Specific Diseases

Pulmonary Vascular Diseases

Pulmonary vascular diseases include pulmonary hypertension secondary to heart disease (postcapillary disorders),

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Infections Diseases of the Lung

Preoperative evaluation and treatment should follow the basic guidelines outlined in the introduction to this section; treatment of the underlying disease should be completed before all but emergency surgery is performed. It bears repeating that viral respiratory infections do affect respiratory function by giving rise to increased airflow obstruction (especially in the small airways) that may persist for at least 5 weeks. Viral respiratory infections also adversely affect the respiratory mechanisms that defend against bacteria. Within 5 weeks of an upper respiratory infection, children may have an increased incidence of perioperative respiratory tract complications after intubation.^{[551] [552] [553] [554] [555] [556]} It appears appropriate to delay surgery that requires tracheal intubation for all children (and possibly all adults) for 5 weeks after an upper respiratory infection.^{[551] [552] [553] [554] [555] [556]} However, in afebrile outpatient ASA I and II children with no lung disease or findings who underwent noncavitary, nonairway surgery lasting less than 3 hours, Elwood and coauthors reported that there was no association between either recent URI or active URI and desaturation, wheeze, cough, stridor, or laryngospasm causing desaturation.^[540]

Even though elective surgery should be postponed whenever infectious diseases of the lung are present, patients undergoing emergency surgery often have nosocomial infections and immunocompromised systems. The predominant pathogens for nosocomial pneumonia are gram-negative bacilli, Staphylococcus aureux, Haemophilus influenzae, anaerobes, and pneumococci. Furthermore, tuberculosis has been increasing since 1985, probably because of reactivation in patients infected with HIV. Tuberculosis leads to chronic pulmonary and systemic symptoms. Affected patients may have malaise, headache, fever, hemoptysis, and extrapulmonary diseases affecting the skin, cervical lymph nodes, kidneys, pericardium, and meninges. Active disease is treated with isoniazid and rifampin for 9 months. Therapy should probably be started before surgery; for patients coming from countries with a high incidence of resistance to isoniazid, initial therapy might include more than two drugs. Administration of treatment before these emergency patients (many of whom have adult respiratory distress syndrome) are brought to the operating room might include initiation of anti-infective therapy, optimization of fluid status and gas exchange, and therapy for the underlying pathophysiologic process.^{[580] [581] [582] [583] [584] [585]}

Chronic Obstructive Pulmonary Disease

Treatment of COPD (reactive airways) may include the use of β-adrenergic drugs, parasympatholytic agents (especially for exercise-induced asthma), systemic or inhaled corticosteroids, and leukotriene antagonists.^{[502] [503] [504] [505] [506] [507] [508] [509] [510] [511] [512] [513] [514] [586]} An estimated 5% of the population has bronchospasm. Some investigators recommend using inhaled bronchodilators as first-line drugs and reducing the dose of inhaled steroids, such as beclomethasone dipropionate, budgesonide, mometasone, or fluticasone, which are inactivated after absorption. However, in large doses, these "inhaled" steroids can suppress adrenal function, and supplemental systemic corticosteroids may be needed at times of stress (see earlier discussion under the section on adrenocortical malfunction). Preoperative assessment must include gaining knowledge of drug regimens and their effects and education of the patient regarding proper use of an inhaler ( Table 27-45 ) because these drugs can interact dangerously with anesthetics (see the last section of this chapter) or can be used inappropriately and therefore produce side effects without maximum benefit.^{[502] [503] [504] [505] [506] [507] [508] [509] [510] [511] [512] [513] [514]} No known interaction between the inhaled anticholinergic ipratropium bromide and muscle relaxants has been reported. Patients can feel fine at rest but must be tested by exercise or spirometry to document the degree of

TABLE 27-45 -- Procedures for correct use of a metered-dose inhaler

Remove the cap and hold the inhaler upright.

Shake the inhaler.

Tilt the head back slightly and exhale steadily to functional residual capacity.

Position the inhaler by using a spacer between the actuator and the mouth.

Press down on the inhaler while taking a slow, deep breath (3 to 5 seconds).

Hold the full inspiration for at least 5 and up to 10 seconds, if possible, to allow the medication to reach deeply into the lungs.

Repeat inhalations as directed. Waiting 1 minute after inhalation of the bronchodilator may permit subsequent inhalations to penetrate more deeply into the lungs and is necessary to ensure proper dose delivery.

Rinse the mouth and expectorate after using the inhaler.

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COPD takes several forms. Bronchial asthma, which occurs in 3% to 5% of the population, is characterized by reversible airway obstruction. When airway obstruction is partially reversible (by steroids or adrenergic mediators), it is often accompanied by chronic bronchitis. Some of the drugs may improve aspects of lung function other than bronchial muscle tone.^[554] The majority of patients with a history of chronic cough and production of sputum on most days for 3 months a year for at least 2 years have chronic bronchitis. These patients are (or almost always have been) smokers, although environmental and occupational or genetic predisposition may contribute to hypertrophy of the mucous glands in the major airways, to hyperplasia of the goblet cells, and to edema and inflammation of the airways. They will have a decreased DLCO, whereas patients with pure bronchospasm will have a normal DLCO. Hyperinflation of the air spaces, abnormal dilation, and destruction of acinar units distal to the terminal bronchiole define emphysema. The destruction of alveolar membranes is believed to be related to an imbalance favoring destructive proteases (the most important of which are neutrophil derived) over protective circulating antiproteases (the most important of which is α₁ -antitrypsin). Cigarette smoking increases the protease-antiprotease ratio. The destruction of alveolar structures limits expiratory airflow by decreasing both elastic lung recoil and radial lung traction, and the loss of alveolar capillary blood volume results in decreased DLCO. Cystic fibrosis is characterized by dilatation and hypertrophy of the bronchial glands, mucous plugging of the peripheral airways, and often, bronchitis, bronchiectasis, and bronchiolectasis. For all these conditions, the measures recommended earlier in this section, as well as appropriate hydration to allow for mobilization of secretions, should be followed.

Interstitial and Immune Lung Diseases

Included in this heterogeneous group of diseases are the hypersensitivity lung diseases, environmental exposure diseases, inorganic dust diseases, radiation-induced lung disease, sarcoidosis, collagen vascular disorders (systemic lupus erythematosus, polymyositis, dermatomyositis, Sjögren's syndrome, rheumatoid arthritis, systemic sclerosis), Goodpasture's syndrome, idiopathic pulmonary hemosiderosis, Wegener's granulomatosis, and the autoimmune diseases.^[588] CT scans localize pulmonary inflammation and have become the primary decision-making tool in diagnosing infiltrative lung disease.^{[589] [590]} Many of these disorders affect not only the lungs but also the blood vessels, the conduction system of the heart, the myocardium, the joints (including those of the upper airway and larynx), and the renal, hepatic, and central nervous systems as well. The reader is referred to a textbook of internal medicine to aid in understanding the pathophysiologic processes and full preoperative assessment of these conditions. Therapy for these conditions includes the use of anti-inflammatory drugs, corticosteroids, and immunosuppressive therapies.

Neoplasms

Solitary nodules are tumors that are less than 6 cm in diameter, surrounded by lung parenchyma, and not associated with adenopathy or pleural effusion. The cure rate for bronchogenic carcinoma manifested as a solitary nodule is 50%—much better than the "cure" rate for other manifestations.^[591] (It should be remembered that tuberculosis can mimic cancer so closely that surgery has even been performed.) Blood studies, including calcium and alkaline phosphatase levels, and liver function studies help confirm that the neoplasm has not disseminated. If these studies and the history and physical examination show no abnormal findings, it is unlikely that bone, brain, or hepatic MRI or CT scanning techniques will indicate metastasis. Surgery need not await the results of these tests because few patients not found to have metastatic disease by simple blood tests, history, and physical examination will prove to have such disease detected by these scans. Survival depends on the stage of the tumor and the age of the patient.^[592]

Surgical resection is the primary therapy for non-small cell carcinomas (e.g., adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). These carcinomas account for 75% of all lung carcinomas, 12% of all malignant tumors, and 20% of all cancer deaths in the United States.^[593] Success of surgery can be predicted by the stage of the tumor. The most widely accepted staging system for these carcinomas is the tumor-node-metastasis (TNM) classification. In this system, T1 lesions are smaller than 3 cm in diameter, T2 lesions are larger than 3 cm, T3 lesions invade the chest call mediastinum or diaphragm, and T4 lesions invade the heart or great vessels. The designation N0 indicates no lymph node involvement; N1, tracheobronchial or hilar lymph node involvement; and N3, contralateral or supraclavicular lymph node involvement. M0 connotes no metastases, and M1, systemic metastases.

Patients in stage I who have small primary tumors (T1N0M0) usually undergo lobectomy and have a 5-year survival rate of 50%. Surgical procedures that spare the pulmonary parenchyma—wedge resection or bronchial sleeve resection—are reserved for patients with COPD and heart disease, although thoracoscopic resection may radically improve localization and tolerance of procedures. Patients in stage II (T1N1M0 or T2N1M0) also undergo total resection and have a 5-year survival rate of 30%. Patients in stage IIIa (T3N0M0 or T1 or T2N2M0) undergo resection for cure but currently have a 5-year survival rate of only 17%.^[592] Postresection radiotherapy has not been demonstrated to improve survival as yet, and mass screening programs do not lead to a better prognosis (see Chapter 25 sections on lead and length time biases). Diagnostic typing and staging often involve percutaneous transthoracic aspiration, which is associated with a 30% incidence of pneumothorax.^[592]

The combination of chemotherapy and radiation therapy is the current treatment of choice for small cell carcinomas of the lung.^[594] Oat cell (small cell) carcinoma of

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Anaphylaxis, Anaphylactoid Responses, and Allergic Disorders Other than Those Related to Lung Diseases and Asthma

Anaphylactic and Anaphylactoid Reactions

Anaphylaxis is a severe life-threatening allergic reaction. Allergic applies to immunologically mediated reactions, as opposed to those caused by pharmacologic idiosyncrasy, by direct toxicity or drug overdosage, or by drug interaction.^{[590] [595] [596]} Anaphylaxis is the typical immediate hypersensitivity reaction (type I). Such reactions are produced by immunoglobulin E (IgE)-mediated release of pharmacologically active substances. These mediators in turn produce specific end-organ responses in the skin (urticaria), the respiratory system (bronchospasm and upper airway edema), and the cardiovascular system (vasodilation, changes in inotropy, and increased capillary permeability). Vasodilation occurs at the level of the capillary and postcapillary venule and leads to erythema, edema, and smooth muscle contraction. This clinical syndrome is called anaphylaxis. By contrast, anaphylactoid reaction denotes an identical or very similar clinical response that is not mediated by IgE or (usually) an antigen-antibody process.^[597]

In anaphylactic reactions, an injected substance can serve as the allergen itself. Low-molecular-weight agents are believed to act as haptens that form immunologic conjugates with host proteins. The offending substance, whether hapten or not, may be the parent compound, a nonenzymatically generated product, or a metabolic product formed in the patient's body. When an allergen binds immunospecific IgE antibodies on the surface of mast cells and basophils, histamine and eosinophilic chemotactic factors of anaphylaxis (ECF-A) are released from storage granules in a calcium- and energy-dependent process.^[595] Other chemical mediators are rapidly synthesized and subsequently released in response to cellular activation. These mediators include slow-reacting substance of anaphylaxis (SRS-A), which is a combination of three leukotrienes; other leukotrienes^[598] ; kinins; plateletactivating factors; adenosine; chemotactic factors; heparin tryptase; chymase; and prostaglandins, including the potent bronchoconstrictor prostaglandin D₂ , eosinophil growth and activating factors, mast cell growth factors, and proinflammatory and other factors that contribute to the IgE isotype switch.

The end-organ effects of the mediators produce the clinical syndrome of anaphylaxis. Usually, a first wave of symptoms, including vasodilation and a feeling of impending doom, is quickly followed by a second wave as the cascade of mediators amplifies the reactions. In a sensitized patient, onset of the signs and symptoms caused by these mediators is usually immediate but may be delayed 2 to 15 minutes or, in rare instances, as long as 2.5 hours after the parenteral injection of antigen.^{[598] [599]} After oral administration, manifestations may occur at unpredictable times.

Mast cell proliferation, together with severe progressive inflammation, contributes to the worsening of symptoms that occurs even after an allergen load is no longer present. The antigen present in cells and lymphocytes, as well as activated mast cells, starts to make cytokines. These proinflammatory cytokines recruit more inflammatory cells, which promotes tissue edema and mediates a second wave of mast cell degranulation. This second wave can promote recurrence of severe symptoms 6 to 8 hours later and necessitates, some believe, at least 8 hours of continued ICU-like observation.

In addition, there are multiple effector processes by which biologically active mediators can be generated to produce an anaphylactoid reaction. Activation of the blood coagulation and fibrinolytic systems, the kiningenerating sequence, or the complement cascade can produce the same inflammatory substances that result in an anaphylactic reaction. The two mechanisms known to activate the complement system are called classical and alternative. The classical pathway can be initiated through IgG or IgM (transfusion reactions) or plasmin. The alternative pathway can be activated by lipopolysaccharides (endotoxin), drugs (Althesin^[597] ), radiographic contrast media,^[600] membranes (nylon tricot membranes for bubble oxygenators^[601] ), cellophane membranes of dialyzers,^[602] vascular graft material, ^[603] latex or latex-containing products,^{[604] [605]} and perfluorocarbon artificial blood. The most common agents that are responsible for intraoperative anaphylaxis are muscle relaxants.^[606] However, latex accounts for a significant number of these reactions, and the incidence of intraoperative anaphylaxis caused by latex is increasing. It is now probably the second most important cause of intraoperative anaphylaxis. In addition, histamine can be liberated independent of immunologic reactions.^[607] Mast cells and basophils release histamine in response to chemicals or drugs. Most narcotics can release histamine ^[607] and produce an anaphylactoid reaction, as can radiographic contrast media,^[600] d-tubocurarine, ^[608] and thiopental. What makes some patients susceptible to release of histamine in response to drugs is unknown, but hereditary and environmental factors may play a role.

Intravenous contrast material is probably the most frequently used agent that causes anaphylactoid reactions. Because diagnostic (skin and other) tests are helpful only in IgE-mediated reactions, pretesting is not useful for contrast reactions. Pretreatment with diphenhydramine, cimetidine (or ranitidine), and corticosteroids has been reported to be useful in preventing or ameliorating anaphylactoid reactions to intravenous contrast material^{[600] [609]} and perhaps to narcotics and chymopapain.^{[610] [611]} Unfortunately, very large doses of steroids (1 g of methylprednisolone intravenously) may be necessary to obtain a beneficial effect.^[612] The efficacy of large-dose steroid therapy has not been confirmed. Other common substances associated with anaphylactic or anaphylactoid reactions that might merit preoperative therapy include antibiotics, volume expanders, and blood products^{[595] [613] [614]} ( Table 27-46 ). The anesthesiologist should be prepared preoperatively to treat an anaphylactic or anaphylactoid response.

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In some cases, a patient with a history of an anaphylactic or anaphylactoid reaction must receive a substance suspected of producing such a reaction (e.g., iodinated contrast material). In addition, some patients have a higher than average likelihood of having a reaction, thus warranting well-planned pretreatment and therapy for possible anaphylactic and anaphylactoid reactions.^[595]

Minimizing Risks Preoperatively

Although virtually all evidence on this subject is merely anecdotal, enough consistent thought recurs through the literature to justify proposing an optimal approach to these problems. First, predisposing factors should be sought; patients with a history of atopy or allergic rhinitis should be suspected as being at risk. Because anaphylactic and anaphylactoid reactions to contrast media occur 5 to 10 times more frequently in patients with a previously suspected reaction, consideration should be given to the administration of both H₁ and H₂ receptor antagonists for 16 to 24 hours before exposing these patients to a suspected allergen. H₁ receptor antagonists appear to require this much time to act on the receptor. Volume status should be optimized,^[595] and perhaps large doses of steroids (2 g of hydrocortisone) should also be administered before exposing patients to agents associated with a high incidence of anaphylactic or anaphylactoid reactions.^{[612] [613] [615]} Older patients and patients taking β-adrenergic blocking drugs present special problems; they are at higher risk of having complications from both pretreatment (especially vigorous hydration) and therapy for anaphylactic reactions and are less responsive to treatment regimens.^[616] One approach is to avoid drugs likely to trigger anaphylactic or anaphylactoid reactions or alter the treatment protocol for this group. Drawing blood for later analysis, especially of tryptase, can be useful in clarifying the diagnosis.^[617]

With the increasing incidence of latex hypersensitivity, attempts have been made to make much of the operating room environment latex free; however, costs and preferences have resulted in the continued use of latex-containing gloves in many hospitals. In allergic patients, care should be taken to ensure that no latex-containing products are present in the operating room.

Primary Immunodeficiency Diseases

Primary immunodeficiency diseases are usually manifested early in life as recurrent infections. Along with survival achieved with antibiotic and antibody treatment have come new prominent features: cancer and allergic and autoimmune disorders. Hereditary angioneurotic edema is an autosomal dominant genetic disease characterized by episodes of angioneurotic edema involving the subcutaneous tissues and submucosa of the GI tract and airway and often manifested as abdominal pain. These patients have a functionally impotent inhibitor or deficiency of an inhibitor to complement component C1. Treatment of an acute attack is supportive because epinephrine, antihistamines, and corticosteroids often fail to work. Plasma transfusions have been reported to resolve attacks or make them worse (theoretically by supplying either C1 esterase inhibitor or previously depleted complement components). The severity of attacks can be prevented or decreased by drugs that are either plasmin inhibitors (e.g., epsilon-aminocaproic acid [EACA] and tranexamic acid) or androgens (e.g., danazol). Because trauma can precipitate acute attacks, prophylactic therapy with danazol, intravenous EACA, plasma, or all three is recommended before elective surgery. Reports have also described the successful use of a partially purified C1 esterase inhibitor in two patients.^{[618] [619]}

Most of the 1 in 700 persons who have selective IgA deficiency (i.e., <5 mg/dL) have repeated serious infections or connective tissue disorders. ^[620] These infections commonly involve the respiratory tract (e.g., sinusitis, otitis) or GI tract (manifested as diarrhea or malabsorption, or both). If the patient has rheumatoid arthritis, Sjögren's syndrome, or systemic lupus erythematosus, the anesthetist should consider the possibility of isolated IgA deficiency. However, patients with this disorder can be otherwise healthy. Because antibodies to IgA may develop in these patients if previously exposed to IgA (as might occur from a previous blood transfusion), subsequent blood transfusions can cause anaphylaxis, even when they contain washed erythrocytes. Transfusions should therefore consist of blood donated by another IgA-deficient patient.

Many immunomodulators are now being given to augment cancer treatments ^[621] ; no interactions between these modulators, no effects on the incidence of immune reactions during anesthesia, and no interactions with anesthetic effects have been reported except those regarding immune-suppressing drugs (see the last section of this chapter).