Chapter 60. Endocrine Surgery and Intraoperative Management of Endocrine Conditions

1. Endocrine diseases are common comorbid conditions in surgical patients.

2. The patient's type of diabetes mellitus must be known and the differing therapies of Types 1 and 2 appreciated.

3. Frequent monitoring of glucose levels is a mainstay in the management of the diabetic patient undergoing anesthesia and surgery.

4. Tight perioperative glucose control is no longer generally recommended. Consider keeping glucose levels less than 150 to 180 mg/dL.

5. Hypothyroid patients may exhibit sensitivity to sedative and hypnotic drugs used perioperatively. Hemodynamic instability should be anticipated.

6. Hyperthyroid patients may exhibit dehydration, hemodynamic instability and are at particular risk for tachydysrhythmias, metabolic or vascular decompensation, and thyroid storm.

7. The airway is a key consideration in patients undergoing thyroid surgery.

8. Pheochromocytoma patients require careful preoperative preparation, and plans must be made to manage hemodynamic extremes during surgery.

9. Glucocorticoid deficiency in patients at risk for adrenal suppression should be anticipated.

10. The implications of growth hormone excess (acromegaly) and adrenal steroid excess (Cushing disease) should be considered when preparing patients for pituitary surgery.

Endocrine diseases are common comorbid conditions in patients undergoing surgery. The consequences of a coexisting endocrine disorder may have an impact on anesthetic and immediate perioperative management. Diabetes mellitus (DM) is the most common comorbid endocrine condition, affecting as many as 20% of patients scheduled for surgery and requiring anesthesia.1,2 The prevalence of thyroid disease is approximately 20% in the general population, so large numbers of patients who present for nonendocrine surgery have concomitant diagnoses of a thyroid disorder.

The surgical condition may result in part or entirely from the endocrine disorder, for example, vasoocclusive disease in the patient with DM requiring peripheral vascular surgery. Alternatively, the surgery may directly target endocrine tissue, either for biopsy or for excision. The pathophysiologic implications of the endocrine lesion and of surgical manipulation of the diseased tissue must be understood in the context of anesthetic and perioperative management.3 The most common endocrine surgery involves the thyroid gland.

This chapter reviews the immediate perioperative implications of major endocrine disorders and addresses the specific issues encountered in surgery for common endocrine pathologies.

DM is a condition with an absolute (Type 1) or a relative (Type 2) deficiency of insulin. Chapter 13 discusses the complex physiology of DM. Recent comprehensive reviews discuss perioperative glucose management.2,4,5 A fundamental concept is that the Type 1 diabetic patient has an absolute requirement for continuous exogenous insulin.1 In the absence of insulin, despite a normal or low blood sugar concentration, the patient with Type 1 DM will develop ketoacidosis. The pharmacokinetic profiles of the various insulin preparations warrant careful consideration (Table 60-1).6 Without a source of glucose in the perioperative period, a patient may develop hypoglycemia from the residual effects of a long-acting insulin preparation.

In the immediate perioperative period, it is generally recommended that patients receive regular insulin by intravenous (IV) bolus or IV infusion. The uptake of intramuscular or subcutaneous insulin may be unpredictable in the perioperative period because of changes in tissue perfusion.2,4,5

Patients with Type 2 DM can be managed with diet, an oral agent, insulin, or combinations of drugs including one of the newer medications (incretin mimetics, pramlintide). The pharmacokinetic and pharmacodynamic profiles of oral hypoglycemic agents differ markedly (Table 60-2). Some oral agents (eg, sulfonylureas) remain active for 24 hours, predisposing the patient to hypoglycemia during fasting. Other oral agents act as insulin sensitizers, improving the postreceptor action of insulin. Insulin sensitizers and incretin mimetics do not cause hypoglycemia when used in single-agent therapy. Some of these agents are newly introduced into clinical practice,7,8,9 so experience with their use in surgical patients during the perioperative period is limited. Clinicians may soon encounter patients treated with bromocriptine, an old drug with a good safety profile. The metabolic control is likely achieved by a central mechanism, possibly in the hypothalamus.10

Clinical Features of DM

Although both major types of DM can share a number of clinical features, such as the presence of neuropathy, peripheral vascular, cardiovascular, and renal disease, and a predisposition to infection (see Chapter 13), an appreciation of the essential and distinctive features of each type is important.

Type 1 DM

The patient with Type 1 DM usually is first diagnosed at a young age, but the disease may occur at any stage of life. Obesity is not a predisposing factor for Type 1 DM, unlike Type 2 DM. Conventional teaching holds that the patient with Type 1 DM is generally thin or of normal body habitus, but obesity may be present as a comorbid condition. The patient with Type 1 DM has an absolute requirement for chronic insulin therapy to prevent diabetic ketoacidosis (DKA). As a general rule, patients with Type 1 DM are sensitive to the effects of insulin compared to patients with Type 2 DM, and therefore receive relatively small doses of insulin to both control blood sugar levels and prevent DKA. Acute medical or surgical conditions can precipitate DKA (diagnostic criteria are listed in Table 60-3). Consequently, these patients may arrive urgently in the operating room and require surgical intervention (ie, due to trauma, acute abdomen, abscess, ischemic limb, coronary artery bypass grafting [CABG]) but may have a concurrent metabolic derangement. Therefore, intraoperative anesthetic management of the patient with Type 1 DM may include treatment of DKA.

Diabetic Ketoacidosis

Features of DKA (Table 60-3) include circulatory depression, as acidosis and metabolic derangements can reduce cardiac contractility and peripheral vascular tone.11 Hyperglycemia with attendant hyperosmolarity produces osmotic diuresis, resulting in hypovolemia. Abnormalities often include hyperglycemia (although glucose usually is <500 mg/dL), intracellular dehydration, hyperkalemia, and hyponatremia. Dehydration frequently is severe because of poor oral intake due to the primary illness and is exacerbated by hyperglycemia-induced osmotic diuresis. Plasma potassium (K+) levels can be elevated because metabolic acidosis drives K+ from the intracellular space to extracellular fluids. Insulin concentrations are insufficient to maintain intracellular K+ levels, so total body K+ actually is depressed (reduced by 3-10 mEq per kilogram body weight). Measured sodium (Na+) concentrations are artificially lowered approximately 1.6 mEq/L for every 100 mg/dL that the glucose level is elevated above 100 mg/dL. Thus the serum Na+ level of a severely hyperglycemic patient may not reliably reflect the degree of dehydration. Plasma hypophosphatemia and hypomagnesemia commonly result from excessive urinary losses in DKA.

Management of DKA includes repletion of intravascular volume with electrolytes and water to resolve fluid deficits and help restore blood pressure, tissue perfusion, and glomerular filtration. Initial volume resuscitation usually is accomplished with normal saline even in the setting of hypernatremia. Vigorous hydration also decreases glucose levels by 20% to 40%. Insulin therapy (regular insulin by IV bolus and subsequent infusion) is crucial in treating DKA. Insulin inhibits gluconeogenesis and ketone production in the liver, and decreases lipolysis in adipose tissues. Insulin administration must be continued if acidosis or ketosis persists, even though glucose levels have normalized. During administration of insulin when plasma glucose concentrations decrease to less than 250 mg/dL, an infusion containing 5% dextrose (eg, D5NS, 100 mL/h) will prevent hypoglycemia. Blood glucose levels should be monitored every hour, with frequent electrolyte determinations.

Potassium and phosphate replenishment are essential for insulin's action. These electrolytes should be replaced carefully, after first verifying that the patient has normal renal function and adequate urine output. Ensure proper function of the IV access as extravasation of potassium can cause tissue damage. Rapid potassium administration can precipitate dysrhythmias. Potassium can be replaced with an equal mixture of potassium chloride and potassium phosphate.

• Serum K+ <3 mEq/L, give K+, 40 mEq/h
• Serum K+ <4 mEq/L, give K+, 30 mEq/h
• Serum K+ <5 mEq/L, give K+, 20 mEq/h
• Serum K+ ≥5 mEq/L, no replacement

Consideration should be given to bicarbonate therapy only for severe acidosis (eg, when arterial pH falls to <7.0) or hemodynamic instability, or for patients with cardiac rhythm disturbances. Following administration of bicarbonate, arterial pH levels should be monitored.

An emerging form of diabetes associated with obesity and presenting with ketoacidosis is called Flatbush Type 2 DM. Most or almost all of these patients can be treated with oral agents after initial management with intensive insulin therapy. Initial treatment of ketoacidosis in the patient with Flatbush Type 2 DM is the same as for the typical Type 1 DM patient.

Type 2 DM

Patients with Type 2 DM generally are older, obese, and subject to metabolic syndrome, a complex pathophysiologic state characterized by hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hypertension, and Type 2 DM.12-14 In patients with metabolic syndrome, the cardiovascular risk of anesthesia and surgery may elevate markedly. Hypercoagulability is 1 feature of metabolic syndrome potentially relevant to these patients, who may be prone to thrombosis as a result of their surgical conditions or the consequences of surgery and anesthesia.15 Of burgeoning clinical importance is the growing population of young, typically obese, patients with Type 2 DM. The practitioner encounters a juvenile or adolescent patient with the combined anesthetic management challenges of youth, obesity, and diabetes. Type 2 DM may occur in young, nonobese adolescents (maturity-onset diabetes of the young [MODY]) because of autosomal dominant inheritance of a mutation in the glucokinase gene that results in impaired hepatic glucose uptake and reduced insulin secretion.

A fundamental concept of Type 2 DM is that patients with the condition usually produce sufficient insulin to avoid DKA, the severe metabolic consequence of absolute insulin deficiency seen in patients with Type 1 DM. However, patients with Type 2 DM have reduced cellular responses when insulin binds to its receptor. Patients are described as being resistant to the hypoglycemic actions of insulin. To achieve normal glucose levels, patients with Type 2 DM may require doses of insulin that are large compared to doses required for Type 1 DM therapy.

Initial medical therapy in the ambulatory Type 2 DM patient includes administration of agents to increase endogenous insulin release, reduce intestinal uptake of carbohydrates, or increase peripheral sensitivity to insulin. When these measures are insufficient to normalize blood sugars, insulin therapy should be initiated, but patients may require very high insulin doses. New classes of therapeutic agents, currently represented by pramlintide and agents acting along the incretin pathway, increase insulin secretion, reduce postprandial glucagon secretion, and suppress hepatic glucose production.8,8a,16

Hyperglycemic Hyperosmolar Nonketotic Coma

Hyperglycemic hyperosmolar nonketotic coma (HONK), also known as hyperglycemic hyperosmolar syndrome, is a clinical syndrome encountered in some Type 2 diabetic patients with decompensated DM.11 Features include hyperglycemia, hyperosmolarity, and dehydration (typical water deficit 10-12 L). Severe ketosis is rare, but mild acidemia can be caused by starvation ketosis, inadequate circulation, and lactic acidosis (Table 60-3). The precipitating factors for HONK are similar to those of DKA (Table 60-4). Patients presenting for surgery, especially urgent procedures, may have HONK as a comorbid condition requiring management during administration of their anesthetics. The classic presentation of patients with HONK includes fatigue, blurred vision, polydipsia, polyuria, leg cramps, and weight loss. The laboratory findings of HONK are related to dehydration and hypovolemia. Derangements in serum electrolyte levels occur, and hemoconcentration causes increases in blood levels of hemoglobin, protein, calcium, amylase, lactate dehydrogenase, and transaminases. Some patients present a mixed picture, with features of both DKA and HONK (Table 60-3).

Fluid administration in the setting of HONK is crucial. The rate of fluid administration depends on the patient's volume status, total body water deficit, serum osmolarity, and renal and cardiac function. Normal saline (2-3 L) is an appropriate fluid bolus in a patient with adequate cardiac and renal function, and serum osmolarity less than 320 mOsm/L. Even larger fluid boluses may be required if serum osmolarity is greater than 320 mOsm/L. In hypotensive patients who do not respond to aggressive crystalloid administration, colloidal or vasopressor infusions are additional treatments. Central venous pressure or pulmonary arterial monitoring may help guide therapy, especially in patients with HONK who are elderly and at significant risk for concomitant cardiovascular disease.

Medical therapy for HONK includes a low-dose, continuous IV infusion of insulin. If no decrease in glucose levels occurs over the first 2 to 4 hours, doubling the insulin infusion rate every hour until a response occurs is recommended. Potassium chloride usually is administered as part of the fluid regimen. The total body potassium deficits encountered in HONK are modest compared to DKA because of the absence of acidosis (see guidelines for potassium replacement in DKA). Potassium acetate and/or potassium phosphate can be used in order to avoid excessive chloride levels. Bicarbonate need not be given unless lactic acidosis causes arterial pH to decrease to less than 7.0. Thrombotic/embolic events are common complications of HONK. Prophylaxis against thrombosis warrants consideration. Should thrombosis occur, an anticoagulating dose of IV heparin or low-molecular-weight heparin anticoagulation is indicated.

Perioperative Insulin/Glucose Management

As a rule, long-acting oral hypoglycemic agents (sulfonylurea drugs) should not be given before surgery to reduce the risk of hypoglycemia, signs and symptoms of which may be masked by general anesthesia. It is unlikely that insulin sensitizers will produce hypoglycemia. Theoretically, inhibitors of glucagon secretion (eg, GLP-1 analogues) may lead to hypoglycemia in the fasting state. However, the actions of these drugs are glucose dependent; they should have no effects when blood sugars are low. Nevertheless, prudence suggests that agents acting along the incretin pathway and pramlintide should be held on the day of surgery. Patients with Type 2 DM treated with insulin are at risk for hyperglycemia if their insulin is withheld completely. Typically, these patients receive about half of their usual morning insulin dose in the form of long-acting insulin preparations, such as NPH insulin. Short-acting insulins are omitted. Patients with Type 1 DM must receive some insulin. In this population, half of the usual morning dose of long-acting insulin may be appropriate before surgery. One key to management is frequent monitoring of glucose levels in all patients with DM. As a general rule, diabetic patients should undergo their anesthetic and surgical procedures as early in the day as possible. This limits the perturbations caused by prolonged fasting and disruption of customary diabetes medical regimens.

Recently, more patients have been managed with their insulin requirements supplied by continuous and bolus infusions delivered by an insulin pump. Recommendations for the perioperative period for patients with pumps include (1) maintaining the basal infusion rate of insulin, (2) omitting any preprandial insulin boluses in the fasting patient, (3) monitoring of glucose levels at frequent intervals, and (4) resuming the usual diet and insulin therapy regimen as soon as possible.16 However, the anesthesiologist must recognize that these pumps deliver the insulin dose subcutaneously. Uptake of the drug from this depot may be affected by alterations (usually reductions) in tissue perfusion that are commonly encountered during surgery or the perioperative period.3 Consequently, depending on the surgical circumstances, it may be advantageous to interrupt the continuous subcutaneous administration of insulin by pump and to substitute carefully titrated IV infusions of insulin. To decide on the initial IV insulin infusion rate, first determine the total 24-hour basal insulin dose typically administered by the subcutaneous infusion. Divide this basal dose by 24. Start the IV infusion with this number of units of regular insulin per hour, again with close monitoring of blood glucose and serum potassium levels.

Intraoperative Insulin Therapy

A variety of regimens exist for IV infusion of regular insulin in the operating room. For the routine surgical population, the "Vellore regimen" has been evaluated.18 Other schemes also are acceptable2,19 as long as glucose and potassium levels are closely monitored and treated when necessary. Table 60-5 outlines 1 practical method of insulin administration in the operating room that is used at our institutions. Cardiac surgical patients20 and pediatric surgical patients11 may benefit from regimens tailored to the special needs of these particular populations.

Perioperative Glucose Target Range

Several studies providing evidence for the clinical benefits of tight glucose control (eg, 80-110 mg/dL) in critically ill patients led to initially enthusiastic adoption of intensive insulin therapy (IIT) regimens. Later reports demonstrated adverse (eg, hypoglycemia) or neutral effects of IIT. Current expert opinion suggests keeping glucose below 180 mg/dL in the critically ill patient.3,4,22-24 Few data exist to guide intraoperative glucose management practices. In some surgical situations (eg, neurovascular procedures or carotid endarterectomy) associated with significant risk for cerebral ischemia, it might be argued that blood glucose levels should be more tightly controlled to avoid hyperglycemia. For other procedures, the optimum insulin regimen and the ideal range of blood glucose levels for routine anesthetics remain undetermined.23,25,26

Glucose Monitoring

Glucose monitoring is the foundation for safe and effective glucose management and perioperative insulin therapy. Clinicians use point-of-care testing with various devices or send arterial or venous blood samples to a central laboratory for analysis.3,4 The technology for glucose analysis is complex.27 Unrecognized pitfalls exist with the convenient handheld devices, and clinicians must recognize that multiple factors have an impact on the accuracy of the result, upon which therapeutic decisions may be based.28 Potential confounding factors include anemia, hypoxemia, hyperoxia, the presence of other sugars, elevated triglyceride, bilirubin, urea or uric acid levels, and perhaps also blood pH and body temperature.

Metformin

Metformin is an oral hypoglycemic agent of the biguanide class with an important role in Type 2 diabetes therapy, particularly because of its favorable effects on cardiovascular mortality.29 This drug, which has multiple pharmacologic effects, has also been associated with the serious side effect of lactic acidosis, which may become life threatening. Whether metformin causes lactic acidosis or exacerbates lactic acidosis resulting from other conditions remains undetermined.30,31, When administered according to guidelines and avoiding contraindications including renal and hepatic insufficiency and a history of alcohol abuse, the incidence of lactic acidosis is very low.29 In conditions where tissue hypoxia already exists (including circulatory failure) or circulatory insufficiency is anticipated (eg, major surgery), it is prudent to withhold metformin. In anticipation of IV radiologic contrast exposure, metformin should be stopped and not restarted until the creatinine level has been checked to confirm baseline renal function. Recognizing that conclusive data do not exist to support their suggested guidelines, Jones et al32 and Vreven and De Kock33 proposed that metformin be withdrawn 2 days before general anesthesia and reinstated when renal function is demonstrated to be stable. This is not universally practiced. Metformin should not produce hypoglycemia in the fasting preoperative patient.

Steroid (Glucocorticoid) Therapy: Implications for DM

Administration of pharmacologic doses of glucocorticoids increases resistance to insulin action by inhibiting glucose uptake into muscle and fat.34 In many patients the effect is primarily postprandial hyperglycemia. Thus morning fasting glucose levels are only mildly elevated, but glucose levels rise substantially after meals in the afternoon and evening.

Glucose levels will increase in patients with known diabetes. Glucocorticoid therapy reveals previously undiagnosed insulin resistance in 25% of all patients receiving such treatment.18 The hyperglycemia resulting from glucocorticoid therapy can be managed with insulin, oral hypoglycemic agents, or combination therapy. When glucocorticoid therapy is tapered, insulin resistance decreases with a lag of 1 to 3 days. Hyperglycemia therapies (eg, insulin infusions) must then be reduced to avoid hypoglycemia. The complexities of the patient's regimen for controlling hyperglycemia must be considered when managing medications and glucose in the perioperative period.

Postoperative stress usually leads to excess endogenous glucocorticoid production and consequent insulin resistance. This may result in hyperglycemia lasting 1 to 3 days after the procedure or for as long as significant infection or pain-related stress is present. Treatment of this manifestation of hyperglycemia is accomplished by administering a long-acting insulin plus a short-acting insulin at mealtime in the patient who is able to eat. Other patients may require regular insulin administered by IV infusion.

Counterregulatory Hormones

Glucagon

Alpha cells of the pancreatic islet secrete glucagon. Glucose is the most important regulator of glucagon secretion. Hyperglycemia decreases glucagon secretion. Hypoglycemia stimulates glucagon secretion via direct effects on islets and via central nervous system pathways activated by hypoglycemia. β-Adrenergic receptor activation stimulates glucagon secretion.36 Glucagon acts primarily on the liver to increase both glycogenolysis and gluconeogenesis. Increased glucose output balances glucose utilization during the fasting state to maintain euglycemia.37 Patients with hepatic or pancreatic insufficiency are theoretically at risk for hypoglycemia as a result of lack of glucagon effects. In addition, β-blocker therapy potentially reduces glucagon secretion, thereby potentially increasing the risk of hypoglycemia. The implication for anesthetic management is the need to monitor glucose levels frequently in patients at risk and to intervene as needed.

Epinephrine

Epinephrine and glucagon are the most important hormones maintaining euglycemia during the fasting state.38 The central nervous system reacts to hypoglycemia by stimulating the secretion of epinephrine. Activation of pancreatic α-adrenergic receptors by epinephrine inhibits insulin secretion. β-Adrenergic receptor activation stimulates the secretion of glucagon. Epinephrine, via β2-adrenergic receptors, also acts directly on the liver to increase glycogenolysis and gluconeogenesis. Therefore, patients at risk for blunted sympathetic responses, either following neuraxial anesthesia or from receiving β-blocker therapy, may fail to react normally to hypoglycemia. The implication for anesthetic management is, again, a need to anticipate potential hypoglycemia, with close monitoring of glucose levels in patients at risk, and to treat as needed.

Glucocorticoids and Growth Hormone

Growth hormone (GH) and cortisol play minor roles in the restoration of euglycemia after hypoglycemia. The prevention of cortisol secretion and GH deficiency does not inhibit restoration of euglycemia after hypoglycemia.39 The hyperglycemic response to the combination of glucagon, epinephrine, and cortisol is larger than the response to each of these hormones given individually, suggesting that synergism contributes to normal physiologic responses to hypoglycemia.40

Hypoglycemic Unawareness

Some patients with long-standing DM and frequent bouts of hypoglycemia lose their normal sympathetic response to low blood sugar levels. The failure to consciously recognize low blood sugar levels is known as "hypoglycemic unawareness." Fasting in the perioperative period, particularly in the setting of continued insulin therapy administered by infusion pump, may predispose these patients to potentially dangerous hypoglycemia. The anesthesiologist cannot rely on such patients to symptomatically monitor their own blood glucose levels and to respond appropriately, even when managed with regional anesthesia and minimal sedation. Blood glucose measurement, and appropriate therapy, is essential for these patients.

DM: Implications for Anesthesia

Although general anesthesia may be mandatory for some surgical procedures, other options (including regional anesthesia or neuraxial anesthesia) exist for some situations.41 Neuraxial anesthesia may provide an advantage by blocking "stress responses" to surgery involving counterregulatory hormones such as epinephrine and glucocorticoids. Regional or neuraxial block anesthetic techniques may allow some diabetic patients to return to their customary diets earlier than they would if given general anesthesia, facilitating resumption of chronic diabetes regimens. Metabolic control in the diabetic patient may be improved by regional anesthetic techniques, at least in some patient populations.42 Regional anesthesia or neuraxial techniques may also be useful for patients with diabetic gastroparesis who are at elevated risk for aspiration under general anesthesia, or who may be difficult to intubate because of stiff joints (including the temporomandibular joints and the cervical spine) associated with their disease. In addition, preexisting autonomic neuropathy may compound the effects of sympathectomy produced by neuraxial block. Data suggest that cerebrospinal fluid (CSF) composition differs between patients with DM and healthy patients, and that this difference correlates with enhanced sensitivity to neuraxial drugs.43

There is some concern that patients at risk for diabetic neuropathy may be more likely to develop peripheral nerve injury in association with regional or neuraxial techniques, either from local anesthetic toxicity or mechanical trauma from the block needle.44 Only a small amount of published evidence addresses these issues. Blumenthal et al describes 1 patient with a preexisting, nondiabetic, asymptomatic polyneuropathy who developed symptomatic neuropathy after a peripheral nerve block.45 Hebl et al reported 2 patients in a retrospective series who developed exacerbations of preexisting neuropathy after neuraxial anesthesia or analgesia. Both patients had Type 2 DM.46 These authors suggest that local anesthesia toxicity is a possibility. Adjuvants (eg, clonidine) may prove beneficial in providing desired anesthetic effects with smaller doses of local anesthetics, thereby reducing toxicity risks.47 McAnulty and Hall48 conclude that there is no evidence to indicate that regional anesthesia alters overall surgical morbidity and mortality in the diabetic patient population. Consequently, a well-conducted anesthetic, regardless of specific technique, probably is the most important factor in the care of the diabetic patient. Of note, general anesthesia often masks the autonomic response to hypoglycemia, and changes in vital signs can easily be misinterpreted as a response to increased surgical stimulation rather than hypoglycemia. Consequently, close monitoring of glucose levels in patients at risk for hypoglycemia and appropriate therapy are essential.

Specific Surgical Procedures and Glucose Homeostasis

Total pancreatectomy eliminates insulin-producing islet cells as well as cells secreting the counterregulatory hormone glucagon. This surgery renders the patient a Type 1 diabetic with an absolute requirement for insulin therapy. The biologic effect of insulin molecules bound to cellular receptors lasts for approximately 1 hour, but the chemical half-life of insulin in the circulation is just a few minutes. Consequently, following a total pancreatectomy, the need for insulin therapy to prevent DKA begins within 60 minutes of devascularizing the pancreatic islets.

Surgery for insulinoma or glucagonoma poses particular management challenges. Glucagonoma may cause elevations in glucose and resistance to insulin during surgery, so glucose levels should be monitored closely and managed as needed. Insulinomas may cause life-threatening, profound hypoglycemia. There can be wide swings of glucose levels perioperatively. Frequent measurements of glucose and therapeutic interventions (IV insulin or IV glucose administration) may be necessary.

Thyroid diseases comprise the second most common endocrine conditions appearing as comorbidities in patients presenting for surgery of any kind. Hypothyroidism and hyperthyroidism have significantly different implications for anesthetic management. Where possible, assessment of the current status of the patient's thyroid condition provides information useful for predicting sensitivity to drugs commonly administered in the perioperative period, hemodynamic responses during surgery and anesthesia, and physiologic perturbations potentially requiring investigation and treatment, such as electrolyte disorders and adrenal insufficiency.49 Coagulation disorders (hypercoagulability with hyperthyroidism and coagulopathy with severe hypothyroidism) have recently drawn attention.50 Medical treatment of altered thyroid function (hypothyroidism or hyperthyroidism) may require several weeks to achieve a new steady state. In general, mildly hypothyroid patients can proceed to elective surgery without delay. Postponement of elective surgery may be indicated to allow for the evaluation and treatment of hyperthyroidism and to allow for the medical management of hypothyroid patients with more than mild to moderate thyroid insufficiency.

Implications of Hyperthyroidism

The clinical features of hyperthyroidism result from excess thyroid hormone and enhanced β-adrenergic activity.49,51 Etiology, manifestations, and medical management of thyroid disorders are discussed in detail in Chapter 13. Endocrinologists distinguish thyrotoxicosis, which is a general term for excessively elevated thyroid hormone of any cause (including excessive exogenous thyroid hormone), from hyperthyroidism, in which thyroid gland hypersecretion is the reason for excessive thyroid hormone activity. Table 60-6 summarizes the clinical features of hyperthyroidism and thyrotoxicosis that are particularly relevant to the anesthetic management of thyroid surgery, or of nonthyroid surgery that cannot be postponed until the patient is rendered euthyroid. Atrial dysrhythmias, including atrial fibrillation, and premature atrial contractions, tachycardia, systolic hypertension, ischemic cardiac disease, and congestive heart failure should be specifically considered when planning an anesthetic for the hyperthyroid patient.52-54 Muscle weakness may impair perioperative respiratory reserve. β-Adrenergic blockade is the mainstay of anesthetic management. High doses of β-blockers may be required to control cardiac manifestations of hyperthyroidism in the immediate perioperative period.

Implications of Hypothyroidism

The clinical features of hypothyroidism result from a deficiency of thyroid hormone action.49,55,56 Etiology, manifestations, and medical management are discussed in detail in Chapter 13. The clinical features that are particularly relevant to the anesthetic management of thyroid or nonthyroid surgery that cannot be postponed until the patient is rendered euthyroid are summarized in Table 60-6. Bradycardia, diastolic hypertension, congestive heart failure (systolic and diastolic dysfunction), pericardial or pleural effusions, seizures, depressed mentation or frank coma, hypothermia, coagulopathy, and ileus should be specifically considered when evaluating for suspected hypothyroidism. The patient may have a blunted hypercapnic or hypoxic ventilatory drive. Adrenal cortical insufficiency may impair normal stress responses. Laboratory findings include hyponatremia and hypoglycemia.

Pharmacologic Implications

Minimum Alveolar Concentration

Conventional anesthetic wisdom holds that thyroid status does not alter the minimum alveolar concentration. Data from studies of experimental animals using agents such as halothane and cyclopropane support this assertion.57,58 Data from studies of humans or of any species on the interaction of thyroid status with minimum alveolar concentration for newer potent inhalational agents such as desflurane and sevoflurane have not been reported. As demonstrated in rats, thyroid status may alter the metabolism of the older potent inhalational anesthetics halothane, enflurane, and methoxyflurane,59 but the clinical relevance of this finding for commonly used, newer agents is not reported.

Altered Drug Metabolism/Sensitivity

Conventional wisdom holds that hypothyroidism increases the sensitivity to sedative, analgesic, and anesthetic medications.55 Evidence supporting this concept is limited to older drugs without recent studies.60 One case report cites the accumulation of midazolam in prolonged sedation of a critically ill patient with hypothyroidism as a comorbid condition.61 Whether this observation can be generalized to all hypothyroid patients or to the use of other commonly administered sedative, hypnotic, and analgesic agents remains unproven.

Amiodarone

Amiodarone is widely used for the management of atrial and ventricular dysrhythmias. The amiodarone molecule contains approximately 37% iodine by weight, resulting in the delivery of large amounts of iodine to patients receiving standard doses of the drug. The effects of amiodarone therapy on thyroid function are complex, and patients may become either hypothyroid or hyperthyroid when their cardiac electrophysiologic disturbances are treated with amiodarone.51,62,63 Consequently, patients presenting for surgery who are receiving chronic amiodarone therapy may warrant consideration of their risk for thyroid dysfunction in the perioperative period.

Exophthalmos: Anesthetic Implications

Exophthalmos, a clinical feature of Graves disease, results from the accumulation of retroorbital fat and swollen ocular muscles resulting in proptosis (Fig. 60-1). The eyelid may not cover the globe, and the exposed cornea and prominent globe are subject to mechanical trauma, including pressure injury. With significant proptosis, corneas are at risk for drying; consider the use of ointments or lubricants and ensure that the eyes are closed during surgery.

Management of Severe Hyperthyroidism or Thyroid Storm in Urgent Surgery

Severe hyperthyroidism is a relative contraindication to anesthesia and surgery. When extreme hyperthyroidism progresses to physiologic decompensation with circulatory collapse, altered mental status, and hyperthermia, the diagnosis is thyroid storm, a life-threatening condition that ideally should be medically controlled before a patient is brought to surgery (Table 60-7). If an operation cannot be delayed, the patient must be rapidly prepared in order to limit the effects of the endocrine disorder on the clinical course. Mainstays of therapy include medications to control thyroid gland production of thyroid hormone, β-adrenergic blockers to blunt sympathetic effects, glucocorticoids, and circulatory support.64,65 Iopanoic acid is a valuable treatment option now available only in Europe. The drug may be particularly useful in the setting of amiodarone-induced thyrotoxicosis.64,66 In the United States, saturated solution of potassium iodide (SSKI) may be used in combination with β-adrenergic blockers.67,68

Thyroid Surgery

Anesthetic Options

General anesthesia is commonly administered for thyroid surgery. General anesthesia has the advantages of patient comfort, amnesia, and immobility, along with control of the airway. Airway control often is achieved by intubation with a cuffed endotracheal tube.69 However, use of the laryngeal mask airway (LMA) has been considered an option for airway control because intraoperative inspection of vocal cord function and glottic structures can be accomplished with a fiberoptic scope.70-75 Direct visualization may be particularly valuable if the surgical procedure places a recurrent laryngeal nerve (RLN) at significant risk. An advantage of the technique is that the RLN can be continuously monitored throughout the surgical procedure if the fiberoptic scope is left in place, allowing real-time identification of compromised RLN function. Because some patients may require endotracheal intubation but also benefit from continuous direct observation of glottic structures, Hillermann et al75 proposed the use of a small-diameter (5.0-mm inner diameter) endotracheal tube together with an LMA through which a fiberoptic scope was positioned. This setup allows control of the airway with a cuffed endotracheal tube while permitting visual monitoring of RLN function.

Muscle relaxants facilitate endotracheal intubation and may constitute 1 component of anesthesia maintenance. Muscle relaxants may interfere with motor monitoring of the RLN or other nerves placed at risk by the surgical procedure. Partial pharmacologic paralysis may permit motor nerve monitoring in some situations76 if the level of muscle relaxation is closely monitored.

An alternative to general anesthesia is regional anesthesia with supplemental local anesthetic infiltration as needed.77-80 Advantages of regional anesthesia include the ability to assess spontaneous respiration and the voice as indicators of RLN integrity during the procedure. In addition, regional anesthesia provides the possibility of early postoperative pain control with little or no need for systemic analgesics and could be used in conjunction with general anesthesia.81-83 However, recent clinical studies do not demonstrate particularly effective pain relief with regional blocks.84,85 A consideration in planning a regional anesthetic is that systemic absorption of epinephrine, a common additive to local anesthetic solutions, may exacerbate tachycardia or other tachydysrhythmias encountered in hyperthyroid patients. Thus epinephrine should be given cautiously or avoided entirely.

Unilateral and bilateral deep cervical plexus block or superficial cervical plexus block with local supplementation has been described for thyroid surgery. Deep cervical plexus block carries the associated risk of anesthetizing the phrenic nerve with resulting diaphragm dysfunction. Unilateral or bilateral diaphragmatic dysfunction may precipitate respiratory distress, especially if the surgical procedure disturbs RLN function with airway compromise. However, little or no change of the forced vital capacity (FVC) measured by incentive spirometry was detected in 21 patients undergoing thyroid surgery with bilateral deep cervical plexus block, and no patient experienced subjective respiratory distress.78 A study that focused on the analgesic efficacy of cervical plexus block administered in conjunction with general anesthesia for thyroid surgery reported no subjective respiratory complaints among the 39 subjects.81 However, the study did not include any quantitative objective assessments of respiratory function. Deep cervical plexus block may impair RLN function when the anesthetic spreads to block the vagus nerve. Although this would not affect the direct stimulation of an RLN (as for electromyographic [EMG] monitoring) during surgery, the ability to assess spontaneous vocal cord function would be compromised by anesthetizing the vagus nerve with a deep cervical plexus block. Superficial cervical plexus block avoids the potential airway or respiratory problems of a deep cervical plexus block, but may not provide sufficient analgesia for the deeper structures of the neck that may be involved in the surgery.

Cervical epidural anesthesia has been used successfully for parathyroid surgery in patients maintained awake to evaluate their vocal cord function.82 Significant decreases in FVC were encountered, but other measured respiratory variables remained stable, with minimal subjective respiratory compromise. Because the airway and respiratory considerations for thyroid and parathyroid surgery are comparable, the findings suggest that cervical epidural anesthesia may provide an anesthetic option for thyroid surgery where general anesthesia is not desirable.

Taken together, the findings of small clinical studies suggest that regional anesthesia may be suitable for appropriately selected patients, but more definitive investigation, particularly of the incidence of perioperative respiratory complications, is needed. Lack of airway control, in a situation where the location of the surgical site complicates establishing emergency airway control, is a disadvantage of regional anesthesia techniques.

Anatomic Concerns

Situated at the base of the anterior neck, the thyroid gland lies in close proximity to major vascular structures, including the internal jugular veins and the carotid arteries (Figs. 60-2 and 60-3).86 Distortion of normal anatomic relationships, as in the case of a large goiter or a thyroid cancer, can complicate the insertion of an internal jugular catheter (Fig. 60-4). The thyroid gland wraps around the trachea in a nearly circumferential fashion. Direct extension of thyroid cancers into the trachea may obstruct the lumen. Large thyroid masses sometimes compress the tracheal lumen (Fig. 60-5) or distort the subglottic or supraglottic airway (Figs. 60-6 and 60-7). Some thyroid masses penetrate or compress the esophagus with implications for the patient's nutritional status. Insertion of nasogastric or orogastric tubes also may be complicated.

Emergency airway algorithms contain a provision for establishing a surgical airway, either by cricothyrotomy or by tracheostomy. Extension of thyroid tissue rostrally over the cricothyroid membrane, or caudally toward the sternal notch, positions this highly vascular tissue directly in front of the airway. Thyroid isthmus tissue may be encountered even in routine tracheostomy placement.87 A cadaver study reported a high incidence of percutaneous tracheostomy catheters malpositioned so as to puncture the thyroid isthmus.88 Complications of surgical airway insertion related to thyroid tissue or vessels have been reported.89 Hemorrhage can easily complicate attempts to establish a surgical airway.

Other structures in close proximity to the thyroid gland include the parathyroid glands, which are placed at risk during thyroid surgery, and the recurrent and superior laryngeal nerves, which supply the larynx.90,91

Airway Concerns

Airway management is a principal anesthetic concern in thyroid surgery. Thyroid masses can affect the airway in the supraglottic region. Lingual thyroid tissue arising from the base of the tongue may obstruct the oropharynx, compromising spontaneous respiration,92 mask ventilation, and direct laryngoscopy. Thyroid masses invading or compressing the glottis potentially compromise visualization of the glottic opening or passage of an endotracheal tube through the vocal cords. Bouaggad et al93 studied 320 patients scheduled for thyroidectomy in an analysis of potential factors helpful for predicting difficult endotracheal intubation. Endotracheal intubation was found to be easy in 36.9% of patients, and the investigators encountered only minor difficulties in 57.8% of the study group. The study concluded that the presence of a large goiter is not itself predictive of a difficult endotracheal intubation. However, multivariate analysis identified the presence of Cormack grade III or IV view and the presence of a cancerous mass as independent predictors of a difficult oral intubation. Potential risk factors for difficult airway management include the body mass index, Mallampati class, thyromental distance, neck mobility, and airway compression.

Thyroid masses within the thorax compromise the airway in the subglottic region by external compression of the trachea or direct extension into the airway. Preoperative imaging studies94 and flow–volume loops may provide information useful for planning the approach to the airway.

Laryngeal Nerve Monitoring: Anesthetic Implications

Several methods have been described to monitor the function of the RLN, which controls the function of the vocal cords and other nerves at risk, such as the external branch of the superior laryngeal nerve, which supplies the cricothyroid muscle and therefore regulates voice pitch.95,96 Most attention has been devoted to monitoring the RLN. Monitoring techniques generally require some form of direct RLN stimulation. Function following stimulation usually is detected by (1) direct visualization of the cords via a fiberoptic scope (see above), (2) palpation of the larynx during RLN stimulation,97 (3) EMG monitoring using recording electrodes inserted directly into the laryngeal muscles,98 or (4) EMG monitoring via endotracheal tubes fitted with external sensing electrodes.99 Nerve monitoring often has an impact on anesthetic management by the need for a special method of airway control (eg, LMA vs cuffed endotracheal tube) or the need to avoid muscle relaxants as part of the anesthetic technique.

Perioperative Complications of Thyroid Surgery

Laryngeal Nerve Injury

A major complication of thyroid surgery that usually appears early (immediately or within hours) in the postoperative period is airway obstruction attributable to RLN injury with resultant narrowing of the glottic opening. A unilateral RLN palsy would not produce significant respiratory compromise if the contralateral nerve and vocal apparatus function normally. However, bilateral nerve palsy, as from a new unilateral RLN injury in the setting of a preexisting deficit on the other side, can produce complete closure of the glottis and respiratory obstruction. Prompt endotracheal intubation may be lifesaving.

Estimates of the overall incidence of unilateral temporary RLN palsy after major thyroid surgery range from 1.2% to 1.4%, to 5.1% to 8.7%.100-104 Estimates of the incidence of permanent nerve palsies range from 0.4% to 0.6%, to 0.9% to 1.4%.100-104 Factors associated with an increased likelihood of RLN injury include surgery for thyroid cancer or Graves disease, reoperation, and extensive neck and lymph node dissections. Positive identification of the RLN and documentation of its integrity during the course of surgery are associated with a reduced likelihood of palsies in the postoperative period. Despite extensive investigation, the question of whether intraoperative RLN monitoring confers protection against RLN injury after surgery remains without a definitive answer.105-114 Monitoring may facilitate visual identification of the RLN, as in cases of reoperation or anatomic variants of nerve position. Of note, endotracheal intubation alone may account for 7% to 11% of all RLN paralyses.115

Hypocalcemia

Damage to parathyroid glands during thyroid surgery can cause reduced secretion of parathyroid hormone (PTH), resulting in hypocalcemia. Positive identification of the parathyroid glands at the time of surgical dissection can prevent postoperative hypocalcemia. Estimates of the prevalence of temporary hypocalcemia range from 8.3% to 27.5%, and estimates of permanent hypocalcemia range from 1.7% to 5.1%.100,101 Patients with acute hypocalcemia can present with paresthesias, muscle cramps, stridor, dysrhythmias, or seizures. Some studies suggest that the circulating PTH level obtained during surgery or in the immediate postoperative period is predictive of laboratory or symptomatic evidence of hypocalcemia.116,117

Hemorrhage

The thyroid bed is extremely vascular. Inadequate hemostasis may result in the formation of hematomas. Rapid onset of life-threatening airway obstruction is a known complication of thyroid (and parathyroid) surgery. Consideration should be given to prompt intubation to preserve airway patency, even before a return to the operating room for neck exploration. Decompression of the neck at the bedside by opening the wound is a potentially lifesaving option.95 The use of surgical drains is advocated, at least in selected circumstances, to prevent the accumulation of blood or serous fluid in the closed potential space of the neck.105

Obstruction of venous drainage from the head by large intrathoracic thyroid masses sometimes results in superior vena cava syndrome (Fig. 60-8). Resection of such lesions may be compromised by substantial blood loss.

Positioning Injuries

Thyroid surgery typically is accomplished with the patient in the supine position with the neck extended and the arms wrapped and supported at the patient's side (Fig. 60-9). Cervical spine conditions may limit the ability to extend the patient's neck safely or comfortably. A pressure injury to the occipital nerves has been described in a patient with the potential risk factors of obesity and DM undergoing thyroid surgery.118 Risk of ulnar neuropathy related to positioning of the arms at the sides with the potential for pressure on the elbow should be considered. In addition, patients with proptosis from Graves ophthalmopathy may be at particular risk for corneal abrasions, drying of the cornea, or pressure injuries to the globe.

Patients may present for surgery to treat parathyroid disease (parathyroidectomy) or require surgery in the setting of disorders of calcium homeostasis. Anesthetic considerations for parathyroidectomy substantially overlap with many of the issues encountered in thyroid surgery. These concerns include monitoring of RLN function, risks of postoperative hypocalcemia and postoperative neck hematoma, and positioning.105,119 Manifestations of renal insufficiency are particularly important for patients presenting for parathyroidectomy to treat secondary or tertiary hyperparathyroidism.

Advanced preoperative imaging techniques facilitate the identification of abnormal parathyroid tissue, sometimes permitting less invasive surgery with achievement of therapeutic goals.79,105,120 However, failed explorations persist as a surgical problem. Rapid intraoperative immunoassay for PTH can assist the surgeon in determining whether pathologic parathyroid tissue has been identified and removed.121 In patients with secondary hyperparathyroidism, propofol does not affect PTH levels.122 It is not known if propofol affects PTH levels in patients with primary or tertiary hyperparathyroidism.

Anesthesia options for parathyroid surgery include general anesthesia with or without endotracheal intubation, and regional anesthesia techniques.78,82,105,123 One advantage of regional anesthesia is the avoidance of nausea and vomiting, which is common following parathyroid surgery.124

Implications of Hypocalcemia

Hypocalcemia is a feature of many medical conditions (Table 60-8). Of particular relevance to the anesthesiologist planning to take a hypocalcemic patient to the operating room are critical illness conditions, including pancreatitis or fat embolism syndrome, hepatic or renal failure, and rhabdomyolysis. Detection of hypocalcemia should provide an impetus to comprehensively evaluate the overall condition of a patient to ascertain whether other significant disorders are present.

Features of hypocalcemia of particular relevance to perioperative management include a predisposition to laryngospasm, cardiac dysrhythmias, muscle weakness, hypotension, congestive heart failure, altered mental status, and coagulopathy (see Chapter 13). Massive transfusion with attendant citrate intoxication, especially in the setting of hepatic insufficiency, is a commonly encountered clinical situation with a significant risk for hypocalcemia that may exacerbate the hemodynamic and metabolic disturbances of complicated surgery. Hypocalcemia should be considered in the differential diagnosis of altered mental status following emergence from a craniotomy. Particularly when symptomatic, hypocalcemia should be treated if total calcium is less than 7.5 g/dL. Of note, alkalosis decreases ionized calcium 0.1 mg/dL (0.25 mEq/L) for every increase of 0.1 pH unit. Total calcium is not affected by pH changes.

Treatment of hypocalcemia in the perioperative setting is best accomplished with IV calcium chloride, although calcium gluconate is another option. Clinicians should recognize that 1 g of calcium chloride solution (13.5 mEq or 273 mg elemental calcium) provides 3 times the amount of elemental calcium present in 1 g of calcium gluconate (4.5 mEq or 93 mg elemental calcium). Serial blood ionized calcium measurements should guide therapy. Of note, concentrated calcium solutions may be caustic to peripheral veins and should be administered cautiously.

Implications of Hypercalcemia

Hypercalcemia is a feature of many medical conditions (Table 60-9). The detection of hypercalcemia warrants evaluation for the possible presence of other major physiologic disturbances, including pheochromocytoma, adrenal insufficiency, and acromegaly. Hypercalcemia should be considered in the differential diagnosis of altered mental status in the perioperative period.

Features of hypercalcemia of particular relevance to perioperative management include a predisposition to cardiovascular disturbances, such as dehydration, dysrhythmias, cardiac conduction disturbances, hypertension, catecholamine resistance, and sensitivity to digitalis.

Muscular weakness caused by hypercalcemia can exacerbate respiratory insufficiency. Nervous system manifestations can include seizures or altered sensorium. Positioning should take into account the risk of fracturing osteopenic bone. Urgent treatment of hypercalcemia may be required in the operating room or in the immediate perioperative period. First-line therapy includes IV hydration and diuresis. Treatment modalities are summarized in Table 60-10.

Pheochromocytomas are neuroendocrine tumors arising from chromaffin cells in the adrenal medulla.125 These tumors may be benign or malignant. The secretion of vasoactive substances, including the catecholamines (dopamine, norepinephrine, and epinephrine), leads to clinical manifestations of the tumors. Neuroendocrine chromaffin tumors that arise outside of the adrenal medulla are referred to as paragangliomas.126,127 Because the clinical presentation and management issues are similar, the anesthetic implications of pheochromocytoma and paraganglioma are discussed together. Several excellent reviews of the pathophysiology, presentation, and perioperative management of pheochromocytoma appear in the literature.125-131

Clinical Manifestations of Pheochromocytoma

As reviewed in Chapter 13, the clinical manifestations of a pheochromocytoma in a patient depend on the profile of catecholamine secretion. Tumors secreting primarily norepinephrine are associated with sustained or episodic hypertension. If epinephrine is the major secreted catecholamine, tachycardia, tachydysrhythmias, and hypotension often result. Dopamine is the major catecholamine secreted by some tumors, and hypotension is the significant clinical feature. However, the overall manifestations of pheochromocytoma are variable, often paroxysmal or episodic, and sometimes similar to other conditions such as severe hyperthyroidism126,127 or preeclampsia.125 If a patient is diagnosed with pheochromocytoma, rapid, extreme perturbations in hemodynamics or other signs and symptoms can be anticipated and should be promptly and appropriately managed in the operating room, postanesthesia care unit (PACU), or intensive care unit (ICU). The undiagnosed patient poses a significant management challenge in the perioperative period because the differential diagnosis of extreme physiologic perturbations is so extensive and treatments differ markedly.

For the anesthesiologist, particularly salient clinical features of pheochromocytoma are hypertension, tachycardia and dysrhythmias, cardiac ischemia or myocardial dysfunction, insulin resistance with hyperglycemia, intravascular volume depletion, and lactic acidosis. Patients may present in shock, caused by either the secreted products of the tumor or some complication of the disease, such as myocardial infarction, cardiac failure, or dissected/ruptured aorta. Acute manifestations of an unsuspected pheochromocytoma must be considered in the differential diagnosis of many intraoperative clinical scenarios.

Preoperative Preparation

A patient with a known pheochromocytoma scheduled for tumor resection undergoes extensive preparation for the procedure. Preoperative medical management has been reviewed.125,126,132 The major concerns are as follows:

1. Control of elevated blood pressure

2. Repletion of intravascular volume

3. Assessment of end-organ consequences of the disease (eg, cardiomyopathy)

4. Recognition of the potential impact of conditions associated with a pheochromocytoma (eg, multiple endocrine neoplasia type II, von Hippel-Lindau syndrome)

5. Normalization of glucose and electrolyte levels

A number of regimens have been reported to reduce blood pressure in the preoperative period in preparation for surgery to resect a pheochromocytoma. (See also Chapter 13.) α-Adrenergic blockade has been widely used. Phenoxybenzamine, a nonselective, noncompetitive, α-adrenergic blocker that covalently binds to α-adrenergic receptors, has been a mainstay of therapy.125,129,130,133 Competitive blockers selective for the α1 subtype of α-adrenergic receptors (eg, doxazosin) have been used to successfully prepare patients for surgery.134

A potential advantage of competitive, selective α1-blockade is that once the tumor has been resected and excess catecholamine release eliminated, α-adrenergic receptors can return quickly to normal function, for example, in regulating vascular tone and blood pressure. A disadvantage of competitive α-adrenergic blockade is the possibility that massive concentrations of catechols released by the tumor can overwhelm the competitive receptor antagonist, resulting in clinical manifestations including hypertension. Covalent, noncompetitive deactivation of α-adrenergic receptors, as with phenoxybenzamine, can withstand a surge in circulating catechol levels. However, following resection of the tumor and removal of excess circulating catecholamines, permanent deactivation of α-adrenergic receptors by phenoxybenzamine may result in hypotension refractory to α-adrenergic agonists for days until new receptors are synthesized.126,127,135

Tachycardia is one consequence of elevated catecholamine levels. β-Adrenergic blockade is commonly used to control tachycardia. However, β-blockade must not be instituted before initiation of α-blockade so that α-adrenergic activation would be unopposed in the vasculature, resulting in dangerous elevation of blood pressure.136 α-Adrenergic blockade is physiologically complex because activation of α2-adrenergic receptors, which are presynaptic, reduces catecholamine secretion, whereas activation of α1-adrenergic receptors, which are postsynaptic, causes vasoconstriction. A theoretical advantage of drugs such as doxazosin lies in their selectivity for α1-adrenergic receptors so that the normal regulatory activities of presynaptic α2-receptors are not impaired, as in the case with the nonselective agent phenoxybenzamine. Urapidil, another selective α1-antagonist deliverable by IV infusion, provides similar advantages.137

Other approaches to preoperative control of blood pressure use calcium channel blockers such as nicardipine,138 the mixed α- and β-receptor antagonist labetalol,139 infusions of magnesium,128,140-142 and treatment with metyrosine,143 which inhibits catecholamine biosynthesis. The aims of preoperative preparation are to prevent an acute hypertensive crisis before entering the operating room and then to minimize catecholamine-induced hemodynamic changes during anesthesia and surgery. With adequate preoperative preparation, which has been defined as a systemic blood pressure stabilized below 160/90 mm Hg with only modest orthostatic hypotension, rare ventricular extrasystoles, and no electrocardiographic evidence of ischemia, perioperative mortality from pheochromocytoma has dropped to less than 3%.127,133 However, intraoperative hemodynamic lability (both hypertension and hypotension) requiring treatment remains a persistent challenge.133

Anesthesia for Pheochromocytoma Resection

Laparoscopy is currently the favored surgical approach for abdominal pheochromocytoma resection.125,127,144-146 However, open surgery may be required depending on the exact location of the lesion (eg, neck paraganglioma) or the anatomic features of an abdominal tumor. Epidural anesthesia provides one option for hemodynamic control.140 Infusions of nitroprusside, nitroglycerin, magnesium sulfate, esmolol, fenoldopam, phentolamine, urapidil, dexmedetomidine, and nicardipine are reported to successfully control hemodynamics in a readily titratable fashion (Table 60-11).135,137,138,142,147 Case reports suggest that remifentanil infusions fail to blunt episodes of hemodynamic lability.148,149 Careful reading of various publications advocating the advantages of particular agents for controlling hemodynamics during pheochromocytoma surgery reveals that, in fact, multiple drugs of different classes often are administered in combination. Appropriate sedation contributes to hemodynamic control in the perioperative period.125

During administration of the anesthetic, the usual triggers for hemodynamic activation, such as laryngoscopy, may result in exaggerated hemodynamic responses in a patient with pheochromocytoma. Insufflation of the abdomen with CO2 for laparoscopy may stimulate the release of catecholamines from tumors,126 and direct manipulation of the tumor may precipitate the rapid secretion of vasoactive substances.125,150 Once the major draining vein of the tumor is ligated, plasma catecholamine levels generally decline precipitously. Hypotension often ensues. Volume repletion, infusions of α-adrenergic agonists such as phenylephrine, and cessation of vasodilators can be used to support hemodynamics. However, as discussed in the section on preoperative preparation, phenoxybenzamine produces sustained deactivation of α-adrenergic receptors, which limits the response to phenylephrine. Vasopressin may circumvent this problem.151 Hypoglycemia should be specifically anticipated and treated as needed.125,127

No particular anesthetic technique is specifically indicated, or contraindicated, for pheochromocytoma surgery. Agents known to cause the release of catecholamines, such as ketamine, ephedrine, meperidine, and desflurane, should be used with care or avoided entirely. Whereas neuraxial anesthesia produces sympathectomy (thereby blunting physiologic autonomic responses to surgical stimulation) and may be a useful adjunct to general anesthesia, especially for postoperative analgesia, the release of catecholamines from tumor cells is not prevented by spinal or epidural anesthetics.

The choice of monitors and vascular access should take into account the need to assess volume status and cardiac performance, and the utility of a central route for delivering vasoactive or inotropic drugs. An arterial line likely will be useful.133 Central venous access and pulmonary arterial catheter insertion remain important considerations. Prys-Roberts126 reported few pulmonary arterial catheter insertions in a large series of pheochromocytoma resections. Consider the use of intraoperative transesophageal echocardiography (TEE), particularly if there is concern for Takotsubo cardiomyopathy.129 Volume loss due to surgical bleeding during pheochromocytoma or paraganglioma resection typically is on the order of a few hundred milliliters, although plans for volume access should take into account potential overall volume depletion, especially in the patient who has not been well prepared for surgery, and the location of the tumor. General preparations should include planning for postoperative care in a setting capable of monitoring and treating volume, hemodynamic, and metabolic concerns.

Surgeons approach lesions of the adrenal cortex by both laparoscopic and open methods. Anesthetic considerations resemble those for other procedures in the abdomen or retroperitoneum. The physiology of adrenal cortical hormones and pathophysiologic conditions of the adrenal cortex are covered in Chapter 13. In general, an excess or deficiency of the mineralocorticoid aldosterone and of adrenal sex steroids has little impact on perioperative anesthetic management, as long as their existence is recognized and medical management is appropriate, including control of blood pressure and treatment of any electrolyte imbalances.

Adrenalectomy for Primary Adrenal Hypercortisolism

For the patient undergoing surgery on 1 adrenal cortex for primary hyperadrenal cortisolism, anesthesia considerations include the consequences of prolonged production of excess cortisol. Relevant features of this condition are summarized in Table 60-12. Hypertension may be particularly difficult to treat during surgery. Plasma glucose levels are likely to be high, requiring therapy. Prolonged excess cortisol levels affect body habitus and can potentially complicate airway management, positioning, and vascular access. Osteoporosis renders the patient at risk for fractures, even with minimal mechanical stress. In general, mineralocorticoid function is preserved in primary adrenal hypercortisolism. Following unilateral adrenalectomy, mineralocorticoid replacement probably is unnecessary. Because the function of the opposite normal adrenal cortex may be suppressed, glucocorticoid replacement will be required in the early postoperative period until the hypothalamic–pituitary–adrenal (HPA) axis recovers. This may take several weeks. Because the half-life of cortisol is several hours, an Addisonian crisis likely will not develop in the operating room. However, glucocorticoid replacement therapy must be started early in the postoperative period.

If the patient undergoes bilateral adrenal resection, replacement of both a glucocorticoid and a mineralocorticoid ultimately will be necessary.152

Adrenal Insufficiency

As reviewed in Chapter 13, native adrenal cortex function may be absent or suppressed by a variety of conditions. Administration of exogenous glucocorticoid is the most common reason for native adrenal suppression. Key features of adrenal insufficiency are summarized in Table 60-12. Of particular relevance in the perioperative period, adrenal insufficiency warrants consideration in the differential diagnosis of refractory hypotension.

In the 1950s, case reports described perioperative deaths of patients who were chronically treated with glucocorticoids and found to have adrenal atrophy.153 The concept emerged that patients at risk for adrenal insufficiency should receive glucocorticoid supplementation in the perioperative period. Risk fa ctors for adrenal suppression and perioperative adrenal insufficiency include prolonged glucocorticoid therapy and doses of steroids exceeding prednisone 5 to 7.5 mg/d or equivalent for 3 weeks or longer.154 Table 60-13 lists the relative potencies of a variety of common glucocorticoids and their mineralocorticoid activities. Recovery from adrenal cortical suppression is variable but may take up to 1 year. Thus patients treated with glucocorticoids within 12 months of surgery are considered to be at risk for adrenal suppression. Provocative testing with cosyntropin may help identify patients at risk for adrenal suppression, but such evaluation is expensive and cumbersome, and the biochemical results may not correspond to clinical events.155

An accepted regimen for perioperative patients that was developed without formal clinical trials calls for the administration of hydrocortisone in "stress" doses. Typically, at least 3 doses of hydrocortisone, 100 mg IV, are administered every 8 hours, followed by tapering of the dose over several days to the patient's baseline steroid regimen. However, this commonly accepted stress-dose steroid regimen has been questioned, based on an increased understanding of physiologic stress responses and glucocorticoid secretion.155 Baseline normal cortisol production may be as low as 10 to 15 mg/d,156-158 rather than 30 mg or more as once believed.159 Thus, even if extreme surgical stresses result in a 10-fold increase in cortisol production,160 100 to 150 mg of exogenous cortisol or glucocorticoid equivalent should suffice to sustain hemodynamics and metabolism in the absence of any endogenous HPA axis activity. Of note, Leopold et al161 did identify larger increases in glucocorticoid production in a group of joint replacement patients; however, these elevations were transient.

The requirement for exogenous glucocorticoid support has been tested in controlled clinical studies of patients chronically treated with steroids.162-164 The chief end point in these studies was blood pressure or heart rate. Withholding steroid supplementation resulted in minimal evidence of hemodynamic instability. Based on these results and the limited number of similar studies in animals and humans, a graded approach to steroid supplementation has been recommended for patients believed to be at risk for adrenal insufficiency in the perioperative period. Recommendations take into account the anticipated magnitude of surgical stress. Table 60-14 combines the recommendations from several sources.136,155,165 Of note, prolonged tapering of exogenous glucocorticoid therapy does not appear to be essential, as long as baseline therapy is resumed within a few days of surgery.166 These recommendations should not necessarily be taken to apply to critically ill patients who come to the operating room from an ICU setting. Some evidence suggests that adrenal insufficiency occurs in at least some critically ill patients,154 particularly those with sepsis. Such patients may require large doses of supplemental steroids for prolonged periods.

Etomidate

The favorable hemodynamic properties of the IV induction agent etomidate give this drug an important place in the anesthesiologist's armamentarium. However, unique among all anesthetic agents, etomidate inhibits the mitochondrial enzyme 11β-hydroxylase, an essential enzyme in the biosynthetic pathway for steroids. An induction dose of etomidate reduces cortisol and aldosterone production for approximately 8 hours. Repeated doses or infusions of etomidate have more prolonged suppressant effects on steroid production, which may become clinically relevant. Consequently, the use of etomidate should be evaluated in the context of the patient's adrenal reserve. Interestingly, prolonged administration of etomidate has been used as a therapeutic strategy to control glucocorticoid levels in severe Cushing disease.167

Anatomy of the Pituitary Gland

The pituitary gland lies within a recess of the sphenoid bone, the sella turcica. The gland is composed of 2 major subdivisions, the anterior pituitary and the posterior pituitary. Magnetic resonance imaging (MRI) readily visualizes these structures because the posterior pituitary appears as a bright spot on T1 weighted images, as shown in the sagittal view in Fig. 60-10A. Structures next to the pituitary are shown in the coronal view in Fig. 60-10B.

The posterior pituitary contains axon terminals of specialized neurons arising within the supraoptic and paraventricular nuclei of the hypothalamus. These nerves secrete oxytocin and vasopressin (antidiuretic hormone [ADH]). Thus the posterior pituitary is a direct extension of the brain. In contrast, the anterior pituitary derives embryologically from the Rathke pouch; it is composed primarily of epithelial cells. It does not have direct neuronal connections to the brain. The anterior pituitary is dependent on a vascular conduit, the pituitary portal plexus, which directly links the hypothalamus to the anterior pituitary gland. The portal plexus is a venous plexus and is the major source of blood flow to the anterior pituitary, which has little or no arterial blood supply.

Pituitary Lesions

Pituitary lesions can be placed in broad categories according to their functional effects. Lesions can cause mass effects, anterior pituitary hyperfunction, or anterior pituitary hypofunction.

Pituitary adenomas arise from anterior pituitary cells; therefore, they almost always are located in the sella turcica. They compose approximately 10% to 15% of all intracranial neoplasms. Adenomas less than 1 cm in diameter typically are referred to as microadenomas, whereas adenomas with diameters of 1 cm or greater are commonly referred to as macroadenomas.168,169 Macroadenomas and some microadenomas can be visualized by MRI following IV infusion of gadolinium. Autopsy studies reveal that 25% of individuals have asymptomatic pituitary adenomas. Only adenomas with endocrine syndromes as a result of hyposecretion or hypersecretion, or that cause symptomatic mass effects on adjacent brain structures, come to medical attention. The prevalence of diagnosed pituitary adenomas is 8.9:100,000.169

In addition to pituitary tumors, many other masses appear in the sella or parasellar region.168,170 Meningiomas, craniopharyngiomas, chordomas, and metastatic carcinomas occasionally appear as pituitary masses. Benign sellar cysts derive primarily from the Rathke cleft; they frequently are asymptomatic and are found incidentally. Infiltrative diseases mimicking masses in the pituitary include sarcoidosis, lymphocytic hypophysitis, histiocytosis X, and tuberculosis.

Classification of Pituitary Adenomas

Pituitary adenomas are classified by either their hypersecretory product or their lack of hormonal secretion (nonsecretory pituitary adenomas).168,170 Some tumors secrete more than 1 pituitary hormone (plurihormonal adenomas). The most common combination seen in these tumors is GH and prolactin.171 Other pituitary adenomas do not secrete bioactive hormone but may secrete the α- or β-subunits of the glycoprotein hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), or thyroid-stimulating hormone (TSH).

Clinical Symptoms of Pituitary Masses

Because the pituitary gland lies adjacent to the cavernous sinus, temporal lobes, and sphenoid sinus (Figs. 60-10 and 60-11), the presentation of pituitary lesions occasionally includes other clinical symptoms (Table 60-15). Palsies of extraocular muscles, sensory disturbances in the first and second branches of the fifth cranial nerve, temporal lobe seizures, and cerebrospinal fluid (CSF) rhinorrhea may bring a patient to medical attention.168 Disorders of both the hypothalamus and pituitary can compress or infiltrate the optic chiasm, resulting in a variety of visual field abnormalities affecting peripheral vision (superolateral visual field defect).

Pituitary Hypofunction: Causes, Presentation, and Treatment of Hypopituitarism

Causes of Deficient Pituitary Hormone Secretion

Many disorders cause hypopituitarism by affecting either the hypothalamus or the pituitary gland. Pituitary adenomas are the most common cause of hypopituitarism.168,172 Other less common causes are listed in Table 60-16.

Diagnosis of Deficient Pituitary Hormone Secretion

Although the diagnosis of some pituitary deficiencies can be inferred based on history and clinical findings, demonstrating hormone deficiencies by biochemical testing is essential to establishing the diagnosis of hypopituitarism. A more detailed description of hypothyroidism and cortisol insufficiency can be found in the thyroid and adrenal sections of Chapter 13. A variety of tests can be performed to evaluate the reserve of each of the pituitary hormones. It is extremely important to make the diagnosis of adrenocorticotropic hormone (ACTH) and/or TSH deficiency, because these anterior pituitary hormones are essential to surviving perioperative stress.168,172 Destruction of the posterior pituitary, stalk compression, or stalk section results in a complete or relative lack of ADH. ADH causes the renal tubules to reabsorb water. Lack of ADH results in failure to concentrate urine, producing dilute urine (low specific gravity and low osmolality), despite dehydration with an elevated blood osmolality. Urine output can exceed 1 to 2 L/h, resulting in severe dehydration, hypernatremia, and vascular collapse.172,173

Treatment of Deficient Pituitary Hormone Secretion

The aim of treatment is to replace the hormonal deficiencies needed for normal function and to treat the underlying disease process.168,173 In most instances, replacement of hormone deficiencies can be accomplished by oral, IV, cutaneous (skin patch), subcutaneous, or nasal administration of deficient hormones. The dose usually is the same from day to day, with the exception of glucocorticoid replacement, which must be increased during times of stress (see the section Adrenal Cortex and Perioperative Management of Glucocorticoids for a detailed discussion of baseline and stress doses of glucocorticoids). As a general rule, glucocorticoid replacement therapy should be given first. Thyroid hormone replacement therapy should never be given before glucocorticoids have been replaced in order to avoid precipitating an Addisonian crisis.168,173

Pituitary Hypersecretion and Neoplasia

Pathophysiologic causes of pituitary hormone hypersecretion include hyperplasia of 1 or more cell types in the anterior pituitary, driven by the excessive production of hypothalamic releasing factors. Tumors in the hypothalamus (hamartomas, gangliocytomas) or in the periphery (carcinoids, islet cell tumors) may secrete these factors. However, the most common cause for pathologic hypersecretion of anterior pituitary hormones is pituitary adenoma.168,170 The most common pituitary adenoma is a prolactinoma.174 The lesions with greatest significance for anesthetic management are corticotroph and somatotroph adenomas.

Prolactinomas

The prolactinoma is the most common pituitary adenoma.174 In women most tumors present as microadenomas, whereas in men macroadenomas predominate. Symptoms due to compression of local structures thus are generally found in men.168 Signs and symptoms associated with hyperprolactinemia mainly relate to reproductive tissues and function, including amenorrhea and impotence.

Treatment of patients with a prolactinoma depends on the size of the adenoma and the degree of symptoms. If the adenoma is small and endocrine consequences are minor, management is conservative because most lesions will not enlarge. Adenomas requiring therapy generally respond to medical management with the dopamine agonists bromocriptine or cabergoline.168,176 By stimulating D2 receptors on the adenoma, these drugs cause a reduction in tumor size and inhibit prolactin synthesis and secretion. Most adenomas will regrow, however, if therapy is stopped. If tumors resist medical therapy, transsphenoidal (TSP) surgery is performed. Surgical success rates are high for microadenomas (>70%), but postoperative recurrence may reach 50% over 5 years.176 Macroadenomas are difficult to cure by surgery, with success rates of approximately 30%. Conventional external radiation is not very effective and is used as a last resort.168,176

Somatotroph Adenomas

GH hypersecretion is almost always due to a pituitary adenoma. GH hypersecretion causes gigantism in children and adolescents (before closure of the epiphyses) and acromegaly in adults. Acromegaly, largely a disorder of middle age, has a peak incidence between the ages of 40 and 50 years. If untreated, it is associated with a 2- to 3-fold increased mortality due to cardiovascular disease (hypertension, cardiomyopathy, arrhythmias, stroke), cancer (especially adenocarcinoma of the colon), and respiratory impairment.170

Acromegaly leads to profound physical deformity due to skeletal overgrowth (bone and cartilage) and fibroblast proliferation under the influence of insulin-like growth factor (IGF)-1. This is particularly manifested in the facial bones, where enlargement of the mandible results in protrusion of the jaw (prognathism), dental malocclusion, and often an increased space between the teeth (Fig. 60-12). Facial features are thickened, coarsened, or swollen, making skin creases very pronounced, partly due to sodium and water retention and increased glycosaminoglycan accumulation in the skin. The lips, tongue, and tissue in the posterior pharynx become very large (Fig. 60-13). Increased cartilaginous growth contributes to the very prominent nose. Enlargement of the hands and feet result in the common complaint that ring, glove, and shoe sizes increase. Arthralgias are particularly common (75%) due to cartilaginous overgrowth in the joints, resulting in misalignment and destabilization of the joints and ultimately joint destruction. Other manifestations of acromegaly are listed in the Table 60-17. It is important to make the diagnosis of acromegaly early to prevent irreversible, devastating complications.168

Because of the insidious nature of the disease and delays in diagnosis, most individuals with acromegaly have macroadenomas when they come to medical attention. Approximately 30% have microadenomas. TSP surgery successfully removes approximately 80% of microadenomas. Only approximately 30% of individuals with macroadenomas have a surgical cure.168 Radiation therapy is only partly successful in reducing GH hypersecretion to normal, although preliminary data using radiosurgery therapy suggest a 60% cure rate over 4 years. Several medical treatments have become available to control GH hypersecretion and, in some cases, tumor growth. These medications, which include somatostatin analogues and blockers of dopamine receptors, can be given singly or in combination.

Successful treatment of acromegaly results in the reduction of left ventricular hypertrophy and some improvement of diastolic function (increase in transmitral peak flow velocity and decreased isovolumic relaxation time).177,178 However, skeletal and soft-tissue changes persist and may pose challenges when patients require surgery and anesthesia for conditions other than their pituitary disease.

Corticotroph Adenoma

Cushing disease is the condition of excess ACTH secretion from the pituitary gland. The major cause is pituitary adenoma. Table 60-12 summarizes the clinical characteristics of glucocorticoid excess relevant to perioperative management.

Pituitary secretion of ACTH normally is under negative feedback inhibition by circulating cortisol. ACTH and cortisol can be suppressed in individuals with ACTH-secreting pituitary adenomas when they receive sufficiently large doses of exogenous glucocorticoids. Dexamethasone, a semisynthetic steroid, is often used for this purpose because it does not interfere with cortisol radioimmunoassays. By administering graded doses of dexamethasone (Liddle test) to individuals suspected of having Cushing syndrome and measuring ACTH and cortisol levels, it is possible to distinguish individuals having ACTH-secreting adenomas, adrenal adenomas, and ectopic ACTH secretion (eg, oat cell carcinoma, medullary thyroid carcinoma, islet cell tumors, pheochromocytoma) from individuals who simply are obese, stressed, or abuse alcohol.

Alternatively, measurement of a late-night plasma or salivary cortisol level can be used to distinguish individuals with Cushing disease from normal individuals. This discrimination is based on the normal physiologic diurnal variation of cortisol levels, which peak at around 8 AM and have their nadir at around midnight. Thus a normally suppressed midnight cortisol level excludes the diagnosis of Cushing disease. In some patients, midnight cortisol levels are elevated, but MRI fails to demonstrate a pituitary adenoma (60% of cases due to the small size of ACTH-secreting pituitary adenomas; macroadenomas are rare). In this situation, a corticotropin-releasing hormone (CRH) stimulation test can be performed with sampling of venous blood draining the pituitary gland.

Treatment of Cushing disease is primarily surgical, with removal of the pituitary adenoma by TSP surgery. For individuals not cured by surgery, treatment options include conventional radiation or radiosurgery therapy, with or without medical therapy. Medications used in the management of Cushing disease and their mechanisms of action are summarized in Table 60-18.

Thyrotroph Adenomas

Thyrotroph adenomas are rare pituitary adenomas.168,170 Most of these tumors are macroadenomas; therefore, they may be associated with mass effects. Their principal clinical presentation is thyrotoxicosis due to excessive TSH secretion. A goiter occurs in more than 90% of cases. Graves disease is often misdiagnosed in these patients. Inappropriately elevated TSH levels (for the levels of thyroid hormones) and the absence of ophthalmopathy allow differentiation between the 2 disorders. Surgery is the primary therapy for a thyrotroph adenoma, but complete removal often is difficult because of the large size of these tumors. Radiation therapy and/or medical therapy with octreotide are used for treating persistent disease. Octreotide is very effective in reducing TSH secretion to normal and reversing thyrotoxicosis, but is not very effective in shrinking tumors.

Nonsecreting Adenomas

Most (90%) nonsecreting pituitary adenomas are actually glycoprotein hormone–producing adenomas, manufacturing various subunits of glycoprotein hormones including α-subunit, β-LH, and β-FSH.171 Because these subunits are biologically inactive, clinical syndromes usually are not observed. As a result, most of these tumors come to medical attention because of mass effects and/or hypopituitarism.

Treatment depends on the size of the adenoma. Small adenomas do not necessarily require treatment if they do not compress local structures or cause hypopituitarism. Periodic MRI can assess their rate of growth. Large tumors are treated by TSP surgery. Bulky residual or recurrent tumor is treated by radiotherapy. Complete resection of the tumor is not necessary. Relief of compressive symptoms is adequate. If hypopituitarism persists following surgery or is caused by surgery, replacement therapy is given. Occasionally, anterior pituitary function recovers after decompression of the residual normal anterior pituitary cells.168

Anesthetic Considerations for Pituitary Surgery

Most sellar lesions are accessible by a TSP approach.173,179-181 The nares is the preferred route for entering the sella (Fig. 60-14A). However, this approach may not be anatomically feasible, so the surgeon may achieve adequate exposure by dissecting over the palate with an incision above the maxillary teeth (sublabial approach; Fig. 60-14B). Consequently, the surgeon and anesthesiologist share the head during TSP surgery. General endotracheal anesthesia is indicated. To prevent the accumulation of secretions, blood, or CSF in the airway or stomach, a throat pack typically is inserted.

Preoperative assessment requires an understanding of the implications of the patient's endocrine condition. Nonsecreting adenomas, prolactinomas, and the rare adenomas secreting glycoprotein hormones generally have little impact on anesthetic management. Patients with Cushing disease may have all the features of sustained cortisol excess. Potential anesthetic concerns with these patients include airway management, positioning, glucose and electrolyte disturbances, and control of blood pressure. Some patients with Cushing disease have refractory hypertension that poses a significant treatment challenge.

Patients with acromegaly have a propensity for ischemic cardiac disease as well as myocardial dysfunction. Cardiac status should be specifically assessed before surgery. Because of the skeletal and soft tissue effects of sustained exposure to GH, patients with acromegaly may present substantial challenges in airway management. Mask ventilation and conventional direct laryngoscopy may be difficult or impossible (Fig. 60-15). Advanced airway management devices may be required. Consideration should be given to awake fiberoptic intubation in selected patients.

For most patients undergoing TSP surgery, standard monitoring and routine IV access suffice.173 The addition of an arterial line may be indicated for patients with comorbidities, or Cushing disease or acromegalic patients with refractory hypertension or cardiac issues. Volume loss likely will be minimal, so large-bore IV access usually is unnecessary. However, the sella is situated near major vascular structures, and the need to augment IV access may develop during surgery.

The transnasal TSP surgical procedure is only moderately stimulating, and postoperative pain control requirements are modest.172 Early hypertension during the surgical procedure may be a result of the application of vasoconstrictors to the nasal mucosa by the surgeon, with subsequent systemic effects. Watch for hypotension if the patient is positioned with the head elevated. Surgical procedures generally terminate abruptly, so the anesthesiologist must titrate drugs carefully to permit a prompt and smooth emergence. It is highly desirable for the patient to be able to maintain his or her own airway without support or the need for bag-mask positive-pressure ventilation following extubation. The dura has been opened at the surgical site, which now communicates with the nasal passages. Positive-pressure ventilation can, in theory, cause the introduction of air or infectious material through the dural opening into the CSF space.

Some centers use intraoperative MRI techniques to assist the surgeon in gauging the extent of dissection or resection. This poses some additional concerns for easy access to the patient's airway. In addition, preparations include ensuring the availability of MRI-compatible equipment (eg, monitoring devices and the anesthesia machine itself).

Postoperative Care after Pituitary Surgery

Patients are at risk for diabetes insipidus immediately after surgery.173,182 Monitoring includes frequent determinations of serum sodium levels and meticulous recording of daily weight and fluid balance, with hourly measurement of urine output and assessment of urine specific gravity every 4 hours. A triphasic course is often seen. Early ADH deficiency is attributed to immediate perioperative neuronal damage, followed a few days later by excess ADH release and associated hyponatremia from retrograde neuronal death and release of ADH stores. Finally, permanent deficiency of ADH develops with return of diabetes insipidus.

The vasopressin analogue desmopressin should be administered postoperatively when urine output exceeds fluid intake and the serum sodium level rises. Careful monitoring of body weight, fluid balance, urine specific gravity, and plasma sodium level should continue daily to avoid electrolyte abnormalities. Desmopressin therapy starts with a single dose at bedtime in a patient diagnosed with partial central diabetes insipidus to avoid hyponatremia. Patients with acromegaly can have salt and water diuresis after successful tumor removal. Such patients should not be immediately treated with vasopressin.

With the exception of patients with Cushing disease, all patients undergoing pituitary surgery should be placed on steroids appropriate for surgical stress. The rate of decrease in steroid dose should be guided by clinical and hemodynamic status after surgery. In an uncomplicated postoperative course, taper steroids to physiologic replacement doses over 2 to 3 days. Patients with Cushing disease should not be placed on glucocorticoid replacement immediately after surgery, but cortisol levels should be checked every 6 hours and replacement therapy initiated as needed.

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