Anesthetic Implications of Concurrent Diseases

Preoperative and Preprocedure Diabetes Mellitus

Diabetes mellitus is a heterogeneous group of disorders that have the common feature of a relative or absolute insulin deficiency. The disease is characterized by a multitude of hormone-induced metabolic abnormalities, diffuse microvascular lesions, and long-term end organ complications. The diagnosis of diabetes is made with a fasting blood glucose level greater than 110 mg/dL (6.1 mmol/L), and impaired glucose tolerance is diagnosed if the fasting glucose level is less than 110 mg/dL (6.1 mmol/L) but greater than 100 mg/dL (5.5 mmol/L). Diabetes can be divided into two very different diseases that share the same long-term end-organ complications. Type 1 diabetes is associated with autoimmune diseases and has a concordance rate of 40% to 50% (i.e., if one of a pair of monozygotic twins had diabetes, the likelihood that the other twin would have diabetes is 40%-50%). In type 1 diabetes, the patient is insulin deficient, principally from autoimmune destruction of the pancreatic β cells, and susceptible to ketoacidosis if insulin is withheld. Type 2 diabetes has a concordance rate approaching 80% (i.e., genetic material is both necessary and sufficient for the development of type 2 diabetes). [CR] How markedly the aging and end-organ effects of these genes are expressed is based on lifestyle choices of food and physical activity. These patients are not susceptible to the development of ketoacidosis in the absence of insulin, and they have peripheral insulin resistance through multiple defects with insulin action and secretion. Patients with non–insulin-dependent (type 2) diabetes account for the majority (>90%) of the diabetic patients in Europe and North America. These individuals tend to be overweight, relatively resistant to ketoacidosis, and susceptible to the development of a hyperglycemic-hyperosmolar nonketotic state. Plasma insulin levels are normal or increased in type 2 diabetes but are relatively low for the level of blood glucose. This hyperinsulinemia by itself is postulated to cause accelerated cardiovascular disease. Gestational diabetes develops in more than 3% of all pregnancies and increases the risk of developing type 2 diabetes by 17% to 63% within 15 years.

Type 1 and type 2 diabetes differ in other ways as well. Contrary to long-standing belief, a patient’s age does not allow a firm distinction between type 1 and type 2 diabetes; type 1 diabetes can develop in an older person, and clearly, type 2 diabetes can develop in overweight children. Type 1 diabetes is associated with a 15% prevalence of other autoimmune diseases, including Graves disease, Hashimoto thyroiditis, Addison disease, and myasthenia gravis.

Over the next decade, the prevalence of diabetes is expected to increase by 50%. This growth is primarily the result of the increase in type 2 diabetes caused by excessive weight gain in adults and now also in the pediatric population. Large clinical studies show that long-term, strict control of blood glucose levels and arterial blood pressure, along with regular physical activity, results in a major delay in microvascular complications and perhaps indefinite postponement of type 2 diabetes in patients.

The common administered drugs can be classified into eight major groups: acarbose, biguanides (e.g., metformin), dipeptidyl peptidase-4 inhibitors (e.g., sitagliptin, saxagliptin, vildagliptin), glucagon-like peptide-1 receptor agonists (e.g., albiglutide, dulagutide, or exenatide), meglitinide (e.g., repaglinide or nateglinide), sodium-glucose transport protein 2 inhibitors (e.g., canagliflozin or empagliflozin), sulfonylureas (e.g., glibenclamide, glipizide, glimepiride, gliquidone), and thiazolidinediones (e.g., pioglitazone or rosiglitazone). [CR]

Patients with insulin-dependent diabetes tend to be younger, nonobese, and susceptible to the development of ketoacidosis. Plasma insulin levels are low or un-measurable, and therapy requires insulin replacement. Patients with insulin-dependent diabetes experience an increase in their insulin requirements in the post-midnight hours, which may result in early morning hyperglycemia (dawn phenomenon). This accelerated glucose production and impaired glucose use reflect nocturnal surges in secretion of growth hormone (GH). Physiologically normal patients and diabetic patients taking insulin have steady-state levels of insulin in their blood. Absorption of insulin is highly variable and depends on the type and species of insulin, the site of administration, and subcutaneous blood flow. Nevertheless, attainment of a steady state depends on periodic administration of the preparations received by the patient. Thus it seems logical to continue the insulin combination perioperatively that the patient had been receiving after assessing previous blood glucose control. [CR]

The major risk factors for diabetic patients undergoing surgery are the end-organ diseases associated with diabetes: cardiovascular dysfunction, renal insufficiency, joint collagen tissue abnormalities (limitation in neck extension, poor wound healing), inadequate granulocyte production, neuropathies, and infectious complications. Thus a major focus of the anesthesiologist should be the preoperative and preprocedure evaluation and treatment of these diseases to ensure optimal preoperative and preprocedure conditions. Poor preoperative glucose control, as measured by the hemoglobin A _1C (glycosylated hemoglobin) level, is an independent predictor of worse perioperative outcome.

Glucotoxicity

Long-term tight control of blood glucose has been motivated by concern for three potential glucotoxicities, in addition to the results from major randomized outcome studies involving diabetic patients.

• 1.

  Glucose itself may be toxic because high levels can promote nonenzymatic glycosylation reactions that lead to the formation of abnormal proteins. These proteins may weaken endothelial junctions and decrease elastance, which is responsible for the stiff joint syndrome (and difficult intubation secondary to fixation of the atlanto-occipital joint), as well as decrease wound-healing tensile strength.

• 2.

  Glycemia also disrupts autoregulation. Glucose-induced vasodilation prevents target organs from protecting against increases in systemic blood pressure. A glycosylated hemoglobin level of 8.1% is the threshold at which the risk for microalbuminuria increases logarithmically. A person with type 1 diabetes who has microalbuminuria of greater than 29 mg/day has an 80% chance of experiencing renal insufficiency. The threshold for glycemic toxicity differs for various vascular beds. For example, the threshold for retinopathy is a glycosylated hemoglobin value of 8.5% to 9.0% (12.5 mmol/L or 225 mg/dL), and that for cardiovascular disease is an average blood glucose value of 5.4 mmol/L (96 mg/dL). Thus different degrees of hyperglycemia may be required before different vascular beds are damaged. Another view is that perhaps severe hyperglycemia and microalbuminuria are simply concomitant effects of a common underlying cause. For instance, diabetic patients in whom microalbuminuria develops are more resistant to insulin, insulin resistance is associated with microalbuminuria in first-degree relatives of patients with type 2 diabetes, and persons who are normoglycemic but subsequently have clinical diabetes are at risk for atherogenesis before the onset of disease.

Diabetes itself may not be as important to perioperative outcome as are its end-organ effects. Epidemiologic studies segregated the effects of diabetes itself on the organ system from the effects of the complications of diabetes (e.g., cardiac, nervous system, renal, and vascular disease) and the effects of old age and the accelerated aging that diabetes causes. Even in patients requiring intensive care unit (ICU) management, long-standing diabetes does not appear to be as important an issue as the end-organ dysfunction that exists and the degree of glucose control in the perioperative or periprocedure and ICU periods. ^6b,8-13

The World Health Organization’s surgical safety checklist bundle suggests control with a target perioperative blood glucose concentration of 6 to 10 mmol/L (acceptable range, 4-12 mmol/L) or 100 to 180 mg/dL. Poor perioperative glycemic control has a significant impact on the risk of postoperative infection across a variety of surgical specialities. Different regimens permit almost any degree of perioperative control of blood glucose levels, but the tighter the control desired, the greater the risk of hypoglycemia. Therefore, debate regarding optimal control during the perioperative period has been extensive. Tight control retards all these glucotoxicities and may have other benefits in retarding the severity of diabetes itself. Management of intraoperative glucose may be influenced by specific situations, such as the following: the type of operation, pregnancy, expected global CNS insult, the bias of the patient’s primary care physician, or the type of diabetes.

Much of the research on perioperative control is derived from studies in the ICU, as opposed to the operating room. The first major trial demonstrating the benefit of tight glucose control was in medical ICU patients in Leuven, Belgium. The most recent trial was from the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) group. In this randomized controlled trial, the investigators examined the associations between moderate and severe hypoglycemia (blood glucose, 41-70 mg/dL [2.3-3.9 mmol/L] and ≤40 mg/dL [2.2 mmol/L], respectively) and death among 6026 critically ill patients in ICUs. Intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. The optimal perioperative management has been reviewed elsewhere. Guidelines have been developed on the use of insulin infusions in the critical care unit to achieve these goals ( Table 32.1 ).

Diabetes and Accelerated Physiologic Aging

Adverse perioperative outcomes have repeatedly and substantially correlated with the age of the patient, and diabetes does cause physiologic aging. When one translates the results of the Diabetes Control and Complications Trials into age-induced physiologic changes, a patient with type 1 diabetes who has poor control of blood glucose ages approximately 1.75 years physiologically for every chronologic year of the disease and 1.25 years if blood glucose has been controlled tightly. A patient with type 2 diabetes ages approximately 1.5 years for every chronologic year of the disease and approximately 1.06 years with tight control of blood glucose and blood pressure. Thus when providing care for a diabetic patient, one must consider the associated risks to be those of a person who is much older physiologically; the physiologic age of a diabetic patient is considerably older than that person’s calendar age just by virtue of having the disease.

Obesity and lack of physical exercise seem to be major contributors to the increasing prevalence of type 2 diabetes. As with type 1 diabetes, tight control of blood glucose, increased physical activity, and reduction in weight appear to reduce the accelerated aging associated with type 2 diabetes, and possibly delay the appearance of the disease and aging from it substantially. Although such a reduction in aging should reduce the perioperative risk for diabetic patients, no controlled trials have confirmed this theory.

The key to managing blood glucose levels perioperatively in diabetic patients is to set clear goals and then monitor blood glucose levels frequently enough to adjust therapy to achieve these goals. [CR]

Other Conditions Associated With Diabetes

Diabetes is associated with microangiopathy (in retinal and renal vessels), peripheral neuropathy, autonomic dysfunction, and infection. Diabetic patients are often treated with angiotensin-converting enzyme (ACE) inhibitors, even in the absence of gross hypertension, in an effort to prevent the effects of disordered autoregulation, including renal failure.

Preoperatively, assessment and optimization of treatment of the potential and potent end-organ effects of diabetes are at least as important as assessment of the diabetic patient’s current overall metabolic status. The preoperative evaluation of diabetic patients is also discussed in Chapter 31 .

The presence of autonomic neuropathy likely makes the operative period more hazardous and the postoperative period crucial to survival. Evidence of autonomic neuropathy may be routinely sought before the surgical procedure. Patients with diabetic autonomic neuropathy are at increased risk for gastroparesis (and consequent aspiration of gastric contents) and for perioperative cardiorespiratory arrest. Diabetic patients who exhibit signs of autonomic neuropathy, such as early satiety, lack of sweating, lack of pulse rate change with inspiration or orthostatic maneuvers, and impotence, have a very frequent incidence of painless myocardial ischemia. Administration of metoclopramide, 10 mg preoperatively to facilitate gastric emptying of solids, may be helpful ( Fig. 32.1 ). Interference with respiration or sinus automaticity by pneumonia or by anesthetic agents, pain medications, or sedative drugs is likely the precipitating cause in most cases of sudden cardiorespiratory arrest. Measuring the degree of sinus arrhythmia or beat-to-beat variability provides a simple, accurate test for significant autonomic neuropathy. The difference between the maximum and minimum heart rate on deep inspiration is normally 15 beats/min, but it is 5 beats/min or less in all patients who subsequently sustain cardiorespiratory arrest.

Other characteristics of patients with autonomic neuropathy include postural hypotension with a decrease in arterial blood pressure of more than 30 mm Hg, resting tachycardia, nocturnal diarrhea, and dense peripheral neuropathy. Diabetic patients with significant autonomic neuropathy may have impaired respiratory responses to hypoxia and are particularly sensitive to the action of drugs that have depressant effects. These patients may warrant continuous cardiac and respiratory monitoring for 24 to 72 hours postoperatively, although this has not been tested in a rigorous, controlled trial. In the absence of autonomic neuropathy, outpatient surgery is preferred for a diabetic patient if possible (see Table 32.1 ). [CR]

Emergency Surgery

Many diabetic patients requiring emergency surgery for trauma or infection have significant metabolic decompensation, including ketoacidosis. Frequently, little time is available to stabilize the patient, but even a few hours may be sufficient for correction of any fluid and electrolyte disturbances that are potentially life-threatening. It is futile to delay surgery in an attempt to eliminate ketoacidosis completely if the underlying surgical condition will lead to further metabolic deterioration. The likelihood of intraoperative cardiac arrhythmias and hypotension resulting from ketoacidosis will be reduced if intravascular volume depletion and hypokalemia are at least partially treated. During the initial resuscitation phase of ketoacidosis bicarbonate should initially be avoided with crystalloid fluids, potassium repletion, and intravenous insulin therapy favored. [CR]

Insulin therapy is initiated with a 10-unit intravenous bolus of regular insulin, followed by continuous insulin infusion. The rate of infusion is determined most easily by dividing the last serum glucose value by 150 (or 100 if the patient is receiving steroids, has an infection, or is considerably overweight [body mass index ≥35]). The actual amount of insulin administered is less important than is regular monitoring of glucose, potassium, and arterial pH. The maximum rate of glucose decline is fairly constant, averaging 75 to 100 mg/dL/h, regardless of the dose of insulin because the number of insulin binding sites is limited. During the first 1 to 2 hours of fluid resuscitation, the glucose level may decrease more precipitously. When serum glucose reaches 250 mg/dL, the intravenous fluid should include 5% dextrose.

The volume of intravenously administered fluid required varies with the overall deficit; it ranges from 3 to 5 L and may be as large as 10 L. Despite losses of water in excess of losses of solute, sodium levels are generally normal or reduced. Factitious hyponatremia caused by hyperglycemia or hypertriglyceridemia may result in this seeming contradiction. The plasma sodium concentration decreases by approximately 1.6 mEq/L for every 100 mg/dL increase in plasma glucose greater than normal. Initially, balanced crystalloid solution is infused at a rate of 250 to 1000 mL/h, depending on the degree of intravascular volume depletion and cardiac status. Some measure of left ventricular volume should be monitored in diabetic patients who have a history of myocardial dysfunction. Approximately one third of the estimated fluid deficit is corrected during the first 6 to 8 hours and the remaining two thirds over the next 24 hours. [CR]

The degree of acidosis is determined by analysis of arterial blood gases and detection of an increased anion gap (see also Chapter 48 ). Acidosis with an increased anion gap (≥16 mEq/L) in an acutely ill diabetic patient may be caused by ketones in ketoacidosis, lactic acid in lactic acidosis, increased organic acids from renal insufficiency, or all three disorders. In ketoacidosis, plasma levels of acetoacetate, β-hydroxybutyrate, and acetone are increased. Plasma and urinary ketones can be measured semiquantitatively with Ketostix and Acetest tablets. The role of bicarbonate therapy in diabetic ketoacidosis is controversial, but could be considered in severe acidemia and hemodynamic instability as myocardial function and respiration are known to be depressed at a blood pH lower than 7.00 to 7.10. This careful consideration is because rapid correction of acidosis with bicarbonate therapy may result in alterations in CNS function and structure. These alterations may be caused by (1) paradoxical development of cerebrospinal fluid and CNS acidosis from rapid conversion of bicarbonate to carbon dioxide and diffusion of the acid across the blood-brain barrier, (2) altered CNS oxygenation with decreased cerebral blood flow, and (3) the development of unfavorable osmotic gradients. After treatment with fluids and insulin, β-hydroxybutyrate levels decrease rapidly, whereas acetoacetate levels may remain stable or even increase before declining. Plasma acetone levels remain elevated for 24 to 42 hours, long after blood glucose, β-hydroxybutyrate, and acetoacetate levels have returned to normal; the result is continuing ketonuria. Persistent ketosis with a serum bicarbonate level less than 20 mEq/L in the presence of a normal glucose concentration is an indication of the continued need for intracellular glucose and insulin for reversal of lipolysis.

The most important electrolyte disturbance in diabetic ketoacidosis is depletion of total-body potassium. Deficits range from 3 to 10 mEq/kg body weight. Serum potassium levels decline rapidly and reach a nadir within 2 to 4 hours after the start of intravenous insulin administration. Aggressive replacement therapy is required. The potassium administered moves into the intracellular space with insulin as the acidosis is corrected. Potassium is also excreted in urine because of the increased delivery of sodium to the distal renal tubules that accompanies volume expansion. Phosphorus deficiency in ketoacidosis as a result of tissue catabolism, impaired cellular uptake, and increased urinary losses may give rise to significant muscular weakness and organ dysfunction. The average phosphorus deficit is approximately 1 mmol/kg body weight; no clear guidance for replacement exists, but replacement is appropriate in patients with cardiac dysfunction, anemia, respiratory depression, or if the plasma phosphate concentration is less than 1.0 mg/dL.

Anticipated Newer Treatments of Diabetes

At least three major changes in the care of diabetic patients have made it to the clinical trial stage:

• ▪

  Implanted (like a pacemaker) glucose analyzer with electronic transmission to a surface (watch) monitor

• ▪

  New islet transplantation medication that makes islet cell transplants much more successful and rejection medication less hazardous

• ▪

  Medications such as INGAP (islet neogenesis–associated protein) peptide, which may cause regrowth of normally functioning islet cells (without the need for transplantation)

Some of these treatments may radically change the therapies used in the perioperative period. If regrowth of islet cells becomes common, type 1 diabetes could all but disappear; if implanted minute-to-minute glucose reading is possible, tight control may be much easier and more expected.

Insulinoma and Other Causes of Hypoglycemia

Hypoglycemia in persons not treated for diabetes is rare. Hypoglycemia in nondiabetic patients can be caused by such diverse entities as pancreatic islet cell adenoma or carcinoma, large hepatoma, large sarcoma, alcohol ingestion, use of β-adrenergic receptor blocking drugs, haloperidol therapy, hypopituitarism, adrenal insufficiency, altered physiology after gastric or gastric bypass surgery, hereditary fructose intolerance, ingestion of antidiabetic drugs, galactosemia, or autoimmune hypoglycemia. The last four entities cause postprandial reactive hypoglycemia. Because restriction of oral intake prevents severe hypoglycemia, the practice of keeping the patient NPO (nothing by mouth) and infusing small amounts of a solution containing 5% dextrose greatly lessens the possibility of perioperative postprandial reactive hypoglycemia. The other causes of hypoglycemia can cause serious problems during the perioperative period.

Symptoms of hypoglycemia fall into one of two groups: adrenergic excess (tachycardia, palpitations, tremulousness, or diaphoresis) or neuroglycopenia (headache, confusion, mental sluggishness, seizures, or coma). All these symptoms may be masked by anesthesia, so blood glucose levels should be determined frequently in at-risk patients to ensure that hypoglycemia is not present. Because manipulation of an insulinoma can result in massive insulin release, this tumor should probably be operated on only at centers equipped with a mechanical pancreas. Perioperative use of the somatostatin analogue octreotide, which suppresses insulin release from such tumors, makes the perioperative period safer in anecdotal experience.

Hyperlipoproteinemia, Hyperlipidemia, and Hypolipidemia

Hyperlipidemia may result from obesity, estrogen or corticoid therapy, uremia, diabetes, hypothyroidism, acromegaly, alcohol ingestion, liver disease, inborn errors of metabolism, or pregnancy. Hyperlipidemia may cause premature coronary, peripheral vascular disease, or pancreatitis.

Coronary events can be decreased by treating individuals with even normal levels of low-density lipoprotein (LDL) cholesterol with statins (3-hydroxy-3-methylglutaryl–coenzyme A [HMG-CoA] reductase inhibitors )—through an increase in high-density lipoprotein (HDL) and a decrease in LDL cholesterol levels. This approach has markedly decreased the rate of myocardial reinfarction in high-risk patients. Secondary prevention efforts were successful when these high-risk patients stopped smoking, reduced their arterial blood pressure, controlled stress, increased physical activity, and used aspirin, folate, β-blocking drugs, angiotensin inhibitors, diet, and other drugs to reduce their levels of LDL and increase their levels of HDL.

Although controlling the diet remains a major treatment modality for all types of hyperlipidemia, the drugs fenofibrate and gemfibrozil, which are used to treat hypertriglyceridemia, can cause myopathy, especially in patients with hepatic or renal disease; clofibrate is also associated with an increased incidence of gallstones. Cholestyramine binds bile acids, as well as oral anticoagulants, digitalis drugs, and thyroid hormones. Nicotinic acid causes peripheral vasodilation and should probably not be continued through the morning of the surgical procedure. Probucol (Lorelco) decreases the synthesis of apoprotein A-1; its use is associated on rare occasion with fetid perspiration or prolongation of the QT interval, or both, and sudden death in animals.

The West of Scotland Coronary Prevention Study and its congeners produced convincing evidence that drugs in the statin class prevent the morbidity and mortality related to arterial aging and vascular disease, as well as their consequences, such as coronary artery disease (CAD), stroke, and peripheral vascular insufficiency. Thus, the statins—lovastatin (Mevacor), pravastatin (Pravachol), simvastatin, fluvastatin, atorvastatin (Lipitor), and rosuvastatin (Crestor)—are mainstays of therapy, limited by patient tolerance most commonly secondary to musculoskeletal complaints. [CR]

However, the report of Downs and coworkers from the Air Force/Texas Coronary Atherosclerosis Prevention Study went further. This report showed a 37% reduction in the risk for first acute major coronary events in patients who had no risk factors and normal (average) LDL cholesterol levels. In this study lovastatin did not alter mortality rates, but that had been true for many early short-term trials with the statins. Although much of the effect of the statins has been attributed to their lipid-lowering effects, statins also influence endothelial function, inflammatory responses, plaque stability, and thrombogenicity. In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released a new clinical practice guideline for the treatment of blood cholesterol in people at high risk for cardiovascular diseases. They now advocate statin therapy for the following:

• ▪

  Patients who have cardiovascular disease (coronary syndromes, previous myocardial infarction [MI], stable or unstable angina, previous stroke or transient ischemic attack, or peripheral artery disease)

• ▪

  Patients with an LDL cholesterol level of 190 mg/dL or higher

• ▪

  Patients with diabetes (type 1 or 2) who are between 40 and 75 years old

• ▪

  Patients with an estimated 10-year risk of cardiovascular disease greater than 7.5% (the report provided formulas for calculating 10-year risk)

The 2014 National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia further emphasize the use of statins as a first-line therapy for dyslipidemia, but emphasize the inclusion of non-high density lipoprotein in addition to LDL as markers for risk. They further advocated for management of other atherosclerotic cardiovascular disease risk factors including high blood pressure, tobacco use, and diabetes mellitus. [CR]

Statins are drugs that block HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Their use is occasionally accompanied by liver dysfunction, CNS dysfunction, and severe depression not related to the high cost of each drug and its congeners. Based on the available evidence, statin therapy should be continued in patients already taking these drugs. Other drugs that reduce LDL and increase HDL cholesterol and decrease triglycerides are docosahexaenoic acid (an ω-3 fatty acid) and niacin. Statins also provide the substantial benefit of reversing inflammation in arteries, as evidenced by their ability to decrease highly specific C-reactive protein and pull cholesterol from plaque.

Hypolipidemic conditions are rare diseases often associated with neuropathy, anemia, and renal failure. Although anesthetic experience with hypolipidemic conditions has been limited, some specific recommendations can be made: continuation of caloric intake and intravenous administration of protein hydrolysates and glucose should be continued throughout the perioperative period.

Obesity

Obesity is a risk factor for perioperative morbidity. In the study of Medicare claims in which obese patients were matched to non-obese patients undergoing surgery, the obese patients displayed increased odds of wound infection, renal dysfunction, urinary tract infection, hypotension, respiratory events, 30-day readmission, and a 12% longer length of stay. Although many conditions associated with obesity (diabetes, hyperlipidemia, cholelithiasis, gastroesophageal reflux disease, cirrhosis, degenerative joint and disk disease, venous stasis with thrombotic or embolic disease, sleep disorders, and emotional and altered body image disorders) contribute to chronic morbidity in these patients, the main concerns for the anesthesiologist have been the same since the 1970s—derangements of the cardiopulmonary system.

Morbid obesity with minimal or no coexisting pulmonary conditions (e.g., no obesity-hypoventilation syndrome or chronic obstructive pulmonary disease [COPD]) is referred to here as “simple” obesity. In simple obesity, the pathophysiology of mild alterations in daytime gas exchange and pulmonary function may also result from compression and restriction of the chest wall and diaphragm by excess adipose tissue. Typically, in obese patients, the expiratory reserve volume and functional residual capacity are most affected and are reduced to 60% and 80% of normal, respectively. Care must be taken with medication choice and dosing, as simple obese patients may be more sensitive to sedative and narcotic agents leading to hypoventilation. [CR]

Other Eating Disorders: Anorexia Nervosa, Bulimia, and Starvation

Many endocrine and metabolic abnormalities occur in patients with anorexia nervosa, a condition characterized by starvation to the point of 40% loss of normal weight, hyperactivity, and a psychiatrically distorted body image. Many anorectic patients exhibit impulsive behavior, including suicide attempts, and intravenous drug use is much more common than in the general population. Acidosis, hypokalemia, hypocalcemia, hypomagnesemia, hypothermia, diabetes insipidus, and severe endocrine abnormalities mimicking panhypopituitarism may need attention before patients undergo anesthesia. Similar problems occur in bulimia (bulimorexia), a condition that may affect as many as 50% of female college students and is even unintentionally present in many older adults. As in severe protein deficiency, anorexia nervosa and bulimia may be accompanied by the following: alterations on the electrocardiogram (ECG), including a prolonged QT interval, atrioventricular (AV) block, and other arrhythmias; sensitivity to epinephrine; and cardiomyopathy. Total depletion of body potassium makes the addition of potassium to glucose solutions useful; although, fluid administration can precipitate pulmonary edema in these patients and should be monitored judiciously. Esophagitis, pancreatitis, and aspiration pneumonia are more frequent in these patients, as is delayed gastric emptying. One review reported that in patients with severe anorexia, a body mass index less than 13 kg/m ² , marked hypoglycemia or leukocytopenia lower than 3.0 × 10 ⁹ /L, or both, potentially fatal complications frequently occur. Intraoperatively, glucose or catecholamine administration may lead to disturbance of electrolytes or fatal arrhythmia. Intensive care and early nutritional support as soon as possible postoperatively are important to prevent surgical site infection with close monitoring for refeeding syndrome.

Physiologic Properties of Adrenocortical Hormones

Adrenocortical Hormone Excess

Adrenocortical Hormone Deficiency

Patients Taking Steroids for Other Reasons

Adrenal Cortex Function in Older Adults

Production of androgens by the adrenal gland progressively decreases with age; this change has no known implications for anesthesia. Plasma levels of cortisol are unaffected by increasing age. Levels of CBG are also unaffected by age, a finding suggesting that a normal fraction of free cortisol (1%-5%) is present in older patients. Older patients have a progressively impaired ability to metabolize and excrete glucocorticoids. In normal individuals, the quantity of 17-hydroxycorticosteroids excreted is reduced by half by the seventh decade. This decreased excretion undoubtedly reflects the reduced renal function that occurs with aging. When excretion of cortisol metabolites is expressed as a function of creatinine clearance, the age difference disappears. Further reductions in cortisol clearance may reflect impaired hepatic metabolism of circulating cortisol.

The rate of secretion of cortisol is 30% slower in older adults. This reduced secretion may be an appropriate compensatory mechanism for maintaining a normal cortisol level in the presence of decreased hepatic and renal clearance of cortisol. The reduced cortisol production can be overcome during periods of stress, and even extremely old patients (>100 years old) display an entirely normal adrenal response to the administration of ACTH and to stresses such as hypoglycemia.

Both underproduction and overproduction of glucocorticoids are generally considered diseases of younger individuals. The highest incidence of Cushing disease of either pituitary or adrenal origin occurs during the third decade of life. The most common cause of spontaneous Cushing disease is benign pituitary adenoma. However, in patients older than 60 years in whom Cushing disease develops, the most likely cause is adrenal carcinoma or ectopic ACTH production from tumors usually located in the lung, pancreas, or thymus.

Hyperthyroidism

Although hyperthyroidism is usually caused by the multinodular diffuse enlargement in Graves disease (also associated with disorders of the skin or eyes, or both), it can also occur with pregnancy, thyroiditis, thyroid adenoma, choriocarcinoma, or TSH-secreting pituitary adenoma. Five percent of women have thyrotoxic effects 3 to 6 months postpartum and tend to have recurrences with subsequent pregnancies. Major manifestations of hyperthyroidism are weight loss, diarrhea, warm and moist skin, weakness of large muscle groups, menstrual abnormalities, osteopenia, nervousness, jitteriness, intolerance to heat, tachycardia, cardiac arrhythmias, mitral valve prolapse, and heart failure. When the thyroid is functioning abnormally, the cardiovascular system is most at risk. When diarrhea is severe, the associated dehydration and electrolyte abnormalities should be corrected preoperatively. Mild anemia, thrombocytopenia, increased serum alkaline phosphatase, hypercalcemia, muscle wasting, and bone loss frequently occur in hyperthyroidism. Muscle disease usually involves the proximal large muscle groups; it has not been reported to cause respiratory muscle paralysis. In the apathetic form of hyperthyroidism (seen most commonly in persons >60 years old), cardiac effects predominate and include tachycardia, irregular heart rhythm, atrial fibrillation (in 10%), heart failure, and occasionally, papillary muscle dysfunction.

Although β-adrenergic receptor blockade can control the heart rate, its use is challenging in the setting of heart failure. However, a decreasing heart rate may improve heart-pumping function. Thus hyperthyroid patients who have fast ventricular rates and in heart failure, requiring emergency surgery, can be safely given short-acting β-blockers guided by clinical response. If slowing the heart rate with a small dose of esmolol (50 μg/kg) does not aggravate the heart failure, the physician should administer more esmolol, and titrate to effect. Antithyroid medications include propylthiouracil and methimazole, both of which decrease the synthesis of T ₄ and may enhance remission by reducing TSH receptor antibody levels (the primary pathologic mechanism in Graves disease). Propylthiouracil also decreases the conversion of T ₄ to the more potent T ₃ . However, the literature indicates a trend toward preoperative preparation with propranolol and iodides alone. This approach is quicker (i.e., 7-14 days vs. 2-6 weeks); it shrinks the thyroid gland, as does the more traditional approach; it decreases conversion of the prohormone T ₄ into the more potent T ₃ ; and it treats symptoms but may not correct abnormalities in left ventricular function. Regardless of the approach, antithyroid drugs should be administered on a long-term basis and on the morning of the surgical procedure. If emergency surgery is necessary before the euthyroid state is achieved, if subclinical hyperthyroidism progresses without adequate treatment, or if hyperthyroidism is out of control intraoperatively, intravenous administration of esmolol, 50 to 500 μ/kg, could be titrated to restore a normal heart rate (assuming the absence of heart failure). In addition, intravascular fluid volume and electrolyte balance should be restored. However, administering propranolol or esmolol does not always prevent “thyroid storm.” No specific anesthetic drug is preferred for surgical patients who have hyperthyroidism.

A patient with a large goiter and an obstructed airway can be managed in the same way as any other patient with a problematic airway. In this type of case, reviewing CT scans of the neck preoperatively may provide valuable information regarding the extent of compression. Maintenance of anesthesia usually presents little difficulty. Postoperatively, extubation of the trachea should be performed under optimal circumstances for reintubation in the event that tracheomalacia (the tracheal rings have been weakened and the trachea collapses) developed.

Of the many possible postoperative complications including: nerve injury, bleeding, metabolic abnormalities, and thyroid storm (discussed in the next section); bilateral recurrent laryngeal nerve trauma and hypocalcemic tetany are the most feared. Bilateral recurrent laryngeal nerve injury (secondary to trauma or edema) causes stridor and laryngeal obstruction as a result of unopposed adduction of the vocal cords and closure of the glottic aperture. Immediate endotracheal intubation is required, usually followed by tracheostomy to ensure an adequate airway. Fortunately, Lahey Clinic records indicate that this rare complication occurred only once in more than 30,000 thyroid operations. Unilateral recurrent nerve injury often goes unnoticed because of compensatory overadduction of the uninvolved cord. However, we often test vocal cord function before and after this operation by asking the patient to say “e” or “moon.” Unilateral nerve injury is characterized by hoarseness, whereas aphonia characterizes bilateral nerve injury. Selective injury to the adductor fibers of both recurrent laryngeal nerves leaves the abductor muscles relatively unopposed, and pulmonary aspiration is a risk. Selective injury to the abductor fibers leaves the adductor muscles relatively unopposed, and airway obstruction can occur.

The intimate involvement of the parathyroid gland with the thyroid gland can result in inadvertent hypocalcemia during surgery for thyroid disease. Complications related to hypocalcemia are discussed in the later section on this disorder.

Because postoperative hematoma can compromise the airway, neck and wound dressings are placed in a crossing fashion (rather than vertically or horizontally) and should be examined for evidence of bleeding before a patient is discharged from the recovery room.

Thyroid Storm

Thyroid storm is the name for the clinical diagnosis of a life-threatening illness in a patient whose hyperthyroidism has been severely exacerbated by illness or surgery. Thyroid storm is characterized by hyperthermia or pyrexia, tachycardia, and striking alterations in consciousness. Its clinical appearance is similar to malignant hyperthermia, pheochromocytoma, and neuroleptic malignant syndrome, further complicating the differential. [CR] No laboratory tests are diagnostic of thyroid storm, and the precipitating (nonthyroidal) cause is the major determinant of survival. Therapy can include blocking the synthesis of thyroid hormones by administering antithyroid drugs and the release of preformed hormone with iodine. Blocking the sympathetic nervous system symptoms with reserpine, α- and β-receptor antagonists, or α ₂ drugs may be exceedingly hazardous and requires skillful management with constant monitoring of the critically ill patient.

Thyroid dysfunction, either hyperthyroidism or hypothyroidism, develops in more than 10% of patients treated with the antiarrhythmic agent amiodarone. Approximately 35% of the drug’s weight is iodine, and a 200-mg tablet releases approximately 20 times the optimal daily dose of iodine. This iodine can lead to reduced synthesis of T ₄ or increased synthesis. In addition, amiodarone inhibits the conversion of T ₄ to the more potent T ₃ . These patients receiving amiodarone are in need of special attention preoperatively and intraoperatively, not just because of the arrhythmia that led to such therapy, but to ensure that no perioperative dysfunction or surprises result from unsuspected thyroid hyperfunction or hypofunction.