Life Threatening Asthma

By Donald R. Elton, MD, FCCP Lexington Pulmonary and Critical Care

Introduction
Asthma mortality has been increasing in recent years. Various experts have debated why this is so but several facts are apparent from the available data. First, most patients who die of asthma do not die in the hospital. Most do not die suddenly and have frequently been in the midst of an exacerbation for several days. Near fatal asthma is a risk factor for fatal asthma. Many, if not most, inhospital asthma fatalities are a result of barotrauma. Clearly, outpatient asthma mortality could be improved by identifying those patient s at risk for fatal asthma and making sure they know when to seek medical care. Inpatient asthma mortality requires recognition, on the part of the care giver, of the causes and prevention of barotrauma.

Pathophysiology
Asthma has been called eosinophillic bronchitis which reflects the important role of eosinophils in mediating the asthmatic response. Everyone has some degree of airway reactivity which means that an inflammatory response will be elicited in anyone if the stimulus is strong enough. For some people it might take Clorox fumes, histamine, or methacholine to elicit this response while for others mere exposure to cold air could lead to the same result. Bronchial provocation testing is a pulmonary function test where a known airway irritant such as methacholine or histamine is aerosolized with pre and post exposure FEV1 measurements to determine the threshold dose necessary to bring about a given decrease in FEV1. A patient with severe asthma would require a small dose of the irritant while a patient with very non-reactive airways would require a higher dose to get the same decrease in lung function. Airway reactivity may be an inherited trait or it may result from a chemical or biological exposure, lasting long after the exposure has come and gone. Once a sufficient stimulus has reached the patient, a cascade of events takes place involving many chemical mediators of inflammation. These mediators result in inflammation (infiltration of tissues by inflammatory cells), edema, mucus hypersecretion, and smooth muscle contraction (bronchospasm).

Natural History
Just as airway reactivity, varies from person to person, the typical history of an asthmatic varies. Some patients will only be symptomatic as children while others will only become symptomatic in middle age, perhaps as a component of other chronic lung diseases. One important characteristic of asthma is that lung function should be essentially normal between exacerbations, unlike the emphysema patient, who always has abnormal lung function. This is why bronchial provocation testing is sometimes required to actually diagnose asthma since routine pulmonary function studies may frequently be normal when a

patient is doing well. In a particular asthmatic attack, there are really two phases consisting of the early (histamine related) and late (inflammatory) reactions. The early reaction typically lasts for the first hour of treatment and results in an early response to therapy that may then relapse into the later, second phase reaction two to eight hours later. Because of this biphasic nature of a typical asthma attack, one must be careful not to discharge a patient from the emergency department too soon only to have a severe relapse occur away from the hospital. The initial reaction tends to respond well to inhaled bronchodilator agents while the late response requires the use of corticosteroids that have a delayed action thus they should be given early during the patient's ER visit to avoid the second stage relapse.

Initial Evaluation
The initial evaluation of the asthmatic patient should be intended to determine which patients are at risk for dying from their asthma but to prevent inappropriate ER discharges and to help determine the course of therapy to be used. The initial evaluation of an asthma attack consists of the physical examination and peak expiratory flow measurement. Breath sounds are an important part of the physical examination but it is easy to misjudge the severity of an attack using breath sounds. Many patients with severely reduced lung function will have fairly silent chests with little audible wheezing. As they improve with therapy, their wheezing may become much louder as wheezing is dependent upon airflow. Other physical findings associated with severe asthma include cyanosis (a very grim finding), altered mentation (time to intubate), increased use of accessory muscles of respiration, increased pulsus parodoxis, upright posture, and absence of breath sounds. Peak flow measurement is fairly simple and inexpensive and can objectively (within the limits of patient effort) stage airway obstruction much more accurately than physical examination and should be a part of every asthmatic's initial ER evaluation. PEFR (Peak Expiratory Expiratory Flow Rate) measurement is used not only to stage the disease but also to assess the response, or lack of response, to therapy. All patients with more than mild asthma should have their own PEFR meters that they keep at home so they will know their own normals and can give physicians and others objective information on the severity of a given attack over the telephone. For most of my adult asthmatic patients that have normal PEFR readings in the 300400 LPM range, I advise them to notify me if their PEFR falls below 250 LPM with treatment and to expect that I'll probably put them on a tapering dose of oral steroids and I tell them that if their PEFR falls below 150 LPM they need to get to the ER, via the 911 system if possible as patients tend to develop respiratory failure at PEFR values below about 80 LPM. PEFR meters cost less than $20 and last until you step on them. Patients with severe asthma should have chest radiographs, primarily to look for evidence of infection (pneumonia) and barotrauma (pneumothorax or pneumomediastinum). These are not that useful in milder cases and rarely show more than mild hyperinflation. Blood gasses don't add much to acute asthma management prior to intubation since intubation should be based primarily on ability to oxygenate and altered mental

status rather than any particular value for pH or PCO2.

Initial Treatment
The initial priority in asthma therapy is providing oxygen (there have been many malpractice suits lost because this step was skipped). Next comes the use of inhaled beta-2 agonist medications. Studies have been done that basically show little advantage of using nebulizers as opposed to repeated use of metered dose inhalers though most physicians tend to use nebulizers since the acutely dyspneic patient will frequently not be likely to be an expert at MDI use. On any ER patient presenting with asthma, I go ahead and establish IV access and give an initial high dose of steroid, typically Solu-medrol. Again, oral steroids work almost as quickly as IV but I tend to at least give the first dose IV as many of these patients will be borderline theophylline toxic and will be at risk of vomiting which will raise the question of whether the oral medication was actually delivered adequately. Inhaled anticholinergic drugs such as Atrovent or Atropine can be given but I've not been impressed with their efficacy in my experience (though I'll try most anything in the non-responding patient with severe asthma). Theophylline and Aminophylline are falling out of favor in the acute management of asthma as many studies in recent years have failed to show any additional benefit in terms of improved lung function or prevented hospital admission when theophylline products are added to beta-2 agonist therapy. There is some thought that these products might have some usefulness in the late response or perhaps used as anti-inflammatory agents but bottom line data is lacking. Theophylline products have a much higher toxicity and many patients presenting to the ER will already have toxic levels. Given the relative lack of efficacy when compared to beta-2 agonist agents, one should be very careful if they are used, and loading doses should generally be avoided in patients in whom a drug level measurement is not available prior to the bolus.

How to dose aerosolized medications

Aerosol therapy is a very inexact science. There is very little relationship between the amount of medication put in a nebulizer cup and the amount actually delivered to the site of action in a given patient. The percentage of a nebulized dose of a drug that is actually delivered to the site of action is influenced by patient size (smaller patients have smaller minute volumes and thus breath in less drug), airway size (smaller airways result in more rain out before the site of action), breathing pattern (higher inspiratory flows result in more inertial impaction of droplets before the site of action), nebulizer used (this influences particle size and aerosol density), flow rate of the driving gas, mask or mouthpiece type in use, mouth vs nose breathing, use of airways such as endotracheal tubes, use of ventilators to deliver the medications, placement of nebulizers in ventilator circuits, whether the ventilator is a volume ventilator or a continuous flow system and probably many other factors. Because of these problems, many of which are not controllable, dosage should be based on patient response, good and bad (i.e. give enough to get the effect you're looking for and back off when toxic effects become unmanageable). In pediatric patients (or smaller patients in general) it will be necessary to actually increase the

amount of drug placed in the nebulizer to get similar therapeutic effects as they have several factors (smaller minute volumes and smaller airways) that result in their automatically getting less drug to the site of action. In the severe asthmatic, I typically use a standard concentration of drug (i.e. 0.5 cc in 2.5 cc of saline in the case of albuterol) and either give this aerosol continuously or via rapidly repeated doses until the patient responds with improved flow rates or gets unacceptable side effects (which are rarely encountered). I have given albuterol by continuous nebulization as long as 48 hours around the clock in a few severe patients with little trouble though electrolytes such as potassium and magnesium need to be monitored during therapy as beta-2 agonists will lower these.

When & Whether to Intubate

Why ask why? Remember that one of the largest causes of mortality in acute asthma in hospitalized patients is a result of barotrauma. Because of the very prolonged time constants in asthmatics (high airway resistance causing longer passive expiratory times), any mechanical ventilation using a respiratory rate much higher than 4 or so breaths per minute will result in a dangerous sequence of events. First, there will be air-trapping owing to inadequate expiratory time, this then leads to increased alveolar pressure and Auto-PEEP, which, in turn, leads to reduced venous return, a cardiac tamponade effect, and reduced cardiac output and blood pressure. It is not unusual for Auto-PEEP levels to exceed 30 cm H2O pressure in asthmatics, even those ventilated at respiratory rates less than 10 breaths per minute. Remember that in most asthmatics in respiratory failure, the problem is not one of muscle strength or even oxygenation but is one of respiratory mechanics, namely airway resistance, that is incompatible with effective ventilation at normal minute volumes. Because of these factors, it can be dangerous to put a patient with an acute severe asthma attack on a mechanical ventilator. The other side of this issue, of course, is that patients can die of respiratory failure and/or hypoxia thus one needs to know when the risks of respiratory failure exceed the risks of the treatment (ventilation). There are no absolute rules here but think about how respiratory failure results in death. The primary mechanism is hypoxia. Few patients die because their PaCO2 gets too high or because their pH gets too low. Hence, if adequate oxygenation can be maintained, there is still some time to direct therapy toward the underlying cause of respiratory failure, namely, the increased airway resistance. Again, all acute asthmatics should receive oxygen therapy. This buys time for other more definitive therapy to work. Watch for evidence of muscle fatigue and/or CO2 narcosis (which will eventually result in respiratory arrest). Typical signs are decreased respiratory effort in spite of increased loads, and altered mental status. My general method is to hold off on intubating an asthmatic until I'm unable to maintain adequate oxygenation or until the patient develops altered mental status (confusion, unresponsiveness, coma etc). Until these indicators are present, there is still time (though maybe not much time) to continue continuous inhaled beta-2 agonist therapy and steroids. Using this method I've had patients with CO2's transiently in the 90's stay awake and alert and wind up

not needing the ventilator after another 15 minutes of aerosol therapy. This sort of approach, of course, requires constant monitoring by the physician at the bedside with frequent (if not continuous) assessment and re-assessment of the response to therapy.

After Intubation
Remember that as outlined above, intubation and mechanical ventilation are not a treatment for asthma but are only a treatment for respiratory failure and/or hypoxia. Once a patient is intubated, the treatment for asthma should be continued if not intensified with the use of continuous aerosolized bronchodilators and steroids, as well as IV steroids and optionally IV bronchodilators (usually Brethine (terbutaline)). The goals of mechanical ventilation in acute asthma are primarily to keep a patient alive while you wait on the asthma therapy to work, hopefully without killing the patient with the ventilator. Normal blood gasses are NOT the goal of mechanical ventilation in asthma. Adequate oxygenation with a minimum of barotrauma is the goal. It is frequently necessary to use very low respiratory rates (less than 6 breaths per minute in some cases) to avoid dangerous Auto-PEEP and its resultant sequelae. Patients, should in most cases, be pharmacologically sedated and paralyzed both to prevent dyssynchronous ventilation (bucking the vent) and to decrease the rate of metabolism and thus the requirement for ventilation and oxygenation. Fever should be treated to lower the metabolic rate if it is present. Auto-PEEP should be measured hourly initially and adjusted to a safe level (probably less than 10 in most patients though IV volume loading of the patient will make them more tolerant from a blood pressure stand-point). As Auto-PEEP decreases (signifying a reduced airway resistance) the respiratory rate can slowly be increased to correct the expected respiratory acidosis that most severe asthmatics on the ventilator will have when ventilated at low rates. Once breath sounds are clearing up, the continuous bronchodilator dosing can be made intermittent and sedation and paralysis can be weaned as can the ventilator itself in most cases. In most cases, mechanical ventilation will only be necessary for a few days (sometimes just a few hours will be adequate) though I've had some difficult cases require ventilation as long as two weeks with severe wheezing until right before weaning.

After Extubation
Patients who have been mechanically ventilated for asthma are in a very high risk group for mortality from asthma. They and their families should know this so they will take future attacks very seriously. They should be reminded that most asthma mortality occurs outside of the hospital and they should be very familiar with using a peak flow meter to monitor their progress.

References
Olsen GN: Asthma Concepts & Control in Olsen, GN: Basic Handouts in Pulmonary Medicine, 2/92. Nowak RM, Pensler MI, Sarkar DD, et al. Comparison of peak expiratory flow and FEV1.0 admission criteria for acute bronchial asthma. Ann Emer Med 1982;

11:64-69. Guidelines for the Diagnosis and Mangement of Asthma, National Heart, Lung, and Blood Institute, NIH, US Dept HHS, August 1991. Miller TP: Identification, treatment of adults at increased risk of fatal asthma, Today in Medicine, Nov/Dec 1992. Fish, JE: Status Asthmaticus in Current Therapy in Allergy, Immunology and Rheumatology.