Chapter 10. Severe Asthma and COPD

Obstructive airway disease is the most common chronic pulmonary pathology encountered in emergency medicine. Its most common etiology, asthma, is characterized by bronchoconstriction and airway hyperresponsiveness to certain stimuli. These stimuli trigger inflammatory mediators that lead to airway inflammation, mucosal edema, and, ultimately, reversible bronchospasm.1

Conversely, chronic obstructive pulmonary disease (COPD) is a disorder characterized by abnormal tests of expiratory flow demonstrating air flow obstruction that becomes fixed and does not change markedly over a period of months. It is a multifocal pathology encompassing the triad of emphysema, chronic bronchitis, and asthma.2 The increasing prevalence and the large burden these disease entities impose on emergency medical care make the diagnosis and management of acute exacerbations vital to any health care provider.

Approximately 22.5 million Americans had asthma in 2005, conferring an estimated financial burden of $19.7 billion in annual health care costs.3 In the United States, there are approximately 2 million emergency department visits per year for acute asthma, with 12 million people reporting having had asthma “attacks” in the past year.4 Approximately 2–20% of all ICU admissions are attributed to severe asthma, with intubation and mechanical ventilation necessary in up to one third of ICU admissions5 and mortality rates in patients receiving intubation ranging from 10% to 20%.6

COPD is the fourth most common cause of death in the United States, the third most common cause of hospitalization, and the only cause of death that is increasing in prevalence. The mortality of all patients while hospitalized for a COPD exacerbation is approximately 5–14%,7 while mortality of COPD patients admitted to an ICU for an exacerbation is 24%. For patients 65 years or older and discharged from the ICU after treatment of a COPD exacerbation, the 1-year mortality is 59%.7

Asthma is characterized by airway inflammation with an abnormal accumulation of inflammatory mediators in response to various stimuli. Acutely this accumulation leads to a reversible reduction of airway diameter caused by smooth muscle contraction, vascular congestion, bronchial wall edema, and thickened secretions.

Chronic asthma can lead to airway remodeling, with subepithelial collagen deposition and increased airway resistance that manifests as a progressive decline in forced expiratory volume in 1 second (FEV1) measurements. Once airway remodeling has occurred, the pathologic changes may become irreversible.

Pathologic findings in patients with chronic asthma include bronchial wall thickening due to inflammation and edema, bronchial narrowing or obstruction, and the presence of mucus plugs that at times may be large and thick. This airway narrowing leads to alveolar hyperinflation and, in a subset of patients, may lead to the formation of bullae, the potential for bullae rupture, and the development of pneumothoraces (Figures 10-1 and 10-2).

COPD is a triad of disease entities that includes the pathophysiology of asthma as well as incorporates the irreversible changes associated with both chronic bronchitis and emphysema. Chronic bronchitis is defined by excessive mucus production resulting in airway obstruction and hyperplasia of mucus-producing glands. Damage to the endothelium impairs mucociliary function that inhibits the clearance of bacteria and mucous. Inflammation and secretions, worse because of the decreased mucus clearance, provide the obstructive component of this disease. Emphysematous changes (described below) may be present to a variable degree and are usually centrilobar rather than pan lobar. This leads to increased cardiac output in an attempt to compensate for decreased ventilation. The resulting rapid circulation through a poorly ventilated lung represents a V/Q mismatch with hypoxemia and polycythemia. Eventually, hypercapnia and respiratory acidosis develop that lead to cor pulmonale. The development of cor pulmonale ultimately produces clinical evidence of right heart failure and produces the classic “Blue Bloater” appearance.

Emphysema is defined by destruction of airways distal to the terminal bronchiole. Pathologically, this disease involves the gradual destruction of alveolar septae and of the pulmonary capillary bed, leading to decreased ability to oxygenate blood. The body compensates with hyperventilation and the lowering of cardiac output. This V/Q mismatch results in relatively limited blood flow through a fairly well-oxygenated lung (as opposed to chronic bronchitis where there is rapid circulation through a poorly ventilated lung). The low cardiac output ultimately leads to systemic tissue hypoxia and pulmonary cachexia. Eventually these patients develop muscle wasting and weight loss and are identified as “pink puffers.”

The diagnosis, severity, clinical course, and response to treatment of all obstructive lung diseases (OLDs) can best be evaluated objectively by testing pulmonary function. OLD causes a delay in emptying lung volume. Normally, an individual can forcefully expel all of the air in the lungs (the vital capacity) within 4–6 seconds. In established OLD, patients may continue to expire during a forced expiratory maneuver for 10–20 seconds or more.

While all individuals have flow limitation during a forced expiration, those with obstructive airway disease demonstrate flow limitation with less effort and at lower airflow. The three lung abnormalities that reduce flow during forced expiration are decreased lung recoil pressure, increased resistance of the airways, and increased tendency of airways to collapse. Decreased lung recoil pressure causes a lower distending pressure between the airway and the surrounding pleural pressure, promoting a tendency for the airways to narrow. Increased resistance of the airways, especially in the periphery of the lung, creates increased pressure drops along the airways during expiration, thus promoting the tendency of the airways to constrict before the entire tidal volume is expelled. Bronchial smooth muscle constriction, inflammatory products encroaching upon the airway lumen, and decreased tethering of the airway by the alveolar septa also cause airways to collapse more easily.8

The airflow limitation in emphysema can be attributed to the decreased elastic recoil of the lung, in chronic bronchitis to the increased peripheral airway resistance, and in asthma to the increased tendency of airways to collapse.8

Asthma classically presents with a triad of symptoms that include cough, wheeze, and shortness of breath. However, certain patients may present with only one or two of these symptoms. Patients may complain of chest tightness or bandlike constriction across their chest. The cough may be dry or productive with pale yellow sputum. Wheezing may be subjective in patients familiar with the term and used to describe a variety of sounds including upper airway noises from the throat or nares. Since many of these complaints are consistent with many pulmonary pathologies, it can be hard to diagnose asthma based on chief complaint alone. However, certain historical clues such as episodic symptoms, characteristic triggers, and personal or family history of atopy or asthma as a child raise the likelihood.

In terms of how and why COPD patients present, there are four major causes of acute decompensation in COPD patients: (1) superimposed respiratory illness, (2) noxious environmental exposure, (3) noncompliance with medications, and (4) continued cigarette smoking. Patients complain of dyspnea, cough, and increased sputum production. During acute exacerbations, patients may also present with wheezing, particularly with exertion. As the disease becomes more chronic, intervals between acute exacerbations lessen. Patients may also complain of morning headaches, which are attributed to increased hypercapnia while asleep leading to worsening respiratory acidosis.

The spectrum of disease that presents to the emergency department is vast and the severity of exacerbation can progress in minutes. Caregivers should be familiar with the risk factors for death from asthma (Figure 10-3),9 and if there is only time for an abbreviated history, it should be focused on the predictors of fatal outcomes: a prior asthma attack severe enough to require intubation and mechanical ventilation, prior ICU admissions/hospitalizations, and an increased frequency and use of rescue inhalers.

On physical examination, widespread, high-pitched, musical wheezes are characteristic of asthma; however, these findings are nonspecific and may be absent in severe obstruction. The most concerning physical findings suggestive of air flow obstruction include conversational dyspnea or inability to speak at all, tachypnea (RR >30), tachycardia (HR >130), and a prolonged expiratory phase of respiration (decreased I:E ratio). More ominous signs include tripod positioning, retractions, and pulsus paradoxus (a fall in systolic blood pressure greater than 12 mm Hg during inspiration).

Signs indicating impending respiratory failure include a silent chest (no wheezing is worse than wheezing), inability to recline or lay supine in the stretcher, altered mental status, and paradoxical respirations (Figure 10-4).1

Pulmonary function tests are critical tools in the diagnosis and management of OLD exacerbations. Measurement of peak expiratory flow rate (PEFR) and spirometry are the tests most often used in the diagnosis of asthma or an exacerbation and the best objective evaluation for risk stratifying patients, monitoring response to therapy, and determining final disposition in exacerbations of OLD.

The PEFR, or “peak flow,” is measured during a brief, forceful exhalation. The resulting measurements are highly dependent on the patient's expiratory effort and technique. Serial measurements performed at presentation and 30–60 minutes after initial treatment are recommended.10 However, in patients experiencing a severe or life-threatening exacerbation with impending respiratory failure, PEFR testing is not warranted and should not preclude immediate therapy.

Spirometry, which includes measurement of FEV1 and forced vital capacity (FVC), provides additional objective information in the diagnosis and management of OLD. Variable/reversible airflow obstruction is the hallmark of asthma. Progressively worsening fixed airflow obstruction is the hallmark of COPD. Since bronchospasm is not the major pathologic mechanism behind COPD, the improvement in pulmonary function measurement during therapy is less than that of asthmatics.

Indicators for admission to the hospital include PEFR less than 100 mL/min or FEV1 less than 1 L prior to treatment, PEFR or FEV1 less than 40% baseline/predicted, failure of PEFR to increase greater than 10% following initial treatment, and PEFR that does not reach 80% of predicted following aggressive therapy.9

Pulse oximetry measurement is desirable in all patients with acute exacerbations of OLD to exclude hypoxemia. However, an isolated pulse oximetry reading at triage is not predictive in most cases, and serial monitoring can provide more subtle evidence for or against the need for hospital admission.

Routine laboratory studies are not contributory in the evaluation of exacerbations of OLD, but are used to diagnose or exclude other conditions, detect or confirm impending respiratory failure and theophylline toxicity, and diagnose comorbid conditions that might compromise therapy.

Arterial blood gas (ABG) measurement provides important information in severe asthma exacerbations. The test may reveal dangerous levels of hypercapnia secondary to poor ventilation due to exhaustion. ABGs are indicated in patients with fatigue or exhaustion, suspected hypoventilation, SaO2 <90%, or PEFR <25% predicted after aggressive therapy. In COPD patients, ABG values are helpful in determining whether inadequacy of ventilation (hypercapnia) is an acute decompensation or a chronic compensation.

Chest radiographs in exacerbations of obstructive disease are usually nondiagnostic, but are indicated to rule out secondary causes of wheezing (i.e., congestive heart failure, pneumothorax, pneumomediastinum, pneumonia, etc.).

The goals of therapy for acute exacerbations of OLD remain constant throughout the spectrum of the disease process: improving hypoxemia, reversal of acute bronchospasm, and prevention of post-therapy relapse. The primary treatment consists of the administration of oxygen, inhaled β2-agonists, and systemic corticosteroids; these should be given to all patients with acute exacerbations requiring medical evaluation. The severity of the asthma exacerbation determines the intensity of treatment and the frequency of patient monitoring (Figure 10-5).9

In addition to the primary treatments, therapy with inhaled ipratropium bromide is typically added to the other agents. Ipratropium bromide competitively inhibits muscarinic cholinergic receptors to produce bronchodilation. It works synergistically with β2-agonists and has been shown to reduce hospitalizations in patients with severe airflow obstruction.10 It reduces bronchoconstriction in the central airways that may explain the better therapeutic outcomes when treating COPD—as opposed to asthma—exacerbations.

Intensive therapy with inhaled bronchodilators and systemic corticosteroids is usually sufficient to reduce airflow obstruction and alleviate symptoms in patients with exacerbations of OLD. A small percentage of patients, however, will show signs of worsening ventilation. It is recommended that intubation not be delayed once it is deemed necessary,10 and it is this subset of patients that the rest of the chapter will focus on.

Intubation and mechanical ventilation in OLD is complex and fraught with potential complications. Therefore, prevention of intubation is an important goal in the treatment of severe, acute OLD. Various second-line therapies have been suggested and bear consideration for critically patients who would otherwise require intubation.

Intravenous magnesium sulfate can be considered in patients with life-threatening exacerbations and those whose exacerbations remain severe after 1 hour of intensive conventional treatment.11,12 Magnesium sulfate is thought to inhibit bronchial smooth muscle contraction by inhibiting intracellular influx of calcium. The dose is usually 2 g over 20 minutes in adults and 25–75 mg/kg in children (up to a maximum of 2 g), and its selective use is common.13

Heliox is a mixture of oxygen and helium that decreases airway resistance by reducing airflow turbulence in the lungs, thus reducing the work of breathing. It is available in a variety of percentages. An 80:20 mix (80% helium, 20% oxygen) contains about the same amount of oxygen as room air, but mixes with higher percentages of oxygen are available. The higher the helium content, the less viscous the mixture, so the greater the tendency toward laminar flow and a lower work of breathing. However, the higher the helium content, the lower the oxygen content, and the greater the tendency toward hypoxia. For patients with severe exacerbations of their disease, the National Asthma Education and Prevention Program Expert Panel Report 3 calls this form of therapy promising but gives it a conditional recommendation citing the need for a large multicenter study.10

Noninvasive positive pressure ventilation (NPPV) is a respiratory assist therapy in which positive airway pressure is delivered throughout the entire respiratory cycle. There are two principal forms used: continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). BiPAP differs from CPAP in that the pressure support is “bilevel,” or biphasic, with a higher pressure offered during inhalation than during exhalation or between cycles.

In OLD, some gas remains trapped in alveoli at end expiration causing levels of positive end-expiratory pressure (PEEP) above those seen in normal physiology. Since this PEEP comes from within the lung itself, it is termed “auto-PEEP.” It may seem counterintuitive to then apply additional external PEEP, but studies have shown that a low level of applied CPAP may offset the deleterious effects of auto-PEEP.14 The proposed mechanism is externally applied PEEP both delays or prevents airway collapse (reducing or relieving airway obstruction) and lessens the work of breathing (allowing extra time for other modalities to exert their effect). The addition of inspiratory pressure support to CPAP (aka BiPAP) improves tidal volume in proportion to the amount of pressure applied.

NPPV has prevented intubations in a variety of respiratory conditions in addition to OLD exacerbations. Randomized control trials have demonstrated that NPPV decreases respiratory rate, dyspnea, Paco2, length of stay, and rates of intubation as well as improves mortality in COPD exacerbations.15 Pathophysiologically, acute asthma exacerbations are similar in mechanism but there is less literature supporting NPPV in the treatment of asthma exacerbations.16

According to the National Asthma Education and Prevention Program Expert Panel Report 3, a trial of NPPV before intubation and mechanical ventilation should be considered in select patients with acute asthma exacerbation and respiratory failure, provided they are alert and can tolerate and cooperate with the therapy.16 Initial settings call for an initial expiratory pressure of 3 cm H2O increased every 15 minutes to a maximum of 5 and an initial inspiratory pressure of 8 cm H2O increased every 15 minutes to a maximum pressure of 15 or until the respiratory rate is less than 25 breaths/min.17 Nebulizer therapy should be continued throughout the administration of NPPV. Many facilities use a dedicated NPPV machine, although some practitioners prefer to administer NPPV using a traditional ventilator; this way, if the patient fails NPPV therapy and requires intubation, the ventilator is already in place.

Criteria for Intubation

In spite of all efforts for prevention of intubation, patients may still decompensate and require intubation and mechanical ventilation. Clinically, there are four major indications for intubation: (1) cardiac arrest, (2) respiratory arrest or profound bradypnea, (3) physical exhaustion, and (4) altered mental status such as lethargy or agitation. Patients may tell you, “I am too tired to breathe,” or “I can't go on any more”; these statements alone are ominous and should trigger a consideration for intubation.

Objectively, an ABG may be helpful and indicate failed noninvasive therapy and the need for intubation. An ABG showing progressive hypoxemia, hypercapnia, and respiratory acidosis in a patient who has changes in mental status should immediately trigger airway intervention.18 Even a normal pH or Pco2 should prompt consideration of intubation since normalization of these values may indicate tiring of the respiratory muscles.

Intubation Technique

Intubation with a rapid sequence of sedation followed by muscle paralysis is the preferred method for airway control in the emergency department setting.19 Airway control should be obtained by an experienced care provider because even minor manipulation of the airway during an acute OLD exacerbation can lead to laryngospasm and worsen bronchospasm.

Of the available sedatives used during RSI, ketamine and propofol offer the best therapeutic advantages during an OLD exacerbation. Ketamine stimulates the release of catecholamines and may have a direct relaxation effect on bronchial smooth muscle, leading to bronchodilation.20 Side effects include hypersecretion, hypertension, arrhythmias, and hallucinations, although pretreatment with atropine may reduce or eliminate some of these. It is contraindicated in patients with ischemic heart disease, hypertension, preeclampsia, and increased intracranial pressure.

Propofol is a short-acting sedative with bronchodilatory effects. It has a rapid onset of action and is very short acting which allows for rapid awakening. It is an excellent alternative for patients with elevated blood pressure during the peri-intubation period. Some practitioners also prefer propofol because it can be easily used for ongoing sedation.

Setting the Ventilator

The physiology of patients with OLD exacerbations presents a unique and complex challenge when these patients are placed on mechanical ventilation. Inhalation, controlled by the ventilator, is unchanged or even improved. But exhalation becomes an entirely passive process dependent only on patient variables. Since the patient's condition is one of airway obstruction, air can easily get into the patient, but may not be able to get out. This can lead to severe lung hyperinflation (auto-PEEP), which can ultimately lead to hypotension and barotrauma.21 Therefore, ventilatory strategies that reduce hyperinflation are crucial.

There are three ventilator strategies used to reduce hyperinflation and auto-PEEP in the intubated asthmatic patient (Table 10-1): (1) reduction of the respiratory rate, (2) reduction of tidal volume, and (3) shortening of inspiration by increasing the inspiratory flow rate to allow more time for exhalation during each respiratory cycle.

Reduction of tidal volume is limited by the progressive effect on the amount of dead space in the lung, so increasing the pressure limitation (up to 100 cm H2O) may be necessary to ensure delivery of a full tidal volume.22 Typically a reduction to an acceptable level of auto-PEEP (10–15 cm H2O) can be obtained by tweaking the first two strategies. But if the respiratory rate cannot be sufficiently lowered to reduce hyperinflation, inspiratory time can be shortened to allow for more time in the exhalation phase. Furthermore, increasing the flow rate and using a square wave flow pattern shorten inspiratory time, do not represent a significant danger for barotrauma, and reduce the possibility of auto-PEEP.22

Of course, decreasing the respiratory rate can cause hypercapnia. In this subset of patients, hypercapnia is usually well tolerated and safer than (over)ventilating to a normal Paco2 and causing harmful hyperinflation. This strategy is termed “permissive hypercapnia.” Anoxic brain injury and severe myocardial dysfunction are contraindications to permissive hypercapnia because of the potential for hypercapnia to dilate cerebral vessels, constrict pulmonary vessels, and decrease myocardial contractility.22

Having objective data to help determine the severity of lung hyperinflation is central to assessing patients and adjusting ventilator settings. In practice, two relatively easy to measure pressures are used as surrogate markers of lung inflation: auto-PEEP and plateau pressure (Pplat). Accurate measurements of Pplat and auto-PEEP require patient–ventilator synchrony and absence of patient effort, although paralysis is generally not required. Neither parameter has been validated as a predictor of complications of mechanical ventilation, but experts agree that complications are rare when Pplat is less than 30 cm H2O and auto-PEEP is less than 15 cm H2O.23

Medical Management

As with all intubated patients, effective sedation is paramount. Sedation allows for synchrony between the patient and the ventilator and prevents self-extubation and auto-PEEP from a rapid spontaneous respiratory rate. Propofol is a good sedative because not only can it be easily titrated, but it possesses bronchodilatory properties as well.22

Neuromuscular blockade during mechanical ventilation might reduce the risk of barotrauma, avoid coughing and dyssynchronous breathing, and allow the respiratory muscles to rest. However, prolonged use can cause myopathy, particularly when used in conjunction with corticosteroids, and so is only recommended in patients in whom deep sedation alone does not allow synchrony with the ventilator.

Systemic corticosteroids and inhaled β-agonists are the mainstay of asthma therapy prior to intubation, and should be continued while on mechanical ventilation, as well. High flow aerosolized (HFA, aka multidose inhaler [MDI]) or nebulizer treatments should be added to the ventilator circuit.23

Treatment Complications

Persistent or worsening hypoxemia suggests the development of a complication from mechanical ventilation. Complications that must be considered include right mainstem intubation, pneumothorax, gastric distention, endotracheal tube dislodgement, tube blockage, aspiration, bronchospasm, and ventilatory malfunction. Each of these must be considered and the patient reassessed after any intervention.

Hypotension can be caused directly by the physiology of mechanical ventilation. The increase in intrathoracic pressure caused by mechanical ventilation leads to a reduction in preload and a decrease in cardiac output. These effects can be avoided by preventing complications caused by elevated intrathoracic pressure such as hyperinflation, gastric distention, and pneumothoraces. Medications used for sedation and neuromuscular blockade can also be a culprit. A fluid bolus is useful if not contraindicated. Adjusting the ventilator to prevent ventilator causes of hypotension as well as an apnea trial for 30–60 seconds in a preoxygenated patient may be prudent in helping differentiate the cause of hypotension. If no reversible cause is found and hypotension remains critical, then inotropic support is indicated.

Critical lung hyperinflation can produce deleterious effects such as decreasing preload to the right ventricle, increasing pericardial pressure causing tamponade physiology, and predisposing to a tension pneumothorax. If cardiac arrest presents with pulseless electrical activity (PEA), all potential causes of PEA should be considered, recognizing the increased risk of pneumothorax and tamponade physiology. If clinical signs of tension pneumothorax are present (unequal breath sounds, tracheal deviation, subcutaneous emphysema), needle decompression should be performed followed by tube thoracostomy. Note that puncturing a hyperinflated lung during chest tube insertion can produce a rush of air similar to releasing a tension pneumothorax but will not improve ventilation.22 In this case, the tube should be repositioned or another tube inserted.

Barotrauma is a well-known complication of mechanical ventilation, but the issue of development of barotrauma in relation to airway pressure, PEEP, and tidal volume is controversial. In asthmatic patients, a VEI (total exhaled volume over 20–60 seconds, after a machine-delivered breath) of greater than 20 mL/kg correlates with barotrauma24; however, this measurement is not routinely obtained in most ICU settings.

Weaning and extubation criteria have not been validated for patients with acute exacerbations of OLD. A recommended approach is to perform a spontaneous breathing trial in an awake patient once Paco2 normalizes, airway resistance is less than 20 cm H2O, and neuromuscular weakness has not been identified.22 After extubation, observation in an ICU setting is recommended for an additional 12–24 hours. Once the patient is stable enough for discharge, patient education, systemic corticosteroids, and proper use of β-agonist therapy must be reinforced along with timely follow-up with a pulmonologist or his or her primary care provider to help prevent further exacerbations.