Case conference

CASE CONFERENCE Alan Jay Schwartz, MD, MSEd William A. Lell, MD, Editors

CASE 1989- 1

Case Presentation

A 55year-old Filipino man presented with a history of exertional chest pain. Three years ago he was found to have high-grade lesions in the circumflex and left anterior descending (LAD) coronary arteries. He did well on medical management until shortly before this admission, when only minimal activity would bring on his angina. His history was negative for a myocardial infarction. A treadmill test done on admission was markedly positive. Coronary studies showed high-grade obstructive disease in all three major vessels and an ejection fraction of 62%. His cardiac history revealed significant risk factors including a positive family history, hypercholesterolemia, hypertension, and a ten-packyear history of smoking prior to his quitting in 1959. His cardiac medicines at the time of admission were prazosin, potassium, isosorbide dinitrate and sublingual nitroglycerin. There was also a vague history of rheumatic fever as a child. The patient was allergic to penicillin and possibly allergic to iodine (dye). He had no previous anesthetic experiences and stated that he developed “hay fever” during certain times of the year, for which he used theophylline and an albuterol inhaler, both of which he was taking at Richard E. Buckingham, Jr. MD, Department of Cardiac Anesthesia, Swedish Hospital Medical Center, Seattle, Terry R. Rogers, MD, Pulmonary and Critical Care Services, Swedish Hospital Medical Center, Seattle, Ian H. Sampson, MD. Department of Anesthesiology, Mt Sinai School of Medicine, NY. Address reprint requests to Richard E. Buckingham. Jr, MD, Department of Cardiac Anesthesia, Swedish Hospital Medical Center, Seattle, WA 98104. 0 1989 by Grune & Stratton, Inc. 0888-6296/89/0301-0019$03.00/0

the time of admission. He denied ever having had an asthmatic attack. Physical exam revealed a small-framed, well-developed, well-nourished male weighing 129 lbs and measuring 5 feet 3’/2 inches. Blood pressure was 166/85 mmHg and pulse rate was 68 BPM and regular. No chest wall deformities were present, and the lungs were clear to both auscultation and percussion. No wheezing was noted by two different examiners. Laboratory tests were all within normal limits including a hemoglobin of 14.8 g/dL, hematocrit of 42.6%, platelet count of 291,000/ PL, protime of 11.4 set, bleeding time of 4.5 min, fibrinogen of 377 mg/dL, thrombin time of 10.9 set, and PTT of 33.3 sec. Electrolytes and urinalysis were within normal limits. A pre-op chest x-ray was read as normal. The patient was scheduled for coronary bypass surgery on the morning following his admission. Premeditation consisted of 10 mg of diazepam orally, one and one half hours before going to the operating room (OR), and 8 mg of morphine with 0.3 mg of scopolamine intramuscularly (IM) one hour later. On arrival in the operating room, a radial arterial catheter was easily placed. Blood pressure was 155/60 mmHg, and a blood gas showed the PaO, was 88 mmHg, and PaCOz was 51 mmHg on room air. A pulmonary artery catheter showed a pressure of 28/ 12 mmHg with a mean of 19 mmHg, pulmonary capillary wedge pressure (PCWP) of 10 mmHg, and central venous pressure (CVP) of 6 mmHg. Additional monitoring before induction included Doppler-cuff blood pressure (which agreed with that obtained in the other arm by arterial catheter), and the electrocardiogram (ECG) leads II and V,. After preoxygenation, the anesthetic induction was begun with 30 mg of morphine, 10 mg of diazepam, 10 mg of pancuronium, 150 mg

Journal of Cardiothoracic Anesthesia, Vol3, No 1 (February), 1989: pp 109- 118

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of thiamylal, and 0.8 mg of scopolamine. The patient was easily intubated with a 9.0-mm endotracheal tube and placed on a ventilator with a minute volume of 9 liters. The stimulus of intubation increased the heart rate from 52 to 85 BPM and the systolic blood pressure from 130 to 150 mmHg. Blood gases at this time showed a PaO, of 426 mmHg and a PaCO, of 49 mmHg. Breath sounds at this time were normal with no evidence of wheezing. Shortly before the start of surgery, 50% N,O and 1% isoflurane were started. Breath sounds obtained from an esophageal stethoscope continued to be normal. Forty minutes after the start of surgery, the patient was placed on cardiopulmonary bypass (CPB). During the time that he was on the heart-lung machine, the ventilator was shut off and no attempt was made to alter the mixture within the lungs or to apply any airway pressure or humidity. Upon completion of three vein bypass grafts and a single left internal mammary artery (IMA) graft to the LAD, the surgeon requested that the lungs be inflated to check the length of the IMA graft. When the bag was squeezed, no gas could be moved into the lungs even with a positive pressure of 60 cm H20. Examination of the surgical field revealed that the lungs were partially collapsed and that they did not distend with positive pressure on the anesthesia bag. A quick check of the anesthesia machine and circuit revealed everything to be in working order. No sounds could be heard through the esophageal stethoscope when ventilation was attempted. The cuff was let down on the endotracheal tube and the tube was suctioned, without any improvement in ventilation. A presumptive diagnosis of airway blockage was made, and the patient was examined by bronchoscopy through the endotracheal tube while still on CPB. This revealed nothing abnormal. It was then decided that the patient was suffering from extremely severe bronchospasm. He was given an intravenous (IV) loading dose of 250 mg of aminophylline, 0.8 mg of atropine, 1,000 mg of methylprednisolone, and ventilation was started with halothane. A metered dose inhaler (MDI) adapter was placed between the endotracheal tube connector and the circle ‘Y’ connector, and 650 pg (one pull) of metaproterenol was instilled into the circuit as the bag was vigorously squeezed.

CASE 1989-l

This was repeated a few moments later as airway resistance decreased, and then a third time five minutes later. The combination of these therapeutic interventions allowed relatively effective ventilation although there was still significant “air trapping” and profound expiratory wheezing. The patient’s respiratory status, however, continued to improve. Once the peak inspiratory pressure had decreased to 45 cm of H,O, the patient was weaned off of CPB. By the time the chest was ready to be closed, the patient still had expiratory wheezes, but little evidence of air trapping as noted on observation of the lungs. Blood gases obtained at this point were pH 7.46; PaCO, 44 mmHg; PaO, 559 mmHg, and HCO,30.8 mEq/L. The patient’s intensive care unit course was unremarkable. He was extubated 13 hours after arriving in the unit. The aminophylline infusion which had been running at 0.5 mg/kg/hr was discontinued shortly therafter. Methylprednisolone was gradually tapered and discontinued on the third postoperative day. Theophylline, 300 mg every eight hours, was started, and the patient was discharged on a regimen of this medication and his albuterol inhaler. DISCUSSION*

Bronchospasm occurring during anesthesia is an infrequent problem even in patients with irritable airways. Cases such as this one, in which the bronchospasm is so complete as to effectively prohibit movement of air into the lungs, are exceedingly rare. This is fortunate because the diagnosis of bronchospasm is most often made by observing “air trapping” and hearing expiratory wheezes. When no air can be moved into the lungs, the diagnosis is much more difficult to make. As in this case, it is usually one of exclusions, ie, excluding the other causes of airway obstruction. As a general rule, it is easier to try to prevent bronchospasm from occurring than it is to treat it.’ During the preoperative visit, the anesthesiologist can get an idea if a given patient is at risk, and assess the severity of the patient’s pre-existing lung disease. Certainly the history is important, eg, the “hay fever” mentioned by the

*Richard

E. Buckingham,

Jr, MD.

CASE

1989-1

patient in this case presentation. It should be determined if the condition of a patient at risk can be made more optimal. Chest physiotherapy, intermittent positive pressure breathing (IPPB), bronchodilator therapy, pulmonary medicine consultation, and aminophylline to establish a preoperative therapeutic blood level may be considered.2,3 If the patient has been on pulmonary medicines these should be continued. If not, the previously mentioned drug therapy can be considered, as can chromolyn sodium inhalation. The latter drug must be given in advance, as it works by preventing degranulation of mast cells. Therefore, it is not a good drug for treating bronchospasm once it occurs, but is useful for pretreating susceptible individuals. Antibiotics should be given if there is evidence of acute or chronic infection. It is also desirable to have the patient properly hydrated and in electrolyte balance. If there is a component of heart failure contributing to the patient’s lung problems (ie, cardiac asthma), then treatment for this condition should be instituted or optimized. Psychologic factors play an important role in intrinsic asthma. Therefore, time spent reassuring this type of patient and helping him achieve the proper frame of mind may have some physical benefits. After the patient has been evaluated, the anesthetic management should be considered. There is some controversy over whether or not “drying agents” should be used as part of the premedication?6 It can be argued both ways. Atropine can decrease secretions and cause further plugging of air passages and an increase in irritability by the dryness. On the other hand, atropine may prevent bronchospasm mediated through vagal reflexes. By not giving an anticholinergic drug, parasympathetic blockade is lost, and the increased amount of secretions can trigger bronchospasm. There is less controversy about giving diphenhydramine or other H,receptor blocking drugs.2*3They not only inhibit histamine-mediated bronchospasm, but also have sedative actions. When it comes to choices for an anesthetic agent, inhalational agents are usually recommended.3 These drugs are all equally potent direct bronchodilators. Problems can arise, however; at least one (enflurane) has been implicated in causing bronchospasm,7 and halothane carries

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the risk of initiating or exacerbating preexisting dysrhythmias, especially if cardiac stimulating drugs are used.8 Ketamine has also been advocated.‘*” However, its mechanism of action is probably through an increase in sympathetic stimulation, which may be undesirable in cardiac patients. Some drugs should be avoided. Morphine (as was administered in this case) was a poor choice because of its known ability to release histamine. Other drugs to be avoided because of histamine release are meperidine, d-tubocurarine, and trimethaphan. Thiobarbiturates cause an undesirable increase in parasympathetic tone and have recently been shown to cause histamine release in a human skin mast cell preparation.” Once the anesthetic is underway, if either “air trapping” or expiratory wheezing is observed, it is imperative to rule out other causes. Most of these have to do with partial obstruction of the airway or mechanical problems with the anesthetic apparatus. Consideration should be given to a kinked endotracheal tube, mainstem bronchus intubation, bevel of the endotracheal tube against the tracheal wall, cuff overinflation, cuff herniation over the end of the tube, mucus plug, secretions, foreign bodies, kinked delivery hoses, malfunctioning rebreathing valves, etc. Light anesthesia and stiffness of the chest wall can sometimes mimic bronchospasm, as can a tension pneumothorax. The anesthesiologist should inspect the surgical field, especially if the chest is open, and should switch from the ventilator to the “bag and educated hand” method of ventilation.12 At this time the anesthesia circuit can be assessed. When hand ventilation is used, both sides of the patient’s chest should be auscultated and the sounds compared with those heard after intubation. Air should be removed from the endotracheal tube cuff and the breath sounds checked again. The tube should be suctioned to assure patency and to make sure that the problem is not secretions in the trachea causing the problem directly or being the initiating irritant in reflex bronchospasm. The tube should be pulled back to ensure that it is not close enough to the carina to initiate reflex bronchospasm. Since light anesthesia or inadequate muscle relaxation can be thought of as a mechanical problem, an additional dose of muscle relaxant will rule this out.

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CASE 1989- 1

If bronchospasm is diagnosed, a treatment cascade should be initiated, and all anesthesiologists have their own routines. Bronchial tone is controlled by the autonomic nervous system, with parasympathetic and alpha-adrenergic stimulation causing bronchoconstriction, while beta-adrenergic stimulation (specifically beta,) causes bronchodilatation. These effects are mediated through cyclic adenosine monophosphate (CAMP) and cyclic guanosine monophosphate (cGMP) as shown in Fig 1. Beta, stimulation increases the amount of CAMP by enhancing the action of the enzyme, adenyl cyclase. Alpha adrenergic stimulation has an inhibitory effect on adenyl cyclase. Cholinergic stimulation increases cGMP, which causes bronchoconstriction. Substances such as histamine and slowreacting substance of anaphylaxis (SRS-A) can act directly on bronchi to cause bronchoconstriction without going through CAMP or cGMP. Finally, the diameter of the lumen can also be affected by other factors besides bronchiolar muscular tone, such as edema of the mucosal cells lining the bronchi. Table 1 lists the factors and drugs responsible for bronchodilatation as P-adrenergic

well as likely mechanisms; while Table 2 lists the factors and drugs likely to cause bronchoconstriction with probable mechanisms. If the bronchspasm is not too severe, one treatment modality can be tried at a time until something works. If the bronchospasm is severe, several treatments should be started at once as was done in this case. If the patient is not on halothane, enflurane, or isoflurane, and if his blood pressure will tolerate it, one of these agents should be started. On the other hand, all inhalational agents that the patient was on at the time his bronchospasm developed should be discontinued, as they have all been suspected of causing bronchospasm. If N20 is being used, it should be discontinued. If helium is available, it can be added to the inspired O,, up to a concentration of 70%. This mixture is approximately ‘/3as dense as 100% 0, and will be more effective at delivering O2 into the alveoli while the turbulent flow conditions of asthma exist. A loading dose of aminophylline can be given IV. Atropine can either be given IV or can be administered through the endotracheal tube, or ipratropium bromide can be tried.13 Beta,-agonists can be given via a MDI,‘4,‘5 and lidocaine can be given through the endotracheal tube or IV. If another anesthetic agent is required, thought should be given to ketamine because of its sympathetic stimulation.g COMMENTARY+

w

direct effects

BRONCHIOLAR direct effects

Cholinergx

Fig 1. Factors and drugs that affect bronchiolar tone. Under normal conditions, tone is controlled by the autonomic nervous system. with parasympathetic and aadrenergic stimulation causing bronchoconstriction, while fl-adrenergic stimulation causes bronchodilatation. These effects ere mediated through CAMP end cGMP.

From the perspective of a practicing pulmonologist, this case highlights a number of features that outline the difficulties in dealing with the adult who has asthma. Asthma, in one form or another, is the most common illness present in the spectrum of respiratory diseases. Very few patients who have asthma know, or will admit, that they have asthma. The reasons for this are many, and include (1) never having been told, (2) never having the diagnosis made, (3) fear of accepting the reality of the disease, and (4) misunderstanding of what asthma represents. Many people still believe that asthma is actually a process of neurotic origin and reflects a socially unacceptable weakness. The examiner should be aware of the possi-

‘Terry R. Rogers, MD.

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CASE 1989- 1 Table 1. Bronchodilator

Mechanisms

Factoror Drug

Mechanism

Sympathetic nervous system

Increases adenyl cyclase activity

Metabolic products

Relax bronchiolar musculature (direct affect)

CO2 Lactic acid Beta,-agonists

Increase adenyl cyclase activity

Epinephrine lsoproterenol Ephedrine Terbutaline Metaproterenol lsoetharine Albuterol Bitolterol Muscarinic cholinergic blockers

Block formation of cGMP

Atropine Scopolamine lpratropium Alpha-adrenergic blockers Phentolamine

Block inhibitcry effect of alpha-stimulation on adenyl cyclase (same effect as stimulating adenyl cyclase)

Phenoxybenzamine Methylxanthines Caffeine

Increase CAMP by inhibiting its breakdown by phosphodiesterese

Theobromine Theophylline Aminophylline Steroids

Enhance sympathetic effects: block ATPase, thereby allow-

Prednisolone

ing more (adenosine triphosphate) ATP to be available to

Hydrocortisone

form CAMP; block mediator release from mast cells, and

Methylprednisolone

decrease edema formation

Prednisone Beclomethasone Chromolyn sodium

Blocks mediator releasa

Prostaglandins E, and E,

Increase adenyl cyclase activity

Lidocaine

Blocks local reflexes

General Anesthetics

Relax bronchiolar musculature (direct effect and block local

Diethyl ether

reflexes)

Halothane Enflurane lsoflurane Ketamine

ble presence of bronchial hyper-responsiveness. It is imperative to recognize when the history given actually represents the presence of asthma, with its attendant dangers, and not some other less important or transient illness. The case discussed above reflects this warning. Despite actually taking specific bronchodilator medicine, the patient admitted only that he had “hay-fever.” The examiner must interpret the information

Sympathetic stimulation

given and not simply accept the presumed diagnosis relayed by the patient. Adults with asthma will describe a wide spectrum of symptoms,‘6 which rarely include wheezing. A recurrent and hacking cough, usually associated with a sense of irritation or tickle, is commonly related. Other frequent complaints are chest tightness, mucus production, shortness of breath, or hoarseness (Table 3). The

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Table 2. Factor

or

Bronchoconstrictor

Mechanisms

Drug

Mechanism

Parasympathetic nervous system

increases cGMP activity

Alpha-adrenergic nervous system

Inhibits adenyl cyclase

Brain stem reflexes

Increase cGMP activity

Local reflexes

Increase cGMP activity

Alpha-agonists

Inhibit adenyl cyclase

Phenylephrine Methoxamine Beta-Blockers

Decrease adenyl cyclase activity

Propranolol Metoprolol Timolol Esmolol Nadolol Labetalol Acebutolol Atenolol Muscarinic cholinomimetics

Increase cGMP

Neostigmine Pyridostigmine Physostigmine Edrophonium Mast-cell mediators

Act directly on the bronchiolar musculature

Serotonin SIX-A Histamine Kinins Histamine-releasing drugs

Release histamine that acts directly on the bronchiolar musculature

Morphine Meperidine D-tubocurarine Trimethaphan Metocurine Thiopental Thiamylal Methohexital Vagomimetic drugs

Increase cGMP activity

Thiopental Acetylcholine Pilocarpine Carbachol Prostaglandins F,, and D,

Inhibit adenyl cyclase

ACE Inhibitors

Possibly direct or mediated effect on the bronchiolar musculature

Captopril Enalopril Lisinopril

timing of the symptoms is also telling. It is very common for patients to describe worsening of their symptoms in the face of certain circumstances. These include most types of exercise, including walking, stair climbing, or package

carrying. Symptoms also worsen when the individual assumes the supine position at night. The exact cause of increased bronchial irritability in the horizontal position is not known, but it identifies underlying asthma. Cough or irritation in a

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Table 3.

List of Common Symptoms

of Patients

With Asthma Cough Frequent throat clearing Chest tightness Tickle in throat or chest Congestion Chronic chest cold Shortness of breath Cannot exhale air

patient with asthma is almost always precipitated by a deep breath to laugh or talk; thus, coughing with the deep breaths of the physical exam or in response to a humorous event is common. The patient will have hoarseness, phlegm, or worsening cough towards the end of the day, particularly if he uses his voice a lot. Commonly encountered airborne substances are frequently needed to precipitate symptoms and are avoided by sensitive patients. Cigarette smoke, perfumes, candle fumes, paint fumes, cooking odors, and diesel exhaust are often mentioned as causative agents. The point must be re-emphasized, however, that the majority of people with such symptoms, even when they initiate the request for evaluation, rarely volunteer the complete spectrum and symptoms which they experience; therefore, directed and pointed questions must be asked by the suspicious examiner. An additional reminder must be offered regarding acclimatization on the part of the patient, a process by which the patient slowly accepts the constellation of symptoms he experiences, thus losing objectivity concerning their possible seriousness. Thus, a person with a hacking, asthmatic cough often is forced to come to the doctor by the person who has to listen to it, rather than bring himself for medical attention. The description of the symptoms’ appearance is also usually noteworthy. A common story is that of a bad “chest cold” occurring weeks or months previously, followed by persistence of the types of complaints listed above. The exact reason for the appearance of bronchial hyperreactivity as a consequence of inflammation is unknown, but it is in part a heightened activity of the parasympathetic component of bronchial control, thereby disrupting the normal homeostatic balance. This disruption, with its attendant clinical asthmatic problems, accounts for many adults with intrinsic or nonallergic asthma, and it

is this group, with its widely divergent symptom possibilities, about which there must be continual diagnostic and thus preventative therapeutic concern. With the above in mind, the interviewer pressed for time should be alerted by a story of nagging cough or persistent throat tickle and should pursue a line of questioning to further define the extent of the patient’s irritable airway. Variability of symptoms is the reality; thus expectant, receptive, history-taking is paramount. Furthermore, it has been well-demonstrated that patients with asthma usually underestimate the severity of their symptoms,” thus placing themselves in a potentially dangerous position when they are facing a difficult operative and postoperative period. In most instances, asthma can be diagnosed through an informed history, but if there is any question about the presence or severity of asthma, spirometry before and after bronchodilators, or even a screening methacholine challenge test, will help to resolve the issue.” Almost all patients with asthma will have a heightened bronchospastic response, reflected in decreased flow rates when exposed to gradually increased doses of methacholine. Airway obstruction is then reversed with inhalation of a bronchodilator. Most pulmonary function labs should be able to perform at least a screening test. Methacholine, which mimics the acetylcholine of the parasympathetic (vagal) system, is commercially available, and the test is not difficult to administer. An additional diagnostic consideration, particularly germane in the cardiac or hypertensive patient, is the possibility of bronchial hyper-reactivity as a reaction to one of the ACE inhibitors. Cough, congestion or wheezing occur in at least 5% to 10% of patients receiving these medications,” and the possibility must be explored in any patient receiving enalopril or captopril. The need to identify asthma is highlighted by the frightening process described in this case conference, so that preventive treatment can be given to avoid this sequence of events. Such preventive therapy starts with continuation of previously administered medications. The patient taking chronic aminophylline therapy should receive this medication in a continuous IV form as soon as he is no longer allowed oral intake preoperatively, in a dose comparable to

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the chronic oral dose. Inhaled beta-agonist therapy should also be continued preoperatively, particularly if the patient has a late starting time for his surgery. The use of corticosteroids, because of the possible side effects, is of concern to both patients and physicians alike, since they play a very important role in the therapy of asthma.20 Clearly, the patient receiving long-term steroids must continue to receive this medication not only for treatment of the asthma, but for the potential of decreased endogenous corticoids secondary to adrenal suppression. Perioperative steroids are favored in patients with an active asthmatic bronchitic component, whether they have been receiving them or not. Not only is the administration of short-term steroids relatively safe, it will reduce the need for excessive theophylline or catecholamine therapy and their attendant cardiotoxic effects. Furthermore, steroids uniquely address a major component of the airway pathophysiology, namely inflammation. This therapeutic action is not shared by other medications used in the therapy of asthma.20 A suggested schedule would be 80 mg of methylprednisone, IV, with preoperative medications, another 80 mg at the completion of surgery, then a tapering dose of 80 mg, twice a day for 24 hours, 40 mg twice a day for 24 hours, and 20 mg twice a day for the final doses, if the patient’s condition warrants such cessation. In the meantime, other therapy including theophylline and antibiotics, if indicated, can be continued. Steroids should be given for acute, severe bronchospasm, but will be of little acute benefit; thus the therapeutic focus will shift to agents which can be administered either IV, subcutaneously, or by inhalation. A theophylline loading dose of 3 to 5 mg/kg followed by a 0.7 mg/kg/h continuous infusion should be started. Terbutaline, 0.25 mg, can be given subcutaneously and repeated in 15 minutes if necessary. One of the inhaled beta-agonists, such as albuterol or metaproterenol, may be administered via inhalation, as can atropine (1 to 2 mg) or ipratropium bromide’l using either an in-line nebulizer or a metered dose inhaler.” In an extreme situation, an isoproterenol infusion may be effective, but the risks of cardiac toxicity must be weighed.22 From a mechanical or ventilation standpoint, consideration may be given to two addi-

CASE 1989- 1

Table 4.

Step Therapy

for Asthma

Theophylline 3 to 5 mg/kg loading dose 0.7 mg/kg/h infusion Catecholamine Terbutaline, 0.25 mg, subcutaneously twice per day Inhaled via nebulizer a. Albuterol, 2.5 mg b. Metaproterenol. 15 mg, or by metered dose inhaler Steroids Methylprednisone, 1 to 4 mg/kg, 1st dose Taper as condition allows Other Atropine. 1 to 2 mg, via nebulizer lpratropium bromide via MDI Mechanical Fiberoptic bronchoscopy Controlled hypoventilation

tional procedures. Rapid fiberoptic bronchoscopy to ensure a patent airway is prudent, but if the lungs remain stiff and nonventilated, then controlled hypoventilation could be attempted to reduce peak airway pressure.23 This technique requires constant oxygen saturation monitoring and the use of a bicarbonate infusion to maintain a pH above 7.25, and is clearly a therapy to be used only when all else fails. A brief summary of steps to take in asthma therapy is shown in Table 4. The key to management of asthma, whether in the office or in the operating room, rests upon recognizing its presence no matter what form it takes. Adequate preventive therapy can then be administered to diminish considerably any unwanted clinical surprises. COMMENTARYt

This case and its subsequent discussion illustrate the problems related to the diagnosis and management of bronchospasm during general anesthesia. The previous commentator has stressed preoperative diagnostic features of the asthmatic patient. A few remarks must be made on the recently available anticholinergic, ipratropium bromide, and its potential use in the preoperative and intraoperative periods. Airway reactivity in humans comprises both a sympathetic and a parasympathetic com‘Ian H. Sampson,

MD.

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ponent. 24The relative contribution of these two systems to bronchoconstriction in clinical airways disease, such as asthma, bronchitis, or emphysema remains unknown.25 However, it appears to be through the parasympathetic nervous system that reflex changes in bronchial caliber are initiated by anesthesia procedures related to the airway. The pressure of an endotracheal tube or the introducetion of potentially irritating substances into the airway or esophagus may induce bronchoconstriction through afferent and efferent pathways involving the vagus nerve. 26*27This vagal reflex may be blocked, presumably centrally, by ketamine2’ or deep barbiturate anesthesia.29 Both limbs of the reflex can be interrupted by local anesthetics. The efferent limb is specifically interrupted by cholinergic antagonists which block cholinergic receptors located on airway smooth muscle.26 In the past, the preoperative or intraoperative use of cholinergic antagonists, such as atropine, has been advocated in order to block or reverse parasympathetic airway reflexes. However, as mentioned by the case presenters, the side effects of these agents on pulmonary secretion volume and viscosity are unwanted, and systemic effects can be troublesome. Ipratropium bromide is a synthetic quaternary ammonium cogener of atropine which,

when administered through a metered dose inhaler or by aerosol, has the bronchodilating properties of atropine. It has minimal effect on the volume or viscosity of tracheal mucus and produces little reduction of ciliary frequency or tracheal mucus velocity.30 Bronchodilatation following ipratropium is primarily a local, site-specific effect. Since it is a quaternary ammonium compound, it is insoluble in lipids and crosses cell membranes s10wly~~; hence ipratropium is poorly absorbed, with minimal systemic effect and a wide therapeutic margin. It has been described as a topical atropine that causes clinically insignificant changes in heart rate or blood pressure.30 Although ipratropium may be useful only as an adjuvant to the bronchodilatation achieved with adrenergic agents in status asthmaticus, its potential role in preventing or reversing anesthesia-related bronchospasm could prove considerable. Currently, one of the few reported side effects of its use is pupillary dilatation following leakage of the aerosol during administration via a face mask.j2 Administration of ipratropium by a metered dose inhaler in the awake patient, or via an endotracheal tube connector during anesthesia, should reduce the risk of this complication.

REFERENCES 1. Newhouse MT, Dolovich MB, Eng P: Control of asthma by aerosols. N Engl J Med 3 15:870-874, 1986 2. Kingston HGG, Hirshman CA: Perioperative management of the patient with asthma. Anesth Analg 63:844-855, 1984 3. Yao FSF: Asthma-Chronic Obstructive Pulmonary Disease (COPD), in Yao FSF and Artusio JF Jr (eds): Anesthesiology-Problem-oriented Patient Management. Philadelphia, Lippincott, 1988, pp 3-25 4. Barrett JP: Editorial views: Clinical epilog on bronchomotor tone. Anesthesiology 42:1-3, 1975 5. Aviado DM: Regulation of bronchomotor tone during anesthesia. Anesthesiology 42:68-80, 1975 6. Hirshman, CA: Airway reactivity in humansanesthetic implications. Anesthesiology 58:170-177, 1983 7. Lowry CJ, Fielden BP: Bronchospasm associated with enflurane exposure: Three case reports. Anaesth Intensive Care 4:254-258, 1976 8. Wcod M: Inhalational anesthetic agents, in Wood M and Wood AJJ (eds): Drugs and Anesthesia. Baltimore, Williams & Wilkins, 1982, p 576-592 9. Rajanna P, Reddy JN, Gupta PK: Ketamine for the relief of bronchospasm during anesthesia. Anaesthesia 37:1215, 1982

10. Hug CC Jr: Pharmacology-anesthetic drugs, in Kaplan JA (ed): Cardiac Anesthesia, Philadelphia, Grune & Stratton, 1979, p 24-26 11. Hirshman CA, Edelstein BS, Ebertz JM, et al: Thiobarbiturate-induced histamine release in human skin mast cells. Anesthesiology 63:353-356, 1985 12. Buckingham RE Jr: Bronchospasm in patient with coronary artery bypass graft, in Reves JG and Hall, KD (eds): Common Problems in Cardiac Anesthesia. Chicago, Year Book Medical Publishers, 1987, pp 265-274 13. Gold MI, Marcia1 E: An anesthetic adapter for all metered dose inhalers. Anesthesiology 68:964-966, 1988 14. Gold MI: Treatment of bronchospasm anesthesia. Anesth Analg 54:783-786, 1975 15. Gold MI: A convenient and accurate Anesthesiology 28:1102-l 104, 1967

during nebulizer.

16. Spector SL, Farr RS: The heterogeneity of asthmatic patients-an individualized approach to diagnosis and treatment. J Allergy Clin Immunol57:499-511, 1976 17. McFadden ER Jr, Kiser R, deGroot WJ: Acute bronchial asthma. Relations between clinical and physiologic manifestations. N Engl J Med 288:221-225, 1973 18. Chatham

M, Bleecker

E, Norman

P, et al: A

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screening test for airways reactivity. An abbreviated choline inhalation challenge. Chest 82:15-18, 1982 19. Popa V: Captopril-related (and -induced?) ma. Am Rev Respir Dis 136:999- 1000, 1987 20. Fanta CH, Rossing TH, McFadden corticoids in acute asthma: A critical controlled Med 74:845-851, 1983 21. Barnes PJ: Using anticholinergics tage. J Respir Dis 8:84-95, 1987 22. Ziment I: Pharmacology agents, in Respiratory Pharmacology adelphia, Saunders, 1970, p 158-167

methaasth-

ER: Glucotrial. Am J

to best advan-

of sympathomimetric and Therapeutics. Phil-

23. Menitove SM, Goldring RM: Combined ventilator and bicarbonate strategy in the management of status asthmaticus. Am J Med 898-901, 1983 24. Widdicombe JC, Sterling nervous system and breathing. Arch 329,197O

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