1 Define reactive airway disease, in particular, asthma

The term reactive airway disease (RAD) is used to describe a family of diseases that shares an airway sensitivity to physical, chemical, or pharmacologic stimuli. This sensitivity results in a bronchoconstrictor response and is seen in patients with asthma, chronic obstructive pulmonary disease (COPD), emphysema, viral upper respiratory illness, and other disorders.

Asthma is defined by the American Thoracic Society as “a disease characterized by an increased responsiveness of the trachea and bronchi to various stimuli manifested by a widespread narrowing of the airways that changes in severity either spontaneously or as a result of therapy.” Asthma is manifested by episodes of dyspnea, cough, and wheezing. These symptoms are related to the increased resistance to airflow in the patient’s airways.

2 What are the different types of asthma?

Although the common denominator lies in airway hyperreactivity, patients may fit into two subgroups: allergic (extrinsic) and idiosyncratic (intrinsic). Many believe that the terms extrinsic and intrinsic should be discarded. Underlying all types of asthma are airway hyperreactivity, inflammation, and an interaction between allergic and nonallergic stimuli.

Allergic asthma is thought to result from an immunoglobulin E–mediated response to antigens such as dust and pollen. Among the mediators released are histamine, leukotrienes, prostaglandins, bradykinin, thromboxane, and eosinophilic chemotactic factor. Their release leads to inflammation, capillary leakage in the airways, increased mucus secretion, and bronchial smooth muscle contraction.

Idiosyncratic asthma is mediated by nonantigenic stimuli, including exercise, cold, pollution, and infection. Bronchospasm is caused by increased parasympathetic (vagal) tone. Although the primary stimulus differs, the same mediators as allergic asthma are released (and some patients with allergic asthma have enhanced vagal tone).

3 What diseases mimic asthma?

Upper and lower airway obstruction from tumor, aspirated foreign bodies, or stenosis

Left ventricular failure (cardiac asthma) and pulmonary embolism

Gastroesophageal reflux and aspiration

Viral respiratory illnesses (e.g., respiratory syncytial virus)

Allergic reactions and anaphylaxis

A careful history and physical examination will differentiate these diseases from primary reactive disease

4 What are the important historical features of an asthmatic patient?

Duration of disease

Frequency, initiating factors, and duration of attacks

Has the patient ever required inpatient therapy? Did the patient require intensive care admission or intubation?

What are the patient’s medications, including daily and as-needed usage, over-the-counter medications, and steroids?

5 What physical findings are associated with asthma?

The most common physical finding is expiratory wheezing. Wheezing is a sign of obstructed airflow and is often associated with a prolonged expiratory phase. As asthma progressively worsens, patients use accessory respiratory muscles. A significantly symptomatic patient with quiet auscultatory findings may signal impending respiratory failure because not enough air is moving to elicit a wheeze. Patients also may be tachypneic and probably are dehydrated; they prefer an upright posture and demonstrate pursed-lip breathing. Cyanosis is a late and ominous sign.

6 What preoperative tests should be ordered?

The patient’s history guides the judicious ordering of preoperative tests. A mild asthmatic maintained on as-needed medication who is currently healthy will not benefit from preoperative testing. Symptomatic patients with no recent evaluation deserve closer attention.

The most common test is a pulmonary function test, which allows simple and quick evaluation of the degree of obstruction and its reversibility (see Chapter 9). A comparison of values obtained from the patient with predicted values helps to assess the degree of obstruction. Severe exacerbation correlates with a peak expiratory flow rate (PEFR) or forced expiratory volume in 1 second (FEV₁) of less than 30% to 50% of predicted, which for most adults is a PEFR of less than 120 L/min and an FEV₁ of less than 1 L. Tests should be repeated after a trial of bronchodilator therapy to assess reversibility and response to treatment.

Arterial blood gases are usually not helpful. Electrocardiograms, chest radiographs, and blood counts are rarely indicated for evaluation of asthma unless particular features of the patient’s presentation suggest alternative diagnoses (e.g., fever and rales suggesting pneumonia).

7 Describe the mainstay of therapy in asthma

The mainstay of therapy remains inhaled β-adrenergic agonists. Selective β₂-agonists such as albuterol, terbutaline, and fenoterol offer greater specificity for β₂-mediated bronchodilation and fewer side effects (e.g., β₁-associated tachydysrhythmias and tremors). Albuterol can be nebulized or administered orally or by metered-dose inhaler (MDI). Terbutaline is effective via nebulizer, subcutaneously, or as a continuous intravenous infusion (beware of hypokalemia, lactic acidosis, and cardiac tachydysrhythmias with intravenous use). Epinephrine is available for subcutaneous use in severely asthmatic patients. Patients with coronary artery disease have difficulty with tachycardia and need the more β₂-specific agents. Routinely the inhaled route is preferred.

8 What other medications and routes of delivery are used in asthma?

Corticosteroids: Reverse airway inflammation, decrease mucus production, and potentiate β-agonist-induced smooth muscle relaxation. Steroids are strongly recommended in patients with moderate-to-severe asthma or patients who have required steroids in the past 6 months. Onset of action is 1 to 2 hours after administration. Methylprednisolone is popular because of its strong antiinflammatory powers but weak mineralocorticoid effect. Side effects include hyperglycemia, hypertension, hypokalemia, and mood alterations, including psychosis. Long-term steroid use or prolonged use with muscle relaxants is associated with myopathy. Steroids may be given orally, via MDI, or intravenously.

Anticholinergic agents: Cause bronchodilation by blocking muscarinic cholinergic receptors in the airways, therefore attenuating bronchoconstriction caused by inhaled irritants and associated with β-blocker therapy. They are particularly valuable in patients with COPD or with severe airway obstruction (FEV₁ <25% predicted). Ipratropium, glycopyrrolate, and atropine may be given via nebulizer; and ipratropium is available in an MDI.

Theophylline: The use in asthma is controversial. Theophylline has some bronchodilatory effects and improves diaphragmatic action. Such benefits must be weighed against a long list of side effects: tremor, nausea and vomiting, palpitations, tachydysrhythmias, and seizures. Until definite proof is available, many investigators suggest that theophylline therapy should be initiated only in patients with acute asthma who do not improve with maximal β-agonist and corticosteroid therapy. Careful monitoring of serum levels is mandatory. Theophylline is the oral preparation; whereas aminophylline, its water-soluble form, is for intravenous use.

Cromolyn sodium: A mast cell stabilizer useful for long-term maintenance therapy. Patients younger than 17 years of age and with moderate-to-severe exercise-induced asthma appear to benefit the most. Side effects include some minimal local irritation on delivery. Cromolyn sodium may be administered via multidose inhaler or as a powder in a turboinhaler. Cromolyn sodium is not effective and in fact is contraindicated in acute asthmatic attacks.

Leukotriene modifiers: Relative newcomers in the treatment of mild-to-moderate asthma. These drugs either selectively compete with LTd4 and LTe4 receptors or directly inhibit the lipoxygenase pathway of arachidonic acid metabolism. At this time their use is limited to long-term treatment in a select group of patients.

Methotrexate or gold salts: Patients with severe asthma may require one of these medications. Both have undesirable side-effect profiles and are reserved for patients who have major difficulties with corticosteroids (Table 38-1).

TABLE 38-1 Useful Medications for Patients with Reactive Airway Disease

COPD, Chronic obstructive pulmonary disease; .MDI, metered-dose inhaler; RAD, reactive airway disease,

9 What is the best approach to preoperative management of the patient with reactive airway disease?

Patients should be classified according to the urgency of the operation required and their particular history of reactive airways.

Patients who are scheduled for elective procedures but are actively wheezing are probably best cancelled, administered therapy, and rescheduled.

Asymptomatic patients on no medications currently and with no recent bouts of asthma and no history of serious illness may require no therapy or, at most, inhaled β-agonists.

Mild asthmatics (FEV₁ >80%) with ongoing or recent symptoms should definitely have β-adrenergic therapy before surgery.

Moderate asthmatics (FEV₁ 65% to 80%) should continue their β-adrenergic therapy and either double their inhaled steroid dose for a week before surgery or start oral steroids 2 days before surgery. When symptomatic, these patients should start β-adrenergic and oral steroid therapy. Important factors to consider before beginning steroids include the following:

Have the patients had intensive care admissions or mechanical ventilation related to their asthma?

Have steroids been administered in the past 6 months?

Are the patients at risk for adrenal insufficiency?

Severe asthmatics (FEV <65%) should be on β-adrenergic therapy and be given 2 days of oral steroids before surgery. Patients with FEV₁ <70% have improvements in pulmonary function with either inhaled β-adrenergic or oral steroids with only 1 day of therapy. Combining β-adrenergic and oral steroid therapy also significantly decreases postintubation wheezing when compared to β-adrenergic therapy alone. Finally patients having upper abdominal or thoracic surgery and emergency cases are at particular risk and deserve aggressive therapy.

10 Review the pros and cons of induction agents in asthmatic patients

Intravenous induction agents used in asthmatic patients include oxybarbiturates, thiobarbiturates, ketamine, and propofol. Thiobarbiturates constrict airways in laboratory investigations and may have a loose association with clinical bronchospasm. The most common cause of bronchospasm is the stimulus of intubation, and large doses of barbiturates are required to block this effect successfully. Ketamine has well-known bronchodilatory effects secondary to the release of endogenous catecholamines with β₂-agonist effects. Ketamine also has a small, direct relaxant effect on smooth muscles. Propofol decreases both airway resistance and airway reflexes after administration. Intravenous lidocaine is a useful adjunct for blunting the response to laryngoscopy and intubation.

Mask induction with halothane or sevoflurane is an excellent method to block airway reflexes and to relax airway smooth muscles directly. These agents are much more palatable to the airway than isoflurane or desflurane.

Atracurium and mivacurium are commonly used muscle relaxants that have demonstrated histamine release and may cause bronchoconstriction. Vecuronium, rocuronium, pancuronium are not associated with histamine release. Cis-atracurium is associated with less histamine release relative to atracurium.

11 What agents may be used for maintenance anesthesia?

Sevoflurane, halothane, and isoflurane are effective in blocking airway reflexes and bronchoconstriction; sevoflurane appears to be the most effective. Inhaled anesthetics have been used in the intensive care unit to provide bronchodilation in intubated patients with severe asthma, improving indices of respiratory resistance (inspiratory and expiratory flows), decreasing hyperinflation, and lowering intrinsic positive end-expiratory pressure (PEEP).

Opioids at higher doses block airway reflexes but do not provide direct bronchodilation. Morphine remains controversial because of its histamine-releasing activity. Anesthetics relying primarily on opioids may cause problems with respiratory depression at emergence (particularly in patients with COPD with an asthmatic component).

Neuromuscular blocking agents with a benzylisoquinolinium nucleus such as d-tubocurarine, atracurium, and mivacurium release histamine from mast cells on injection. They also may bind directly to muscarinic receptors on ganglia, nerve endings, and airway smooth muscle. Both mechanisms theoretically may increase airway resistance. Relaxants with an aminosteroid nucleus such as pancuronium and vecuronium continue to be used safely in asthmatic patients. In patients with bronchospasm neuromuscular blocking agents improve chest wall compliance, but smooth muscle airway tone and lung compliance remain the same. Prolonged use of muscle relaxants in ventilated asthmatic patients is associated with increases in creatine kinase and clinically significant myopathy.

12 What are the complications of intubation and mechanical ventilation in asthmatic patients?

The stimulus of intubation causes significant increases in airway resistance. Lung hyperinflation occurs when diminished expiratory flow prevents complete emptying of the alveolar and small airway gas. Significant gas trapping may cause hypotension by increasing intrathoracic pressure and reducing venous return. Pneumomediastinum and pneumothorax are also potential causes of acute respiratory decompensation.

Several measurements of ventilator function may give some insight into a patient’s improving or worsening status. Plateau pressures (the pressure measured at end inspiration and before expiration starts, averaged over a 0.4-second pause) correlate loosely with complications at pressures greater than 30 cm H₂O. Auto-PEEP is the measurement of end-expiratory pressure (taken at end expiration while the expiratory port is momentarily occluded) and may correlate with alveolar pressures in the bronchospastic patient. However, auto-PEEP does not specifically correlate with complications. Plateau pressure and auto-PEEP measurements require a relaxed patient.

Patients on prolonged high-dose corticosteroids and muscle relaxation are at risk for a severe myopathy. Pancuronium and vecuronium are the worse offenders, but all muscle relaxants are suspect.

Several strategies for mechanically ventilating bronchospastic patients have been developed:

Pressure-support ventilation allows for spontaneous ventilation in the sedated patient with less work of breathing and less risk of barotrauma AND IF MANDATORY BREATHS ARE REQUIRED.

Increase expiratory time by decreasing ventilator rate, increasing inspiratory flow rates to decrease inspiratory time, and directly increasing the inspiratory-to-expiratory ratio.

Be careful of ventilator-applied PEEP.

Decrease minute volume, allowing controlled hypoventilation and permissive hypercapnia.

13 What are the causes of intraoperative wheezing and the correct responses to asthmatic patients with acute bronchospasm?

Causes include airway secretions, foreign body, pulmonary edema (cardiac asthma), obstructed endotracheal tube, endotracheal tube at the carina or down a main-stem bronchus, allergic or anaphylactic response to drugs, and asthma. A number of medications cause wheezing in asthmatic patients, including β-blockers, muscle relaxants, and aspirin.

After carefully checking the endotracheal tube and listening for bilateral breath sounds, increase the inspired oxygen to 100% and deepen the anesthetic if hemodynamically tolerated by the patient. Provoking factors such as medication infusions, misplaced endotracheal tubes, or other causes of airway stimulation should be corrected. Manipulating the ventilator (see question 14) may help. Administer medications as suggested in Question 7.

14 Describe the emergence techniques for asthmatic patients under general endotracheal anesthesia

Awake and deep extubations are alternatives in patients under general endotracheal anesthesia. The endotracheal tube is a common cause of significant bronchospasm, and its removal under deep-inhaled anesthetic in a spontaneously ventilating patient often leads to a smooth emergence. Deep extubations should be avoided in patients with difficult airways, morbidly obese patients, and patients with full stomachs.

15 What new therapies are available to anesthesiologists treating asthmatic patients in bronchospasm?

Magnesium sulfate: Has been administered to patients in status asthmaticus. Hypothetically magnesium interferes with calcium-mediated smooth muscle contraction and decreases acetylcholine release at the neuromuscular junction. Magnesium reduces histamine- and methacholine-induced bronchospasm in controlled studies, but so far clinical studies have failed to show a significant response.

Heliox: A blend of helium and oxygen that decreases airway resistance, peak airway pressures, and PaCO₂ levels when administered to spontaneously and mechanically ventilated patients. The mixture contains 60% to 80% helium and 20% to 40% oxygen and is less dense than air. The decrease in density allows less turbulent flow and significant declines in resistance to flow. The device for heliox administration in intubated patients is cumbersome unless the anesthesia machine is already equipped.

Lita-Tube: This endotracheal tube allows intraoperative instillation of lidocaine at and below the cords of the intubated patient. This technique decreases airway stimulation from the endotracheal tube and may prevent reflex bronchospasm.

Extracorporeal oxygenation: Using veno-venous oxygenation and CO₂ removal allows for minimal ventilatory support (lung rest) and the removal of dangerously high CO₂ with resulting improvement in pH.