Lesson 15, Volume 16—Near-Fatal Asthma

By Mark D. Siegel, MD, FCCP

Objectives

  1. Identify which patients are at risk for fatal and near-fatal asthma.
  2. Describe the pathophysiology of near-fatal asthma.
  3. Describe the mechanisms contributing to and the consequences of dynamic hyperinflation.
  4. Understand the major options available for the treatment of near-fatal asthma.
  5. Understand the principles of mechanical ventilation for the management of intubated asthmatic patients.

Key words

airways inflammation; asthma; barotrauma; hyperinflation; mechanical ventilation; permissive hypercapnia

Abbreviations

autoPEEP = intrinsic positive end-expiratory pressure; DHI = dynamic hyperinflation; DVT = deep venous thrombosis; FRC = functional residual capacity; I:E = inspiratory/expiratory; MDI = metered-dose inhaler; NFA = near-fatal asthma; Pel = elastic recoil pressure of the respiratory system; Ppk = peak airway pressure; Ppl = plateau pressure; Pr = pressure related to airway resistance; Raw = airway resistance; Te = expiratory time; E = minute volume; VT = tidal volume

"The best treatment of status asthmaticus is to treat it three days before it occurs."—Thomas L. Petty, MD, Master FCCP1

Few tragedies exceed the loss of an otherwise healthy person to asthma. Although largely preventable, asthma deaths are not rare, occurring approximately 5, 000 times per year in the United States.2 Life-threatening attacks requiring ICU admission, intubation, and mechanical ventilation are far more common.

In the last two decades, improved treatment for those requiring mechanical ventilation has radically improved short-term prognosis. This review will describe the epidemiology of near-fatal asthma (NFA), characterize its pathology and pathogenesis, and summarize current management principles, emphasizing a safe and effective approach to mechanical ventilation.

Epidemiology

From 1982 to 1991, the annual age-adjusted mortality from asthma increased from 13.4 to 18.8 per million.3 Blacks, women, and inner-city patients are at greatest risk.4 Given the right conditions, almost any asthmatic can develop a fatal or near-fatal attack.5

McFadden6 has emphasized four factors predisposing patients to severe attacks: pre-existing obstruction, airway lability, a stimulus, and patient response. Specific risk factors include prior severe attacks (especially those requiring mechanical ventilation), nonadherence to therapy, age > 40 years, and cigarette smoking (Table 1).5,7-10 A diminished ability to sense and respond to airway obstruction occurs in some.11

Table 1—Risk Factors for Near-Fatal Asthma

Prior severe attacks
Nonadherence to therapy
Poor asthma self-management skills
High baseline peak-flow variability
Frequent b-agonist use
Inadequate use of inhaled corticosteroids
Age > 40 yr
Cigarette smoking
Prior barotrauma
Hospitalization despite chronic oral corticosteroid use
Psychiatric illness
Recreational drug and alcohol abuse
Diminished ability to sense and respond to airway obstruction
Female sex
Poor socioeconomic status

Frequent b-agonist use is closely linked to fatal asthma.7,8 Although some cite b-agonists as an independent risk factor for severe disease, it is more likely that frequent use simply identifies patients with poorly controlled asthma. In contrast, an inverse correlation exists between the number of containers of inhaled corticosteroids used per year and the risk of fatal attacks.12

Pathogenesis and Pathology

Autopsy studies have provided much of the information available on the pathology of severe asthma.13 Key features include mucus plugging in small and medium-sized airways, vascular dilatation, airway edema, increased volume and size of submucosal glands, desquamation of airway epithelial cells, an inflammatory cellular infiltrate, goblet cell hyperplasia, bronchial smooth muscle hypertrophy, and thickening of the epithelial basement membrane (Fig 1).14,15 The degree of inflammation and changes in epithelial integrity, bronchial smooth muscle, and mucus glands parallel disease severity.15

Figure 1. Airway pathology in fatal asthma. Key findings include thickening of the basement membrane (thin arrow), a marked inflammatory infiltrate (dashed arrow), a disordered airway epithelium (thick arrow), and a large endobronchial mucus plug (asterisk). Courtesy of Drs. Geoffrey Chupp and Robert Homer, Yale University School of Medicine.

Reports have traditionally emphasized the importance of eosinophils and their by-products, such as major basic protein.16,17 More recent data highlight the central role of neutrophils and their mediators, particularly in severe asthma.18-20 Unlike eosinophils, which decrease quickly with corticosteroid treatment, neutrophils persist in the airways of mechanically ventilated patients with NFA.19 Proinflammatory mediators predominate over anti-inflammatory ones, particularly cytokines and chemokines (tumor necrosis factor-a, interleukin-1b, interleukin-8, interleukin-5), leukotrienes, reactive oxygen species, and nitric oxide metabolites.19,21-23

Most patients present after several days of symptoms, with extensive airway inflammation, epithelial desquamation, and mucus plugging. In contrast, the smaller group presenting with "sudden asphyxic asthma" tend to have fewer eosinophils, a predominance of neutrophils, and less mucus.15,24

Pathophysiology

Most asthma deaths result from asphyxia before patients reach the hospital.25 Mucus plugging and diffuse bronchoconstriction and airway edema wreak havoc on lung mechanics and gas exchange. Increased airway resistance promotes hyperinflation and air trapping. Compliance may decrease as total lung capacity is approached, although this is inconsistent.5

Gas exchange abnormalities are almost universal.5,26-28 Hypoxia results from ventilation/perfusion mismatch and hypoventilation as respiratory failure ensues. The PaCO2 may be low, normal, or high, depending on the severity of obstruction and the patient's ability to ventilate.26 Factors promoting hypercapnia include ventilation/perfusion mismatch, increased dead space, increased CO2 production, and relative hypoventilation, the latter resulting from an increased work of breathing, disordered mechanics, and respiratory muscle fatigue. Importantly, even patients destined to develop respiratory failure may be hypocapnic at first. Hypercapnia generally ensues as ventilatory failure progresses.

In some patients, wide pleural pressure swings can result in pulsus paradoxicus, which correlates well with disease severity.5,27,29 Factors promoting pulsus paradoxicus include (1) increased left ventricular afterload during vigorous inhalation and (2) inadequate left ventricular filling due to right ventricular dilation, which causes intraventricular septal shift, decreased pulmonary blood flow, and external compression of the heart by the hyperinflated lungs

Pulsus paradoxicus may be absent in patients who are fatiguing and cannot generate large negative pleural pressures.5

Clinical Presentation and Initial Evaluation

Attacks of NFA are usually precipitated by viral upper respiratory tract infections, heavy allergen exposure, nonadherence to outpatient therapy, air pollution, changes in the weather, or emotional stress.28 In predisposed patients, aspirin and nonsteroidal anti-inflammatory drugs can precipitate attacks.30

Patients predisposed to NFA tend to underestimate symptom severity,11 making it challenging to discern how long patients have been ill before presentation. Tragically, at least 90% present after several days of worsening symptoms, missing the opportunity for effective treatment.10 In 10%, the onset is more rapid and asthma progresses over a period of minutes to hours. The latter patients tend to have a lower FEV1 at presentation and, in contrast to slower-onset cases, their attacks are less commonly triggered by infection.31

Patients with NFA are generally dyspneic, anxious, and diaphoretic, typically sitting upright, tachycardic and tachypneic, and using accessory muscles. Physical examination reveals diffuse wheezing or, if air movement is poor, no breath sounds at all. The severity of wheezing correlates poorly with the degree of obstruction.5 An increased pulsus paradoxicus correlates well with severe airflow obstruction and can be demonstrated on an arterial line tracing if available.5,27,29,32 The absence of accessory muscle use and pulsus paradoxicus does not exclude severe obstruction, particularly when respiratory muscle failure develops.5 Patients may become somnolent as respiratory failure looms.

Laboratory findings are nonspecific. The white blood cell count may be elevated because of stress and this finding does not necessarily indicate infection. Increased blood eosinophils may be seen in allergic patients. An increased lactate level is common and most likely relates to high-dose catecholamine therapy, although increased production by respiratory muscles and decreased clearance due to circulatory failure may contribute.5,33

Careful clinical assessment is critical. In general, at least one arterial blood gas measurement is needed. Hypoxia tends to be modest and can easily be overcome by supplemental oxygen. Patients can be hypocapnic or hypercapnic.26 Early in the presentation, hypocapnia reflects compensatory hyperventilation, which can lead to respiratory failure if not corrected. In contrast, hypercapnia on initial presentation may respond to treatment.5 A steadily rising PaCO2 reliably indicates impending respiratory collapse and the need for mechanical ventilation.

The chest radiograph commonly reveals hyperinflation (Fig 2) and, in 34% of patients, may show significant findings such as focal infiltrates, pulmonary vascular congestion, or pneumothorax.5,34 The ECG usually shows sinus tachycardia, although a right ventricular strain pattern has been described.5 The peak expiratory flow rate tends to be < 30 to 50% of the predicted value or the patient's personal best.5 Although valuable, great care should be taken with peak flow measurements because the effort can worsen bronchospasm.5,35 The failure to improve the peak expiratory flow rate after 30 min of treatment correlates with a severe course and the need for hospitalization.5

Figure 2. Chest radiograph in a patient intubated for severe asthma, demonstrating severe hyperinflation.

The diagnosis of acute, severe asthma is generally straightforward. Still, it is important to consider alternative diagnoses, especially if the presentation is atypical, the patient is older, or if a prior diagnosis of asthma has not been established (Table 2).5,36,37 Potential life-threatening mimics include congestive heart failure, anaphylaxis, upper airway obstruction, and pulmonary embolism. Other considerations include COPD, pneumonia, vocal cord dysfunction, and, as a diagnosis of exclusion, hyperventilation disorder.5 Upper airway obstruction, particularly vocal cord dysfunction, may become self-evident when there is no evidence of lower airway obstruction after intubation.37

Table 2—Differential Diagnosis of Severe Asthma

Congestive heart failure/myocardial infarction
Pulmonary embolism
Upper airway obstruction

Epiglottitis
Foreign body aspiration
Tumor
Anaphylaxis/angioedema

COPD
Bronchiolitis
Vocal cord dysfunction
Hyperventilation syndrome
Acute bronchitis/pneumonia

 

Management

ICU Admission

Persistent severe obstruction despite treatment mandates admission to the ICU.5 Related indications include respiratory arrest, depressed mental status, and arrhythmia.5 The need for frequent albuterol treatments may, out of necessity, require ICU admission, but also signifies a patient population at risk for deterioration.

Bronchodilators

Short-acting inhaled b-agonists, such as albuterol, metaproterenol, or isoetharine, are essential. Treatment must be given frequently and in high doses because airway narrowing adversely affects the dose-response curve and duration of action.5 Medication can be delivered either with a metered-dose inhaler (MDI) and spacer or via nebulization. In nonintubated patients, reasonable doses include 2.5 mg of albuterol by nebulization every 15 to 20 min or 4 to 6 puffs (360 to 540 mg) every 10 to 20 min using an MDI/spacer.5

In mechanically ventilated patients, it is critical to ensure drug delivery, recognizing that inadequate systems may deposit too much medication on ventilator tubing and deliver little to the patient.5,38 Doses should be titrated until a physiologic benefit, such as decreased peak airway pressure, is demonstrated or until side effects such as tachycardia occur.5,38 Both MDIs and nebulizers can be effective.38,39 If an MDI is chosen, a spacer ashould be used and medication instilled through the ventilator circuit's inspiratory limb.5 If a nebulizer is used, it should be placed close to the airway opening, humidifiers stopped, and peak inspiratory flow rates decreased to approximately 40 L/min to minimize turbulence, watching carefully for worse air trapping.5 Few data support parenteral delivery, except perhaps in young patients in whom inhaled therapy has failed.

Both theophylline and ipratropium have been used as adjunct bronchodilators. Theophylline is associated with many side effects, particularly tachyarrhythmias, nausea, and reflux. Concurrent medications, such as cimetidine, ciprofloxacin, and macrolides, can raise theophylline levels and induce toxicity.5 Although its use is controversial, theophylline may help some patients who are not responding to high-dose albuterol and steroids.40 In patients without therapeutic blood levels, a 5-mg/kg load can be given over a 30-min period, followed by a maintenance dose of 0.4 mg/kg/h.40

Although published results are inconsistent, ipratropium, combined with high-dose albuterol, may improve bronchodilation.41 Treatment is generally well tolerated. A dose of 0.5 mg delivered by nebulization or 4 to 10 puffs (72 to 180 mg) by an MDI/spacer can be given every 1 to 4 h.5,40

Corticosteroids

High-dose parenteral corticosteroids, at least the equivalent of 40 mg of methylprednisolone every 6 h, are essential.5,42 Benefits may occur within 1 to 2 h, although in the sickest asthmatics, a response may not be apparent for days.43 Airway eosinophils decrease almost immediately, whereas neutrophils may persist or even increase after corticosteroid treatment is started.18,19 Although data are lacking, some authors have suggested a role for inhaled corticosteroids as well.5

Adjunct and Experimental Therapy

A variety of adjunct therapies have been proposed for NFA. The best studied is heliox, usually an 80/20 or 70/30 mixture of helium and oxygen, which can be delivered by face mask in nonintubated patients or through the inspiratory limb of the ventilator circuit in those who are intubated.40 Because helium is less dense than nitrogen, airflow across narrowed airways tends to be laminar or at least less turbulent.40 Higher oxygen concentrations cannot be used because the helium concentration becomes insufficient, making heliox less useful in those with severe hypoxia. In some patients, however, heliox may improve oxygenation, even with a lower fraction of inspired oxygen.44

Heliox can improve lung mechanics in some patients and, in those who are not intubated, decrease the work of breathing and potentially "buy time" while waiting for corticosteroids to work.40,45,46 Improved airway mechanics can be seen in intubated patients as well.47 If used in this population, however, ventilators must be recalibrated to ensure accurate measurement of the tidal volume (VT) and fraction of inspired oxygen.40 Heliox may improve the delivery of aerosolized medications as well.48

High-dose IV magnesium may help some patients, at least in part by interfering with calcium-mediated smooth muscle contraction and decreasing acetylcholine release from parasympathetic nerve endings.49,50 In one emergency department study, IV magnesium was associated with decreased admission rates and improved FEV1.49 In another report, IV magnesium decreased airway resistance in intubated patients.50 Other studies have been unable to demonstrate benefit, however.40 A trial of IV magnesium, 2 g over a 20-min period, may be reasonable when standard therapy fails.40 Although generally safe, toxic levels can cause hypotension and loss of deep tendon reflexes. Caution must be exercised in patients with impaired renal function.40

An IV form of the leukotriene-receptor antagonist montelukast may be helpful. In a recent placebo-controlled study of 191 patients with asthma refractory to albuterol, IV montelukast at 7 or 14 mg improved FEV1 by a mean of 0.18 L at 20 min and 0.22 L at 60 min, the latter a 13.6% improvement from baseline.51 Further work is necessary before IV montelukast can be recommended for general use.

Mechanical Ventilation

Positive pressure mechanical ventilation is life-saving in patients with respiratory failure. Although older studies emphasized the morbidity and mortality associated with mechanical ventilation,52 dramatic improvements have occurred since Darioli and Perret's landmark study,53 which established the safety and effectiveness of permissive hypercapnia. Survival is now the rule in most but not all recent studies when techniques to minimize hyperinflation are used.4,5,53-56

Noninvasive Positive Pressure Ventilation

Some patients with respiratory failure may benefit from a trial of noninvasive positive pressure ventilation (NIPPV). Potential advantages include comfort, decreased need for sedation and neuromuscular blockade, and a lower risk of nosocomial pneumonia.5 Disadvantages include lack of airway control and possible skin pressure ulceration. In one series, NIPPV was used in 17 patients for an average of 16 h.57 NIPPV was generally well tolerated and only two patients required intubation. In a more recent report, NIPPV was used in 27 of 132 patients admitted to the medical ICU for status asthmaticus; 5 of the 7 subsequently required intubation.4 Randomized, controlled trials are needed to better define the role of NIPPV.

Intubation and Mechanical Ventilation

Determining precisely when to intubate is a challenging but critical decision. Except for patients with obvious respiratory failure, it may be difficult to distinguish initially between those destined to respond to bronchodilators and those who will fail. Even patients who initially have respiratory acidosis may improve sufficiently to avoid intubation. Indications for intubation include progressive respiratory failure, altered mental status, and hemodynamic instability, regardless of the results of arterial blood gas testing.5

Dynamic Hyperinflation

Most of the dangers of mechanical ventilation relate to dynamic hyperinflation (DHI) caused by severe airway obstruction.55,56,58 In contrast to patients without obstruction who exhale to functional residual capacity (FRC) between breaths, patients with NFA may have insufficient time to reach FRC, especially when the minute volume (E) is high (Fig 3). As a result, the end exhalation volume gradually rises until a new equilibrium, FRC', is reached.

Figure 3. The development of DHI. In patients without significant airway obstruction (A), lung volumes return to FRC after each breath. In contrast, in patients with severe obstruction (B), particularly in the presence of hyperventilation, airflow limitation prevents exhalation to FRC between breaths, leading to gradual hyperinflation. As the lungs continue to inflate and the airways increase in caliber, a new equilibrium is reached at end exhalation, FRC'.

DHI has two major consequences: hemodynamic compromise and barotrauma. Hemodynamic compromise is caused by high intrathoracic pressure, which in turn leads to (1) decreased venous return; (2) pulmonary vascular compression and increased right ventricular afterload; (3) decreased left ventricular preload caused by right ventricular dilation and shift of the intraventricular septum towards the left; and (4) external compression of the heart by the hyperinflated lungs.

The goal of mechanical ventilation, in addition to ensuring oxygenation, is to minimize DHI. Unfortunately, the severity of DHI and the risks it entails are difficult to quantify and do not correlate well with the physical examination or chest radiograph findings. Instead, pressures measured at the airway opening are generally used, particularly the plateau pressure (Ppl), the peak airway pressure (Ppk), and intrinsic positive end-expiratory pressure (autoPEEP).

The Ppl, measured during an end-inspiratory breath hold, essentially equates with the elastic recoil pressure of the respiratory system (Pel), which is directly related to the degree of lung inflation and inversely related to respiratory system compliance. A Ppl of approximately 30 to 35 cm H2O has been invoked, particularly in patients with the acute respiratory distress syndrome, as a threshold pressure beyond which lung overdistention may occur.59 Few data show a clear correlation between Ppl and complications in patients with asthma, however.55 Additionally, Ppl can be measured accurate only in a patient who is breathing passively, and thus it is impossible to measure in those who are actively inhaling or exhaling.

The Ppk measurement represents the sum of elastic recoil pressure and pressure related to airway resistance:

Ppk = Pel + Pr

The Pr is the product of the inspiratory flow rate and airway resistance (Raw):

Pr = flow rate x Raw

Pr is insignificant in normal individuals in whom Raw is negligible. In patients with high Raw, however, Pr can be significant. In fact, the difference between the Ppk and Ppl is a helpful way to measure Pr and is useful for detecting a response to therapy.

Some caveats must be considered, however, when interpreting the Pr. First, in addition to reflecting changes in Raw, the Pr also reflects changes in the set inspiratory flow rate, so that changes may reflect differences in ventilator settings rather than the patient's mechanics. An increase in the inspiratory flow rate can increase the Ppk dramatically. Thus, interpretation of the significance of the Ppk – Ppl difference must take the inspiratory flow rate into account. In general, Ppk correlates poorly with the risk of DHI-related complications,55 probably because it overestimates the degree to which airway pressure is transmitted to the distal airways and alveoli, as airway pressure drops across areas of resistance in the larger airways (Fig 4).

Figure 4. Drop in airway pressure across resistance. High peak airway pressures detected at the airway opening may greatly exceed those present in the distal airways and alveoli, due to pressure drops across areas of obstruction, decreasing in this example from 60 to 20 cm H2O.

Measurements of autoPEEP are frequently used to assess DHI.55 AutoPEEP is measured by occluding the airway during an end-expiratory breath hold. The pressure measured reflects the Pel of the respiratory system at end exhalation. In normal individuals exhaling to FRC, this pressure should be 0 cm H2O. However, in patients unable to exhale fully between breaths, expiratory flow continues and a persistent positive driving pressure can be detected. In NFA, however, autoPEEP reflects the degree of DHI only loosely, and may significantly underestimate DHI when airway occlusion occurs, eg, due to mucus plugging (Fig 5). Similarly, autoPEEP correlates poorly with response to treatment and the risk of complications.55,60 As with the Ppl, autoPEEP can be measured only in relaxed patients.5

Figure 5. The problem with autoPEEP: When airways become entirely occluded (eg, by mucus plugs), measured autoPEEP may significantly underestimate the pressures present in the distal airways and alveoli in lung units that do not communicate with the airway opening. AP = autoPEEP. Reprinted with permission from Leatherman and Ravencraft.60

In contrast to these measurements, the volume at end inspiration, measured by inducing apnea and collecting exhaled gas in a spirometer over a 60-s period, correlates well with the risk of DHI-related complications.55,56 Unfortunately, measurement of volume at end inspiration requires neuromuscular blockade and is not readily performed in most ICUs.

Although none of the measurements of DHI is perfectly sensitive or specific, the Ppl is probably most practical. A useful goal is to keep the Ppl < 25 cm H2O if possible.56,61 Whichever measure is used, however, it is essential to monitor patients for DHI-related complications such as shock or barotrauma. In hypotensive patients, improved hemodynamics occurring in response to lowering the Ve strongly suggests DHI.

Ventilation Strategies

Ventilation strategies designed to minimize DHI improve outcome in patients with NFA.53,55,56,62 Since Darioli and Perret's landmark article in 1984, the mortality rate among asthmatics requiring mechanical ventilation has dropped precipitously. As long as oxygenation is adequate, most patients do well when ventilation goals are relaxed, even if hypercapnia ensues.63

In general, an initial E of < 115 mL/kg (eg, with a VT of 8 to 10 mL/kg and a respiratory rate of 11 to 14 breaths/min) is unlikely to cause excessive hyperinflation.55,61 In contrast to COPD, positive end-expiratory pressure is generally not useful in asthma and may increase lung volume.64,65 Some suggest that a combination of synchronized intermittent mandatory ventilation with pressure-support ventilation may be less likely to cause hyperinflation than assist-control ventilation in spontaneously breathing patients.5 In sedated, paralyzed patients, ventilator mode is unimportant.

The chief goal of mechanical ventilation is to minimize DHI by ensuring sufficient expiratory time (TE). Ways to increase TE include (1) increasing the inspiratory flow rate to decrease inspiratory time, (2) decreasing the respiratory rate, and (3) decreasing the VT.

An increased TE can be achieved much more effectively with the latter two interventions (Fig 6). Although an increase in the inspiratory flow rate generally decreases the inspiratory/expiratory (I:E) ratio, the absolute increase in TE tends to be modest when the E is low. Concerns that an increase in the IFR can worsen hyperinflation by inducing hyperventilation are not supported by recent data in COPD.66

Figure 6. Impact of changes in ventilator settings on lung volumes and measures of DHI. Note that lung volumes are most closely related to E. At any given E, a decrease in TE is associated with decreases in Ppk, but increases in lung volume and Ppl. Reprinted with permission from Tuxen and Lane.58

Decreases in E have a more dramatic impact on the degree of hyperinflation than changes in inspiratory flow rate (Fig 6, Fig 7).58 At low E, increases in inspiratory flow rates do not ameliorate hyperinflation significantly, even with substantial decreases in the I:E ratio. In contrast, decreases in the E, effected by decreasing either respiratory rate or VT, can have a dramatic impact on DHI by substantially increasing TE (Fig 7).

Figure 7. Changes in ventilator settings and their impact on I:E ratio and TE. Note that doubling the inspiratory flow rate (I) causes a dramatic decrease in the I:E ratio but only a modest increase in TE. In contrast, a 40% decrease in the respiratory rate (II) not only decreases the I:E ratio but also substantially increases the TE. RR = respiratory rate; PIFR = peak inspiratory flow rate.

Decreases in E predictably increase the PaCO2, although, because dead space may decrease, the rise in PaCO2 may be smaller than expected.5 Hypercapnia must be considered a necessary consequence of protective ventilation techniques, not a goal itself. Hypercapnia is generally well tolerated, in part due to an extensive regulatory system, including intracellular buffers, which mitigate against decreases in the intracellular pH.63

Side effects of hypercapnia include cerebral vasodilation and edema, decreased myocardial contractility, systemic vasodilation, and pulmonary vasoconstriction.5,63 If possible, the PaCO2 should be maintained at < 90 mm Hg and acute increases should be avoided.5,63 Exogenous bicarbonate is generally unnecessary.

Permissive hypercapnia is potentially dangerous in patients with intracranial lesions (eg, large strokes or mass lesions) who may develop intolerable increases in intracranial pressure.63 In addition, the intracellular acidosis associated with hypercapnia may be tolerated poorly by patients with underlying myocardial dysfunction. The risks of hyperinflation need to be weighed against the significant risks of hypercapnia in these populations.63

Patients generally require heavy sedation and sometimes neuromuscular blockade to minimize the ventilatory response to hypercapnia.5,67 Various regimens are potentially effective, although a combination of a narcotic (eg, fentanyl) and a benzodiazepine (midazolam or lorazepam) or propofol should be adequate. As patients improve, it is important to try continuously to increase ventilation towards normal, moving expeditiously to extubation when safe.

Complications

Complications associated with intubation are similar for NFA and other critical illnesses, and include nosocomial pneumonia, stress gastritis, deep venous thrombosis (DVT), pulmonary embolism, and malnutrition. Patients requiring prolonged mechanical ventilation may be predisposed to sepsis and multiple organ dysfunction.4 Appropriate measures to avoid complications include using agents to neutralize gastric acid secretion (most commonly a histamine-receptor blocker), DVT prophylaxis (usually low-dose subcutaneous heparin), appropriate bed positioning, and timely extubation when the patient improves. Enteral feeds should be started when feasible.

Complications specifically associated with NFA include shock and barotrauma, even when optimal ventilator techniques are used. Though difficult, it is critical to differentiate shock related to DHI from tension pneumothorax. Physical examination findings (eg, unilateral hyperresonance, decreased breath sounds, and tracheal shift) that might be expected in tension pneumothorax may be difficult to detect. Although a definitive diagnosis may require a chest radiograph, rapid deterioration in the patient's condition may not allow enough time to obtain one.

If hypotension and increased airway pressure occur, the patient should be immediately disconnected from the ventilator and bagged slowly (eg, 2 or 3 breaths/min) or not at all (if the patient's oxygen saturation is adequate, temporary apnea is generally tolerated).5,56 If the hypotension is a result of DHI, blood pressure should improve quickly, often within seconds. The patient can then be reconnected to the ventilator with a decrease in the E.

Hypotension resulting from tension pneumothorax should not respond to hypoventilation. The side with the pneumothorax can sometimes be identified by a combination of findings, including decreased breath sounds, hyperresonance, and tracheal shift. If the patient has a reasonable blood pressure and oxygen saturation, it is acceptable to wait for a chest radiograph before decompressing the presumed pneumothorax.56 However, if the patient is unstable, decompression must precede definitive testing; the physician should recognize that both hemithoraces may need to be treated or that, in some cases, the wrong diagnosis may be made.

The use of neuromuscular blockade is associated with several potential complications, including prolonged mental status depression due to the high levels of sedation required, skin breakdown, and increased risk of DVT. Prolonged neuromuscular weakness is particularly common and can be prevented only partially by monitoring the quantity of neuromuscular blockade given and the use of peripheral nerve stimulators.67 The concurrent use of neuromuscular blockade and high-dose corticosteroids is strongly associated with a severe myopathy, occurring in approximately 30% of patients, with clinical manifestations that can range from mild weakness to quadriparesis that may take weeks or longer to resolve.68-70 The development of myopathy is strongly associated with the duration of neuromuscular blockade.70 Neuromuscular blockade should therefore be discontinued as soon as it is safe to do so.

Outcome and Follow-up

Most patients who present alive to the hospital will, with standard care, survive their acute illness. Although some respond quickly to therapy, others, especially those who present only after several days of symptoms, may take longer. Since the landmark study by Darioli and Perret53 establishing the benefit of controlled hypoventilation, the mortality associated with mechanical ventilation for asthma has generally ranged from 0 to 4%,53,55,71 a substantial decrease compared with the mortality rate of up to 38% reported in studies from the late 1960s through the early 1980s.52

One recent study, in contrast, showed a 21% mortality rate among patients requiring mechanical ventilation.4 Factors associated with increased mortality included an increased APACHE (acute physiology and chronic health evaluation) II score, increased PaCO2, decreased arterial pH, the development of sepsis, and multiple organ dysfunction. Although not statistically significant, all patients who died were female. Tension pneumothorax and cardiac arrest prior to medical ICU admission were common in nonsurvivors.4 The authors speculated that inadequate prehospital care, excessively aggressive positive pressure ventilation prior to arrival at the hospital, and nosocomial infections may have contributed to the high mortality rate.4

Patients who survive an episode of acute, severe asthma frequently succumb to repeat attacks. One study found mortality rates of 10.1% at 1 year, 14.4% at 3 years, and 22.6% at 6 years after mechanical ventilation.72 The need for careful outpatient monitoring and treatment, preferably in a subspecialty clinic, is critical. Careful follow-up, including regular peak flow monitoring, close physician communication, patient education, and a therapeutic plan centered around the use of inhaled corticosteroids should decrease the risk of recurrent attacks.

Summary

Managing patients with NFA is one of the most difficult challenges facing critical care physicians. Although any asthmatic is theoretically at risk for life-threatening attacks, it is becoming clear that those with NFA are a unique group characterized by poor baseline asthma control and severely inflamed airways. Fortunately, advances in management, emphasizing high doses of corticosteroids and safe mechanical ventilation techniques, ensure survival in the vast majority who come to the ICU. Still, the severe morbidity associated with NFA makes it critical that outpatient management be enhanced to prevent this dread disorder.

 

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