Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

CHAPTER 1 – Lens Pathology and Systemic Disease

A cataract is defined as a clouding of the normally clear crystalline lens of the eye. The different types of cataracts include nuclear-sclerotic, cortical, posterior subcapsular, and mixed. Each type has its own location in the lens and risk factors for development, with nuclear-sclerotic cataracts being the most common type of age-related cataract. The leading cause of blindness worldwide, cataracts affect more than 6 million individuals annually.[8] Indeed, cataract surgery is the most frequently performed surgical procedure in the United States with more than 1.5 million operations annually.[9] Over half the population older than age 65 years develop age-related cataracts with related visual disability.[10] Yet, despite extensive research into the pathogenesis and pharmacologic prevention of cataracts, there are no proven means to prevent age-related cataracts.

Although age-related cataracts are the most frequently encountered variety, cataracts may be associated with dermatologic diseases such as incontinentia pigmenti, exogenous substances, genetic diseases, hematologic diseases, infections, and metabolic perturbations ( Table 1-3 ).

TABLE 1-3   -- Conditions Associated with Cataracts






Chromosomal Anomalies



Trisomy 13



Trisomy 18



Trisomy 21



Turner's syndrome



Dermatologic Diseases



Incontinentia pigmenti



Exogenous Substances


















Metabolic Conditions



Diabetes mellitus



Fabry's disease












Lowe's syndrome






Refsum's disease



Wilson's disease






Infectious Diseases
























Varicella zoster



Exogenous substances that can trigger cataracts include corticosteroids, [11] [12] [13] phenothiazines, naphthalene, ergot, parachlorobenzene, and alcohol.[14] Metabolic conditions associated with cataracts include diabetes mellitus, Fabry's disease, galactosemia, hepatolenticular degeneration (Wilson's disease), hypoparathyroidism, hypothyroidism, phenylketonuria, Refsum's disease, and xanthomatosis. Another metabolic disorder important in the differential diagnosis of congenital cataracts is Lowe's (oculocerebrorenal) syndrome. In this X-linked disorder, cataract is frequently the presenting sign, with other abnormalities appearing later. These anomalies include mental and growth retardation, hypotonia, renal acidosis, aminoaciduria, proteinuria, and renal rickets, requiring calcium and vitamin D therapy.[15] [16] Other concomitants include osteoporosis and a distinctive facies (long with frontal bossing). Although lens changes may be seen frequently in heterozygous female children also, affected male children commonly have obvious, dense, bilateral cataracts at birth. They may also be afflicted with associated glaucoma. Interestingly, carrier females in their second decade of life have significantly higher numbers of lens opacities than age-related controls; however, absence of opacities is no guarantee that an individual is not a carrier. Anesthetic management includes careful attention to acid-base balance and to serum levels of calcium and electrolytes. The administration of drugs excreted by the kidney should be observed carefully, and nephrotoxins should be avoided. The patient with osteoporosis should be positioned on the operating table with extreme gentleness.

Infectious causes of cataracts include herpes, influenza, mumps, polio, rubella, toxoplasmosis, vaccinia, and varicella zoster.[17] Chromosomal anomalies associated with cataracts include trisomy 13 (Patau's syndrome), trisomy 18 (Edward's syndrome), and trisomy 21 (Down syndrome). In Patau's and Edward's syndromes, congenital cataracts frequently occur in conjunction with other ocular anomalies, such as coloboma and microphthalmia. Cataracts have also been reported with Turner's syndrome (XO).

An additional type of lens abnormality that can be associated with major systemic disease is ectopia lentis ( Table 1-4 ). Displacement of the lens can be classified topographically as subluxation or luxation. Luxation denotes a lens that is dislocated either posteriorly into the vitreous cavity or, less commonly, anteriorly into the anterior chamber. In subluxation, some zonular attachments remain and the lens remains in its plane posterior to the iris, albeit tilted in one direction or another.

TABLE 1-4   -- Conditions Associated with Ectopia Lentis



Ocular Conditions






Congenital glaucoma



High myopia



Intraocular tumor









Systemic Diseases









Marfan's syndrome



Sulfite oxidase deficiency



Weill-Marchesani syndrome



The most common cause of lens displacement is trauma, although ectopia lentis may also result from assorted other ocular diseases, such as intraocular tumor, congenital glaucoma, uveitis, aniridia, syphilis, or high myopia. Inherited defects and serious systemic diseases, such as Marfan's syndrome, homocystinuria, Weill-Marchesani syndrome, hyperlysinemia, and sulfite oxidase deficiency, are also associated with ectopia lentis. Indeed, lens displacement occurs in approximately 80% of patients with Marfan's syndrome.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Glaucoma and Systemic Disease

Glaucoma is a condition characterized by elevated intraocular pressure (IOP), resulting in impairment of capillary blood flow to the optic nerve and eventual loss of optic nerve tissue and function. Two different anatomic types of glaucoma exist: open-angle or chronic simple glaucoma and closed-angle or acute glaucoma. (Other variations of these processes occur but are not especially germane to anesthetic management. Glaucoma is, in fact, not one disease, but many.)

With open-angle glaucoma, the elevated IOP exists in conjunction with an anatomically patent anterior chamber angle. It is thought that sclerosis of trabecular tissue produces impaired aqueous filtration and drainage. Treatment consists of medication to produce miosis and trabecular stretching. Commonly used eyedrops include epinephrine, echothiophate iodide, timolol, dipivefrin, and betaxolol. Carbonic anhydrase inhibitors such as acetazolamide can also be administered by various routes to reduce IOP by interfering with the production of aqueous humor. All these drugs are systemically absorbed and can, therefore, have anticipated side effects.

It is important to appreciate that maintenance of IOP is determined primarily by the rate of aqueous formation and the rate of aqueous outflow. The most important influence on formation of aqueous humor is the difference in osmotic pressure between aqueous and plasma. This concept is illustrated by the equation:

where K = coefficient of outflow, OPaq = osmotic pressure of aqueous humor, OPpl = osmotic pressure of plasma, and CP = capillary pressure. The fact that a small change in solute concentration of plasma can dramatically affect the formation of aqueous humor and hence IOP is the rationale for administering hypertonic solutions, such as mannitol, to reduce IOP.

Fluctuations in aqueous outflow can also markedly change IOP. The primary factor controlling aqueous humor outflow is the diameter of Fontana's spaces, as illustrated by the equation:

where A = volume of aqueous outflow per unit of time, r = radius of Fontana's spaces, Piop = IOP, Pv = venous pressure, η = viscosity, and L = length of Fontana's spaces. When the pupil dilates, Fontana's spaces narrow, resistance to outflow is increased, and IOP rises. Because mydriasis is undesirable in both closed- and open-angle glaucoma, miotics such as pilocarpine are applied conjunctivally in patients with glaucoma.

The aforementioned equation describing the volume of aqueous outflow per unit of time clearly underscores that outflow is exquisitely sensitive to fluctuations in venous pressure. Because an elevation in venous pressure results in an increased volume of ocular blood as well as decreased aqueous outflow, it is obvious that considerable increase in IOP occurs with any maneuver that increases venous pressure. Hence, in addition to preoperative instillation of miotics, other anesthetic objectives for the patient with glaucoma include perioperative avoidance of venous congestion and of overhydration. Furthermore, hypotensive episodes are to be avoided because these patients are purportedly vulnerable to retinal vascular thrombosis.

Although glaucoma usually occurs as an isolated disease, it may also be associated with such conditions as Sturge-Weber syndrome, aniridia, mesodermal dysgenesis syndrome, retinopathy of prematurity, Refsum's syndrome, mucopolysaccharidosis, Hurler's syndrome, Stickler's syndrome, Marfan's syndrome, and von Recklinghausen's disease (neurofibromatosis) ( Table 1-5 ). Additionally, ocular trauma, corticosteroid therapy, sarcoidosis, some forms of arthritis associated with uveitis, and pseudoexfoliation syndrome can also be associated with secondary glaucoma.

TABLE 1-5   -- Partial Listing of Conditions Associated with Glaucoma

Ocular Conditions

Systemic Diseases


Chromosomal anomalies

Anterior cleavage syndrome

Congenital infection syndromes (TORCH)


Hurler's syndrome

Ectopia lentis

Marfan's syndrome


Refsum's disease

Mesodermal dysgenesis


Persistent hyperplastic primary vitreous

Stickler syndrome

Retinopathy of prematurity

Sturge-Weber syndrome


von Recklinghausen's disease







Primary closed-angle glaucoma is characterized by a shallow anterior chamber and a narrow iridocorneal angle that impedes the egress of aqueous humor from the eye because the trabecular meshwork is covered by the iris ( Table 1-6 ). Relative pupillary block is common in many angle-closure episodes in which iris-lens apposition or synechiae impede the flow of aqueous from the posterior chamber. In the United States, the prevalence of angle-closure glaucoma (ACG) is one tenth as common as open-angle glaucoma. In acute ACG, if the pressure is not reduced promptly, permanent visual loss can ensue as a result of optic nerve damage. It is thought that irreversible optic nerve injury can occur within 24 to 48 hours. Therefore, once the diagnosis of acute ACG has been made, treatment should be instituted immediately. Signs and symptoms include ocular pain (often excruciating), red eye, corneal edema, blurred vision, and a fixed, mid-dilated pupil. Consultation with an ophthalmologist should be sought immediately. Topical pilocarpine 2% is administered to cause miosis and pull the iris taut and away from the trabecular meshwork. A topical β blocker also should be considered. If a prompt reduction in IOP does not ensue, systemic therapy with an agent such as mannitol should be considered, but its potentially adverse hemodynamic effects should be weighed in a patient with cardiovascular disease. If medical therapy is effective in reducing IOP to a safe level and the angle opens, an iridotomy/iridectomy can be performed immediately, or it can be delayed until the corneal edema resolves and the iris becomes less hyperemic ( Table 1-7 ).

TABLE 1-6   -- Anesthetic Objectives for Patients with Glaucoma



Perioperative instillation of miotics to enhance aqueous humor outflow



Avoidance of venous congestion/overhydration



Avoidance of markedly increased venous pressure (e.g., coughing or vomiting)



Avoidance of hypotension that may trigger retinal vascular thrombosis



TABLE 1-7   -- Comparison of Open-Angle Versus Closed-Angle Glaucoma

Open-Angle Glaucoma

Closed-Angle Glaucoma

Anatomically patent anterior chamber angle

Shallow anterior chamber

Trabecular sclerosis

Narrow iridocorneal angle

Ten times more common than closed-angle

Iris covers trabecular meshwork



Initially unaccompanied by visual symptoms

Red eye with corneal edema

Can result in blindness if chronically untreated

Blurred vision


Fixed, dilated pupil


Can cause irreversible optic nerve injury within 24–48 hours


Requires emergency treatment



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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Retinal Complications of Systemic Disease

Retinal conditions such as vitreous hemorrhage and retinal detachment are most commonly associated with diabetes mellitus and hypertension ( Table 1-8 ). However, collagen disorders and connective tissue diseases, such as systemic lupus erythematosus, scleroderma, polyarteritis nodosa, Marfan's syndrome, and Wagner-Stickler syndrome, are often associated with retinal pathology. Serious retinal complications have been reported with skin conditions such as incontinentia pigmenti. Additionally, such conditions as sickle cell anemia, macroglobulinemia, Tay-Sachs disease, Neimann-Pick syndrome, and hyperlipidemia can result in vitreoretinal disorders. During the past two decades, cytomegalovirus retinitis has been reported in patients with acquired immunodeficiency syndrome. The condition sometimes progresses to cause retinal detachment.

TABLE 1-8   -- Examples of Conditions Associated with Vitreoretinal Pathology



Diabetes mellitus






Collagen/connective tissue disorders



Marfan's sydrome



Polyarteritis nodosa






Systemic lupus erythematosus



Wagner-Stickler syndrome






Human immunodeficiency syndrome



Incontinentia pigmenti






Neimann-Pick disease



Tay-Sachs disease



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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Having provided a brief overview of the broad spectrum of systemic diseases that can be associated with the major types of serious ocular pathology, the focus shifts to specific disease entities and their anesthetic management.

Marfan's Syndrome

Marfan's syndrome is a disorder of connective tissue, involving primarily the cardiovascular, skeletal, and ocular systems. However, the skin, fascia, lungs, skeletal muscle, and adipose tissue may also be affected. The etiology is a mutation in FBNI, the gene that encodes fibrillin-1, a major component of extracellular microfibrils, which are the major components of elastic fibers that anchor the dermis, epidermis, and ocular zonules.[18] Connective tissue in this disorder has decreased tensile strength and elasticity. Marfan's syndrome is inherited as an autosomal dominant trait with variable expression.

Ocular manifestations of the syndrome include severe myopia, spontaneous retinal detachments, displaced lenses, and glaucoma. Cardiovascular manifestations include dilation of the ascending aorta and aortic insufficiency. The loss of elastic fibers in the media may also account for dilation of the pulmonary artery and mitral insufficiency resulting from extended chordae tendineae. Myocardial ischemia owing to medial necrosis of coronary arterioles as well as dysrhythmias and conduction disturbances have been well documented. Heart failure and dissecting aortic aneurysms or aortic rupture are not uncommon.

The patients are tall, with long, thin extremities and fingers (arachnodactyly). Joint ligaments are loose, resulting in frequent dislocations of the mandible and hip. Possible cervical spine laxity can also occur. Kyphoscoliosis and pectus excavatum can contribute to restrictive pulmonary disease. Lung cysts have also been described, causing an increased risk of pneumothorax. A narrow, high-arched palate is commonly found.

The early manifestations of Marfan's syndrome may be subtle, and therefore the diagnosis may not yet have been made when the patient comes for initial surgery. The anesthesiologist, however, should have a high index of suspicion when a tall young patient with a heart murmur presents for repair of a spontaneously detached retina. These young patients should have a chest radiograph as well as an electrocardiogram and echocardiogram before surgery. Antibiotics for subacute bacterial endocarditis prophylaxis should be considered, as well as β blockade to mitigate against increases in myocardial contractility and aortic wall tension (dP/dT).

The anesthesiologist should be prepared for a potentially difficult intubation ( Table 1-9 ). Laryngoscopy should be carefully performed to circumvent tissue damage and, especially, to avoid hypertension with its attendant risk of aortic dissection. The patient should be carefully positioned to avoid cervical spine or other joint injuries, including dislocations. The dangers of hypertension in these patients are well known. Clearly, the presence of significant aortic insufficiency warrants that the blood pressure (especially the diastolic pressure) be high enough to provide adequate coronary blood flow but should not be so high as to risk dissection of the aorta. Maintenance of the patient's normal blood pressure is typically a good plan. No single intraoperative anesthetic agent or technique has demonstrated superiority. If pulmonary cysts are present, however, positive-pressure ventilation may lead to pneumothorax.[19] At extubation, one should take care to avoid sudden increases in blood pressure or heart rate. Adequate postoperative pain management is vitally important to avoid the detrimental effects of hypertension and tachycardia.

TABLE 1-9   -- Anesthetic Concerns with Marfan's Syndrome



Difficult intubation



Lung cysts



Restrictive pulmonary disease



Dysrhythmias and/or conduction disturbances



Dilation of aorta and pulmonary artery; dissecting/ruptured aortic aneurysms



Aortic and/or mitral insufficiency



Consider antibiotic prophylaxis for subacute bacterial endocarditis.



Myocardial ischemia; heart failure



Consider β blockade.



Propensity to mandibular/cervical/hip dislocation



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Copyright © 2005 Saunders, An Imprint of Elsevier

Graves' Disease

Graves' disease is the most common cause of both pediatric and adult hyperthyroidism. Graves' disease encompasses hyperthyroidism, goiter, pretibial myxedema, and, often but not inevitably, exophthalmos. The condition occurs in conjunction with the production of excess thyroid hormone and affects approximately 3 in 10,000 adults (usually women) typically between 25 and 50 years of age. Graves' ophthalmopathy includes corneal ulcerations and exophthalmos that can be severe. Retro-orbital tissue and the extraocular muscles are infiltrated with lymphocytes, plasma cells, and mucopolysaccharides. The extraocular muscles often are swollen to 5 to 10 times their normal size. If proptosis secondary to infiltrative ophthalmopathy is severe and if muscle function or visual acuity deteriorates, corticosteroid therapy (usually prednisone, 20 to 40 mg/day for adults) is initiated, especially if retrobulbar neuritis develops. Those patients who fail to respond to corticosteroid therapy require surgical intervention. Lateral (Krönlein's) or supraorbital (Naffziger's) decompression is performed.

Graves' disease is thought to be autoimmune in origin, with thyroid-stimulating immunoglobulins directed against thyroid antigens that bind to thyroid-stimulating hormone (TSH) receptors on the thyroid gland. Soft, multinodular, nonmalignant enlargement of the thyroid is typical. There is a strong hereditary component with Graves' disease, and it appears likely that the condition is exacerbated by emotional stress. These patients may have other signs of autoimmune involvement, including myositis and occasionally myasthenia gravis.

Symptoms include weakness, fatigue, weight loss, tremulousness, and increased tolerance to cold. Proptosis, diplopia or blurred vision, photophobia, conjunctival chemosis, and decreased visual acuity may be noted. Cardiac symptoms include a hyperdynamic precordium, tachycardia, and elevated systolic, decreased diastolic, and widened pulse pressures. Atrial fibrillation, palpitations, and dyspnea on exertion may also occur.

The differential diagnosis of Graves' disease includes other causes of hyperthyroidism such as pregnancy that may be associated with the production of an ectopic TSH-like substance, autoimmune thyroiditis, thyroid adenoma, choriocarcinoma, a TSH-secreting pituitary adenoma, and surreptitious ingestion of triiodothyronine (T3) or thyroxine (T4).[20]

The goals of drug therapy in the hyperthyroid patient are to control the major manifestations of the thyrotoxic state and to render the patient euthyroid. The most commonly used agents are the thiourea derivatives propylthiouracil (PTU) and methimazole, which act by inhibiting synthesis of thyroid hormone. (PTU may also inhibit the conversion of T4 to T3.) Owing to the large glandular storage of hormone, 4 to 8 weeks is usually required to render a patient euthyroid with these drugs. Treatment is typically for several months, after which thyroid reserve and suppressive response to thyroid hormone are reevaluated. The major complication of this therapy is hypothyroidism, and the dosage is usually adjusted to the lowest possible once a euthyroid state is attained.[21] Other side effects encountered in patients taking these antithyroid drugs include leukopenia, which may be therapy limiting, as well as agranulocytosis, hepatitis, rashes, and drug fever. It is thought that β-receptor numbers are increased by hyperthyroidism,[22] and β blockers are used to rapidly control such effects of catecholamine stimulation as tachycardia, tremor, and diaphoresis.[23]

The main areas of concern for the anesthesiologist involve the chronic use of corticosteroids, the possibility of perioperative thyroid storm, and the potential challenge of a difficult intubation, owing to tracheal deviation from a large neck mass[24] ( Table 1-10 ). When surgery is planned for the patient with Graves' disease, it is imperative to determine if the patient is euthyroid because the euthyroid state will diminish the risks of life-threatening thyroid storm and of perioperative cardiovascular complications by more than 90%. Achievement of the euthyroid state is assessed by clinical signs and symptoms, plasma hormone levels, and evidence of gland shrinkage. The patient should also be evaluated for associated autoimmune diseases. A chest radiograph, lateral neck films, and computed tomography (CT) of the neck and thorax will determine tracheal displacement or compression. If there is a question about the adequacy of the airway or tracheal deviation or compression, an awake fiberoptic intubation is a prudent approach. Additionally, an armored tube or its equivalent is useful if any tracheal rings are weakened. Liberal hydration is advised if the cardiovascular status will permit this intervention. High dose corticosteroid coverage is indicated, and continuous temperature monitoring is essential. Additionally, the eyes must be meticulously protected.

TABLE 1-10   -- Anesthetic Concerns with Graves' Disease



Difficult intubation secondary to tracheal deviation or compression



Side effects of antithyroid drugs, including leukopenia and hepatitis



Effects of chronic steroid consumption



Meticulous intraoperative eye protection and temperature monitoring



Perioperative thyroid storm



Determine euthyroid state.



Associated autoimmune disease(s)



Weakened tracheal rings



No single anesthetic drug or technique has been proven superior in the management of hyperthyroid patients. However, anticholinergic drugs are not recommended and ketamine should be avoided, even in the patient who has been successfully rendered euthyroid. Sudden thyroid storm secondary to stress or infection is always a possibility, and the clinician must be alert for even mild increases in the patient's temperature or heart rate. Other early signs of thyroid storm include delirium, confusion, mania, or excitement. The differential diagnosis of these symptoms includes malignant hyperthermia, pheochromocytoma crisis, and neuroleptic malignant syndrome. Treatment of thyroid storm is supportive, including infusion of cooled saline solutions, β-blocker therapy, antithyroid drugs, and corticosteroids.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Although rare, homocystinuria is generally considered the second most common inborn error of amino acid metabolism, ranking behind only phenylketonuria in frequency. The incidence of phenylketonuria is about 1:25,000,[26] and that of homocystinuria is approximately 1:200,000.[27] An error of sulfur amino acid metabolism, homocystinuria is characterized by the excretion of a large amount of urinary homocystine, which can be detected by the cyanide-nitroprusside test. A host of assorted genetic aberrations may be linked with homocystinuria, but the most common is a deficiency of cystathionine β synthase, with accumulation of methionine and homocystine. The disorder is autosomal recessive. Disease occurs in the homozygote, but the heterozygote is without risk of developing the potentially life-threatening complications of the condition. Although one third of homocystinurics have normal intelligence, most are mentally retarded.

Ectopia lentis occurs in at least 90% of persons with homocystinuria. Frequently there is subluxation of the lens into the anterior chamber, causing pupillary block glaucoma, necessitating surgical correction. Other ocular findings reported in homocystinuria may include pale irides, retinoschisis, retinal detachment, optic atrophy, central retinal artery occlusion, and strabismus.

Owing to abnormal connective tissue, the skeletal findings are similar to those of Marfan's syndrome. Most patients have arachnodactyly, kyphoscoliosis, and sternal deformity. They also may have severe osteoporosis. Kyphoscoliosis and pectus excavatum may be associated with restrictive lung disease.

It is imperative to appreciate that patients with homocystinuria are extremely vulnerable to thrombotic complications associated with high mortality[28] ( Table 1-11 ). Indeed, an untreated homocystinuric patient may have a perioperative mortality rate as high as 50%. Elevated concentrations of homocystine irritate the vascular intima, promoting thrombolic nidus formation and presumably increasing the adhesiveness of platelets.[29] Other possible causes of the thrombotic tendency include increased platelet aggregation, Hageman factor activation, or enhanced platelet consumption as a result of endothelial damage. Patients with homocystinuria are also at risk for hypoglycemic convulsions secondary to hyperinsulinemia. The latter disturbance is thought to be provoked by hypermethioninemia.[30]

TABLE 1-11   -- Potential Perioperative Concerns with Homocystinuria



Restrictive lung disease



Positioning-induced fractures associated with osteoporosis



Thrombotic complications



Hypoglycemic convulsions



Preoperative measures include a low-methionine, high-cystine diet and vitamins B6 and B12 and folic acid to regulate homocystine levels, as well as acetylsalicylic acid and dipyridamole to prevent aberrant platelet function. Besides appropriate dietary and drug therapy, proper perioperative care involves prevention of hypoglycemia and maintenance of adequate circulation. Patients with osteoporosis must be carefully positioned on the operating table. Glucose levels should be monitored perioperatively. Low-flow, hypotensive states must be assiduously avoided. The patients must be kept well hydrated and well perfused.[31] Anesthetic agents are selected that promote high peripheral flow by reducing vascular resistance, that maintain cardiac output, and that foster rapid recovery and early ambulation. Postoperative vascular support stockings that prevent stasis thrombi in leg veins are indicated.

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Hemoglobinopathies: Sickle Cell Disease

Hemoglobinopathies are inherited disorders of hemoglobin synthesis. There may be structural derangements of globin polypeptides or, as in thalassemia, abnormal synthesis of globin chains. In hemoglobin (Hb) S, for example, a single amino acid (valine) is substituted for glutamic acid in the β chain. This substitution has no effect on oxygen affinity or molecular stability. Nonetheless, in the setting of low oxygen tension, it causes an intermolecular reaction, producing insoluble structures within the erythrocytes that result in sickling.[32] These atypical red cells lodge in the microcirculation, causing painful vaso-occlusive crises, infarcts, and increased susceptibility to infection. Low oxygen tension and acidic environments are major triggers and determinants of the degree of sickling. Sickled cells are thought to produce a rightward shift (P50 = 31 mm Hg) of the oxyhemoglobin dissociation curve to enhance oxygen delivery.

Although ophthalmic pathology such as proliferative retinopathy can occur in all varieties of sickling diseases, it is more common in adults with Hb SC or Hb S thalassemia than in those with Hb SS. Proliferative retinopathy usually appears in the third or fourth decades of life and is the result of vascular occlusion. This occlusion of retinal vessels eventually produces ischemia, neovascularization, vitreous hemorrhage, fibrosis, traction, and retinal detachment or atrophy. However, prophylactic laser photocoagulation has been helpful in reducing the incidence of the aforementioned conditions.

The severity of the anemia depends on the amount of Hb S present. In homozygous SS disease, the Hb S content is 85% to 90%, the remainder being Hb F. Sickle cell thalassemia (Hb SF) is characterized by an Hb S content of 67% to 82% and causes somewhat less severe problems. Indeed, patients with Hb SC and Hb S thalassemia typically have a much more benign course than those individuals with Hb SS and usually have only mild anemia and splenomegaly. Heterozygous persons with Hb SA (sickle trait) rarely have serious clinical problems. However, recent literature suggests some increased risk of stroke and pulmonary emboli or infection after the stress of hypothermic, low-flow cardiopulmonary bypass in patients with sickle trait.[33] This purported risk, however, has not been well quantitated.

Sickle cell disease (Hb SS) is an autosomal recessive condition that occurs most frequently in individuals of African ancestry, although the gene for Hb S also occurs in persons with ancestors from areas endemic for falciparum malaria. Eight to 10 percent of American blacks are heterozygous carriers of Hb S; approximately 0.5% of blacks are homozygous for Hb S disease.

Patients with homozygous sickle cell disease have chronic hemolytic anemia ( Table 1-12 ). Organ damage occurs owing to vaso-occlusive ischemia because sickled cells are unable to traverse narrow capillary beds. Additionally, sickled cells have a propensity to adhere to the endothelium and cause release of vasoactive substances. Chronic pulmonary disease gradually progresses as a result of recurrent pulmonary infection and infarction. Eventually, these individuals develop pulmonary hypertension, cardiomegaly, and heart failure, as well as renal failure.

TABLE 1-12   -- Perioperative Concerns with Sickle Cell Disease






Chronic pulmonary disease



Pulmonary hypertension



Cardiomegaly and heart failure



Renal failure



Extreme vulnerability to dehydration, hypothermia, hypoxia, and acidosis



Hemolytic transfusion reaction resulting from alloimmunization



Multiple problems, including anemia, underlying cardiopulmonary disease, and extreme vulnerability to dehydration, hypothermia, hypoxia, and acidosis place these patients at high perioperative risk. Preoperative management should include correction of anemia. In the past, controversy existed regarding whether these patients should receive a preoperative exchange transfusion with Hb A. Recent data, however, suggest that preoperative transfusion to an Hb level of 10 g/dL, independent of the Hb S percentage, is equally effective in preventing perioperative complications as transfusion designed to establish a level of 10 g/dL and an Hb S level below 30%.[34] Controversy also surrounds the issue of the relative risks of transfusion for simple, brief operative procedures in patients who are minimally symptomatic and considered at low risk for intraoperative vaso-occlusive crises. Clearly, all blood transfusion in this setting carries a high risk of hemolytic transfusion reaction owing to alloimmunization from previous exposure.

In terms of intraoperative management, it is important to appreciate that no difference in morbidity or mortality has been shown among assorted anesthetic agents or between regional and general anesthetic techniques.[35] Factors that precipitate sickle crises, such as dehydration, hypoxia, acidosis, infection, hypothermia, and circulatory stasis, should be meticulously prevented. Intraoperative normothermia should be maintained with fluid warmers, breathing circuit humidification, warming blankets, forced-air warmers, and a well-heated operating room. Adequate perioperative volume replacement is critical; aggressive hydration with crystalloid or colloid is indicated except in the presence of congestive heart failure. Supplemental oxygen and mild hyperventilation are desirable to prevent hypoxemia and acidosis. Although pulse oximetry may be valid with Hb S, it is extremely unreliable in the presence of deoxygenated, polymerized Hb S because aggregation of sickled cells interferes with the light-emitting diode. After surgery, oxygen therapy, liberal hydration, and maintenance of normothermia should be continued for a minimum of 24 hours, because crises may occur suddenly postoperatively. Additionally, adequate analgesia, early ambulation, and pulmonary toilet, including incentive spirometry, are important in preventing serious complications. Postoperative pneumonia in this setting can be fatal.

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Acquired Immunodeficiency Syndrome

Patients with acquired immunodeficiency syndrome (AIDS) frequently develop cytomegalovirus retinitis,[36] a condition treated by the insertion of a slow-release antiviral drug packet into the vitreous. Occasionally, the retinitis will produce a retinal detachment that requires surgical correction.

Many patients with AIDS are extremely ill with cachexia, anemia, and residual respiratory insufficiency from previous episodes of Pneumocystis carinii pneumonia ( Table 1-13 ). In addition to reduced pulmonary reserve, these patients often have limited myocardial reserve as a consequence of the debilitating effects of their underlying disease. The greatest cause of perioperative morbidity and mortality, however, is infection.

TABLE 1-13   -- Perioperative Concerns with Acquired Immunodeficiency Syndrome






Respiratory insufficiency



Reduced myocardial reserve



Vulnerability to infection and pressure sores



Altered drug requirements secondary to hypoglobulinemia



Transmission of HIV or other drug-resistant pathogens



A thorough preoperative assessment of the CD4 (T-helper lymphocyte) cell count, organ function, and volume status is essential. It is mandatory to initiate or continue antibiotic and immune therapy, and organ function must be optimized. Severely debilitated patients may require invasive monitoring, depending to a great degree on the type of surgical procedure being performed, and strict attention must be paid to aseptic technique. Hypoglobulinemia is extremely common in AIDS patients and will reduce drug requirements. Therefore, anesthetic medications must be carefully selected and titrated. Moreover, supplemental oxygen should be provided to prevent perioperative episodes of desaturation. Additionally, these cachectic patients require special precautions to prevent pressure sores. Preemptive pain management may offer protection against additional immune suppression.[37]

It cannot be overemphasized that, because the greatest threat to these patients is infection, strict hygienic practices are critical. Moreover, medical personnel must protect themselves against the hazard of transmission of human immunodeficiency virus (HIV) or of other drug-resistant pathogens by scrupulous adherence to universal precautions.

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Retinopathy of Prematurity

Although Terry[38] first described the pathologic condition in 1942, the neologism retrolental fibroplasia was coined in 1944 by Harry Messenger, a Boston ophthalmologist who was also a Greek and Latin scholar.[39] More recently, however, the term retinopathy of prematurity (ROP) has gained widespread acceptance, because it describes the late cicatricial phase of the disease as well as the earlier acute changes.

ROP is usually associated with extremely low-birth-weight (1000-1500 g) preterm infants and “micropremies” (< 750 g) who require oxygen therapy. It is thought that hyperoxia triggers blood vessel constriction in the developing retina, causing areas of peripheral ischemia, poor vascularization, and neovascularization (proliferation of a network of abnormal retinal vessels), which produces fibrosis, scarring, and retinal detachment. Because advances in neonatology have led to 85% survival rates for extremely low-birth-weight infants, it is not surprising that the prevalence of ROP increased in recent decades. Moreover, the assumption that ROP is caused exclusively by excess oxygen in this population is incorrect, because ROP is a disease of multifactorial origin. [40] [41] [42] The factors associated with the development of ROP are highly interrelated, but Flynn established that low birth weight was the most significant predictor of risk.[43] Common problems of prematurity include respiratory distress syndrome (which is best managed with a combination of antenatal corticosteroids, postnatal surfactant therapy, and effective ventilation), apnea, bronchopulmonary dysplasia, persistent pulmonary hypertension, patent ductus arteriosus, necrotizing enterocolitis, gastroesophageal reflux, anemia, jaundice, hypoglycemia and hypocalcemia, intraventricular hemorrhage, and ROP ( Table 1-14 ).

TABLE 1-14   -- Common Problems with Prematurity






Respiratory distress syndrome



Bronchopulmonary dysplasia



Patent ductus arteriosus



Persistent pulmonary hypertension



Necrotizing enterocolitis






Gastroesophageal reflux









Intraventricular hemorrhage



Retinopathy of prematurity



Postoperative apnea is the most common problem associated with anesthesia in premature infants.[44] Almost 20% of premature infants can be expected to develop this life-threatening complication, with the greatest risk for infants 50 weeks' postconceptual age (equal to gestational age plus chronologic age) and younger.[45] Apnea may result from prolonged effects of anesthetic agents, a shift of the carbon dioxide response curve, or fatigue of respiratory muscles.[46] Liu and colleagues[46] originally recommended continuous cardiopulmonary monitoring for patients younger than 46 weeks' postconceptual age. However, Kurth and colleagues[47] extended these recommendations to include cardiopulmonary monitoring for infants younger than 60 weeks' postconceptual age for a minimum of 12 apnea-free hours after surgery. Although the incidence of postoperative apnea is inversely related to postconceptual age, even full-term infants may occasionally have postoperative apnea.[45] In addition to prematurity as a risk factor, infants with a history of anemia,[48] neonatal apnea spells, respiratory distress syndrome, or pulmonary disease have approximately twice the risk of developing postoperative apnea.

Chronic lung disease, also known as bronchopulmonary dysplasia, remains the primary long-term pulmonary complication among premature infants. It is associated with pulmonary hypertension, abnormalities of postnatal alveolarization, and neovascularization.[49] Infants with chronic lung disease have impaired growth[50] and may also have poor long-term cardiopulmonary function, an increased vulnerability to infection,[51] and a markedly increased risk of abnormal neurologic development.[52] An investigation from the University of Chicago, however, reported that administration of nitric oxide to premature infants with respiratory distress syndrome reduced the incidence of chronic lung disease and death.[53]

Bronchopulmonary dysplasia (BPD) is characterized by lack of a widely accepted definition, but many neonatologists define it as a condition requiring supplemental oxygen after 36 weeks' postmenstrual age.[54] Conditions associated with BPD include prematurity, persistent ductus arteriosus, and prolonged ventilation with high inspiratory pressures and oxygen concentrations. Affected patients have abnormalities in lung compliance and airway resistance that may persist for several years. They also have chronic hypercarbia and hypoxemia. Abnormal chest radiographic findings include hyperexpanded lungs, small radiolucent cysts, increased interstitial markings, and peribronchial cuffing. Treatment typically consists of bronchodilators to reduce airway resistance and diuretics to decrease pulmonary edema. Air trapping during assisted ventilation may be minimized by use of a prolonged expiratory time.

When premature infants undergo anesthesia and surgery, they must be kept warm, because they defend their core temperature at considerable metabolic cost ( Table 1-15 ). The brown fat cells begin to differentiate at 26 to 30 weeks' gestation and, hence, are absent as a substrate buffer in extremely premature infants.[55] Additionally, infants have a greater surface area per volume compared with adults and will, therefore, tend to lose body heat rapidly in a cold environment. Metabolic acidosis is produced by cold stress. The acidosis causes myocardial depression and hypoxia, which in turn further exacerbates the metabolic acidosis. Warming the operating room (85°F [30°C]) and using warming units may help maintain the infant's body temperature. Warming intravenous and irrigation fluids may also be beneficial. Standard monitoring equipment includes an electrocardiograph, stethoscope, blood pressure monitor, temperature probe, pulse oximeter, and capnograph. A pulse oximeter probe placed in a preductal position on the right hand to reflect the degree of oxygenation in blood flowing to the retina can be compared with one located in a postductal position on the left foot to determine the severity of ductal shunting. Although pulse oximetry findings can be used to diagnose hypoxemia, hyperoxia cannot be detected by pulse oximetry. Maintaining the oxygen saturation at 93% to 95% (preductal) places most premature infants on the steep portion of the oxyhemoglobin dissociation curve and avoids severe hyperoxia.[56] It is important to appreciate that the reported levels of expired carbon dioxide may not accurately reflect PaCO2 if the infant has congenital heart disease or major intrapulmonary shunting. In infants, changes in blood pressure, heart rate, and the intensity of heart sounds are helpful indicators of cardiac function, intravascular volume status, and depth of anesthesia. Hepatic and renal function in premature infants is immature and suboptimal, and their anesthetic requirement is considerably less than that of more mature and more robust infants.

TABLE 1-15   -- Anesthetic Management of Premature Infants



Normothermia critical



Reduced anesthetic requirement



Maintain preductal O2 saturation at 93% to 95%



Prolonged expiratory time often helpful



Extubate only when infant is vigorous and fully awake



Postoperative cardiopulmonary monitoring for ≥12 hours



The combination of ventilatory depression from residual anesthetic drugs with immature development of respiratory control centers can cause postoperative hypoventilation and hypoxia as well as apnea. Therefore, these infants must be wide awake and vigorously responsive before they are extubated. When indicated by clinical circumstances, they should be carefully monitored postoperatively for at least 12 hours for signs of apnea, hypoxia, or bradycardia. The margin of safety for premature infants is narrow. They have minimal pulmonary reserve and rapidly become hypoxic.

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Incontinentia Pigmenti

Bloch-Sulzberger syndrome, also known as incontinentia pigmenti, is a rare hereditary disease with dermatologic, neurologic, ocular, dental, and skeletal manifestations ( Table 1-16 ). Inherited via either an autosomal dominant gene or by a sex-linked dominant gene, the condition is observed predominantly in females because it is usually lethal in males.

TABLE 1-16   -- Anesthetic Management of Incontinentia Pigmenti



Control seizures



Careful airway manipulation owing to pegged teeth



Avoid succinylcholine in patients with spastic paralysis



Autonomic hyperreflexia possible with high spinal cord involvement



Skin involvement is typically noted at birth. The dermatopathology begins with inflammatory linear vesicles or bullae that progress to verrucous papillomata and eventually to splashes of pigmentation. By adulthood, however, the aforementioned lesions are replaced by atrophic hypopigmented lesions. Patients are retarded, and spastic paralysis,[57] seizures,[58] microcephaly, hydrocephalus, and cortical atrophy have been reported.

Individuals with incontinentia pigmenti are often blind. In addition to cataracts and strabismus, they may be afflicted with such serious ocular problems as retinitis proliferans and other types of retinopathy,[59] [60] [61] chorioretinitis, uveitis, optic nerve atrophy, foveal hypoplasia,[62] and retinal tears or detachments.

Partial anodontia and pegged or conical teeth are characteristic of the condition. Assorted skeletal anomalies are sometimes present.

The major anesthetic concerns involve the teeth and the central nervous system abnormalities. Owing to the dental pathology, airway manipulation must be performed with care. Succinylcholine should be avoided in patients with spastic paralysis, and patients with a high level of spinal cord involvement might theoretically develop autonomic hyperreflexia. No particular anesthetic technique has been recommended for these patients.

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Retinitis Pigmentosa

Retinitis pigmentosa consists of a group of diseases, frequently hereditary, marked by progressive loss of retinal response, as elicited by electroretinography (ERG). The diseases are characterized by retinal atrophy, attenuation of the retinal vessels, clumping of pigment, and contraction of the field of vision. Retinitis pigmentosa may be transmitted as a dominant, recessive, or X-linked trait and is sometimes associated with other genetic defects.

ERG is a stimulated reflex response study to evaluate a patient for retinitis pigmentosa. The test measures the electrical response of the retina to light stimulation. ERG evaluates the retina and, therefore, should not be equated with visual evoked potential testing, which assesses polysynaptic cortical activity. When ERG is performed in young children, the ophthalmologist may request general anesthesia to enable performance of the test. Although retinitis pigmentosa, absent other genetic abnormalities, does not present any anesthetic challenges related to the patient's medical condition, nonetheless the conditions of the test are unusual and worthy of mention. Similarly, the selection of anesthetic agent is interesting.

ERG is performed in a dark, Faraday cage room with a flashing light source placed over the patient's face. The anesthesiologist frequently must work in cramped quarters, without the usual accoutrements of the operating room, including adequate lighting and a wide range of readily accessible emergency equipment. Additionally, the young patient's face is partially obscured by rather bulky ophthalmologic equipment, and access to the child's airway is less than ideal.

Anesthesia equipment must include a suction apparatus and an immediately available light source. Monitoring should incorporate an electrocardiograph, a pulse oximeter, and an end-tidal carbon dioxide monitor. The airway should be secured with either an endotracheal tube or a laryngeal mask airway.

The choice of anesthetic agents is somewhat traditional rather than truly evidence based. Although ERG is a simple rod-cone reflex response study, anesthetic agents may affect both the amplitude and latency of the ERG responses, thereby distorting the interpretation. Although ketamine is known to cause nystagmus and enhanced electroencephalographic activity, the agent purportedly does not modify ERG responses significantly in rabbits.[63] Indeed, there is a dearth of information available about the effects of anesthetic agents on ERG testing in humans. However, we do know that, in pigs, propofol appears to preserve the photoreceptor response better than thiopental.[64] Furthermore, in dogs, halothane and sevoflurane strongly depress the scotopic threshold response while moderately depressing the b wave and increasing oscillatory potential amplitudes.[65] In rats, photoreceptor and postreceptoral responses recorded under the barbiturate pentobarbital (Nembutal) and the dissociative agent zolazepam (Telazol) differ significantly.[66] Therefore, almost by default, ketamine appears to be the agent of choice for ERG testing in children.

By way of contrast, a brief discussion of visual evoked potentials (VEPs) is indicated. The visual pathway includes the retina, optic nerve, optic chiasm, optic tracts, lateral geniculate nucleus in the thalamus, optic radiation, and occipital visual cortex. Retinal stimulation produces an evoked electrical response in the occipital cortex, which may be altered with impairment of the visual apparatus and associated neural pathways. VEPs are recorded from scalp electrodes positioned over the occipital, parietal, and central areas. They are cortical near-field potentials with long latencies.[67] We have considerably more information about the effects of anesthetic agents on VEPs in humans compared with our meager knowledge in this domain when ERG testing is involved. For example, generally all volatile anesthetics dramatically prolong VEP latency and decrease amplitude in a dose-dependent fashion. [68] [69] With intravenous agents, induction doses of thiopental decrease the amplitude and prolong the latency of VEP waves[70] whereas etomidate produces a small increase in latency with no alteration in amplitude.[71] Ketamine has negligible effect on latency but produces a 60% reduction in amplitude.[72] To date, the available data indicate that opioid and ketamine or propofol-based anesthetic techniques, as well as regimens using low-dose volatile anesthetics without nitrous oxide, allow satisfactory intraoperative recordings of VEPs, with the caveat that there may be a high incidence of false-positive or false-negative results.[73]

In summary, because they represent polysynaptic cortical activity, VEPs are exquisitely sensitive to the effects of anesthetic agents and physiologic factors. They are, furthermore, extremely dependent on appropriate stimulation of the retina and may be adversely affected by narcotic-induced pupillary constriction.[74] In contrast, subcortical potentials such as ERG responses, are probably less sensitive to anesthetic effects.

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Eye Trauma

Eye trauma may be either penetrating or blunt. Special anesthetic considerations apply in the setting of a penetrating eye injury. Open-eye injuries requiring surgical repair vary in severity from a small corneal leak to a totally disrupted globe with damage to the sclera, cornea, iris, and lens, accompanied by loss of vitreous, choroidal vessel hemorrhage, and retinal detachment. Frequently it is difficult to determine the extent of the injury until after the patient has been anesthetized. However, retrobulbar or peribulbar blocks are not recommended in cases of open globes or extensive ocular trauma in which there is a risk of further disrupting the eye.

It is important to appreciate that any additional damage to the eye that transpires after the initial trauma is not necessarily the result of anesthetic drugs and manipulations. In many instances, for example, the patient may have been crying, coughing, vomiting, rubbing the eye, or squeezing the eyelids closed before anesthesia is induced.[75] These maneuvers are known to increase IOP dramatically. Even a normal blink increases IOP by 10 to 15 mm Hg; forced eyelid closure causes an increase in IOP of more than 70 mm Hg, an effect that may be ameliorated by performing a lid block to prevent lid spasm using the O'Brien technique. Increased IOP also results from other forms of external pressure, such as face mask application and from obstructed breathing or Valsalva maneuvers. Additionally, IOP is increased by succinylcholine and endotracheal intubation, especially if laryngoscopy is difficult or prolonged.

Ideal anesthesia for an eye trauma patient with a full stomach requires preoxygenation via a gently applied face mask followed by a rapid-sequence induction with cricoid pressure and a smooth, gentle laryngoscopy and intubation to ensure a stable IOP ( Table 1-17 ). Experts disagree, however, on the best way to accomplish these goals, particularly the issue of selection of a muscle relaxant to secure the airway in the safest fashion without causing either extrusion of intraocular contents or pulmonary aspiration of gastric contents.

TABLE 1-17   -- Anesthetic Management of the Open Eye–Full Stomach Situation



Avoid coughing, vomiting, and direct eye pressure.



Ensure adequate anesthetic depth before attempting laryngoscopy.



Administer appropriate adjuvants and neuromuscular blocker before laryngoscopy.



Perform gentle and brief laryngoscopy.



Maintain and monitor intraoperative paralysis.



Maintain stable venous and arterial pressures.



Prevent periextubation bucking and coughing.



Extubate only when patient is fully awake.



Nondepolarizing neuromuscular blocking agents relax the extraocular muscles and reduce IOP. In general, however, at least 3 minutes must pass before the usual doses of nondepolarizing drugs given in the traditional fashion provide adequate paralysis for endotracheal intubation. During this interval, the unconscious patient's airway is unprotected by a cuffed endotracheal tube and aspiration could occur. Additionally, if paralysis is incomplete, the patient may cough or “buck” on the endotracheal tube, causing an increase in IOP of 40 mm Hg. In contrast, the depolarizing drug succinylcholine provides an opportunity for swift intubation, airway protection, and consistently excellent intubating conditions within 60 seconds. Succinylcholine is rapidly cleared, permitting the patient to return to spontaneous respiration, which is important if the patient has a difficult airway. Succinylcholine, however, increases IOP by approximately 8 mm Hg. This relatively small increase occurs 1 to 4 minutes after intravenous administration of the drug, and within 7 minutes IOP values return to baseline. Factors contributing to the ocular hypertensive effect of succinylcholine are incompletely understood.

A variety of interventions—including pretreatment with acetazolamide, propranolol, lidocaine,[76] narcotics,[77] clonidine,[78] and nondepolarizing relaxants—have been advocated to prevent succinylcholine-induced increases in IOP. None of these interventions, however, consistently and completely blocks the ocular hypertensive response. [79] [80] Therefore, the use of succinylcholine in cases of open globes had traditionally been considered controversial, although this philosophy was based perhaps more on anecdote and “zero tolerance” for a potential anesthesia-related complication than on incontrovertible scientific evidence.[81]

If the anesthesiologist elects to use a nondepolarizing agent instead of succinylcholine, the administration of high-dose (400 μg/kg) vecuronium[82] or enlisting the “priming” technique[83] may accelerate the onset of available nondepolarizing muscle relaxants. With priming, approximately one tenth of an intubating dose of muscle relaxant is followed 4 minutes later by an intubating dose. After an additional 90 seconds, intubation may be accomplished. However, the use of large doses of nondepolarizing agents and the priming technique have serious disadvantages, including the risk of aspiration during the interval when the airway is unsecured and the unpredictable onset of sufficient paralysis to permit intubation without coughing. If high doses of such agents as atracurium or mivacurium are used, histamine release can cause untoward side effects, including hemodynamic instability. Large doses (1.2 mg/kg) of rocuronium do not consistently afford conditions for intubation that are as excellent as those provided by succinylcholine. Rapacuronium, the nondepolarizing agent with a rapid onset, showed promise in this setting, but the occurrence of intractable bronchospasm reported after its administration resulted in its removal from markets in the United States.

An acceptable option, unless contraindicated by such conditions as hyperkalemia or a susceptibility to malignant hyperthermia, is to administer succinylcholine after pretreatment with a defasciculating dose of a nondepolarizing relaxant and, if necessary, an appropriate drug to prevent significant increases in blood pressure associated with laryngoscopy. Cases appear in the literature attesting to the apparent safety of using succinylcholine in the open eye/full stomach setting. [84] [85]

After intubation is safely and smoothly accomplished, the depth of anesthesia and the extent of muscle relaxation must be adequate to ensure lack of movement and to prevent coughing while the eye is open. This is best determined and followed by assessing the effects of peripheral nerve stimulation with a twitch monitor. Moreover, blood pressure should be carefully maintained within an acceptable range, because choroidal hemorrhage is more likely in open-eye situations when hypertension and increased venous pressure are also present. Prophylactic administration of an antiemetic is recommended to prevent postoperative vomiting. When surgery has been completed and spontaneous respiration has returned and the patient is awake with intact reflexes to prevent aspiration, the endotracheal tube is removed. Intravenous lidocaine (1.5 mg/kg) and a small dose of narcotic may be given before extubation to attenuate periextubation bucking and coughing.

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Difficulty in managing the airway is a major cause of anesthesia-related morbidity and mortality and when the proposed surgical procedure involves the airway, consummate skill in airway management is required. This is true for a variety of reasons, not the least of which is that the airway may be compromised preoperatively by edema, infection, tumor, or trauma. Moreover, the anesthesiologist and the surgeon often must share the airway in these scenarios. Therefore, effective communication between the anesthesiologist and the surgeon is critical to effect optimal patient outcome.

Sleep Apnea

Sleep patterns disturbed by snoring are thought to occur in approximately 25% of the population.[86] However, most patients who snore do not have apnea or associated episodes of significant hypoxemia. Nonetheless, obstructive sleep apnea (OSA) is a relatively common disorder among middle-aged adults, especially (obese) Americans. Obesity is a critical independent causative/risk factor. The majority of people who have OSA are obese, and the severity of the condition seems to correlate with the patient's neck circumference.[87] In the minority of OSA patients who are nonobese, causative risk factors are craniofacial and orofacial bony abnormalities, nasal obstruction, and hypertrophied tonsils. Young and colleagues[87] reported that the prevalence of OSA associated with hypersomnolence was 2% in women and 4% in men aged 30 to 60 years.

OSA is defined as cessation of air flow for more than 10 seconds despite continuing ventilatory effort, five or more times per hour of sleep, and is usually associated with a decrease in arterial oxygen saturation of more than 4%. Although this review will focus predominantly on OSA, it should be noted for the sake of completeness that the three types of sleep apnea are obstructive, central, and mixed. Central sleep apnea, much rarer than OSA, is also known as Ondine's curse, an allusion to the mythologic man who was condemned by his rejected lover, a mermaid, to stay awake in order to breathe. Unlike OSA, respiratory efforts temporarily stop in central sleep apnea. Diagnosis is established during polysomnography.

It is generally accepted that many patients with OSA have resultant pathologic daytime sleepiness associated with performance decrements. It has also been well established that patients with severe apnea suffer major health consequences as a result of their condition. Yet, it remains somewhat controversial whether patients with less severe forms of this disease incur the same detrimental consequences, owing to methodologic problems and failure to control for confounding factors in many of the relevant investigations. Clearly, the study design with the greatest methodologic rigor for the identification of long-term health consequences of OSA is the prospective, population-based, cohort study.[88] Most clinical research in OSA, however, has used less rigorous research designs, such as case-control, cross-sectional, or case studies that are more susceptible to problems of bias and less able to establish causality between adverse health consequences and OSA. Thus, few absolute conclusions can be drawn at this time about the long-term consequences of mild to moderate OSA. However, recently published findings from the Sleep Heart Health Study,[89] the Copenhagen City Heart Study,[90] and others[91]demonstrate a firm association between sleep apnea and systemic hypertension, even after other important patient characteristics, such as age, gender, race, consumption of alcohol, and use of tobacco products are controlled for.

Few definitive data exist to guide perioperative management of patients with OSA ( Table 1-18 ). It is not surprising that many anesthesiologists question whether OSA patients are appropriate candidates for ambulatory surgery. The risks of caring for these challenging patients in the ambulatory venue are further amplified by the unfortunate fact that 80% to 95% of people with OSA are undiagnosed[92]; they have neither a presumptive clinical and/or a sleep study diagnosis of OSA. This is of concern because these patients may suffer perioperatively from life-threatening desaturation and postoperative airway obstruction. Moreover, serious comorbidities may be present because prolonged apnea results in hypoxemia and hypercarbia, which can lead to increased systemic and pulmonary artery pressures and dysrhythmias. Cor pulmonale, polycythemia, and congestive heart failure may develop.

TABLE 1-18   -- Anesthetic Management of Patients with Sleep Apnea



Have high index of suspicion with obesity.



Identify and quantify comorbid disease(s).



Perform meticulous airway assessment.



Have low threshold for awake intubation.



Administer sedative-hypnotics and narcotics sparingly.



Use short-acting anesthetic drugs.



Administer multimodal analgesics.



Extubate only when patient is fully awake.



Be able to administer continuous positive airway pressure.



Admit to telemetry ward when indicated.



Sleep apnea occurs when the negative airway pressure that develops during inspiration is greater than the muscular distending pressure, thereby causing airway collapse. Obstruction can occur throughout the upper airway, above, below, or at the level of the uvula. [93] [94] Because there is an inverse relationship between obesity and pharyngeal area, the smaller size of the upper airway in the obese patient causes a more negative pressure to develop for the same inspiratory flow. [94] [95] Kuna and Sant'Ambrogio have also postulated that there may be a neurologic basis for the disease in that the neural drive to the airway dilator muscles is insufficient or not coordinated appropriately with the drive to the diaphragm.[94] Obstruction can occur during any sleep state but is often noted during rapid eye movement (REM) sleep. Nasal continuous positive airway pressure (CPAP) can ameliorate the situation by keeping the pressure in the upper airway positive, thus acting as a “splint” to maintain airway patency.

The site(s) of obstruction can be determined preoperatively by such techniques as magnetic resonance imaging (MRI), CT, and intraluminal pressure measurements during sleep.[96] Some studies suggest that the major site of obstruction in most patients is at the oropharynx, but obstruction can also occur at the nasopharynx, the hypopharynx, and the epiglottis.[97] Obviously, if the surgery is designed to relieve obstruction at one area but a pathologic process extends to other sites,[98] postoperative obstruction is not only possible but probable, especially when one allows for the edema associated with airway instrumentation.

CPAP devices, at least in the recent past, were often not well tolerated by patients. However, many technologic advances have been made with positive airway pressure devices, making these gadgets more easily tolerated. Additionally, weight loss may improve OSA. Recently, atrial overdrive pacing has shown promising results in patients with central or OSA.[99] Interestingly, French investigators serendipitously observed that some patients who had received a pacemaker with atrial overdrive pacing to reduce the incidence of atrial dysrhythmias reported a reduction in breathing disorders after pacemaker implantation. These cardiologists, therefore, initiated a study to investigate the efficacy of atrial overdrive pacing in the treatment of sleep apnea symptoms in consecutive patients who required a pacemaker for conventional indications. They found that atrial pacing at a rate 15 beats per minute faster than the mean nocturnal heart rate resulted in a significant reduction in the number of episodes of both central and obstructive apnea.[99] Postulating that enhanced vagal tone may be associated with (central) sleep apnea, the investigators acknowledged, however, that the mechanism of the amelioration of OSA by atrial overdrive pacing is unclear. Moreover, whether these unexpected findings are germane to the sleep apnea patient with normal cardiac function is uncertain. Gottlieb[100] has tantalizingly suggested that a central mechanism affecting both respiratory rhythm and pharyngeal motor neuron activity would offer the most plausible explanation for the reported equivalence in the improvement of central and OSA during atrial overdrive pacing. Do cardiac vagal afferents also inhibit respiration? Perhaps identification of specific neural pathways might also advance efforts to develop pharmacologic treatment for sleep apnea.

A variety of surgical approaches to treating sleep-related airway obstruction are available. They include classic procedures, such as tonsillectomy, that directly enlarge the upper airway, as well as more specialized procedures to accomplish the same objective. Examples of the latter include uvulopalatopharyngoplasty (UPPP), uvulopalatal flap (UPF), uvulopalatopharyngoglossoplasty (UPPGP), laser midline glossectomy (LMG), lingualplasty (LP), inferior sagittal mandibular osteotomy and genioglossal advancement (MOGA), hyoid myotomy (HM) and suspension, and maxillomandibular osteotomy and advancement (MMO). Another approach is to bypass the pharyngeal part of the airway with a tracheotomy.

Although physicians and surgeons have been treating OSA for more than 25 years, a paucity of long-term, standardized results about the efficacy of different therapies are available. One report, however, suggests that at least 50% of patients with sleep apnea syndrome can be managed effectively with one or a combination of therapies. Nasal CPAP, tracheotomy, MMO, and tonsillectomy typically receive high marks for efficacy,[101] and a recent study of UPPP showed positive results that were maintained for a minimum of 1 year.[102] Another study, combining UPPP with genioglossus and hyoid advancement, reported encouraging results in patients with mild and moderate OSA and multilevel obstruction.[103] However, concern about the long-term results of laser-assisted uvulopalatoplasty (LAUP) for the management of OSA was recently voiced.[104] The response has been characterized as varied and unpredictable. It appears that the favorable subjective short-term results of LAUP deteriorated in time. Postoperative polysomnography revealed that LAUP might lead to deterioration of existing apnea. These findings are probably related to velopharyngeal narrowing and progressive palatal fibrosis inflicted by the laser beam.

There is serious and thoughtful ongoing debate about whether OSA patients should undergo surgery as outpatients. Clearly, there is no one-size-fits-all solution.[92] In deciding a management strategy it is important to consider the patient's body mass index and neck circumference, the severity of the OSA, the presence or absence of associated cardiopulmonary disease, the nature of the surgery, and the anticipated postoperative opioid requirement. It seems reasonable to expect that OSA patients without multiple risk factors who are having relatively noninvasive procedures (e.g., carpal tunnel repair, breast biopsy, knee arthroscopy) typically associated with minimal postoperative pain may be candidates for ambulatory status. However, those individuals with multiple risk factors, or those OSA patients having airway surgery, most probably will benefit from a more conservative approach that includes postoperative admission and careful monitoring. It is imperative to appreciate that these patients are exquisitely sensitive to the respiratory depressant effects of opioids. Additionally, the risk of prolonged apnea is increased for as long as 1 week postoperatively.

Is perioperative risk related to the type of anesthesia (general, regional, or monitored anesthesia care) administered? The limited evidence suggests that the type of surgery probably supersedes in importance the selection of anesthetic technique. Certainly, the use of regional anesthesia may not necessarily obviate the need for securing the airway and may even require emergency airway intervention if excessive amounts of sedative-hypnotics or opioids are administered. Regardless of the type of anesthesia selected, sedation should be administered judiciously. Moreover, it is important to be aware that the American Sleep Apnea Association[105] notes that “It may be fitting to monitor sleep apnea patients for several hours after the last doses of anesthesia, longer than non–sleep apnea patients require and possibly through one full natural sleep period.”

When confronted with an especially challenging OSA patient requiring general anesthesia, a judicious approach may include awake fiberoptic intubation, administering very low-dose, short-acting narcotics, short-acting muscle relaxants, and a low solubility inhalational agent, and infiltrating the surgical site with a long-acting local anesthetic. Extubation should be performed only when the patient is without residual neuromuscular blockade and fully awake, using a tube changer or catheter, and CPAP should be available postoperatively. These high-risk patients should then be admitted to a telemetry ward or intensive care unit because the challenge of maintaining the airway will extend well into the postoperative period. Respiratory events after surgery in OSA patients may occur at any time.

Anesthetic care of the OSA patient is especially challenging, and few definitive data are available to guide perioperative management. The anesthesiologist should begin by having a high index of suspicion for the diagnosis and then seek to identify and quantify associated comorbidities. The major focus of the anesthesiologist of necessity must be on establishing and maintaining the airway, a challenge that will extend well into the postoperative period, especially if the patient is having surgery involving the oropharyngeal or hypopharyngeal area. Depending on the type of surgery, the anticipated amount of narcotic required postoperatively to manage pain, and the patient's condition, outpatient surgery may not be prudent. The roles that effective communication, monitoring, vigilance, judgment, and contingency planning play cannot be overemphasized.

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Recurrent Respiratory Papillomatosis

Recurrent respiratory papillomatosis (RRP) is a disease of viral origin that is caused by human papillomavirus types 6 and 11 (HPV 6 and HPV 11) and is associated with exophytic lesions of the airway that are friable and bleed easily. Although it is a benign disease, RRP has potentially devastating consequences because of its involvement of the airway, the unpredictable clinical course associated with the condition, and the risk of malignant conversion in chronic invasive papillomatosis.

RRP is both the most common benign neoplasm of the larynx among children and the second most frequent cause of childhood hoarseness.[106] The disease is frustrating and often resistant to treatment owing to its tendency to recur and spread throughout the respiratory tract. Although RRP most frequently affects the larynx, the condition can actually involve the entire aerodigestive tract.

The course of the disease is highly variable; some patients undergo spontaneous remission and others experience aggressive papillomatous growth, necessitating multiple surgical procedures over many years. The differential diagnosis of the persistent or progressive stridor and dysphonia associated with RRP in infants includes laryngomalacia, subglottic stenosis, vocal cord paralysis, or a vascular ring (Table 1-19 ).

TABLE 1-19   -- Differential Diagnosis of Infantile Progressive Stridor/Dysphonia






Recurrent respiratory papillomatosis



Subglottic stenosis



Vocal cord paralysis



Vascular ring



In most pediatric series, RRP is typically diagnosed between 2 and 4 years of age, with a delay in correct diagnosis from the time of onset of symptoms averaging about 1 year.[107] The incidence among children in the United States is estimated at 4.3 per 100,000 children, translating into more than 15,000 surgical interventions at a total cost exceeding $100 million annually.[108]

Two distinct forms of RRP are recognized: a juvenile or aggressive form and an adult or less-aggressive form. Adult-onset RRP may reflect either activation of virus present from birth or an infection acquired in adolescence or adulthood. The most common types of human papillomavirus (HPV) identified in the airway are HPV 6 and HPV 11, the same types that cause genital warts. Specific viral subtypes may be correlated with disease severity and clinical course. Children infected with HPV 11, for example, appear to develop greater degrees of airway obstruction at younger ages and have a higher incidence of tracheotomy.[109]

Numerous studies have convincingly linked childhood-onset RRP to mothers with genital HPV infections. Nevertheless, few children exposed to genital warts at birth develop clinical symptoms.[110] Other factors must be operative, such as duration and volume of virus exposure, the behavior of the virus, the presence of local trauma, and patient immunity.

Presenting symptoms include a change in voice, ranging from hoarseness to stridor to aphonia. The stridor can be either inspiratory or biphasic. An associated history of chronic cough and frequent respiratory infections is not uncommon. Children are frequently misdiagnosed initially as having croup, chronic bronchitis, or asthma. Lesions usually are found in the larynx but may also occur on the epiglottis, pharynx, or trachea. The preoperative diagnosis is best made with an extremely small-diameter flexible fiberoptic nasopharyngoscope to more fully establish the extent of airway encroachment.

No single modality has consistently been shown to eradicate RRP. The primary treatment is surgical removal, with a goal of complete obliteration of papillomas and preservation of normal structures. However, in patients in whom anterior or posterior commissure disease or extremely virulent lesions are present, the objective may be revised to subtotal removal with clearing of the airway. It is advisable to “debulk” as much disease as possible, while preventing the complications of subglottic and glottic stenosis, web formation, and diminished airway patency. Whenever possible, tracheostomy is avoided to prevent seeding of papillomas into the distal trachea.

The CO2 laser has been the favored instrument in the eradication of RRP involving the larynx, pharynx, upper trachea, and nasal and oral cavities. However, large, bulky accumulations of papillomas may require sharp dissection. Adjuvant treatments may include interferon alfa-N1,[111] indole-3-carbinol, acyclovir, ribavirin,[112] retinoic acid, and photodynamic therapy.[113] Clearly, the objective of all interventions is to remove as much disease as feasible without causing potentially scarring permanent damage to underlying mucosa in critical areas. Although the CO2 laser is the most commonly used laser for laryngeal RRP, the KTP or argon laser could also be used. Papillomas that extend down the tracheobronchial tree often require the use of the KTP laser coupled to a ventilating bronchoscope for removal. Moreover, the recently developed endoscopic microdébrider is showing promise in terms of possibly causing less laryngeal scarring than the CO2 laser.[114]

The anesthetic management of these patients is often extremely challenging and depends on the site of the lesions, the degree of airway obstruction, and the age of the patient[115] ( Table 1-20 ). The issues are further complicated by the fact that a laser will be used and the anesthesiologist will be sharing the airway with the surgeon. Several approaches should be considered, and each is replete with advantages and disadvantages. A thoughtful risk-benefit analysis is essential. Teamwork and effective communication are critical to optimal outcome. Intraoperative teamwork is enhanced with the availability of video monitors that allow the entire operating room staff to view the surgery as it progresses. Dialogue between the anesthesiologist and the surgeon must continue throughout the procedure, focusing on the current ventilatory status, amount of bleeding, vocal cord motion, concentration of oxygen being administered, and timing of laser use in conjunction with respiration.

TABLE 1-20   -- Anesthetic Options for Recurrent Respiratory Papillomatosis

Intubation Techniques

Nonintubation Techniques

Surgeon gowned and gloved before induction

Same pretreatment and precautions as with intubation

Preoperative dexamethasone


Slow, gentle inhalation induction with continuous positive airway pressure

Insufflation of volatile agents with spontaneous ventilation

Intubate with smaller than usual, laser-safe endotracheal tube

Total intravenous anesthesia with spontaneous ventilation

Eye protection for patient and staff

Jet ventilation with muscle paralysis

FIO2 < 0.3


Awake extubation




The available anesthetic options may be broadly separated into intubation and nonintubation techniques. When the lesions are assumed to be partially obstructing the airway, the best approach is a careful, gentle, smooth induction with sevoflurane or halothane, preferably with an intravenous line in place before induction is initiated. Preoperative dexamethasone, 0.5 mg/kg IV, is routinely given. The surgeon should be present in the operating room, and all the requisite equipment to deal with total airway obstruction should be immediately available. Often a jaw thrust combined with positive pressure in the anesthesia circuit will maintain airway patency. Should complete airway obstruction occur, the anesthesiologist may elect to give an appropriate dose of propofol, if indicated, and attempt intubation with a smaller than usual endotracheal tube. If this attempt fails, the surgeon should try using the rigid bronchoscope or, as a last resort, a transtracheal needle should be placed or tracheotomy performed. The anesthesiologist may then choose among several techniques.

If an intubated technique is elected, this approach has the advantage of allowing the anesthesiologist to maintain control of the airway and of ventilation. However, the endotracheal tube increases the risk of airway fire and may impede surgical exposure and access. The smallest possible laser-safe endotracheal tube should be used that permits adequate ventilation. If a cuffed tube is deemed necessary, the cuff should be filled with methylene blue–colorized saline to provide an additional warning if the cuff is perforated.[116] After the airway has been secured with a laser-safe endotracheal tube, the anesthesiologist has the option to administer muscle relaxants. The child's eyes are protected with moist, saline-soaked gauze eye pads placed over the lids. Additionally, all operating room personnel must wear safety glasses and special laser masks with extremely small pores to minimize exposure to the laser plume. The fraction of inspired oxygen (FiO2) delivered to the patient should be as close to a room air mixture as possible (FIO2 between 0.26 to 0.3). During resection the surgeon must exercise great care to avoid injuring the anterior commissure, and at least 1 mm of untreated mucosa should be left so that a web does not develop. If the surgeon detects disease in the posterior part of the glottis or in the subglottic region, the endotracheal tube obstructs exposure of these areas to the operative field and an alternative means of anesthesia is selected. Often the surgeon will prefer an apneic technique wherein the endotracheal tube is removed intermittently and surgery is performed while the patient's oxygen saturation is monitored. The endotracheal tube is periodically reinserted as needed. Typically, the lungs are reoxygenated for the same period of time that they were apneic before proceeding with the next “cycle.”

Alternatively, a nonintubated technique using spontaneous ventilation with volatile anesthetic agents has been described by several authors. [117] [118] The patient is induced in the aforementioned fashion, and maintenance of anesthesia is continued with sevoflurane or halothane that is insufflated into the oropharynx by attaching the fresh gas flow hose to a side port on the suspension laryngoscope. The larynx is anesthetized with topical lidocaine (not to exceed 4 to 5 mg/kg) before proceeding with further surgical intervention. This is not an ideal (or easy) anesthetic technique because the anesthesiologist must deftly balance the anesthetic depth somewhere between too light (triggering laryngospasm) and too deep (causing apnea). Additionally, the operating room environment becomes contaminated, but a vacuum hose is helpful in extracting exhaled gases and virus particles. Total intravenous anesthesia with an infusion of propofol and remifentanil is also appropriate with this nonintubated, spontaneous ventilation technique.[115] The surgeon, however, may complain of too much laryngeal movement with total intravenous anesthesia because patients anesthetized with these agents breathe slowly but very deeply.

Another anesthetic alternative is the use of jet ventilation. Jet ventilation eliminates the potential for an endotracheal tube fire and allows good visualization of the vocal cords and areas distal to them. However, the technique has the risk of barotrauma and may allow transmission of HPV particles into the distal airway. The jet cannula can be positioned either above or below the vocal cords; placement of the cannula proximal to the end of the laryngoscope decreases the risk of possible pneumothorax or pneumomediastinum. With large laryngeal lesions, narrowed airways, and ball-valve lesions, considerable outflow obstruction may develop, leading to increased intrathoracic pressure and pneumothorax. The anesthesiologist must carefully observe chest excursion and ensure that there is unimpeded exhalation. Muscle relaxants are administered to prevent vocal cord motion. Constant communication between anesthesiologist and surgeon about timing of ventilation in relation to surgical manipulation is required. Excessive mucosal drying and gastric distention are other disadvantages of this approach. At the end of the procedure, the trachea is intubated with a standard endotracheal tube.

The trachea is extubated only when the child is fully awake. High humidity and, occasionally, racemic epinephrine are administered postoperatively. The patient is closely monitored for several hours before discharge, and often an overnight stay is advisable, especially if the disease was extensive and the airway was significantly compromised. Continuous pulse oximetry is mandatory and postoperative steroid administration may be helpful.

The scientific community is aggressively working to improve our knowledge about RRP. A national registry of patients with RRP has been formed through the cooperation of the American Society of Pediatric Otolaryngology and the Centers for Disease Control and Prevention.[119] It is expected that this registry will identify patients who are suitable for enrollment in multi-institutional studies of adjuvant therapies and will more sharply define the risk factors for transmission of HPV and the cofactors that determine the virulence of RRP. No doubt future projects will include development of an HPV vaccine and refinements in surgical techniques to minimize laryngeal scarring.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Cystic Hygroma

Cystic hygroma is a rare, multilocular, benign lymphatic malformation, usually involving the deep fascia of the neck, oral cavity, and tongue, although the axilla may also be affected. This type of lymphangioma is capable of massive growth and can be quite disfiguring. Almost all known cases of cystic hygroma have presented by 5 years of age, with most being observed in the neonatal period.[120]In fact, there are cases described in the literature of antenatal diagnosis of cystic hygroma with fetal airway encroachment detected by screening ultrasound. The few infants who survived to delivery were intubated immediately after the head was delivered, with the placenta functioning as an extracorporeal source of oxygenation until the airway was secured. [121] [122]

As the tumor grows, it often encroaches on surrounding structures such as the pharynx, tongue, or trachea. Dysphagia and various degrees of airway obstruction are not uncommon. These tumors are not responsive to radiation therapy, and multiple surgical resections are often necessary. Because the tumors are not encapsulated, they easily envelop and grow into surrounding structures, preventing complete excision. The ability of cystic hygromas to elude complete extirpation has led to a recrudescence of injection of sclerosing agents intralesionally as either primary or adjunctive therapy.[123] This approach had been abandoned, but the availability of newer, improved agents has led to better results.

Although sudden enlargement of the tumor can cause a true airway emergency, most commonly the children present for elective resection. Because of mechanical complications, the young child may be malnourished or dehydrated. He or she may also have sleep apnea. Stridor is an ominous sign, suggesting imminent airway decompensation. A chest radiograph should be reviewed for tracheal deviation or mediastinal extension. Although CT or MRI will provide more complete information about the full extent of the lesion, the sedation necessary to obtain such studies may cause airway obstruction—an example of “perfection being the enemy of good.”

The patient is given an antisialagogue before anesthesia is administered to minimize secretions that might complicate anesthetic management ( Table 1-21 ). The surgeon is present in the operating room, gowned and gloved, and ready to perform a tracheostomy if necessary. The anesthesiologist must carefully prepare a wide variety of difficult airway equipment in the event of an airway emergency. Clearly, the safest approach in these children is an awake intubation because a marginally adequate airway while the patient is awake may become totally obstructed during induction when the upper airway muscles relax and the tumor fills the airway. However, because many, if not most, pediatric patients will not tolerate an awake intubation, children with cystic hygroma often undergo a slow, meticulous, titrated inhalation induction of anesthesia with preservation of spontaneous ventilation and application of CPAP. When anesthetic depth is adequate, fiberoptic intubation is performed. Often a large, protruding tongue will make oral intubation impossible, so the nasal route is chosen after administration of an appropriate vasoconstrictor to the nostrils. (If an unsuccessful direct laryngoscopy or an attempt at blind nasal intubation is performed initially, these approaches may trigger bleeding that could hamper subsequent attempts at fiberoptic intubation.) When the surgery is completed, it is helpful to perform direct laryngoscopy because the view may have improved significantly after the resection.[115] This information will prove useful in the event that reintubation is required postoperatively.

TABLE 1-21   -- Anesthetic Management of Cystic Hygroma



Evaluate preoperatively for stridor, tracheal deviation, or mediastinal extension.



Determine optimally tolerated position.



Administer preoperative antisialagogue.



Have surgeon gowned and gloved before induction/intubation.



Apply topical vasoconstrictor to nares.



Know that fiberoptic nasotracheal intubation is often necessary.



Perform extubation with caution.



If attempts at fiberoptic intubation are unsuccessful, other options include passing a retrograde wire after asking the surgeon to aspirate fluid from the mass (a request that the surgeon may decline to perform owing to concern about recurrence from an incompletely resected, ruptured sac), using a light wand or Bullard laryngoscope, attempting tactile intraoral tube placement, or trying a blind nasal intubation. In the event that these attempts fail and mask ventilation becomes inadequate, a laryngeal mask airway should be inserted. If this fails to open the airway, an emergency surgical airway should be attempted. In the event that the surgeon is unable to expose the trachea, the only remaining option to save the child may be the performance of femoral cardiopulmonary bypass.[115]

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Copyright © 2005 Saunders, An Imprint of Elsevier

Wegener's Granulomatosis

Wegener's granulomatosis (WG) is a systemic disease of unknown etiology characterized by necrotizing granulomas and vasculitis that classically affects the upper and lower airway and the kidneys. Although the etiology remains unestablished, recent interest has focused on the possible role of Staphylococcus aureus in the pathophysiology of the disease.[124] WG can have a myriad of head and neck manifestations, including mucosal ulceration of the nose, palate, larynx, and orbit, as well as deafness and subglottic[125] or tracheal stenosis. Ocular disease occurs in 50% to 60% of adults with WG[126]and may include such conditions as necrotizing scleritis with peripheral keratopathy,[127] orbital pseudotumor,[126] and ocular myositis,[126] as well as uveitis, vitreous hemorrhage, and central retinal artery occlusion.[128]

Wegener's granulomatosis often starts with severe rhinorrhea, cough, hemoptysis, pleuritic pain, and deafness. However, it is a truly systemic disease and varies widely in presentation. Indeed, the protean manifestations of WG often produce diagnostic delay. Diagnosis is supported by histopathologic studies showing a vasculitis, parenchymal necrosis, and multinucleate giant cells, but tissue biopsy alone is insufficient to establish the diagnosis of WG. The most specific test is a positive antineutrophil cytoplasmic antibody test (c-ANCA).[129]

WG was once fatal. With the advent, however, of long-term treatment with corticosteroids and cyclophosphamide, affected individuals survive longer, and a broader spectrum of the disease has been observed in recent years. The incidence of subglottic stenosis in WG ranges from 8.5% to 23%.[130] It is a significant cause of morbidity and mortality and typically is unresponsive to systemic chemotherapy. Other treatments have included mechanical subglottic dilation (with or without intratracheal steroid injection) and laser therapy, with variable success. Recently, encouraging results in treating subglottic stenosis have been reported with endoscopic insertion of nitinol stents after dilation of the stenotic segment with bougie dilators.[125] Nitinol is a nickel and titanium alloy that has excellent properties, including biocompatibility, kink resistance, and elasticity, thus resembling the tracheobronchial tree. These metal stents are expandable, serving as an intraluminal support to establish and maintain airway patency. They are usually permanent but can be removed if necessary. For the intervention to be successful, however, the diseased segment must begin at least 1 cm below the vocal cords.

Patients with WG often present for ocular, nasal, or laryngeal surgery. The anesthesiologist must anticipate a host of potential problems ( Table 1-22 ). These challenges include dealing with the side effects of chronic corticosteroid and cyclophosphamide therapy as well as the presence of underlying pulmonary and renal disease. Additionally, midline necrotizing granulomas of the airway may cause obstruction or bleeding at intubation. Some degree of subglottic or tracheal stenosis should also be expected. Chest radiography, CT, or MRI of the airway, arterial blood gas analysis, pulmonary function tests, and determinations of blood urea nitrogen and creatinine levels are helpful guides to optimal anesthetic management.

TABLE 1-22   -- Anesthetic Concerns with Wegener's Granulomatosis



Side effects of steroids and cyclophosphamide



Bleeding induced by airway manipulation



Subglottic stenosis



Tracheal stenosis



Reduced pulmonary reserve



Impaired renal function



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Acromegaly is a rare chronic disease of midlife caused by excess secretion of adenohypophyseal growth hormone (GH). (Hypersecretion of GH before epiphyseal closure produces gigantism in younger individuals.) GH acts on a wide variety of tissues, both directly and through release of insulin-like growth factor I (IGF-I), which is released mainly from the liver in response to GH. In addition to stimulating bone and cartilage growth, GH and IGF-I promote protein synthesis and lipolysis while reducing insulin sensitivity and causing sodium retention. Therefore, it is not surprising that acromegaly is characterized by enlargement of the jaw, hands and feet, and soft tissues, as well as diabetes mellitus and hypertension. Severe, chronic hypertension may result in cardiomegaly, left ventricular dysfunction, congestive heart failure, and dysrhythmias. Airway soft tissue overgrowth may produce macroglossia with glossoptosis, vocal cord thickening with hoarseness, and subglottic narrowing. Vocal cord paralysis has also been reported occasionally. Approximately 25% of acromegalics have an enlarged thyroid, which may produce tracheal compression or deviation. Diagnosis is confirmed by elevated 24-hour GH levels in conjunction with increased serum IGF-I levels.

Most pituitary tumors originate in the anterior part of the gland and the overwhelming majority are benign adenomas. Proposed etiologic mechanisms include malfunction of normal growth-regulating genes, abnormal tumor suppressor genes, and changes in genes that control programmed cell death.[131] The prevalence of pituitary tumors is approximately 200 per million of the population,[132] but random autopsy results indicate an incidence as high as 27%,[133] suggesting that the majority of pituitary adenomas are asymptomatic. The most common type of pituitary adenoma causes hyperprolactinemia. Adenomas producing acromegaly and Cushing's disease are more unusual. The annual incidence of acromegaly, for example, is said to be three to eight cases per million.

The primary treatment of acromegaly is surgery, with or without subsequent radiotherapy. However, in the relatively few patients who respond to treatment with dopamine agonists, such as bromocriptine, surgery can be avoided. Somatostatin also inhibits GH release, and long-acting analogues of somatostatin, such as octreotide, may be tried in those who fail to respond to dopamine agonists.[134]

Acromegaly is widely recognized as one of many causes of difficult airway management [135] [136] ( Table 1-23 ). Careful preoperative airway assessment is therefore indicated, paying special attention to the possibility of sleep apnea by questioning the patient about any history of loud snoring, frequent nocturnal awakening, and daytime hypersomnolence. It is imperative to appreciate that the risk of death from respiratory failure is threefold greater in acromegaly.[137] Hypertension is common in acromegalics but usually responds to antihypertensive therapy. Myocardial hypertrophy and interstitial fibrosis are also common and may be associated with left ventricular dysfunction. Thus, indicated preoperative studies often include a chest radiograph, electrocardiogram, and echocardiogram, in addition to lateral neck radiographs and CT of the neck.

TABLE 1-23   -- Perioperative Concerns with Acromegaly



Difficult airway management; suspect sleep apnea



Subglottic narrowing



Tracheal compression or deviation associated with thyroid enlargement












Left ventricular dysfunction



Congestive heart failure



Diabetes mellitus



Venous air embolism



Postoperative anterior pituitary insufficiency and diabetes insipidus



Postoperative cerebrospinal fluid rhinorrhea, meningitis, sinusitis, and cranial nerve palsy



The pituitary fossa can be approached using the transsphenoidal, transethmoidal, or transcranial route. For all but the largest tumors, the transsphenoidal route is preferred, owing to a lower incidence of associated complications. Otolaryngologists often assist neurosurgeons in performing transsphenoidal hypophysectomy, gaining access to the pituitary fossa using a sublabial or endonasal approach. Hormone replacement, including 100 mg hydrocortisone, is administered intravenously at induction, and prophylactic antibiotics are given. An appropriate vasoconstrictor is applied to the nostrils, and care must be taken to prevent hypertension or dysrhythmias. Large face masks and long-bladed laryngoscopes should be prepared, and a fiberoptic laryngoscope should be available. Depending on the airway assessment, an awake fiberoptic intubation may be the preferred approach to securing the airway. The intubating laryngeal mask airway has also been used successfully in patients with acromegaly. Equipment for tracheostomy should be immediately available if airway involvement is extensive.

After intubation, the mouth and pharynx should be packed before surgery commences to prevent intraoperative bleeding into the laryngeal area, which may cause postextubation laryngospasm, and into the stomach, which may trigger postoperative nausea and vomiting.

Some surgeons request that a lumbar drain be inserted in patients with major suprasellar tumor extension. The intention is to produce prolapse of the suprasellar part of the tumor into the operative field by injecting 10-mL aliquots of normal saline as needed. Additionally, if the dura is perforated intraoperatively, the lumbar catheter can be left in situ postoperatively to control any leakage of cerebrospinal fluid.[138]

Transsphenoidal surgery is conducted with the patient supine with a moderate degree of head-up tilt. Careful monitoring for venous air embolism is indicated if the head is elevated more than 15 degrees. Other monitoring should include direct arterial blood pressure, electrocardiography, oxygen saturation, and end-tidal carbon dioxide determination. Visual evoked potentials have limited usefulness because they are very sensitive to anesthetic effects. Any anesthetic approach that is compatible with the exigencies of intracranial surgery is acceptable. Regardless of whether an inhalation agent or total intravenous anesthesia is selected, short-acting agents are administered to allow rapid recovery at the end of surgery. Drugs such as propofol, sevoflurane, and remifentanil are excellent agents to accomplish this objective. At the completion of surgery, pharyngeal packs should be removed. When the patient is awake with reflexes intact, extubation should be conducted, taking care not to dislodge nasal packs or stents. Patients should be carefully observed postoperatively for airway patency. Those with sleep apnea should be carefully followed in a monitored unit, because treatment options such as nasal CPAP cannot be applied after transsphenoidal surgery. Narcotics should be administered with special caution to patients with sleep apnea. Hormone replacement with tapered cortisol therapy is critical postoperatively. In addition to anterior pituitary insufficiency, diabetes insipidus may also develop postoperatively, but most borderline cases resolve spontaneously in a few days as posterior lobe function recovers.[138] Other potential complications include cerebrospinal fluid rhinorrhea, meningitis, sinusitis, and cranial nerve palsy.

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Ludwig's Angina

Ludwig's angina is a potentially lethal, rapidly expanding cellulitis of the floor of the mouth characterized by brawny induration of the upper neck, usually unaccompanied by obvious fluctuation. Spread of the infection along the deep cervical fascia can result in mediastinitis, mediastinal abscess, jugular vein thrombosis, innominate artery rupture, empyema, pneumothorax, pleural and/or pericardial effusion, subphrenic abscess, necrotizing fasciitis, and mandibular or cervical osteomyelitis. Although the inflammation is typically caused by cellulitis, there can also be a component of gangrenous myositis.[139]

Although one can find mention of the symptoms of this condition in writings dating back to Hippocrates, Ludwig's angina was best described initially in 1836 by its namesake, Karl Friedrich Wilhelm von Ludwig. He described this disease as a rapidly progressive gangrenous cellulitis originating in the region of the submandibular gland that extends by continuity rather than lymphatic spread. During the late 19th and early 20th centuries, Ludwig's angina was commonly considered a complication of administration of local anesthetics used to facilitate extraction of mandibular teeth.[140] It was not until later in the 20th century that the actual pathogenesis of the disease was elucidated. In 1943, Tschiassny[141] clarified the unique role that the floor of the mouth played in the development of the disease. He described how periapical dental abscesses of the second and third mandibular molars penetrate the thin inner cortex of the mandible. Because these roots extend inferior to the mandibular insertion of the mylohyoid muscle, infection of the submandibular space ensues. Owing to communication around the posterior margin of the mylohyoid muscle, rapid involvement of the sublingual space occurs, followed quickly by involvement of the contralateral spaces. The unyielding presence of the mandible, hyoid, and superficial layer of the deep cervical fascia limit tissue expansion as edema develops and progresses. This resistance leads to superior and posterior displacement of the floor of the mouth and the base of the tongue. These patients, therefore, have an open-mouth appearance, with a protruding or elevated tongue, and exhibit marked neck swelling. Soft tissue swelling in the suprahyoid region, combined with lingual displacement and the frequent concomitant of laryngeal edema, can occlude the airway and abruptly asphyxiate the patient.

Although the overwhelming preponderance of cases of Ludwig's angina have an odontogenic origin, other risks include sublingual lacerations, penetrating injuries to the floor of the mouth, sialadenitis, compound mandibular fractures, osteomyelitis of the mandible, otitis media, infected malignancy, and abscesses located under the thyrohyoid membrane.[142] Patients typically present with fever, as well as edema of the tongue, neck, and submandibular region. These symptoms can progress to include dysphagia, inability to handle secretions, dysphonia, trismus, and difficulty breathing. Polymicrobial infections are common. The usual offending organisms include streptococci, staphylococci, and Bacteroides.

In the preantibiotic era, Ludwig's angina was associated with mortality rates exceeding 50%. Originally, the extremely sudden manner of death was ascribed to overwhelming sepsis. It was not until the early 20th century that the lethal role of mechanical respiratory obstruction leading to asphyxia was understood.[143] Taffel and Harvey,[144] in 1942, succeeded in reducing mortality to less than 2% by emphasizing early diagnosis and advocating aggressive treatment with wide surgical decompression of the submandibular and sublingual spaces with the patient under local anesthesia. This intervention allowed the elevated base of the tongue to assume an anteroinferior position, thereby preserving the patency of the oropharyngeal airway.

With the increasing availability of antibiotics in the 1940s, a reduction in the incidence of and mortality from Ludwig's angina ensued. Today, aggressive antibiotic therapy in the early stages of the disease has led to a reduced need for surgical decompression and the need for airway intervention ( Table 1-24 ). Patterson and colleagues,[145] for example, reported a series of 20 patients at their institution in whom only 35% required airway control in the form of either tracheotomy or endotracheal intubation. The anticipated need for airway control may differ among groups of patients, with patients who are older and have more comorbidity seeming to be at greater risk for airway obstruction. [146] [147] Additionally, patients who are in poorer condition at the time of presentation may well be in danger of imminent airway closure. Clearly, stridor, difficulty managing secretions, anxiety, and cyanosis are late signs of impending obstruction and should serve as indicators of the need for immediate airway intervention.

TABLE 1-24   -- Anesthetic Concerns with Ludwig's Angina



Early, aggressive antibiotic therapy may obviate need for airway intervention/surgical decompression.



Older, sicker patients purportedly at increased risk for airway obstruction.



Anticipate difficult airway management.



Favor awake fiberoptic intubation with an armored tube or tracheostomy—under local anesthesia.



Airway management may be extremely difficult. Often, preliminary tracheostomy using local anesthesia may be the safest option. Depending on the patient's condition, including the presence or absence of trismus and the ability of the patient to cooperate, other options include an awake fiberoptic intubation, or an inhalation induction, preserving spontaneous respiration, followed by intubation with direct laryngoscopy or fiberoptic assistance. If the oropharynx cannot be visualized by CT, a fiberoptic nasotracheal approach is advised. Needless to say, a surgeon should be present and a tracheotomy kit immediately available when the nonsurgical route to establish the airway is selected. Owing to the potential for continued airway swelling after the endotracheal tube is placed, it seems prudent to insert an armored tube to better protect the airway.

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There has been extraordinary progress in the treatment of many complex ophthalmic and otolaryngologic conditions during the past 25 years. These often complicated patients are presenting for many surgical and diagnostic procedures that did not exist a generation ago. It is essential, therefore, that the anesthesiologist appreciates that few of the conditions presented in this chapter have isolated ophthalmic or ENT pathology. Rather, they frequently are associated with multisystem diseases, and the anesthetic plan must reflect this sobering reality.

Typically, it is inappropriate to insist dogmatically that one anesthetic approach is unequivocally superior to all others in the management of any specific condition, especially the complex entities discussed here. The key to optimal anesthetic management and outcome resides in a comprehensive understanding of the disease process, the surgical requirements, and the effects of our anesthetic agents and techniques on both the individual patient and the proposed surgery.

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Copyright © 2005 Saunders, An Imprint of Elsevier


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