24 Preoperative Assessmentand Perioperative Managementof the Surgical Patient With DiabetesMellitus

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From: Contemporary Cardiology: Diabetes and Cardiovascular Disease, Second Edition Edited by: M. T. Johnstone and A. Veves © Humana Press Inc., Totowa, NJ

24 Preoperative Assessment

and Perioperative Management

of the Surgical Patient With Diabetes Mellitus

Alanna Coolong, ^MD

and Mylan C. Cohen, ^MD , ^MPH

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INTRODUCTION

Patients with diabetes mellitus (DM) are more likely than patients without diabetes to undergo surgery and may be at higher than average risk to suffer perioperative compli- cations, usually because of frequent concomitant cardiovascular disease (CVD). The manifestations of CVD in patients with diabetes are often atypical, making identification and management more difficult (1,2). The role of the physician asked to provide preop- erative consultation is to work with the surgical team in assessing and reducing the risk of complications in the perioperative period, and to identify opportunities to make a favorable impact on long-term health. In caring for the patient with diabetes perioperatively, heightened awareness of the higher incidence of coronary artery disease (CAD), silent ischemia, and increased predisposition to postoperative complications of infection, hy- perglycemia, and hypoglycemia is necessary to permit the best outcomes to occur.

EPIDEMIOLOGY

Perioperative Cardiac Morbidity

Each year in the United States approx 34.1 million patients undergo noncardiac opera- tions (3,4), more than 1 million individuals have noncardiac surgery complicated by perioperative cardiac morbidity and mortality (5). The risk of perioperative cardiac com- plications is substantially higher in patients with CAD, advanced congestive heart failure (CHF), major valvular abnormalities, or significant arrhythmias (3,6,7). The risk of cardiac complications is also institution- and procedure-specific. A higher incidence of complications is associated with intrathoracic, intraperitoneal, and vascular procedures and procedures performed in an emergency (8–10).

Cardiac outcomes have improved over the past decades, and the risk of a perioperative myocardial infarction (MI) is relatively low in the overall surgical population (<2%) (8,11,12). The risk for MI and other complications is higher in patients with a prior MI.

Reports from the 1970s placed the operative risk of reinfarction or cardiac death within 3 months of the previous MI as high as 30%, within 3 and 6 months at 15%, and after 6 months at about 5% (9,10). More recent estimates show an improvement: a 6% risk if within 3 months from the infarct and 2% if between 3 and 6 months (13,14). In a study evaluating the morbidity associated with vascular surgeries between 1955 and 1981, the operative mortality decreased from 8% in the 1950s to 2.9% in 1981(15). The incidence of perioperative MI in elective vascular surgeries has been estimated at 2.8% to 7.3%

(16,17). More recent estimates differentiate between those patients with ischemic heart disease and those without such history. A retrospective study of 6948 patients from the Cleveland Clinic undergoing vascular surgery from January 1989 to June 1997 found the incidence of perioperative MI to be 1.54% (18). Two recent prospective studies found the incidence of perioperative MI after noncardiac surgery in patients with a history of ischemic heart disease to be 4.1–5.6% (19,20).

It is recognized, however, that when a perioperative infarction occurs it carries an

extremely high risk of recurrent cardiac complications, including death, postoperatively

(9,10,18,20–22) and in the long-term (23,24). Mortality for perioperative MI has been

estimated to be from 17% to 41% (18,20,25).

SURGERY IN THE DIABETIC PATIENT

Seventeen million Americans have diabetes and the incidence of the disease is on the rise. The diagnosis of diabetes in US adults increased 61% from 1991 and is projected to more than double by 2050 (26). It has been estimated that a patient with DM has a 50%

lifetime chance of having a surgical procedure (27), and is more likely to undergo par- ticular types of surgeries, related to complications of diabetes. In 1980, 11.3% of opera- tions in diabetic patients were on the cardiovascular system, as compared to 4.3% in nondiabetic patients (28); nearly 12% of all patients undergoing coronary artery bypass surgery have diabetes (29,30). Other surgical procedures performed more frequently in diabetic patients include cataract extraction and vitrectomy, renal transplantation, ulcer debridement, and penile prosthesis implantation (31).

For many reasons, the surgical patient with diabetes has long been regarded as being at high risk for both cardiovascular and noncardiovascular complications. In the early 20th century, diabetic patients were denied all but the most necessary surgery. Over time, the use of insulin and antibiotics, improvements in surgical and anesthetic techniques, intravenous fluid management, and transfusion therapy have all served to improve post- surgical survival. With these advances, postoperative sepsis and ketoacidosis have be- come less common, and cardiovascular complications have become the primary cause of perioperative morbidity and mortality among patients with DM. Data from the 1960s suggest that surgery in the diabetic patient was associated with 4% to 13% mortality, mainly as a result of cardiovascular causes, making surgery a major cause of death in diabetics (32). Although improved anesthetic and surgical techniques and better cardio- vascular treatment have helped decrease the risks, the gains have been partially offset by the increasing age of the diabetic population and the greater complexity of procedures now undertaken in these patients.

However, whether DM is definitely an independent risk factor for adverse perioperative outcomes, cardiac or noncardiac, is debatable. Studies of diabetes as a risk factor are predominantly retrospective, and much of the data is derived from subanalyses of studies looking at a broader surgical population (Table 1).

A modest number of studies show a statistically significant association between dia- betes and adverse operative outcomes (Table 1). In developing their risk index, Eagle and associates found that in 200 patients undergoing major vascular surgery, diabetes was an independent risk factor and predictive of postoperative events or deaths (p = 0.03), sensitivity of 33% (confidence interval [CI], 18–53) and specificity of 96% (CI, 25–100) (33). Other investigators have subsequently reported that DM is a risk factor for adverse cardiac events in patients undergoing noncardiac surgery (34–37). An association was suggested in two other reports (12,38), but failed to reach statistical significance. More recently, L’Italien and colleagues (39) assessed a Bayesian model for perioperative car- diac risk in a cohort of vascular surgical patients, and in the validation of their model they found diabetes to be an independent predictor of adverse outcomes with an odds ratio (OR) of 2.0 (p = 0.048; CI, 1.0–4.1).

Conversely, several studies have shown that outcomes in diabetics and nondiabetics

are not significantly different (Table 1). Two prospective studies by Goldman and asso-

ciates (21) and Pedersen associates (40), failed to show that DM is associated with a

significantly increased risk for perioperative complications. Another prospective study

Table 1 Perioperative Outcomes in Patients With Diabetes Mellitus AuthorStatistical (reference)Surgery datesPatientsSurgeryOverall outcomesDiabetic outcomessignificance Mauney1968–1969365 patients withMajorPostoperativeNo significant increase in ECGNS 1970(48)abnormal ECGsNoncardiacECG changes and MIsChanges or MIs Steen1974–1975587 patients withNoncardiac6.1% had reinfarctions7.4% diabetics had reinfarctionsNS 1978(9)prior MIs5.9% nondiabetics had reinfarctions (121 diabetics) Goldman1975–19761001 patientsNoncardiac1.8% had MIsDiabetes was not a significant factorNS 1978(21)>40 years oldprospective Crawford1955–1981949 patientsAortoiliac3.8% mortalityDiabetes was not a significant factorNS 1981(15)(113 diabetics)(decreased long-term [at 5 and 10 years] survival in diabetics) Von Knorring1975–1977214 patientswithMajor17.7% had MIs23% diabetics had MIsNS 1981(22)evidence of CADNoncardiac17% nondiabetics had MIs Walsh1975–1979175 patientsGallbladder1.1% had MIs1.3% diabetics had MIsNS 1982(49)(80 diabetics)(acute and1% nondiabetics had MIs chronic)5.2% mortality5% diabetic mortalityNS 5.3% nondiabetic mortality Hertzer951 patientsVascular8.8% mortalityDiabetes was not a significant factorNS 1982(50)(284 diabetics) Hjortrup1975–1983224 diabeticsMajor20.5% had general20.5% diabetics had complicationsNS 1985(47)224 nondiabeticsnoncardiac matchedcomplications20.5% nondiabetics had complications 30% of complications were cardiacNS in diabetics 43% of complications were cardiac in nondiabetics Foster1978–19811600 patientsNoncardiacMortality andDiabetics had more eventsp = 0.004 1986(36)CASS patientscardiac morbidity (12% diabetics) Larsen1981–19832609 patientsMajor2.6% had cardiac7.3% diabetics had complicationsRegr coefficient 1987(12)>40 years oldNoncardiaccomplications2.3% nondiabetics had complicationsCardiac event (176 diabetics)0.8% had cardiac1.7% diabetics had cardiac mortalityp = 1.06 mortality0.8% nondiabetics had cardiac mort. Leppo1984–198580 patients forVascular16.8% had cardiac47% patients with events had diabetesNS 1987(38)dip. thalliumevents24% patients without events had diabetes

Eagle1984–1987200 patients forVascular15% had ischemic33% patients with events had diabetesp = 0.03 1989(33)dip. thalliumevents12% patients without events had diabetes (30% diabetics) Younis1984–1989111 patientsforVascular7.2% had MIs30% patients with MIs had diabetesNS 1990(51)dip thallium29% patients without MIs had diabetes (30% diabetics) Pedersen1986–19877306 patientsNoncardiac9.4% had complications 1990(40)(141 diabetics)Nonvascular6.3% had cardiac events9.2% diabetics had cardiac eventsNS Lette355 patients forMajor8.5% had cardiac event47% patients with events had diabetesp = 0.0004 1992(37)dip thalliumNoncardiac19% patients without events had diabetes Hollenberg1987–1989474 male VA patientsNoncardiacPostoperative ischemiaDiabetes was a significant risk factorp = 0.01 1992(34)(105 diabetics) Ashton1987–1989835 male VA patientsNoncardiac1.8% had MIsDiabetes was not a significant factorNS 1993(7)(194 diabetics) Brown1988–1990231 patientsNoncardiac8.2% had cardiac events53% patients with events had diabetesp < 0.005 1993(35)20% patients without events had diabetes L’Italien1984–1991567 patients inVascular8.1% had cardiac events37% patients with events had diabetesp = 0.008 1996(39)“training” set20% patients without events had diabetes 514 patients in7.6% had cardiac events69% patients with events had diabetesp = 0.048 validation” set53% patients without events had diabetes Treiman1964–1988153 patients DMAbdominal aortic5.2% patients with DM had PMIp = 0.0434 1994(41)970 patients non-DM2.1% patients without DM had PMI Melliere1992–1996169 patients DMVascular8.9% mortality in patients with DMp < 0.001 1999(42)834 patients0.8% mortality in patients without DM non-DM Dardik1990–19952335 patientsAbdominal aortic3.5% mortalityDiabetes was not a significant factorNS 1999(43)(168 diabetics) Berry1986–1996856 patientsAbdominal aortic1.3% mortalityDiabetes was not a significant factorNS 2001(44)(106 diabetics) Ballotta1992–1999199 patients DMCEAOverall mortality 0.5%Diabetes was not a significant factorNS 2001(45)348 pts nonDM Rayan1990–1999421 patientsAbdominal aortic1.7% mortality3.8% mortality in patients with DMp = 0.19 2002(46)(52 diabetics)1.4% mortality in patients without DM ECG, electrocardiograph; NS, not significant; MI, myocardial infarction; CASS, Coronary Artery Surgery Study dip thallium, dipyridamole thallium; DM, diabetes mellitus; CEA, carotid endarterectomy.

by Ballotta and associates (45), looking at the perioperative outcome of carotid endart- erectomy in diabetic patients vs nondiabetic patients found no significant difference between the two groups with respect to cardiac morbidity and mortality. Recently, sev- eral studies have compared outcomes between diabetic and nondiabetic patients under- going abdominal aortic aneurysm repair and have found no differences in mortality (43,44,46). Other studies have also shown similar rates of postoperative complications, including perioperative MI, in diabetics and nondiabetics undergoing both vascular and nonvascular surgical procedures (7,9,15,22,47–51).

PATHOPHYSIOLOGY

Pathophysiology of Perioperative Cardiovascular Complications Anesthesia and surgery have profound effects on overall metabolism and on the car- diovascular system, and several mechanisms have been implicated in the pathophysiol- ogy of perioperative cardiac complications. In the perioperative period there can be remarkable changes in the loading conditions of the heart, as a result of either volume loss or volume overload. There is stimulation of the sympathetic autonomic system resulting from hemodynamic changes and from other stressors such as pain and anxiety. Cat- echolamine-mediated tachycardia and hypertension may cause significant myocardial ischemia as a result of a mismatch in oxygen supply and demand, in the setting of fixed CAD or catecholamine-induced coronary spasm (52–54). A hypercoagulable state exists postoperatively, associated with decreased fibrinolytic and increased prothrombotic activity (55–58). Such a milieu may predispose to plaque rupture and coronary thrombo- sis in patients undergoing surgery (59,60). In the setting of these disturbances, the pres- ence of underlying CVD raises the likelihood for complications.

Perioperative Pathophysiology Related to Diabetes Mellitus

The diabetic patient is more likely than the nondiabetic patient to have CAD (61), and cardiovascular causes are responsible for the majority of deaths in diabetic individuals.

In fact, the risk of heart disease mortality is two to four times higher in diabetic patients than in nondiabetics (62). The diabetic patient is more likely to have diffuse CAD with involvement of smaller caliber vessels (63,64). In the event of MI, the incidence of heart failure is higher and the overall in-hospital mortality is higher for diabetic patients than for nondiabetics, especially in women (65). It has been repeatedly demonstrated that a large proportion of the diabetic population has CAD that is manifested atypically (66–

69), making diagnosis more difficult.

DM appears to increase the likelihood of developing CHF from any cause. And aside from identifiable causes, the existence of a cardiomyopathy related specifically to DM has been described, particularly in women, associated with increased cardiovascular mortality (63).

Autonomic dysfunction is estimated to be present in 20% to 40% of patients with

diabetes, and 82% of patients with peripheral neuropathy have evidence for autonomic

dysfunction (70). Autonomic dysfunction is characterized by the loss of appropriate heart

rate and blood pressure (BP) modulation, and may cause significant cardiovascular in-

stability. The diabetic patient with autonomic dysfunction is more likely to have de-

pressed ventricular function (71,72), to suffer an MI or sudden death, and the MI is more

likely to be have been clinically unrecognized (73–76). Autonomic dysfunction may

impair cardiovascular reflexes and prevent the appropriate response to the hemodynamic effects of anesthetic induction and other surgical stresses, and may be related to an increased mortality seen in some diabetic surgical patients.

Insulin normally serves as an anabolic hormone, affecting the metabolism of carbo- hydrates, proteins, and fats. In general, the stress response to surgery produces neurohor- monal changes, which disturb the normal role of insulin, and promote intense catabolism.

In the postoperative period, insulin secretion is normally decreased relative to the degree of hyperglycemia (although absolute levels may be normal or high). Perioperative fasting will tend to induce further catabolism. In the diabetic patient, in the setting of pre-existing insulin deficiency or resistance, the catabolic consequences of surgery are pronounced and severe hyperglycemia and ketosis can develop, along with attendant acidosis, fluid depletion, and electrolyte disturbances (77). To minimize the effects of these metabolic events, attention to glycemic metabolic control is necessary.

Finally, postoperative wound-healing is impaired in the diabetic patient. In vitro and animal models have shown a correlation between impaired deep wound-healing and hyperglycemia, which may cause deficiencies in granulation tissue and collagen, and decreased capillary ingrowth (78,79). Reversible in vitro neutrophil dysfunction is also associated with hyperglycemia (80,81). Neuropathy and occlusive vascular disease are factors likely affecting wound-healing, and experts suggest that surgical success and adequate healing may be related to the presence or absence of these factors, rather than humoral factors or specific levels of blood glucose in the postoperative period (82).

The impact of DM on numerous organ systems can make perioperative management challenging. Years of hyperglycemia may be manifested in abnormalities of the renal, immune, neurological, autonomic, endocrine, and cardiovascular systems, and will have implications for the perioperative course and outcome. The stressful effects of the perioperative period will be pronounced when superimposed on the pre-existing distur- bances related to diabetes and its associated co-morbidities.

RISK ASSESSMENT

The clinician performing the preoperative assessment should evaluate the patient’s current medical status and provide a clinical risk profile that the patient, primary physi- cian, anesthesiologist, and surgeon can use in making treatment decisions. The evalua- tion is intended to identify the patient who is at increased risk for a complication as a result of the proposed procedure, and to identify any patient-related or surgery-specific vari- ables that can be modified to lower the risk. An important part of the evaluation is the decision regarding further testing to identify and characterize the severity and stability of underlying CVD.

CLINICAL EVALUATION Clinical Risk Indices

Various schemata have been developed to risk stratify surgical patients based on

clinical characteristics and comorbidities (Table 2). The vast majority of cardiovascular

complications occur in patients with known cardiac disease, and predominantly in pa-

tients who have or are at risk for CAD (3). Therefore, much of the focus of perioperative

cardiac risk assessment, and the research in the field, is on the identification and manage-

ment of coronary disease. The development of the above models has been based mainly

Table2

Two Commonly Used Indexes of Perioperative Cardiac Risk

Original^a Detsky et al.^a

No. of No. of

Factor Definition points Definition points

Ischemic heart disease MI within 6 months 10 MI within 6 months 10

MI more than 6 months earlier 5

CCS class III angina 10

CCS class IV angina 20

Unstable angina within 6 months 10

Congestive heart S₃ gallop 11 Pulmonary edema within 1 week 10

failure or jugular venous distention any time in the past 5

Cardiac rhythm Rhythm other than sinus or 7 Rhythm other than sinus or 5 PACs on last preoperative ECG PACs on last preoperative ECG

>5 PVCs/minute at any time preop. 7

Valvular heart disease Important aortic stenosis 3 Suspected critical aortic stenosis 20 General medical status PO2 <60 mmHg, 3 Same as for original index

PCO2 >50 mmHg, potassium

<3 mmol/L, bicarbonate <20 mmol/L, BUN >50 mg/dL, creat. >3 mg/dL, abnormal AST, signs of chronic liver disease, patient bedridden for noncardiac causes

Age >70 years 5 >70 years 5

Type of surgery Intraperitoneal, intrathoracic, 3 Emergency operation 10 or aortic operation

Emergency operation 4

MI, myocardial infarction; CCS, Canadian Cardiovascular Society classification of angina; PAC, premature atrial contraction; ECG, electrocardiogram;PVC, premature ventricular contraction; PO₂, partial pressure of oxygen;

PCO₂, partial pressure of carbon dioxide; BUN, blood urea nitrogen; AST, aspartate aminotransferase.

aAdapted with permission from refs. 8,11,213.

on observational or retrospective studies, and little data is available from prospective or randomized studies.

The original Cardiac Risk Index developed by Goldman and colleagues was the first

validated multivariate model developed to predict cardiac complications in a general

surgical population (8). A modified index by Detsky and associates added “significant

angina” and included the type of planned surgery (11). High scores assessed by these

indices, reflecting the presence of multiple risk factors, have proved helpful in risk-

stratifying unselected, consecutive patients undergoing general surgery. In patients un-

dergoing vascular surgery, which is generally considered to be relatively high-risk

surgery, Eagle and colleagues were able to identify patients who were at low risk for

complications by the absence of advanced age, angina, history of ventricular ectopic

activity, Q waves on electrocardiogram (ECG), and DM (33). The American College of

Cardiology (ACC) and the American Heart Association (AHA) jointly published guide-

lines for the perioperative management of noncardiac surgical patients in 1996, which were recently updated (Fig. 1) (83,84).

There is no unified approach to how the diagnosis of DM should be factored into the process of preoperative risk stratification. In the report of the original risk index Goldman noted that the “conspicuously insignificant variables in our analysis includes diabetes,”

and DM was not included as one of the nine risk factors (8). Similarly, diabetes is not included as a risk factor in the index by Detsky (11), and Detsky’s recent position paper on preoperative risk assessment for the American College of Physicians does not address diabetes (85). Eagle’s schema, on the other hand, uses DM as a significant risk factor (33).

Expert opinions can be conflicting, and recent reviews have drawn opposite conclusions (3,82). The ACC/ AHA guidelines on perioperative management include DM among the

“intermediate predictors” for perioperative cardiovascular risk, which were defined as

“well-validated markers of enhanced risk of perioperative cardiac complications which justify careful assessment of the patient’s current status” (83).

Clearly, not all diabetic surgical patients are at high perioperative risk. There is a need to define clinical risk factors that might aid the physician in identifying the individual diabetic patient who is at an increased risk. A significant deficiency of the available epidemiological data is the lack of information on the risk associated with particular subgroups of the diabetic population.

Subgroups of Patients With Diabetes Mellitus

As with surgical patients in general, diabetic patients with manifestations of CVD are at a higher risk in the perioperative period. MacKenzie and associates showed that serious morbidity and mortality in diabetic patients were predicted by the presence of pre-exist- ing cardiac disease. They identified diabetic patients with heart failure and significant valvular disease as being at increased risk, and suggested that diabetics without these two conditions were not likely to have cardiac or noncardiac complication (86). In a study by Zarich and associates (68), all adverse events occurred in patients with clinical markers for coronary disease (history of angina or CHF, pathological Q waves on ECG). No adverse events occurred in the patients without clinical markers of coronary disease, despite the 58% prevalence of abnormal dipyridamole thallium scans, in the setting of similar vascular procedures, anesthetic techniques, and perioperative use of nitroglycerin and hemodynamic monitoring.

Farrow and associates have suggested that DM may be more associated with cardiac events in certain types of surgery (87). These investigators found that diabetes figured prominently as a risk factor in orthopedic procedures, operations of the larynx and tra- chea, and of the upper gastrointestinal tract; it was not a significant factor in laparotomies, esophageal and colorectal surgery, and amputations. Conspicuously absent was major vascular surgery. On the other hand, Hjortrup and colleagues found no difference in the incidence of postoperative complications amongst diabetic patients in three groups of surgical procedures—major abdominal surgery, major vascular surgery, and orthopedic surgery (47).

For diabetics and nondiabetics alike, vascular surgery is undertaken at a higher risk for

cardiac events than many other surgical procedures. The increased risk may be partly

related to the risks inherent to the procedure itself and partly because of the high preva-

lence of concomitant coronary disease in these patients (69,88,89). Patients undergoing

infrainguinal vascular bypass, compared to those having aortic procedures, tend to have

a higher prevalence of CAD (90,91). The increased cardiac morbidity, early and late, observed in patients undergoing peripheral vascular procedures is likely related to the increased prevalence of concomitant CAD.

Institutional factors will influence postoperative outcomes. The experience and exper- tise of the surgical team and the medical consultants in the management of diabetes are likely to favorably affect outcomes. On the other hand, an institution specializing in the management of diabetes may undertake procedures that are more complex and risky, and may attract referrals of high-risk patients.

As discussed previously, patients with autonomic dysfunction are a group of diabetics particularly prone to CVD, associated with increased atypical or silent ischemia, ven- tricular dysfunction, and hemodynamic instability. Diabetic patients who manifest auto- nomic dysfunction are at an increased risk for perioperative hemodynamic instability, cardiorespiratory arrest, and death (92–94). Therefore, the patient with autonomic dys- function should be considered to be at a high risk for perioperative complications. Such a patient may warrant particularly close cardiovascular evaluation, hemodynamic moni- toring, and surveillance for cardiovascular events.

The incidence of postoperative complications is not necessarily related to the duration

of diabetes (67,68,86), and previously has not been felt to be related to the form of

treatment of the diabetes (i.e., insulin vs oral agents) (47,67,68,86). But a recent retro-

spective VA study by Axelrod et al. examining the impact of DM on perioperative

outcomes in patients who underwent major vascular surgery found that patients treated

with insulin were at increased risk for cardiovascular complications (OR 1.48; 95% CI,

1.15–1.91) but not death (95). In their derivation and prospective validation of a simple

index for prediction of cardiac risk in major noncardiac surgery, Lee and associates also

found preoperative treatment with insulin to be an independent predictor of cardiac complications (96). Thus, it would appear that patients with diabetes are not uniformly at risk for adverse outcomes and those patients treated with insulin may represent a subgroup of diabetics at higher risk.

CLINICAL EVALUATION OF THE PATIENT WITH DIABETES MELLITUS

A limitation to the clinical evaluation of the patient with DM is the concern for atypical manifestations of CVD (73,74,97,98). Uncertainty in defining ischemia and MI has important consequences for the reliability of the preoperative assessment and the reliabil- ity of the perioperative surveillance for cardiac events. Physicians, therefore, may not feel as confident in basing their assessment on the clinical evaluation of a diabetic patient, as compared with a nondiabetic patient.

Despite the atypical nature of presentation, careful evaluation can often yield a history of symptoms ascribable to an ischemic event. A number of studies have shown that it is a minority of patients who are asymptomatic at the time of their acute MI and that in most cases symptoms can be determined, albeit atypical in nature in up to 42% of cases (99,100). Atypical symptoms are more common in elderly diabetic patients, as in non- diabetic patients (101). Autonomic dysfunction increases the likelihood for atypical ischemic symptoms and for silent ischemia (73–75). In patients with peripheral vascular disease (PVD), limitations in activity imposed by claudication may make evaluating symptoms of CAD particularly difficult. Therefore, careful attention is required for atypical manifestations in elderly patients, in patients with autonomic dysfunction, and in patients with PVD.

The presence of anginal symptoms in a patient with DM is prognostically important.

There is evidence that diabetics have a higher threshold for feeling angina and, therefore, the presence of symptoms may be indicative of more severe ischemia. Zarich and asso- ciates (68) and Lane and associates (67) found that a history of angina in a patient with DM was associated with a higher incidence of cardiac complications.

With a heightened vigilance the physician can identify historical clues and physical findings which are associated with increased perioperative risk. Additionally, surgery- and institution-specific factors should be considered.

NONINVASIVE TESTING

Preoperative noninvasive testing is intended to evaluate the severity of CAD, whether suspected or already diagnosed. It is also intended to assess the functional capacity of the patient in whom clinical evaluation alone cannot provide that information.

EXERCISE-TOLERANCE TESTING

Exercise-tolerance testing to evaluate exercise capacity and electrocardiocraphic re-

sponse has been used to risk-stratify patients awaiting general noncardiac (102) and

vascular surgery (103,104). The efficacy of the exercise-tolerance test relies greatly on

defining functional capacity, and the predictive value depends on an adequate stress level

( 85% maximal predicted heart rate) during the test. Significant confounders of exercise

testing are any physical condition that will limit the patient’s ability to exercise, such as

claudication resulting from severe PVD, or medications such as G-blockers that might blunt the heart rate response to exercise. Peripheral neuropathy and autonomic neuropa- thy in diabetics impair the ability of the patient to exercise adequately, and may alter the hemodynamic response to exercise (70).

NONINVASIVE IMAGING

The addition of imaging, such as thallium scintigraphy, significantly improves the sensitivity of exercise testing, even if suboptimal levels of stress are achieved (105). In patients who are unable to exercise adequately, pharmacological testing with dipy- ridamole and dobutamine in conjunction with imaging modalities are useful. Dipy- ridamole-thallium scintigraphy has been studied extensively in the preoperative setting.

The utility of thallium defects in predicting perioperative risk has been shown repeat- edly, particularly in vascular patients (33,35,37,89,106–108). The sensitivity for coro- nary disease has been as high as 100%, and the positive predictive value for cardiac complications ranges from 10% to 30% in the larger studies. The extent of abnormality has been found to be significant, and the nature of the defects (i.e., reversible vs fixed).

The probability of long-term event-free survival can also be assessed with these preop- erative results (51,109,110). Perfusion imaging with scintigraphy may have greater func- tional and a prognostic utility than angiography, because perfusion imaging provides information on the extent of myocardium that may be in jeopardy in association with a coronary stenosis.

Although the presence of a transient thallium defect is associated with an increase in the relative risk among patients referred for testing, the association weakens as the test is applied to unselected patients. This applies even in patients with PVD (111,112), considered to be at higher risk to begin with. The importance of combining clinical with scintigraphic data was demonstrated by Eagle and associates (33) (Fig. 2), and subse- quently confirmed in a multicenter study by L’Italien and associates (39).

The data on dobutamine echocardiography to assess perioperative risk are few relative to those available for nuclear perfusion imaging. The positive predictive value ranges from 7% to 23% for deaths or MIs, and the negative predictive value ranges from 93%

to 100% (113,114). The extent of wall motion abnormalities and ischemia manifested by new wall motion abnormalities at low dobutamine doses appear to be significant. Al- though the results seem comparable to perfusion modalities, the published experience is still limited. Stress echocardiography may be potentially useful in evaluating patients with valvular disease.

Resting left ventricular function as determined by echocardiography or radionuclide an- giography is of limited utility in risk stratifying patients. Although patients with a left ventricu- lar ejection fraction of less than 35% may be at risk for developing perioperative CHF, resting left ventricular function is not a reliable predictor of ischemic events (115–117).

USE OF NONINVASIVE IMAGING IN PATIENTS WITH DIABETES MELLITUS

Preoperative nuclear imaging is used extensively in patients with diabetes. Because

CVD is likely to be atypical in patients with diabetes, there has been a tendency to rely

on further testing, particularly thallium scintigraphy, to identify patients with significant

disease. Numerous investigators have shown that in the absence of a history of angina,

CHF, or infarct up to 59% of diabetic patients being evaluated for vascular surgery have abnormal thallium scans (fixed or reversible) (66–69). In comparison, only 17% of as- ymptomatic nondiabetic patients with PVD have reversible defects (118).

Patients with diabetes who have additional coronary risk factors are more likely to have significant thallium abnormalities. Nesto and co-workers studied 165 patients with diabetes and PVD (69), 30 of whom did not have clinical evidence of coronary disease.

Of these 30 patients, 87% of the smokers, 71% of the hypertensives, and all with both of these risk factors had abnormal scans, although the 6 patients without either risk factor had normal scans. Diabetes alone, therefore, is not a strong predictor for the high preva- lence of thallium-perfusion defects observed in diabetic patients, even in the population with PVD. The presence of additional risk factors is more predictive of significant thal- lium abnormalities.

Lane and co-workers studied 101 diabetic patients undergoing dipyridamole thallium scintigraphy prior to vascular surgery (67). An abnormal thallium scan alone was not significantly predictive of cardiovascular risk. However, the specificity and positive predictive value improved with an increasing number of reversible defects. The positive predictive value of the presence of angina was similar to that of two reversible defects.

This was confirmed by Brown and associates (35), who determined that the probability

of perioperative cardiac deaths or nonfatal MI increased relative to the number of thal-

lium-perfusion defects, a relationship more pronounced in patients with DM when com-

pared with nondiabetics. These results suggest that the risk of vascular surgery in patients

with diabetes can be assessed by quantitating the extent of myocardial ischemia by

dipyridamole thallium screening. To assess the utility of dipyridamole thallium in pa-

tients with and without clinical evidence of cardiac disease, Zarich and colleagues pro-

spectively performed dipyridamole thallium scintigraphy in 133 patients with diabetes

undergoing peripheral vascular surgery (more than 90% for limb-threatening ischemia)

(68). Clinical evidence of CAD was found in 57 patients, 36 patients were without clinical

evidence of CAD, and 40 patients were excluded for reasons not related to the thallium

results. All adverse events occurred in patients with clinical markers for CAD (history of

angina or CHF, pathological Q waves on ECG) despite similar vascular procedures,

anesthetic techniques, and perioperative use of nitroglycerin and hemodynamic monitor-

ing. No adverse events occurred in the patients without clinical markers of CAD, despite the 58% prevalence of abnormal dipyridamole thallium scans. Among those with clinical markers of CAD, the number of thallium defects was an independent risk factor for postoperative events. In patients who do not have clinical markers for coronary disease, an abnormal thallium scan may not be predictive of cardiac events perioperatively.

The long-term prognostic value of dipyridamole thallium imaging in diabetics under- going peripheral vascular surgery was evaluated in a prospective study by Cohen and associates (119). The presence of more than two reversible thallium defects was associ- ated with a median survival of only 1.8 years. The thallium findings also further risk- stratified clinically high- and low-risk patients; whereas high-risk patients with normal scans had a median survival similar to low-risk patients (8.6 years), the presence of any thallium abnormality markedly reduced median survival to 3.7 years (p < 0.001). Con- versely, low-risk patients with more than two reversible defects had a median survival of 4 years. Thus, dipyridamole thallium imaging in diabetic patients would seem to identify a subset of patients requiring more aggressive medical or surgical intervention.

Thus, thallium scintigraphy is a powerful tool in the risk assessment of the surgical candidate. Thallium scanning has impressive sensitivity in detecting the presence and severity of CAD. In diabetics and nondiabetics alike, the overuse of the test will lower its predictive value and therefore its clinical utility. Although patients with DM are more likely to have abnormal scans, this does not necessarily translate into an increased perioperative risk. Thallium scanning in diabetics without clinical evidence for CVD has little prognostic utility in the perioperative period. And in patients with clinical evidence for CVD, little is added to the overall assessment by a nuclear scan unless there are multiple defects suggestive of extensive ischemia. As with any diagnostic test, a Baye- sian approach should be applied. Further testing should depend on the likely influence of the test on the overall assessment and how that in turn will affect further management decisions.

ANGIOGRAPHY

The patient who is determined to be at high risk by virtue of the preoperative evaluation should be referred for angiography to define the coronary anatomy. This is done with the expectation that coronary revascularization will be performed if feasible.

Patients with unstable angina or a recent MI warrant evaluation by coronary angiog-

raphy prior to urgent surgery, foregoing preliminary noninvasive testing. Other patients

who are at increased risk for adverse cardiac events and might benefit from angiography

will be identified by clinical factors and noninvasive tests, as outlined above. Guidelines

issued by the ACC and the AHA have outlined generally accepted indications for angiog-

raphy in the nonoperative setting (120,121). In general, the indications for preoperative

coronary angiography should parallel those for the nonoperative setting, and the recent

ACC/AHA guidelines for perioperative cardiac risk assessment incorporated the above

guidelines for angiography (83,84). Recently, Cohen and Eagle compiled the opinions of

30 experts regarding indications for angiography based on specific results of preopera-

tive noninvasive tests (122). There is general agreement that a noninvasive result that

indicates large zones of myocardial ischemia warrants further evaluation. The decision

to pursue angiography should take into account the risk of this procedure itself and

subsequent revascularization.

SPECIAL SITUATIONS: RENAL TRANSPLANTATION

The prevalence of CAD among diabetic patients with end-stage renal disease (ESRD) is as high as 55% (105,122–126). The duration or type of diabetes may not have an effect on the severity of the coronary disease (123,126), but hemodialysis may accelerate ath- erosclerosis (127). There is a striking impact of coronary disease on survival in these patients. Two-year survival ranges from 22% to 45% in diabetics with ESRD (123,126).

Approximately 50% of deaths before (105,126,129,130) and after (131–133) transplan- tation resultfrom cardiac causes, with an average cardiac mortality rate of 7.8% per year.

And in the perioperative period there is an increased incidence of cardiac complications with renal and pancreatic transplants (134,135).

Evaluation of the diabetic renal transplant candidate is fraught with difficulties unique to ESRD. These patients will often have multiple risk factors for coronary disease and will frequently have numerous atypical cardiac and noncardiac complaints, often leading to many false-positive and false-negative clinical assessments.

The experience with noninvasive testing for CAD in patients with ESRD has yielded disappointing results. These patients are frequently unable to achieve adequate stress levels on exercise stress testing (105). In one series, only 7% of the patients achieved target heart rates (136). Various limiting factors include anemia (137), debilitation, PVD, neuropathy (70), and peritoneal dialysis (138).

Although thallium has been shown to increase the sensitivity of exercise testing in these patients (105) and has been found to be useful when combined with dipyridamole in some studies (129,130), the overall predictive value of thallium has been poor. In a series of 45 patients being evaluated for transplantation (only 1 patient with DM included), Marwick and colleagues (139) found that the sensitivity of dipyridamole thallium for CAD compared with angiography was only 37% (much lower than in patients without ESRD) and the specificity 73%. Of prognostic importance is that in this cohort, five of the six cardiac deaths occurred in patients who had normal scans and who all had significant CAD by catheterization. Other studies have confirmed the poor utility of this testing in this particular patient population (128,130,140).

Dipyridamole can have a blunted hemodynamic effect in patients with ESRD as a result of high levels of endogenous adenosine in this population. This may account for a higher false-negative rate of dipyridamole thallium imaging in these patients (141).

Given the grave perioperative and long-term implications of CAD in patients with diabetes and ESRD, and the poor efficacy of noninvasive testing, many experts recom- mend routine angiography prior to transplantation (105,123,126,142–144). If noninvasive assessment is utilized the clinician should have a very high index of suspicion for CAD and a low threshold for referral to coronary angiography.

There is some limited evidence that coronary revascularization improves survival in diabetic patients being considered for renal transplantation. One study showed that in 26 patients randomly assigned to medical treatment or revascularization (angioplasty or coronary bypass surgery) (145) the frequency of cardiac events was lower in patients who underwent revascularization among the insulin-dependent diabetic patients with chronic renal failure.

RISK REDUCTION

After determining the magnitude of perioperative risk, the consultant’s next task is to

make recommendations aimed at lowering the risk. Risk lowering may be achieved by

medical management, preoperative revascularization, and perioperative surveillance. In some instances, changing or canceling the procedure may be necessary. Data for specific recommendations is generally limited, and particularly so for patients with DM.

MEDICAL INTERVENTIONS G-Blockers

Outside of the perioperative period, G-blockers have repeatedly been shown to im- prove survival in the setting of chronic coronary insufficiency and acute coronary syn- dromes. Data is limited regarding use of G-blockade perioperatively. In randomized and nonrandomized studies, G- blockers have been shown to decrease ischemic events, acute MIs, and death in the perioperative period (146–149,150,151). There are no data regard- ing diabetics specifically, however, some clinicians have been reluctant to use G-blockers in patients with DM as a result of the potential effect on an already abnormal chronotropic response, and because of the theoretical concern for predisposing diabetic patients to hypoglycemia and altering the symptoms associated with hypoglycemia (152). On the contrary, G-blockers are well tolerated clinically (153,154). They are clearly beneficial in diabetic patients with CAD (155,156) and the reduction of postinfarction mortality and reinfarction rates associated with G-blockers appears to be especially pronounced in diabetic patients (157–160).

In summary, the benefits of G-blockers in reducing perioperative mortality and MI warrant at least a perioperative course of treatment, although the optimal duration of therapy needing to be better established by clinical trials.

NITRATES

Intravenous nitroglycerin has been used to reverse ischemia in various clinical set- tings, including intraoperatively. However, its prophylactic intraoperative use in two small studies was not associated with improved outcomes (161,162), and may actually lead to cardiovascular decompensation by decreasing preload. Additionally, the vasodilatory effects may be accentuated by the action of various anesthetic agents and by impaired autonomic function. Therefore, nitroglycerin administration should be reserved for the high-risk patient who has required nitrates prior to surgery for the control of angina and for the patient who develops signs of active ischemia.

ANESTHETIC AGENTS

There are many potential approaches to the anesthetic care of the patient with CVD.

Most often the decisions regarding the anesthetic regimen are deferred to the anesthesi- ology team responsible for the patient. Patient co-morbidities and the surgical procedure itself usually outweigh any effects the anesthetic technique may have on outcome (163).

All anesthetic techniques are associated with cardiovascular side effects. Spinal and

epidural techniques can cause neural blockade, particularly sympathetic blockade, and

can bring about profound afterload and preload changes. The intravenous agents used for

induction of anesthesia typically lower the systemic BP by up to 30% in healthy patients,

and often by even more in the hypertensive patient. This lowering is followed shortly

thereafter by a predictable rise in BP during laryngoscopy and intubation. Inhalational

agents may cause myocardial depression and afterload reduction. There are no significant

differences among the commonly used inhalational agents (i.e., isoflurane, halothane,

enflurane) (164). Epidural anesthesia, spinal blocks, and splanchnic nerve blocks have been shown to ameliorate the endocrine, hematological and metabolic response to sur- gery (165–167). Overall, however, studies have failed to show a myocardial benefit of any one regimen (58,167,168).

The consequences of inadequate anesthesia should not be underestimated. Bode re- ported that the highest complication rate was in patients who failed regional anesthesia and were switched over to general anesthesia in the same setting (169). Because of that finding it was recommended that patients who fail regional anesthesia should be brought back on another day.

The use of anesthesia in the diabetic patient involves some special considerations.

Hypoglycemia has occasionally been documented after epidural anesthesia and after infiltration of large amounts of lidocaine (170,171). Ether was associated with hyperg- lycemia and ketosis in the past, but the newer inhalational agents such as halothane and enflurane can be used safely (172). The presence of impaired cardiovascular reflexes may prevent the appropriate response to the hemodynamic effects of anesthesia and surgery, and may be related in part to the increased mortality seen in diabetic surgical patients (92,93). Therefore, particular caution should be used when administering anesthesia to patients with autonomic dysfunction.

REVASCULARIZATION

Retrospective and observational data have suggested that preoperative revascularization may confer some protection in patients who are determined to be at high risk for adverse cardiac outcomes. It should be noted, although, that no randomized, controlled trials have assessed the benefit of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) before noncardiac surgery (173).

Preoperative coronary artery bypass grafting lowers the operative mortality compared to medical therapy in patients undergoing noncardiac surgery. Among 1600 patients enrolled in the Coronary Artery Surgery Study (CASS) registry, Foster and associates (36) found that the operative mortality for noncardiac surgery was similar in patients without significant angiographic disease (0.5%) and in patients who had undergone CABG (0.9%), whereas it was significantly higher (2.4%) in patients with CAD treated medically. There was no significant difference in the incidence of perioperative MI, heart failure, or arrhythmias in the three groups. In a series of 1001 Cleveland Clinic patients undergoing elective vascular surgery (174), the postoperative mortality rate was 1.4% in patients with no CAD, 3.6% in patients with advanced but compensated CAD (well collateralized territory, or already infarcted in area of involved vessel), 1.5% in patients who had preoperative coronary bypass, and 14% in patients with severe but inoperable coronary disease.

The potential benefit of preoperative revascularization must be weighed against the surgical risks of the coronary bypass itself and the delay to the proposed noncardiac surgery. The operative mortality of coronary artery bypass usually exceeds the risks inherent to the proposed noncardiac procedure, 5.3% in the Cleveland Clinic series (174) and 2.3% in the CASS registry (36).

There is data to suggest that patients who have both CAD and PVD are at increased

long-term cardiac risk, and long-term survival seems to be improved in patients under-

going CABG (174,175). This is an effect on the chronic coronary disease rather than an

immediate perioperative benefit. But the decision on whether to pursue revascularization

before noncardiac surgery is controversial. In the short term, the perioperative mortality from elective vascular surgery is lower than prophylactic CABG surgery (176). How- ever, the major cause of long-term mortality in this patient population is cardiac; prompt- ing some physicians to adopt a more aggressive stance on revascularization.

Patients with diabetes have increased morbidity and mortality after coronary revascularization compared with nondiabetic patients (177,178). The randomized By- pass Angioplasty Revascularization Investigation (BARI) trial, although it did not spe- cifically study patients undergoing noncardiac surgery, demonstrated that patients with treated diabetes (with insulin or oral agents) and multivessel disease had a significantly decreased 5.4-year cardiac mortality if assigned to an initial strategy of coronary bypass (5.8%), compared with percutaneous transluminal coronary angioplasty (20.6%) (179).

This survival benefit was pronounced in patients with internal mammary artery grafts, as compared to patients who received only venous conduits. In the diabetic patient with multivessel disease, the decision between angioplasty and bypass surgery should be guided by the results of this trial. In patients with single-vessel coronary disease, percu- taneous revascularization is probably an acceptable, less-invasive alternative. Treatment options for patients with DM will be better defined with the completion of the BARI II trial. The study group in BARI II consists of 2600 patients with type 2 DM and stable CAD who are suitable for elective revascularization. Importantly, this trial should pro- vide greater insight regarding the practice of single or multivessel stenting as it compares to CABG (180).

Several small series have shown a protective benefit from preoperative percutaneous coronary balloon angioplasty, with a lower complication rate than with bypass surgery (181–184). Recently, two studies have looked at postoperative outcomes in patients who have undergone coronary stenting before noncardiac surgery (185,186). Kaluza and associates examined the outcomes of a group of patients who had undergone noncardiac surgery within 6 weeks of stenting. Of 40 patients, there were 7 MIs, 11 major bleeding episodes, and 8 deaths. All deaths and MIs, and 8 of 11 bleeds, occurred in patients undergoing surgery less than 14 days after stent placement. Most deaths were accounted for by stent thrombosis. Wilson and associates, in attempting to determine the optimal delay following stent placement prior to noncardiac surgery, reviewed the clinical course of 207 patients who underwent noncardiac surgery in the 2 months following stent place- ment. Eight patients (4%) died or suffered an MI or stent thrombosis. All 8 patients underwent noncardiac surgery within 6 weeks of stent placement. From these studies, it would seem advisable to wait 6 weeks poststent placement before proceeding with non- cardiac surgery when possible.

In summary, the indications for preoperative revascularization should parallel those in the nonsurgical population. Patients with diabetes awaiting elective noncardiac sur- gery who are found to have high-risk coronary anatomy, and in whom short- or long-term outcome would likely be improved by revascularization, should generally undergo CABG before elective high-risk noncardiac surgery. In patients who have undergone PCI with stent placement, elective noncardiac surgery should be performed at least 6 weeks after stent placement.

PERIOPERATIVE MONITORING

The detection of a cardiovascular event perioperatively ideally would lead to prompt

and appropriate treatment. In the perioperative period, multiple confounders may not

allow for the detection of cardiovascular problems. An altered sensorium as a result of analgesics and sedatives may prevent the patient from appropriately recognizing or ex- pressing symptoms. A focus on the surgical site and related issues may cause the patient and caretakers to mistake cardiovascular symptoms for problems associated with the surgery itself. Atypical symptoms may be further distorted in this context and particularly difficult to characterize; an issue especially relevant in some diabetic patients.

It would seem reasonable, then, to consider the perioperative use of a pulmonary artery catheter in selected patients undergoing procedures deemed high risk. But current evi- dence from randomized trials evaluating the use of pulmonary artery catheters in abdomi- nal aortic surgery and vascular surgery have shown no difference in perioperative MI or mortality (187–189,173,151). The American Society of Anesthesiologists has published guidelines for the intraoperative use of pulmonary artery catheters according to patient disease, surgical procedure, and practice setting (190). The ACC/AHA guidelines are in accordance with these recommendations. And although there is no class I indication for the intraoperative use of pulmonary artery catheters, their use may benefit high-risk patients undergoing procedures in which large intraoperative and postoperative fluid shifts are anticipated (83).

The optimal method for documenting perioperative MI has not been determined.

Various protocols have been examined, although serial electrocardiography and serial cardiac enzymes have been used most commonly. The efficacy of these methods has varied considerably in different studies, depending on the diagnostic criteria used. Rettke and associates found that higher creatinine kinase (CK)-MB levels after abdominal aortic surgery correlated with worse outcomes (191). Charlson and associates demonstrated that electrocardiography immediately after noncardiac surgery and subsequently on the first and second postoperative days had a higher sensitivity than enzyme analysis (192).

Given the fact that CK-MB is released from noncardiac tissue, troponin T and I poten- tially provide better specificity perioperatively (193–199). Adams and associates pro- spectively evaluated 108 patients undergoing noncardiac surgery with baseline echocardiograms, serial ECGs, and serial CK-MB and troponin I. On the third postop- erative day, a repeat echocardiogram was obtained. Eight patients developed new seg- mental wall motion abnormalities; all eight patients had elevations of troponin I, and six patients had elevations of CK-MB. Of the 100 patients without perioperative MI by echocardiography, 19 had elevations of CK-MB, with only 1 with a slight elevation of troponin I (193). In another study evaluating the prognostic significance of troponin T elevation after noncardiac surgery, patients with elevated troponin T had a relative risk for cardiac events of 5.4, whereas CK-MB was not correlated with postdischarge cardiac events (194).

Real-time ST-segment monitoring has been used to detect perioperative ischemia.

Postoperative ischemic changes in the ST segment, especially of prolonged duration in high-risk patients, have been shown to be predictive of perioperative cardiac events (54,200,201) and predictive of worse long-term survival in patients (23). Computerized ST-segment analysis and trending is superior to visual interpretation and will greatly improve the sensitivity of this monitoring modality. Although ST-segment monitoring may detect ischemia, the clinical significance of transient ST-segment changes and their impact on outcome has not been established (202).

Per ACC/AHA guidelines regarding the optimal strategy for surveillance and detec-

tion of perioperative MI in patients with high or intermediate clinical risk undergoing

high- or intermediate-risk surgery, it is recommended that ECGs be obtained at baseline, immediately postoperatively, and on postoperative days 1 and 2 with troponin measure- ments 24 hours postoperatively and on day 4 or hospital discharge (83).

METABOLIC MANAGEMENT

As discussed previously, the catabolic consequences of surgery are pronounced in the diabetic patient, and severe hyperglycemia and ketosis can develop along with acidosis, fluid depletion, and electrolyte disturbances. To minimize the effects of these metabolic events, close attention to glycemic control is necessary. Insulin administration inhibits lipolysis, ketogenesis, and protein catabolism. Glucose administration also helps to in- hibit these. All insulin-dependent patients should be treated with insulin, glucose, and fluids during the perioperative period. Noninsulin-dependent patients may also require insulin.

There is little evidence regarding the ideal level of glycemic control. Hypoglycemia may be associated with neurological effects, and a sympathetic surge and a potentially deleterious cardiovascular response. Therefore, blood glucose levels should be main- tained above 120 mg/dL. To avoid osmotic diuresis and the effects of relative hypoinsulinemia discussed above, blood glucose levels should ideally be maintained below 180 mg/dL (77,82). Hjortrup et al. observed that the mean blood glucose levels preoperatively and during the first postoperative day were significantly lower in the diabetic patient with complications, as compared to the patients without complications (47). More recently, however, studies of patients with DM undergoing cardiac surgery have shown an association between perioperative hyperglycemia and wound infections (203,204,205). These patients have less infectious complications when glycemic control is obtained with a continous insulin infusion and blood glucose was maintained below 200 mg/dL. For elective procedures it is generally felt that good glucose control should be achieved before surgery, and this may mean initiating insulin therapy or changing current dosing (82). This can take several days or even weeks. In this era of cost contain- ment, most patients are admitted on the day of surgery regardless of co-morbidities or fragility of glucose control, thereby complicating metabolic management. Patients with well-controlled noninsulin-dependent diabetes should have oral agents held on the day of surgery until the first postoperative meal. If blood glucose is above 200 mg/dL during the perioperative period, insulin and glucose should be instituted, either in addition to or in place of the oral agent.

Insulin requirements depend on patient and surgical characteristics, and on the post- operative course. The highest insulin requirements occur in patients undergoing cardiop- ulmonary bypass surgery. Obesity, liver disease, steroid therapy, and sepsis will cause higher insulin requirements. However, because of impaired gluconeogenesis patients with hepatic disease are also prone to hypoglycemia during insulin administration (206).

Several regimens exist for perioperative glycemic management. Only a few prospec-

tive randomized studies in small numbers of patients have compared the subcutaneous

and intravenous administration of insulin. Although intravenous regimens yield tighter

control of glucose levels, subcutaneous administration is effective in achieving adequate

control (207–209). Theoretically, the absorption of subcutaneous insulin may be affected

by postoperative interstitial edema and by alterations in cutaneous flow (e.g., during

hypotension, shock, use of vasopressors) (77). Intravenous insulin is recommended for

patients with ketoacidosis who require emergency surgery, for “brittle” diabetics, and for patients in whom insulin requirements are extremely high. The choice of regimen for glycemic control will depend greatly on the treating physician’s familiarity with the various protocols and the insulin requirements of the patient.

The use of subcutaneous insulin is common, and is currently recommended by the Joslin Clinic in Boston (82) for the majority of insulin-requiring patients. One-half or two-thirds of the usual daily dose of protamine or lente insulin is given on the morning of the surgery. Glucose must be infused, usually as a 5% solution. Glucose levels should be measured at 4-hour intervals. Administration of additional subcutaneous regular in- sulin prevents high glucose levels.

A variable rate insulin infusion is an effective alternative for achieving glycemic control. Regular insulin is infused at an initial rate of 0.5 to 1.0 U per hour, along with a glucose infusion at a rate of 5 to 10 g per hour the insulin rate is adjusted according to blood glucose levels. Glucose measurements at one or two hour intervals are required.

This technique has been shown to achieve smooth and rapid glycemic control (208).

A fixed-rate insulin infusion can also be used, as one adjusts the rate of the glucose infusion. However, in patients with high insulin requirements, the administered glucose might not be sufficient to suppress catabolism if the initial insulin dose is low (209). This approach has not yet been evaluated in a large series.

An alternative strategy is the glucose–insulin–potassium method. The three compo- nents are mixed in a single solution. The insulin concentration is adjusted if the blood glucose levels are outside the targeted goals. Any such change requires a new solution to be mixed. However, once the desired proportions are determined for a particular patient it becomes simple to manage (210), assuming stable insulin requirements.

Attention to fluids and electrolytes is extremely important. Potassium levels should be checked regularly. Dextrose is usually administered at a rate of 5 to 10 g per hour, although the optimal glucose required to prevent protein and fat metabolism has not been determined (77). If fluid restriction is necessary, the more concentrated dextrose solu- tions can be used. Lactate supplementation in intravenous fluids may increase glucose levels, as a substrate of gluconeogenesis (77).

ROLE OF THE CONSULTANT

Preoperative risk assessment and perioperative management of the surgical patient is a frequent cause for consultation for family practitioners, internists, cardiologists, and other medical specialists. A critical role of the consultant is to communicate the severity and stability of the patient’s cardiovascular condition and to determine whether the patient is in a reasonable medical condition in the context of the surgical illness. The consultant may recommend changes in medications and suggest preoperative tests or procedures.

A crucial aspect of the consultative process is the exchange of information between the consultant and the physician who has requested the consultation. The consultant’s assess- ment and recommendations must be communicated with brevity and clarity. As well as writing a complete note in the chart or sending a letter, there is no substitute for direct personal contact with the primary physician (211).

Follow-up increases compliance with recommendations (212) and allows for modifi-

cations in the original management plan as the clinical context changes. Many medical

conditions require long-term follow-up, and the involvement of the consultant in the