Endocrine system
A Acromegaly
Definition
Growth hormone (GH) hypersecretion, usually caused by a GH-secreting pituitary adenoma (99% of cases), can produce a highly distinctive syndrome in adults called acromegaly. Acromegaly occurs because of sustained hypersecretion of GH after adolescence. The condition occurs with equal frequency in both sexes. If hypersecretion of GH occurs before puberty—that is, before closure of the growth plates—the individual grows very tall (8–9 feet), a rare condition known as gigantism.
Pathophysiology
The excessive production of GH associated with acromegaly does not induce bone lengthening but rather enhances the growth of periosteal bone. The unrestrained bone growth in patients with acromegaly produces bones that are massive in size and thickness. Bones of the hands and feet (acral) become particularly large. Overgrowth of vertebrae may cause kyphoscoliosis and arthritis.
Soft tissue changes are also prominent with GH hypersecretion. The patient develops coarsened facial features (acromegalic facies), including a large, bulbous nose; a supraorbital ridge overgrowth; dental malocclusion; and a prominent prognathic mandible. The changes in appearance are insidious, and many patients do not seek treatment until the diagnosis is obvious and the disease course is advanced. Overgrowth of the internal organs is less apparent clinically but no less serious. The liver, heart, spleen, and kidneys become enlarged. Lung volumes increase, which may lead to ventilation–perfusion mismatch. Exercise tolerance may be limited because of increased body mass and skeletal muscle weakness.
Cardiomyopathy, hypertension (28% of cases), and accelerated atherosclerosis in patients with acromegaly can lead to symptomatic cardiac disease (congestive heart failure, arrhythmias). Echocardiography often shows left ventricular hypertrophy. Resting electrocardiograms (ECGs) are abnormal in 50% of patients with acromegaly. ST-segment and T-wave depression, conduction defects, and evidence of prior myocardial infarction may be present. The insulin antagonistic effect of GH produces glucose intolerance in up to 50% of patients with acromegaly and frank diabetes mellitus (DM) in 10% to 25% of patients. The insulin antagonistic effect of GH produces glucose intolerance in up to 50% of patients with acromegaly and frank DM in 10% to 25% of patients.
Clinical manifestations
Clinical manifestations resulting from the local effects of the expanding tumor may include headaches (55%), papilledema, and visual field defects (19%), which are caused by compression of the optic nerves and chiasm. Significant increases in intracranial pressure are uncommon. Compression or destruction of normal pituitary tissue by the tumor may lead to panhypopituitarism. Common features of acromegaly are summarized in the box on pg. 58.
Treatment
Treatment for acromegaly is aimed at restoring normal GH levels. The preferred initial therapy for active acromegaly is microsurgical removal of the pituitary tumor with preservation of the gland. The surgical approach to the pituitary tumor most often is via a transsphenoidal route, with the patient in a semi-sitting position. Precautions associated with monitoring of venous air embolism should be part of the anesthesia management plan. Surgical ablation is usually successful in rapidly reducing tumor size, inhibiting GH secretion, and alleviating some symptoms. Administration of octreotide (a long-acting somatostatin analog), pegvisomant (a GH receptor antagonist), and gland irradiation are treatment options for patients who are not surgical candidates.
Anesthetic considerations
Preanesthetic assessment of patients with acromegaly should include a careful examination of the airway. Facial deformities and the large nose may hamper adequate fitting of an anesthesia mask. Endotracheal intubation may be a challenge because these patients have large and thick tongues (macroglossia), enlargement of the thyroid, obstructive teeth, hypertrophy of the epiglottis, and general soft tissue overgrowth in the upper airway. Subglottic narrowing and vocal cord enlargement may dictate the use of a smaller diameter endotracheal tube. Nasotracheal intubation should be approached cautiously because of possible turbinate enlargement.
Preoperative dyspnea, stridor, or hoarseness should alert the anesthetist to airway involvement. Indirect laryngoscopy and neck radiography may be performed for thorough assessment. If difficulties in maintaining an adequate airway are anticipated, a fiberoptic-guided intubation in an awake patient is of proven value. The endotracheal tube should remain in place until the patient is fully awake and has total return of reflexes. The predisposition to airway obstruction in these patients makes assiduous postoperative monitoring of the patient’s respiratory status a wise precaution.
The frequent occurrence of cardiac arrhythmias, coronary artery disease, and hypertension in patients with acromegaly warrants a thorough preanesthetic cardiac evaluation. The increased risk of DM in these patients mandates careful perioperative monitoring of blood glucose and electrolyte levels.
If preoperative assessment reveals impairment of the adrenal or thyroid axis, stress-level glucocorticoid therapy and thyroid replacement should be implemented in the perioperative period.
Entrapment neuropathies, such as carpal tunnel syndrome, are common in patients with acromegaly. An Allen test should be performed before placement of a radial artery catheter because hypertrophy of the carpal ligament may cause inadequate ulnar artery flow.
B Adrenocortical insufficiency
Definition
Primary adrenal insufficiency (Addison’s disease) reflects the absence of cortisol and aldosterone owing to the destruction of the adrenal cortex. In 1855, an English physician, Dr. Thomas Addison, first described a relatively rare clinical syndrome characterized by wasting and skin hyperpigmentation and identified its cause as destruction of the adrenal glands. Primary adrenocortical insufficiency Addison’s disease) becomes apparent when 90% of the gland is destroyed. Tuberculosis is a common cause of primary adrenocortical insufficiency worldwide, but in the United States, most cases are the result of autoimmune dysfunction. Primary adrenocortical insufficiency may also be associated with other autoimmune disorders, such as type 1 diabetes and Hashimoto thyroiditis. Less commonly, primary adrenal insufficiency is congenital or caused by sarcoidosis, human immunodeficiency virus infection, adrenal hemorrhage, malignancy, or trauma.
Clinical manifestations
Clinical symptoms of Addison’s disease reflect destruction of all cortical zones, resulting in adrenal androgen, glucocorticoid, and mineralocorticoid hormone deficiency (see box below).
Weakness and fatigue are cardinal features. Reduced appetite with weight loss, vomiting, abdominal pain, and diarrhea are frequently reported. Hypoglycemia is often present. Volume depletion is a common feature of the disease and may be manifested by orthostatic hypotension. Hyponatremia and hyperkalemia are commonly revealed by laboratory screening.
The adrenal–pituitary axis is intact in primary adrenal insufficiency, and adrenocorticotropic hormone (ACTH) concentrations are elevated as a result of the reduced production of cortisol. Increased melanin formation in the skin and hyperpigmentation of the knuckles of the fingers, toes, knees, elbows, lips, and buccal mucosa may be evident.
Treatment
Treatment for adrenal insufficiency aims to replace both glucocorticoid and mineralocorticoid deficiency. Normal adults secrete 15 to 30 mg of cortisol (hydrocortisone) and 50 to 250 mcg of aldosterone per day. Corticosteroids used for therapy have varying degrees of mineralocorticoid and glucocorticoid effects.
Comparative Pharmacology of Endogenous and Synthetic Corticosteroids
Data from Stoelting RK, Hillier SC. Pharmacology and Physiology in Anesthetic Practice. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2006:462.
A typical oral replacement dose for Addison’s disease may consist of prednisone, 5 mg in the morning and 2.5 mg in the evening, or hydrocortisone, 20 mg in the morning and 10 mg in the evening. If indicated, mineralocorticoid replacement may consist of 0.05 to 0.2 mg/day of fludrocortisone. Standard glucocorticoid doses should be supplemented during periods of surgical stress.
Anesthetic considerations
Anesthetic management for patients with primary adrenal insufficiency should provide for exogenous corticosteroid supplementation. Etomidate should be avoided because it transiently inhibits synthesis of cortisol in physiologically normal patients. Doses of anesthetic drugs should be minimized because these patients may be sensitive to drug-induced myocardial depression. Invasive monitoring (arterial line and pulmonary artery catheter) is indicated. Because of skeletal muscle weakness, the initial dose of muscle relaxant should be reduced, and further doses should be governed by peripheral nerve stimulator response. Plasma concentrations of glucose and electrolytes should be measured frequently during surgery.
Secondary adrenocortical insufficiency
Definition
Secondary adrenocortical insufficiency is caused by ACTH deficiency from two primary etiologies: (1) hypothalamic–pituitary–adrenal (HPA) axis suppression after exogenous glucocorticoid therapy and (2) ACTH deficiency secondary to hypothalamic or pituitary gland dysfunction (tumor, infection, surgical or radiologic ablation). Long-term treatment with glucocorticoids, for any cause, results in negative feedback to the hypothalamus and pituitary gland, decreased ACTH output, and eventual adrenal cortex atrophy. The longer the duration of glucocorticoid administration, the greater the likelihood of suppression, but the precise dose or duration of therapy that produces adrenal suppression is unknown. Sustained and clinically important adrenal suppression usually does not occur with treatment periods less than 14 days. Treatment periods long enough to provoke signs of Cushing syndrome are usually associated with adrenal suppression of clinically significant.
Clinical manifestations
Clinical manifestations of secondary adrenal insufficiency resemble the primary disease except secondary insufficiency is less likely to be associated with severe hypovolemia, hyperkalemia, or hyponatremia because mineralocorticoid secretion is usually preserved. Hyperpigmentation is absent because ACTH levels are low.
Acute adrenal crisis
Acute adrenal crisis is a sudden exacerbation or onset of severe adrenal insufficiency. It is a rare event associated with high morbidity and mortality if allowed to progress unrecognized. A patient with chronic adrenal insufficiency may deteriorate rapidly into an acute insufficiency state as a result of some superimposed stress, such as infection, acute illness, or sepsis. The stress of surgery or trauma in the patient with inadequate adrenal reserves can precipitate acute adrenal crisis in the perioperative period.
Clinical manifestations
Symptoms of adrenal crisis reflect acute deficiency of corticosteroids and include severe weakness, nausea, hypotension, fever, and decreasing mental status. In the surgical setting, hemodynamic instability or cardiovascular collapse may herald adrenal crisis. The index of suspicion for adrenal crisis should be particularly high if the patient has hyperpigmentation, hyponatremia, or hyperkalemia; a history of autoimmune disease (hypothyroidism, diabetes); or recent prior use of exogenous steroids. The anesthetist should be mindful of the adrenal suppressive effects of etomidate. Even a single dose of etomidate for induction of anesthesia can cause acute adrenocortical insufficiency for up to 24 hours and should be avoided in patients susceptible to adrenal insufficiency.
Treatment
Acute adrenal crisis is a medical emergency requiring aggressive treatment of the steroid insufficiency and associated hypoglycemia, electrolyte imbalance, and volume depletion. Early recognition and intervention are crucial steps in altering the course of acute adrenal insufficiency. Initial therapy begins with rapid intravenous (IV) administration of a glucose-containing isotonic crystalloid solution. If the patient is hemodynamically unstable, advanced hemodynamic monitoring and inotropic support may be necessary. Steroid replacement therapy begins with hydrocortisone, 100 mg IV, followed by hydrocortisone, 100 to 200 mg IV over 24 hours. Mineralocorticoid administration is unnecessary with large doses of steroids (hydrocortisone 100–200 mg) because mineralocorticoid effects are present at these doses.
C Cushing’s disease
Definition
Cushing’s syndrome results in diverse complex symptoms, signs, and biochemical abnormalities caused by excess glucocorticoid hormone.
Pathophysiology
The most common cause of Cushing’s syndrome today is the administration of supraphysiologic doses of glucocorticoids for conditions such as arthritis, asthma, various autoimmune disorders, allergies, and a myriad of other diseases.
Endogenous Cushing’s syndrome is most often the result of one of three distinct pathogenic disorders: pituitary tumor (Cushing’s disease), adrenal tumor, or ectopic hormone production.
Cushing’s disease specifically denotes an anterior pituitary tumor cause of the syndrome. The pituitary tumor produces excessive amounts of ACTH and is associated with bilateral adrenal hyperplasia. Patients often develop skin pigmentation as a result of excess ACTH. Cushing’s disease is the most common cause of endogenous Cushing’s syndrome.
Adrenal Cushing’s syndrome is caused by autonomous corticosteroid production (ACTH independent) by an adrenal tumor, usually unilateral. This form of hyperadrenalism accounts for 20% to 25% of patients with Cushing’s syndrome and is usually associated with suppressed plasma ACTH levels. Adrenal tumors that are malignant are usually large by the time Cushing’s syndrome becomes manifest.
Ectopic Cushing’s syndrome results from autonomous ACTH or corticotropin-releasing hormone (CRH) production by extrapituitary malignancies, producing markedly elevated plasma levels of ACTH. Bronchogenic carcinoma accounts for most of these cases. Carcinoid tumors and malignant tumors of the kidney, ovary, and pancreas also can cause ectopic production of ACTH.
Clinical manifestations
Clinical features reflect cortisol excess, either from overproduction of the adrenal cortex or exogenously administered glucocorticoid. The clinical picture includes central obesity with thin extremities, hypertension, glucose intolerance, plethoric facies, purple striae, muscle weakness, bruising, and osteoporosis. Mineralocorticoid effects include fluid retention and hypokalemic alkalosis. Women manifest a degree of masculinization (hirsutism, hair thinning, acne, amenorrhea), and men manifest a degree of feminization (gynecomastia, impotence) because of the androgenic effects of glucocorticoid excess. The catabolic effects of cortisol result in skin that is thin and atrophic and unable to withstand the stresses of normal activity. Patients with Cushing’s syndrome typically gain weight and develop a characteristic redistribution of fat.
Diagnosis
A widely used test for diagnosis of hyperadrenocorticism is measurement of the plasma cortisol concentration in the morning after a dose of dexamethasone. Dexamethasone suppresses plasma cortisol secretion in normal patients but not in those with endogenous hyperadrenocorticism. Diagnosis of Cushing’s syndrome is also based on elevated levels of plasma and urinary cortisol, plasma ACTH, and urinary 17-hydroxycorticosteroids.
Treatment
Treatment for Cushing’s syndrome depends on the cause. Transsphenoidal hypophysectomy is a primary treatment option for Cushing’s disease. Complications occur in fewer than 5% of patients and include DI (usually transient), cerebrospinal fluid rhinorrhea, and hemorrhage.
Adrenal Cushing’s syndrome may be treated by surgical removal of the adrenal adenoma. Because the contralateral adrenal gland is preoperatively suppressed, glucocorticoid replacement may be necessary for several months after surgery until adrenal function returns. Bilateral adrenalectomy in the patient with Cushing’s syndrome is associated with a high incidence of complications and permanent corticosteroid deficiency.
The treatment of choice for an ectopic ACTH-secreting tumor is surgical removal, but this may not always be feasible because of the nature of the underlying process (e.g., metastatic carcinoma). Metyrapone, an 11-β-hydroxylase inhibitor, and mitotane, an agent that blocks steroidogenesis at several levels, may be used to help normalize cortisol levels.
Anesthetic considerations
Important perioperative considerations for the patient with Cushing’s syndrome include normalizing blood pressure, blood glucose levels, intravascular fluid volume, and electrolyte concentrations. The aldosterone antagonist spironolactone effectively decreases extracellular fluid volume and corrects hypokalemia under these conditions.
Osteopenia is an important consideration in positioning the patient for the operative procedure. Special attention must be given to the patient’s skin, which can easily be abraded by tape or minor trauma. Glucocorticoids are lympholytic and immunosuppressive, placing the patient at increased risk for infection and mandating particular enforcement of aseptic techniques as indicated.
The choice of drugs for induction and maintenance of anesthesia is not specifically influenced by the presence of hyperadrenocorticism. Muscle relaxants may have an exaggerated effect in patients with preexisting myopathy, and a conservative approach to dosing is warranted when significant skeletal muscle weakness is present.
If adrenal resection is planned, glucocorticoids may be indicated after resection and administered at doses equivalent to adrenal output for maximum stress. Hydrocortisone, 100 mg IV, followed by 100 to 200 mg IV over 24 hours can be administered and then reduced over 3 to 6 days postoperatively until a maintenance dose is reached.
D Diabetes insipidus
Definition
Diabetes insipidus (DI) reflects the absence of antidiuretic hormone (ADH) owing to the destruction of the posterior pituitary gland (neurogenic DI) or failure of the renal tubules to respond to ADH (nephrogenic DI).
Pathophysiology
Common causes of neurogenic DI include severe head trauma, neurosurgical procedures (trauma to the median eminence, pituitary surgery), infiltrating pituitary lesions, and brain tumors. DI that develops after pituitary surgery is usually transient and often resolves in 5 to 7 days.
Nephrogenic DI may occur in association with an X-linked genetic mutation, hypercalcemia, hypokalemia, and medication-induced nephrotoxicity. Ethanol, demeclocycline, phenytoin, chlorpromazine, and lithium all inhibit the action of ADH or its release.
Clinical manifestations
The hallmark of DI is polyuria. The inability to produce concentrated urine results in dehydration and hypernatremia. The syndrome is characterized by a urine osmolarity less than 300 mOsm/L, urine specific gravity less than 1.010, and urine volumes greater than 30 mL/kg each day. The tremendous urinary water loss produces serum osmolarities greater than 290 mOsm/L and serum sodium concentrations greater than 145 mEq/L. Neurologic symptoms of hypernatremia and neuronal dehydration may be present and include hyperreflexia, weakness, lethargy, seizures, and coma.
The thirst mechanism assumes a primary role in maintaining water balance in awake patients with DI. Ingestion of large volumes of water prevents hyperosmolarity and life-threatening dehydration.
Treatment
Treatment protocols for DI depend on the degree of ADH deficiency. Most patients have incomplete DI and retain some capacity to concentrate their urine and conserve water. Mild cases (incomplete DI) may be treated with medications that either augment the release of ADH or increase the receptor response to ADH. These drugs may include chlorpropamide (sulfonylurea hypoglycemic agent), carbamazepine (anticonvulsant), and clofibrate (hypolipidemic agent).
Significant deficiency (plasma osmolarity levels >290 mOsm/L) may be treated with various ADH preparations. Aqueous vasopressin is commonly used for short-term therapy, and desmopressin is useful for long-term control. Caution is advised when administering these drugs to patients with coronary artery disease or hypertension because of the arterial constrictive action of ADH. Desmopressin (5 to 10 mcg/day intranasally, or 0.5 to 1 mcg twice daily subcutaneously) is often a preferred agent because it has less pressor activity, a prolonged duration of action (6–24 hours), and enhanced antidiuretic properties.
Anesthetic considerations
Preoperative assessment of the patient with DI includes careful appraisal of plasma electrolytes (especially serum sodium), renal function, and plasma osmolarity. Dehydration makes these patients especially sensitive to the hypotensive effects of anesthesia agents. Intravascular volume should slowly be restored preoperatively over a period of at least 24 to 48 hours.
Perioperative administration of vasopressin is usually not necessary in the patient with partial DI because the stress of surgery causes enhanced ADH release. A surgical patient with a total lack of ADH (complete DI) may be managed with desmopressin (1 mcg subcutaneously) or aqueous vasopressin (an IV bolus of 0.1 units followed by a continuous IV infusion of vasopressin at 0.1–0.2 units/hr). Plasma osmolarity, urine output, and serum sodium concentration should be measured hourly during surgery and in the immediate postoperative period. The surgical patient with DI receiving ADH replacement therapy should be monitored for ECG changes indicative of myocardial ischemia.
Isotonic fluids can generally be administered safely during the intraoperative period. If, however, the plasma osmolarity rises above 290 mOsm/L, hypotonic fluids should be considered and the vasopressin infusion increased above 0.2 units/h.
E Diabetes mellitus
Definition
Diabetes mellitus is a complex metabolic derangement caused by relative or absolute insulin deficiency. Diabetes has been called “starvation in a sea of food.” Glucose is present in abundance, but because of lack of insulin or insulin resistance, it is unable to reach cells for energy provision. Guidelines for diagnosing diabetes include a fasting plasma glucose (FPG) level of 126 mg/dL or greater or a random glucose level greater than 200 mg/dL. The FPG diagnostic level was reduced from a previous value of 140 mg/dL based on findings that patients with an FPG of 126 mg/dL are at risk for diabetes-related complications.
Pathophysiology
The incidence of diabetes has increased dramatically over the past 40 years. Today, it affects nearly 21 million people in the United States (almost 7% of our population). The rise can be attributed to a combination of three factors: (1) an overweight population, (2) more sedentary lifestyles, and (3) a rise in the number of elderly persons. As more of our population advances in age into the decades in which most cases of diabetes occur, the impact of the disease will become even more alarming.
About 5% to 10% of people with DM have type 1 DM. This type of DM was formerly known as insulin-dependent diabetes or juvenile-onset diabetes.
Individuals with type 1 DM have an absolute deficiency of insulin and are therefore entirely dependent on exogenous insulin therapy. In the absence of sufficient exogenous insulin, the disease course may be complicated by periods of ketosis and acidosis.
In most cases, type 1 DM is caused by an unusually vigorous autoimmune destruction of the β cells of the pancreatic islets. Environmental factors, such as infection or exposure to specific antigenic proteins, are cited as possible initiators of the immune assault. Patients with type 1 DM are also more likely to have other autoimmune diseases, such as thyroid disease or Addison’s disease. A genetic predisposition for development of the disease also is involved. Type 1 DM usually develops before the age of 30 years, but it can develop at any age. The classic symptoms of type 1 DM appear only when at least 80% of the β cells are destroyed. The remaining β cells usually are eliminated inexorably over 2 or 3 years. In patients with type 1 DM, daily exogenous insulin therapy is essential for life. Some type 1 DM patients may be candidates for pancreatic transplant. The transplantation of isolated pancreatic islets has been plagued by graft survival and islet isolation setbacks, but it holds out promise for a future cure.
Type 2 diabetes mellitus
About 90% to 95% of patients with diabetes have type 2 DM. Type 2 DM is characterized by impaired insulin secretion, peripheral insulin resistance (a decreased number of insulin receptors or an insulin receptor or postreceptor defect), and excessive hepatic glucose production. This form of diabetes was formerly known as non–insulin-dependent diabetes or maturity-onset diabetes.
Type 2 DM occurs in patients who have some degree of endogenous insulin production but who produce quantities insufficient for sustaining normal carbohydrate homeostasis. Insulin levels may be low, normal, or even elevated, but a relative insulin deficiency exists. The ultimate expression is a hyperglycemic state.
Typically, type 2 DM occurs in patients who are older than 30 years of age, obese (80%), and with a family history of the disease. Type 2 DM has an insidious onset; indeed, it is estimated that half of people who have type 2 DM are not even aware of it. The disease course is rarely associated with ketosis or acidosis, but it may be complicated by a nonketotic, hyperosmolar, hyperglycemic state.
Treatment for this class of diabetes consists primarily of oral hypoglycemic agents, exercise, and diet therapy. Weight reduction in the obese diabetic patient improves tissue responsiveness to endogenous insulin and often restores normoglycemia.
The distinction between insulin-treated DM and insulin-dependent DM is important. Some people with type 2 DM may benefit from exogenously administered insulin, especially during times of illness or stress. Those with type 1 DM, on the other hand, are insulin dependent and require exogenous insulin daily to live.
Diabetes associated with other conditions
Diabetes may result from other conditions such as pancreatectomy, cystic fibrosis, or severe pancreatitis. Certain endocrine conditions, including Cushing’s syndrome, glucagonoma, pheochromocytoma, and acromegaly, may also be associated with a diabetic condition. Steroid-induced diabetes may occur in the patient taking supraphysiologic doses of glucocorticoids. Gestational diabetes occurs in approximately 4% of the pregnancies in the United States. Women who have had gestational DM have a 20% to 50% chance of developing type 2 DM 5 to 10 years postpartum.
Long-term diabetic complications
Diabetics are subject to long-term complications that confer substantial morbidity and premature mortality. These complications include extensive arterial disease, cataracts, sensory and motor neuropathy, infection, and autonomic nervous system dysfunction.
Arterial thrombotic lesions in the diabetic population are widely distributed in the extremities, kidneys, eyes, skeletal muscle, myocardium, and nervous system. As a result of these diffuse lesions, diabetes carries a serious risk for the development of microvascular (nephropathy, retinopathy, neuropathy) and macrovascular (atherosclerosis, stroke, coronary artery disease) complications.
Treatment
Treatment includes a diabetic diet, oral hypoglycemic drugs, and exogenous insulin. Non–insulin-dependent diabetes mellitus (NIDDM) is prevented primarily by avoidance or treatment of obesity. Transplantation of pancreatic tissue may be considered in selected patients.
Anesthetic considerations
Diabetes mellitus is the most common endocrine disorder encountered in surgical patients. Long-standing DM predisposes patients to many diseases that require surgical intervention. Cataract extraction, kidney transplantation, ulcer débridement, and vascular repair are some of the operations frequently performed on patients with DM.
Patients with DM have higher morbidity and mortality rates in the perioperative period compared with nondiabetic patients of similar age. Increased complications are not caused by the disease itself but primarily because of organ damage associated with long-term disease. Ischemic heart disease is the most common cause of perioperative mortality in the patients with DM.
For patients with DM, operations should be scheduled early in the day if possible to minimize disruptions in treatment and nutrition regimens. Day stay for minor surgery may be used for patients with well-controlled DM who are knowledgeable about their disease and treatment and who have proper home support.
Preoperative considerations
Patients with DM may come to the operating room with a spectrum of metabolic aberrations and end-organ complications that warrant careful preanesthetic assessment.
Cardiovascular complications account for most of the surgical deaths in patients with DM. The presence of hypertension, coronary artery disease, or autonomic nervous system dysfunctions can result in a labile cardiovascular course during anesthesia. It is essential that the cardiovascular and volume status of the patient be thoroughly evaluated before surgery.
Preoperative ECG is necessary for all adult patients with DM because of the high incidence of cardiac disease.
Autonomic nervous system dysfunction may result in delayed gastric emptying. It is estimated that gastroparesis occurs in 20% to 30% of all patients with DM. These patients are prone to aspiration, nausea and vomiting, and abdominal distention. Many authorities recommend routine preoperative aspiration prophylaxis with histamine (H2) receptor blockers, metoclopramide, or preinduction antacids for patients with DM. Intubation during general anesthesia is a logical choice for patients with gastroparesis.
Patients with significant autonomic neuropathy may have an impaired respiratory response to hypoxia. These patients are especially sensitive to the respiratory-depressant effects of sedatives and anesthetics and require particular vigilance in the perioperative period.
Peripheral neuropathies (paresthesias, numbness in the hands and feet) should be adequately documented in the preanesthetic evaluation. Their presence may affect the decision to use regional anesthesia.
An estimated 30% to 40% of patients with insulin-dependent diabetes mellitus (IDDM) demonstrate restricted joint mobility. Limited motion of the atlanto-occipital joint can make endotracheal intubation difficult. Demonstration of the “prayer sign,” an inability to approximate the palms of the hands and fingers, may help identify patients with tissue protein glycosylation and potentially difficult airways.
Evidence of kidney disease should be sought, and basic tests of renal function (urinalysis, serum creatinine, blood urea nitrogen) should be performed preoperatively. The presence of renal impairment may influence the choice and dosage of anesthetic agents. The use of potentially nephrotoxic drugs should be avoided.
The anesthetist should examine the patient’s history of glycemic control to ensure preoperative optimization of the patient’s metabolic state. A recommended target blood glucose range for the perioperative period is 80 to 180 mg/dL.
Sustained hyperglycemia, which causes osmotic diuresis, should alert the anesthetist to possible fluid deficits and electrolyte depletion. Preoperative levels of electrolytes should be determined for all patients with DM, and adequate hydration and a good urine output should be maintained. Lactate-containing solutions are generally avoided because lactate conversion to glucose may contribute to hyperglycemia. An important part of the preoperative evaluation is a review of oral hypoglycemic and insulin regimens.
Oral hypoglycemic agents
Oral glucose-lowering agents
Oral glucose-lowering agents and insulin are used as adjuncts to diet therapy and exercise for treating patients with type 2 DM. Currently available oral hypoglycemic agents fall into the following classifications: (1) sulfonylureas, (2) α-glucosidase inhibitors, (3) thiazolidinediones, (4) biguanides, (5) nonsulfonylurea secretagogues, and (6) others. Often, patients take a combination of therapeutic agents. The commonly used medications used to treat type 2 diabetes are listed in the following table.
Oral Agents Available for Treatment of Diabetes Mellitus
AMPK, Adenosine monophosphate–activated protein kinase; ATP, adenosine triphosphate; CKD, chronic kidney disease; CVD, cardiovascular disease; D2, dopamine-2; DPP, dipeptidyl peptidase; GLP, glucagon-like peptide; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PPAR, peroxisome proliferator–activated receptor; SB, small bowel.
From Inzucchi SE, Sherwin RS. Type 2 diabetes mellitus. In Goldman L, Schafer AI, et al, eds. Goldman’s Cecil Medicine. 24th ed. Philadelphia: Saunders; 2012:1496.
Insulin preparations
Insulin preparations are generated today by DNA recombinant technology, mimicking the amino acid sequence of human insulin. All insulin formulations in the United States, except for inhaled insulin, are prepared as Unit-100 (100 units/mL).
Insulin preparations differ in onset and duration after subcutaneous administration. In addition to subcutaneous injections, insulin delivery devices (implantable pumps, mechanical syringes) are used to facilitate exogenous administration. The greatest risk with all forms of insulin is hypoglycemia. The major classes of exogenous insulin (regular, rapid acting, inhaled, intermediate acting, and long acting) are listed in the following table.
Pharmacokinetics of Insulin Preparations
IM, Intramuscular; IV, intravenous; NPH, neutral protamine Hagedorn. Subcut, subcutaneous.
It is imperative to know the surgical patient’s normal insulin dosage regimen and treatment compliance. Some patients are on a fixed regimen that consists of a mixture of rapid- and intermediate-acting insulins taken before breakfast and again at the evening meal. Other patients are on multiple injection regimens designed to provide more physiologic glycemic control. To determine the effectiveness and compliance of antidiabetic therapy, hemoglobin A1c (HbA1c glycated hemoglobin) values provide information about the plasma glucose concentration over time. An HbA1c value of 6.5% or greater is indicative of DM.
Intraoperative management
In patients with DM, operations should be scheduled early in the day, if possible, to minimize disruptions in treatment and nutrition regimens. Surgery produces a catabolic stress response and elevates stress-induced counterregulatory hormones. The hyperglycemic, ketogenic, and lipolytic effects of the counterregulatory hormones in patients with DM compound the state of insulin deficiency. For this reason, perioperative hyperglycemia and other metabolic aberrations are common in the surgical patients with DM.
No specific anesthetic technique is superior overall for patients with DM. Both general anesthesia and regional anesthesia have been used safely. General anesthesia, however, has been shown to induce hormonal changes that accentuate glycogenolysis and gluconeogenesis, compounding the patient’s hyperglycemic state. Regional anesthesia may produce less deleterious changes in glucose homeostasis.
The Certified Registered Nurse Anesthetist (CRNA) must be especially careful in positioning and padding patients with DM on the operating table. Decreased tissue perfusion and peripheral sympathetic neuropathy may contribute to the development of skin breakdown and ulceration.
Patients with DM represent a heterogeneous group requiring individualized perioperative care. The specific approach to metabolic management depends on the type of diabetes (type 1 or 2), the history of glycemic control, and the type of surgery being performed. Frequent blood glucose determinations are an integral part of any diabetic management technique. A glucose meter or other accurate and rapid means of monitoring blood glucose levels should be available. At least hourly intraoperative blood glucose measurement is the prudent course for brittle patients with DM, during long surgical procedures, and for major surgery.
