Special Feature
Managing Life-threatening Asthma in the ICU
By Richard Wall, MD, MPH, Pulmonary Critical Care & Sleep Disorders Medicine, Southlake Clinic, Valley Medical Center, Renton, WA, is Associate Editor for Critical Care Alert.
Dr. Wall reports no financial relationship to this field of study.
While only a minority of patients with asthma exacerbations require ICU admission, these patients are challenging to manage because they typically have already failed treatment in the outpatient and emergency department (ED) settings. Among the 450,000 patients hospitalized for acute asthma exacerbations in the U.S. each year, only 4-7% require an ICU stay.1 Although this percentage has declined somewhat in the past decade due to better preventive care, intensivists still commonly see such patients in the ICU. In the current paper, I will review the management of ICU patients with life-threatening asthma (LTA), also commonly referred to as status asthmaticus.
Clinical Presentation and Evaluation
There are two different patterns of LTA: slow-onset and fast-onset (Table 1).2 Most deaths occur in patients with the slow-onset variant, although this is the type that is considered most preventable. Deaths in non-intubated patients are typically due to progressive hypercapnic respiratory failure, mixed respiratory and lactic acidoses, and finally asphyxia. When patients die from asthma, they invariably have extensive airway obstruction with mucous plugs and dynamic hyperinflation, even at autopsy. In mechanically ventilated patients, deaths are occasionally also due to complications such as barotrauma or ventilator-associated pneumonia. Risk factors for death include prior severe exacerbation, prior ICU admission, recent hospitalizations or ED visits, recent need for systemic corticosteroids, blunted sense of dyspnea, psychiatric illness, low socioeconomic status, illicit drug use, and comorbid cardiovascular disease.
During the initial evaluation, one should quickly determine whether the patient has features of impending respiratory failure. These include pulsus paradoxus >25 mm Hg, silent/feeble breath sounds, bradycardia, hypotension, cyanosis, lactic acidosis, confusion/coma, pneumothorax, or pneumomediastinum. If any of these features are present, intubation will likely be necessary. However, intubation is ultimately a clinical decision that must be weighed against the patient's response to therapy.3 For example, an elevated PaCO2 is certainly an ominous sign, but hypercarbia itself does not mandate intubation if the patient is clinically improving.
Measurement of oxygen saturation by pulse oximetry (SpO2) is a useful tool for evaluating patients with LTA. The SpO2 is useful because asthma creates regional V/Q inequalities but little (if any) shunt. In other words, patients with severe LTA are easily oxygenated with an O2 concentration of 28-32%. If a patient with LTA appears refractory to supplemental oxygen, another abnormality such as pneumonia or pulmonary embolism should be sought. Although an arterial blood gas (ABG) is often measured in LTA, serial ABG sampling is not helpful for determining whether a patient is deteriorating or improving.4 If respiratory failure is imminent, the decision to intubate should not be delayed by ABG analysis.
Supplemental O2: Is There Such A Thing as "Too Much?"
Clinicians traditionally believed that high-flow oxygen is harmless in LTA. However, a randomized controlled trial challenged this notion by comparing two oxygen concentrations (28% vs 100%) in 74 adults with acute severe asthma.5 Overall, patients breathing 28% oxygen experienced a fall in their PaCO2. In contrast, patients breathing 100% oxygen showed an increased PaCO2 (p=0.03) and a decreased peak flow (p=0.001). These data suggest that normoxic asthma patients should not be routinely placed on O2 and supplemental O2 should be targeted to maintain SpO2 ≥ 92%.
Pharmacotherapy
β-agonists
Short-acting inhaled β-agonists, such as albuterol, remain a cornerstone of therapy. The inhaled route has faster onset and fewer side effects than systemic routes. The available evidence does not support the use of IV β-agonists, even in severe cases, and they should only be utilized when inhaled therapy is not feasible (eg, excessive coughing).6 Subcutaneous epinephrine is an outdated modality with serious cardiac side effects—its use should likewise be limited to rare cases or LTA due to anaphylaxis.
An inhaled b-agonist will achieve better bronchodilation if the medication is administered in a manner that ensures a high dose and quick delivery to the airways. Thus, the "best" method is actually a pressurized metered-dose inhaler (MDI) with spacer chamber, not a nebulizer. However, this assumes the patient uses the MDI properly. Many clinicians prefer a nebulizer delivery system because it gives the option for continuous nebulization. Although continuous "nebs" are theoretically more beneficial than intermittent nebs, a meta-analysis of randomized trials failed to show any difference between the two methods, except that continuous nebs cause less tachycardia.7 No study has examined the "MDI vs nebulizer" and "intermittent vs. continuous" questions in the ICU.
The newer levalbuterol (Xopenex) has been touted as having a better safety profile than traditional racemic albuterol,8 but its higher cost and insufficient data have left many clinicians unconvinced.9 In addition, no study has examined levalbuterol in the ICU. Although levalbuterol may ultimately prove to be a "better mousetrap," further studies are needed to clarify its dosing, efficacy, and cost-effectiveness.
Anticholinergics
The role of inhaled anticholinergics in LTA is somewhat theoretical, and albuterol is definitely superior to ipratropium. However, combining the two agents appears to confer some advantages.10 In a randomized trial of 180 ED patients with acute asthma,11 the addition of ipratropium (vs albuterol alone) resulted in lower hospital admission rates, improved lung function, and lower costs. Both drugs were administered through a MDI at 10-minute intervals for 3 hours. In a subgroup analysis, the patients most likely to benefit from ipratropium were those with a long duration of symptoms ( ≥ 24 hours) and severe obstruction (FEV1 ≤ 30% of predicted).
Corticosteroids
Systemic corticosteroids should be used in all cases of LTA.12 Although these agents are not bronchodilators, they reduce airway inflammation and speed recovery. Methylprednisolone 160mg/day or hydrocortisone 800mg/day (in divided doses) is generally sufficient. The oral and intravenous routes have equivalent efficacy, but since systemic steroids take 6-24 hours to reach full effect, most clinicians administer the first few doses intravenously.
Several studies suggest that inhaled corticosteroids (ICS) may be beneficial in LTA.13 ICS produce measurable effects in < 3 hours, much quicker than systemic steroids. It is believed that ICS improve b-receptor sensitivity and vasoconstrict airway mucosa. However, it is unclear if ICS confer additional benefits once systemic corticosteroids take effect. With the arrival of nebulized budesonide, ICU clinicians have additional delivery options for ICS, even in mechanically ventilated patients.
Magnesium sulfate
Magnesium is safe and inexpensive when given in the typical dose of 2 gm IV over 20 minutes. Another route is inhaled magnesium. The beneficial mechanism appears to be blockage of smooth muscle contraction. Although there is no evidence to support routine use of magnesium in every asthma attack, studies do suggest a benefit in severe cases.14 Thus, it is reasonable to use magnesium as an adjunct to standard therapy (steroids and β-agonists) in patients who are sick enough to require ICU admission.
Leukotriene antagonists
There is limited data on leukotriene modifiers in acute asthma, and no data exists in ICU patients. A randomized trial of 201 patients with acute asthma examined whether intravenous montelukast conferred additional benefits to standard therapy.15 Overall, FEV1 improved by 15% in the montelukast group compared to 4% in the control group (p=0.007). The difference was seen within 20 minutes and persisted up to 2 hours. Thus, these medications may have an adjunctive role in treatment of LTA, but additional studies are needed.
Methylxanthines
Theophylline and aminophylline are inferior to inhaled β-agonists. They increase the incidence of toxicity (tremor, nausea, tachyarrhythmia) and numerous consensus guidelines advise against their use.1 If a patient is already on theophylline at the time of ICU admission, a serum level should be measured and dosing appropriately adjusted. Otherwise, these medications should not be used except in the most refractory cases.
Heliox
The gas mixture of helium-oxygen (heliox) was introduced in the 1930s. Due to its property of lower air flow resistance, heliox reduces work of breathing and improves gas exchange in patients with bronchospasm. In addition, heliox improves pulmonary drug delivery for MDIs and nebulizers. Despite these advantages, studies have not shown that heliox improves any patient outcomes.16 Thus, its role in LTA remains largely theoretical and it is not recommended for routine use. If clinicians wish to employ heliox, they should never allow its use to delay the most important treatments for LTA: systemic corticosteroids and aerosolized bronchodilators.
One note in mechanically ventilated patients: It is important that O2 (not heliox) be used to propel the actual nebulizer, or else the nebulizer may paradoxically deliver less medication due to helium's low density.17 Maximal efficiency is achieved when the nebulizer is operated with O2 at 6 L/min and the aerosol entrained into a ventilator circuit containing heliox.
Mechanical Ventilation
The goals of mechanical ventilation are to rest the respiratory muscles and to provide adequate oxygenation/ventilation while airway inflammation subsides. The key principle is to avoid dynamic hyperinflation. Due to expiratory airflow limitation, incomplete exhalation of ventilator-delivered breaths can lead to dangerous air trapping. If the patient has a high minute ventilation, air trapping can raise intrathoracic pressures, decrease venous return, and cause hypotension. Alveolar overdistension can also cause barotrauma such as pneumothorax.
The signs suggesting dynamic hyperinflation include: 1) the patient is still exhaling at the moment the ventilator delivers the next breath, 2) hyperinflated chest exam, 3) hemodynamic effects such as tachycardia and hypotension, and 4) the patient's respiratory efforts are unable to trigger a ventilator-assisted breath (auto-PEEP).
The most important way to avoid dynamic hyperinflation is to limit minute ventilation. The initial target for tidal volume should be 5-7 mL/kg predicted body weight. End-inspiratory plateau pressure should be kept < 30-35 cm H2O. Reducing the respiratory rate will often have a dramatic effect on air trapping because this lengthens expiratory time. It should be expected that the PaCO2 will rise in response to the reduced minute ventilation. However, as long as the pH remains ≥ 7.25, most patients tolerate permissive hypercapnia without any problems.
Ventilated patients with LTA need to be appropriately sedated. Opioids, benzodiazepines, and propofol are reasonable choices. Propofol offers the benefits of rapid onset and short half-life, in addition to potential bronchodilating properties. Although neuromuscular blocking agents were once widely used for improving ventilator synchrony, they have been associated with severe myopathy, especially when administered with corticosteroids. Thus, neuromuscular blocking agents should be avoided unless absolutely necessary.
Noninvasive positive pressure ventilation (NPPV) has only been studied in a small number of patients with LTA.1 Patients who do well with NPPV will generally start improving fairly quickly. The successful use of NPPV depends on patient education, patient synchrony with the machine, and perhaps most importantly-the ability of staff to closely monitor the patient. NPPV is not appropriate if the patient is obtunded or uncooperative, hemodynamically unstable, and rapidly deteriorating. Reasonable initial NPPV settings are positive end-expiratory pressure (PEEP; EPAP) ~5 cm H2O and pressure support (inspiratory pressure above EPAP) of ~8 cm H2O.1 If the patient begins failing NPPV, intubation should not be delayed.
Summary
The key to treatment of LTA is prompt, aggressive therapy with the cornerstones of therapy: aerosolized β-agonists and systemic corticosteroids. Other useful adjuncts for which there is reasonably good evidence include inhaled anticholinergics, inhaled corticosteroids, magnesium, and leukotriene modifiers. Non-invasive ventilation can be helpful in certain patients but it requires close patient monitoring and an appropriately trained team who can quickly intubate the patient if necessary. There is weak evidence for heliox, but it is reasonably safe and can be attempted once other therapies have been implemented. Except in rare cases, methylxanthines and IV β-agonists should not be used.
References
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- Shapiro JM. Am J Respir Med. 2002;1(6):409-416.
- Nowak RM, et al. JAMA. 1983;249(15):2043-2046.
- Rodrigo GJ, et al. Chest.2003;124(4):1312-7.
- Travers AH, et al. Chest. 2002;122(4):1200-1207.
- Rodrigo GJ, Rodrigo C. Chest. 2002;122(1):160-165.
- Ameredes BT, Calhoun WJ. (R)-Albuterol for Asthma: Pro [a.k.a. (S)-Albuterol for Asthma: Con]. Am J Respir. Crit Care Med. 2006;174(9):965-969.
- Barnes PJ. Am J. Res Crit Care Med. 2006;174(9):969-972.
- Rodrigo GJ, Rodrigo C. Chest. 2002;121(6):1977-1987.
- Rodrigo GJ, Rodrigo C. Am J Respir Crit Care Med. 2000;161(6):1862-1868.
- Rowe BH, et al. Cochrane Database Syst Rev 2001(1):CD002178.
- Rodrigo GJ. Chest. 2006;130(5):1301-1311.
- Rowe BH, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev. 2000(2):CD001490.
- Camargo CA, et al. Am J Respir Crit Care Med. 2003;167(4):528-533.
- Rodrigo G, et al. Heliox for treatment of exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002(2):CD003571.
- Goode ML, et al. Am J Respir Crit Care Med. 2001;163(1):109-114.
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