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The adrenal gland is divided into the cortex and medulla. The adrenal cortex secretes androgens, mineralocorticoids (eg, aldosterone), and glucocorticoids (eg, cortisol). The adrenal medulla secretes catecholamines (primarily epinephrine, but also small amounts of norepinephrine and dopamine). The adrenal androgens have almost no relevance for anesthetic management and will not be considered further.
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Aldosterone is primarily involved with fluid and electrolyte balance. Aldosterone secretion causes sodium to be reabsorbed in the distal renal tubule in exchange for potassium and hydrogen ions. The net effect is an expansion in extracellular fluid volume caused by fluid retention, a decrease in plasma potassium, and metabolic alkalosis. Aldosterone secretion is stimulated by the renin–angiotensin system (specifically, angiotensin II), pituitary adrenocorticotropic hormone (ACTH), and hyperkalemia. Hypovolemia, hypotension, congestive heart failure, and surgery result in an elevation of aldosterone concentrations. Blockade of the renin–angiotensin–aldosterone system with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or both, is a cornerstone of therapy (and increases survival) in hypertension and chronic heart failure. Aldosterone receptor blockers (spironolactone or eplerenone) added to standard therapy prolong survival in patients with chronic heart failure.
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Glucocorticoids are essential for life and have multiple physiological effects, including enhanced gluconeogenesis and inhibition of peripheral glucose utilization. These actions tend to raise blood glucose and worsen diabetic control. Glucocorticoids are required for vascular and bronchial smooth muscle to respond to catecholamines. Because glucocorticoids are structurally related to aldosterone, most tend to promote sodium retention and potassium excretion (a mineralocorticoid effect). ACTH released by the anterior pituitary is the principal regulator of glucocorticoid secretion. Basal secretion of ACTH and glucocorticoids exhibits a diurnal rhythm. Stressful conditions promote secretion of ACTH and cortisol, while circulating glucocorticoids inhibit ACTH and cortisol secretion. Under nonstressed conditions, endogenous production of cortisol, the most important endogenous glucocorticoid, averages 20 mg/d.
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The structure, biosynthesis, physiological effects, and metabolism of catecholamines are discussed in Chapter 14. Epinephrine constitutes 80% of adrenal catecholamine output in humans. Catecholamine release is regulated mainly by sympathetic cholinergic preganglionic fibers that innervate the adrenal medulla. Stimuli include exercise, hemorrhage, surgery, hypotension, hypothermia, hypoglycemia, hypercapnia, hypoxemia, pain, and fear.
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MINERALOCORTICOID EXCESS
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Clinical Manifestations
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Hypersecretion of aldosterone by the adrenal cortex (primary aldosteronism) can be due to a unilateral adenoma (aldosteronoma or Conn syndrome), bilateral hyperplasia, or in very rare cases carcinoma of the adrenal gland. Some disease states stimulate aldosterone secretion by affecting the renin–angiotensin system. For example, congestive heart failure, hepatic cirrhosis with ascites, nephrotic syndrome, and some forms of hypertension (eg, renal artery stenosis) can cause secondary hyperaldosteronism. Although both primary and secondary hyperaldosteronism are characterized by increased levels of aldosterone, only the latter is associated with increased renin activity. The usual clinical manifestations of mineralocorticoid excess include hypokalemia and hypertension, and an increased ratio of aldosterone–plasma renin activity has been noted in laboratory studies.
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Anesthetic Considerations
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Fluid and electrolyte disturbances can be corrected preoperatively using spironolactone. This aldosterone antagonist is a potassium-sparing diuretic with antihypertensive properties. Intravascular volume can be assessed preoperatively by testing for orthostatic hypotension.
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MINERALOCORTICOID DEFICIENCY
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Clinical Manifestations & Anesthetic Considerations
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Atrophy or destruction of both adrenal glands results in a combined deficiency of mineralocorticoids and glucocorticoids (see the section on Glucocorticoid Deficiency). Isolated deficiency of mineralocorticoid activity almost never occurs.
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GLUCOCORTICOID EXCESS
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Clinical Manifestations
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Glucocorticoid excess may be due to exogenous administration of steroid hormones, intrinsic hyperfunction of the adrenal cortex (eg, adrenocortical adenoma), ACTH production by a nonpituitary tumor (ectopic ACTH syndrome), or hypersecretion by a pituitary adenoma (Cushing disease). Regardless of the cause, an excess of corticosteroids produces Cushing syndrome, characterized by muscle wasting and weakness, osteoporosis, central obesity, abdominal striae, glucose intolerance, menstrual irregularity, hypertension, and mental status changes.
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Anesthetic Considerations
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Patients with Cushing syndrome may be volume overloaded and have hypokalemic metabolic alkalosis resulting from the mineralocorticoid activity of glucocorticoids. These abnormalities should be corrected preoperatively in the manner previously described. Patients with osteoporosis are at risk for fracture during positioning. If the cause of Cushing syndrome is exogenous glucocorticoids, the patient’s adrenal glands may not be able to respond to perioperative stresses, and supplemental steroids are indicated (see the section on Glucocorticoid Deficiency). Likewise, patients undergoing adrenalectomy require intraoperative glucocorticoid replacement (in adults, intravenous hydrocortisone succinate, 100 mg every 8 h has been the traditional stress dose). Although many adrenal tumors are removed uneventfully during laparoscopic surgery, complications of adrenalectomy may include major blood loss and unintentional pneumothorax.
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GLUCOCORTICOID DEFICIENCY
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Clinical Manifestations
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Primary adrenal insufficiency (Addison disease), caused by destruction of the adrenal gland, results in a combined mineralocorticoid and glucocorticoid deficiency. Clinical manifestations are due to aldosterone deficiency (hyponatremia, hypovolemia, hypotension, hyperkalemia, and metabolic acidosis) and cortisol deficiency (weakness, fatigue, hypoglycemia, hypotension, and weight loss).
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Secondary adrenal insufficiency is a result of inadequate ACTH secretion by the pituitary. The most common cause of secondary adrenal insufficiency is prior administration of exogenous glucocorticoids. Because mineralocorticoid secretion is usually adequate in secondary adrenal insufficiency, fluid and electrolyte disturbances are not present. Acute adrenal insufficiency (addisonian crisis), however, can be triggered in steroid-dependent patients who do not receive appropriate glucocorticoid doses during periods of stress (eg, infection, trauma, surgery) and in patients who receive infusions of etomidate. The clinical features of this medical emergency include fever, abdominal pain, orthostatic hypotension, and hypovolemia that may progress to circulatory shock unresponsive to resuscitation.
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Anesthetic Considerations
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Patients with glucocorticoid deficiency must receive adequate steroid replacement therapy during the perioperative period. Patients who have received potentially suppressive doses of steroids (eg, the daily equivalent of 5 mg of prednisone) by any route of administration (topical, inhalational, or oral) for a period of more than 2 weeks any time in the previous 12 months may be unable to respond appropriately to surgical stress and should receive perioperative glucocorticoid supplementation.
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What represents adequate steroid coverage is controversial, and there are those who advocate variable dosing based on the extent of the surgery. Although adults normally secrete 20 mg of cortisol daily, this may increase to more than 300 mg under conditions of maximal stress. Thus, a traditional recommendation was to administer 100 mg of hydrocortisone every 8 h beginning on the morning of surgery. An alternative low-dose regimen (25 mg of hydrocortisone at the time of induction followed by an infusion of 100 mg during the subsequent 24 h) maintains plasma cortisol levels equal to or higher than those reported in healthy patients undergoing similar elective surgery. This second regimen might be particularly appropriate for diabetic patients, in whom glucocorticoid administration often interferes with control of blood glucose.
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Clinical Manifestations
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Pheochromocytoma is a catecholamine-secreting tumor that consists of cells originating from the embryonic neural crest. This tumor accounts for 0.1% of all cases of hypertension. Although the tumor is usually localized in a single adrenal gland, 10% to 15% are bilateral or extraadrenal. Approximately 10% of tumors are malignant. The cardinal manifestations of pheochromocytoma are paroxysmal hypertension, headache, sweating, and palpitations. Unexpected intraoperative hypertension and tachycardia during manipulation of abdominal structures may occasionally be the first indications of an undiagnosed pheochromocytoma. The pathophysiology, diagnosis, and treatment of these tumors require an understanding of catecholamine metabolism and of the pharmacology of adrenergic agonists and antagonists. The Case Discussion in Chapter 14 examines these aspects of pheochromocytoma management.
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Anesthetic Considerations
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Preoperative assessment should focus on the adequacy of α-adrenergic blockade and volume replacement. Specifically, resting arterial blood pressure, orthostatic blood pressure and heart rate, ventricular ectopy, and electrocardiographic evidence of ischemia should be evaluated.
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A decrease in plasma volume and red cell mass contributes to the severe chronic hypovolemia seen in these patients. The hematocrit may be normal or elevated, depending on the relative contribution of hypovolemia and anemia. Preoperative α-adrenergic blockade with phenoxybenzamine (a noncompetitive inhibitor) helps correct the volume deficit, in addition to correcting hypertension. β Blockade should not be initiated prior to α blockade but may be added if there is a need to control heart rate and to reduce arrhythmias provoked by excess catecholamine concentrations. A decline in hematocrit should accompany the expansion of circulatory volume. An underlying anemia may be unmasked by volume expansion.
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Potentially life-threatening variations in blood pressure—particularly during induction and manipulation of the tumor—indicate the usefulness of invasive arterial pressure monitoring. Young patients with minimal or no heart disease do not need a central venous line. Patients with evidence of cardiac disease (or in whom cardiac disease is suspected) may benefit from having a central line (a convenient route of access for administering catecholamines, should they be required) and from intraoperative transesophageal echocardiography.
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Intubation should not be attempted until a deep level of general anesthesia (possibly also including local anesthesia of the trachea) has been established. Intraoperative hypertension can be treated with phentolamine, nitroprusside, nicardipine, or clevidipine. Phentolamine specifically blocks α-adrenergic receptors and blocks the effects of excessive circulating catecholamines. Nitroprusside has a rapid onset of action, a short duration of action, and as a nitric oxide donor can be effective in cases where calcium channel blockers are ineffective. Nicardipine and clevidipine are being used more frequently preoperatively and intraoperatively.
Drugs or techniques that indirectly stimulate or promote the release of catecholamines (eg, ephedrine, hypoventilation, or large bolus doses of ketamine), potentiate the arrhythmic effects of catecholamines (halothane), or consistently release histamine (eg, large doses of atracurium or morphine sulfate) are best avoided.
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After ligation of the tumor’s venous supply, the primary problem frequently becomes hypotension from hypovolemia, persistent adrenergic blockade, and tolerance to the increased concentrations of endogenous catecholamines that have been abruptly withdrawn. Appropriate fluid resuscitation should reflect surgical bleeding and other sources of fluid loss. Assessment of intravascular volume can be guided by echocardiographic assessment of left ventricular filling using transesophageal echocardiography or other noninvasive measures of cardiac output and stroke volume. Infusions of adrenergic agonists, such as phenylephrine or norepinephrine, often prove necessary. Postoperative hypertension is rare and may indicate the presence of unresected occult tumors.
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Overweight and obesity are classified using the body mass index (BMI). Overweight is defined as a BMI of 24 kg/m2 or higher, obesity as a BMI of 30 or higher, and extreme obesity (formerly termed “morbid obesity”) as a BMI of more than 40. BMI is calculated by dividing the weight (in kilograms) by the height (in meters) squared. A great many BMI calculators are available online or as apps for smartphones. Health risks increase with the degree of obesity and with increased abdominal distribution of weight. Men with a waist measurement of 40 in. or more and women with a waist measurement of 35 in. or more are at increased health risk. For a patient 1.8 m tall and weighing 70 kg, the BMI would be as shown in the following formula:
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Clinical Manifestations
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Obesity is associated with many diseases, including type 2 diabetes mellitus, hypertension, coronary artery disease, obstructive sleep apnea, degenerative joint disease (osteoarthritis), and cholelithiasis. Even in the absence of obvious coexisting disease, however, extreme obesity has profound physiological consequences. Oxygen demand, CO2 production, and alveolar ventilation are elevated because metabolic rate is proportional to body weight. Excessive adipose tissue over the thorax decreases chest wall compliance even though lung compliance may remain normal. Increased abdominal mass forces the diaphragm cephalad, yielding lung volumes suggestive of restrictive lung disease. Reductions in lung volumes are accentuated by the supine and Trendelenburg positions. In particular, functional residual capacity may fall below closing capacity. If this occurs, some alveoli will close during normal tidal volume ventilation, causing a ventilation/perfusion mismatch.
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Whereas obese patients are often hypoxemic, only a few are hypercapnic, which when present should be a warning of impending complications. Obstructive sleep apnea (OSA) is a complication of extreme obesity characterized by hypercapnia, cyanosis-induced polycythemia, right-sided heart failure, and somnolence. These patients appear to have blunted respiratory drive and often suffer from loud snoring and upper-airway obstruction during sleep. OSA patients often report dry mouths and daytime somnolence; bed partners frequently describe apneic pauses. OSA has also been associated with increased perioperative complications, including hypertension, hypoxia, arrhythmias, myocardial infarction, pulmonary edema, stroke, and death. The potential for difficult mask ventilation and difficult intubation, followed by upper airway obstruction during recovery, should be anticipated.
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OSA patients are vulnerable during the postoperative period, particularly when sedatives or opioids have been given. OSA patients positioned supine are unusually susceptible to upper airway obstruction. For patients with known or suspected OSA, postoperative continuous positive airway pressure (CPAP) should be considered until the anesthesiologist can be sure that the patient can protect his or her airway and maintain spontaneous ventilation without evidence of obstruction. Both the American Society of Anesthesiologists and the Society of Ambulatory Anesthesia offer guidelines on perioperative management of the patient with OSA (see Chapter 44).
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An OSA patient’s heart has an increased workload, as cardiac output and blood volume increase to perfuse additional fat stores. Arterial hypertension leads to left ventricular hypertrophy. Elevations in pulmonary blood flow and pulmonary artery vasoconstriction from persistent hypoxia can lead to pulmonary hypertension and cor pulmonale.
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Obesity is also associated with hiatal hernia, gastroesophageal reflux disease, delayed gastric emptying, and hyperacidic gastric fluid, as well as with an increased risk of gastric cancer. Fatty infiltration of the liver also occurs and may be associated with abnormal liver tests, but the extent of infiltration does not correlate well with the degree of liver test abnormality.
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Anesthetic Considerations
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For the reasons outlined above, obese patients are at an increased risk for developing aspiration pneumonia. Pretreatment with nonparticulate antacid, H2 antagonists, and metoclopramide should be considered. Premedication with respiratory depressant drugs must be avoided in patients with OSA.
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Before anesthetizing extremely obese patients for major surgery one should attempt to assess cardiopulmonary reserve. Preoperative testing may include such items as chest radiograph, ECG, and arterial blood gas analysis. Physical signs of cardiac failure may be difficult to identify. Blood pressures must be taken with a cuff of the appropriate size. Potential sites for intravenous and intraarterial access should be checked in anticipation of technical difficulties. Obscured landmarks, difficult positioning, and extensive layers of adipose tissue may make regional anesthesia difficult with standard equipment and techniques.
Obese patients may be difficult to intubate as a result of limited mobility of the temporomandibular and atlantooccipital joints, a narrowed upper airway, and a shortened distance between the mandible and sternal fat pads.
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Because of the risks of aspiration and hypoventilation, morbidly obese patients are often intubated for all but short general anesthetics. If intubation appears possibly to be difficult, we recommend using either video laryngoscopy or fiberoptic bronchoscopy. Positioning the patient on an intubating ramp is helpful. Auscultation of breath sounds may prove difficult. Even with controlled ventilation these patients may require increased inspired oxygen concentrations to prevent hypoxia, particularly in the lithotomy, Trendelenburg, or prone positions. Subdiaphragmatic abdominal laparotomy packs can cause further deterioration of pulmonary function and a reduction of arterial blood pressure by increasing the resistance to venous return. Volatile anesthetics may be metabolized more extensively in obese patients. Increased metabolism may explain the increased incidence of halothane hepatitis observed in obese patients. Obese patients may have a prolonged induction and emergence from inhaled anesthetics.
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Theoretically, greater fat stores would increase the volume of distribution for lipid-soluble drugs (eg, benzodiazepines, opioids) relative to a lean person of the same body weight. However, the volume of distribution of, for example, fentanyl or sufentanil is so large that obesity has minimal influence. Water-soluble drugs (eg, NMBs) have small volumes of distribution, which are minimally increased by body fat. Therefore, the dosing of water-soluble drugs should be based on ideal body weight to avoid overdosage.
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Although dosage requirements for epidural and spinal anesthesia are difficult to predict, obese patients typically require 20% to 25% less local anesthetic per blocked segment because of epidural fat and distended epidural veins. Continuous epidural anesthesia has the usual advantages of providing pain relief and potentially decreasing respiratory complications in the postoperative period. Regional nerve blocks, particularly when combined with multimodal pain control, have the additional advantages of not interfering with the postoperative deep vein thrombosis prophylaxis, rarely producing hypotension, and of reducing the need for opioids (see Chapter 48).
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Respiratory failure is a major postoperative problem of morbidly obese patients. The risk of postoperative hypoxia is increased in these patients, especially when there is preoperative hypoxia, and with surgery involving the thorax or upper abdomen. An obese patient should remain intubated until there is no doubt that an adequate airway and tidal volume will be maintained, NMBs are completely reversed, and the patient is awake. This does not mean that all obese patients need be ventilated overnight in an intensive care unit. If the patient is extubated in the operating room, supplemental oxygen should be provided during transportation to the postanesthesia care unit. A 45° modified sitting position will improve ventilation and oxygenation. The risk of hypoxia extends for several days into the postoperative period, and providing supplemental oxygen or CPAP, or both, should be routinely considered. Other common postoperative complications in obese patients include wound infection, deep venous thrombosis, and pulmonary embolism. Morbidly obese and OSA patients may be candidates for outpatient surgery provided they are adequately monitored and assessed postoperatively before discharge to home, and provided the surgical procedure will not require large doses of opioids for postoperative pain control. It is hard to conceive of a better indication for multimodal analgesia.