vitamin K replacement therapy can be given to see if this helps to correct the coagulopathy.

Chronic kidney disease is associated with increased perioperative morbidity from impaired hemostasis secondary to acquired platelet dysfunction, leading to uremic bleeding. Both DDAVP and conjugated estrogen have been used, either alone or concurrently, as prophylaxis prior to surgery or for treatment of acute bleeding. As DDAVP has a limited clinical effect due to tachyphylaxis, it is more commonly used prior to minor surgical procedures (eg, biopsies and endoscopies) whereas conjugated estrogen, which has a longer duration of action of up to 10 days, can be used for elective surgery. Depending on the severity of the platelet dysfunction, platelet transfusion may be indicated. Patients with chronic kidney disease are also frequently anemic from reduced erythropoietin production. Besides tissue hypoxia, anemia can also cause platelet dysfunction by several possible mechanisms. Thus, a decrease in hematocrit may further enhance risk for bleeding and should be corrected prior to surgery. Correction of anemia by use of erythropoietin or transfusion may improve platelet function and is an additional strategy to aide hemostasis in uremic patients.

Given the rising incidence of cardiovascular disease, majority of the population are on aspirin and other antiplatelet agents, including GPIIb/IIIa antagonists, which cause defects in platelet aggregation. The concomitant use of antiplatelet and anticoagulant agents increase the risk of bleeding perioperatively. Prior to surgery, these drugs should be discontinued or avoided in the perioperative period, if safe to do so from a cardiovascular perspective. If needed, platelet transfusion may be indicated prior to surgery or in the case of excessive bleeding.

PROCEDURE-SPECIFIC RISK FACTORS

Type of surgery

The postoperative risk of bleeding, which is the highest contributor to morbidity and mortality in patients with malignant or nonmalignant hematologic disease, is greatly influenced by the type of surgery. A bleeding risk stratification based on the type of surgical or invasive procedures helps predict postoperative risk of bleeding and guide preoperative management (Table 54-5).

Choice of anesthesia

The choice of anesthesia can influence perioperative morbidity and mortality. General anesthesia may reduce myocardial contractibility and cardiac output. This further decreases tissue oxygen-delivery in elderly patients with borderline anemia, and may potentially lead to acute cardiac decompensation, resulting in myocardial ischemia, infarction and/or stroke. Certain inhalational general anesthetic agents can also inhibit the enzymatic activity of glucose-6-phosphate dehydrogenase (G6PD) activity, which leads to acute hemolysis in patients with G6PD deficiency. An awareness of this diagnosis should be communicated to the surgical and anesthetic team and placed in the chart to avoid the use of drugs known to precipitate hemolysis.

CONCLUSION

As the risk of perioperative complications can vary considerably depending on the underlying hematologic disorder, it is important to identify the disorder and its severity. A careful assessment of the benefits of surgery against the risk of perioperative complications is essential. With appropriate perioperative evaluation and management strategies, these patients should be able to undergo the majority of surgeries with risk reduced by managing known risk factors.

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