Asthmatic Exacerbation Case File

Asthmatic Exacerbation Case File

Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 11

A 35-year-old woman with persistent severe  asthma is being seen in the ED. On a  previous admission, she required  mechanical ventilation and was transferred to  the intensive care unit (ICU) for treatment of an asthmatic exacerbation. For the  past week, she has increased her use of a β2 agonist as rescue medication by 6 to 8  times normal, and has nighttime exacerbations every evening. On physical examination  she is in acute respiratory distress with nasal flaring and a quiet chest with  very distant wheezing. An ABG drawn on 30% oxygen shows a pH of 7.35,  PACO2 42 mm Hg, PAO2 89 mm Hg, and bicarbonate (HCO3) of 23 mEq/L. Peak expiratory  flow rates are all below 40% of the patient's predicted range. Her respiratory rate is  30 breaths/minute, heart rate is 110 beats/minute and regular, and blood pressure  is 150/78 mm Hg with a pulsus paradoxicus of 10 mm Hg.

⯈ What is the most important next step in the management of this patient? 

⯈ What other treatment options should be undertaken concurrently? 

⯈ What predictors are present that point to a high likelihood of intubation?

ANSWER TO CASE 11:

Asthmatic Exacerbation

Summary: A 35 -year-old woman who has a severe asthma exacerbation is seen in the ED. She has respiratory failure. The severe respiratory distress is confirmed with an ABO showing an acute respiratory acidosis. A quiet chest on physical examination, overuse of rescue medications, and a history of MV are all warning signs of an acute asthma exacerbation with respiratory failure and the need for rapid-sequence intubation and safe MV.

• Most important next management step: Rapid-sequence intubation and mechanical ventilation.
• Other treatment options: High dose and frequent use of aerosolized bronchodilators with albuterol and ipratropium bromide. IV corticosteroids and magnesium infusion should be started. Low-volume MV is likely ideal. Sedation for anxiety and improved coordination with MV should be used.
• Predictors of high likelihood of intubation: Prior severe asthmatic episode requiring MV, quiet chest, overuse of rescue agents, frequent nighttime exacerbations, and respiratory acidosis.

ANALYSIS

Objectives

1. To understand the pathophysiology of an acute asthma exacerbation. 
2. To describe the classical findings and their correlation with an exacerbation of acute asthma.
3. To understand the correct stepwise treatment of an acute exacerbation of asthma.

Considerations

The patient is in status asthmaticus with hypercarbic respiratory failure. She has a history of a severe asthmatic episode requiring endotracheal tube (ETT) and MV. RSI with MV for relief of respiratory insufficiency is indicated. A large-bore (>8 mm) ETT should be used to facilitate the suctioning of secretions and to decrease resistance to airflow during MV of asthmatic patients. Bronchodilator agents, corticosteroids, and magnesium sulfate should be started immediately. NIV would be useful in more stable patients, and likely not effective in this patient.

Approach To:

Asthmatic Exacerbation

INITIAL PRIORITIES

Providing relief to the failing respiratory system and airway control is foremost here.

"[He} presents with a distressing sense of want of breath and a feeling of great oppression in the chest . Soon the respiratory efforts become violent, and all of the accessory muscles are brought into play. In a few minutes the patient is in a paroxysm of the most intense dyspnea ."

Sir William Osler

APPROACH TO THE ASTHMATIC PATIENT

ICU admissions for refractory asthma range from 2% to 20%, affected somewhat by adherence to best practice protocols. When protocol therapies are used, ICU admissions fall by 41 %; in contrast, when a new group of physicians assumes responsibilities for the ED, admissions generally increase. Aggressive bronchodilation with inhaled short-acting β2-adrenergic agonists (SABA) such as albuterol and recently the addition of ipratropium bromide either in high-volume aerosolized form or via frequent aerosol treatments are indicated. IV corticosteroids for the relief of inflammation and bronchodilation are also used. Steroids increase the number of β2 receptor sites available, thereby enhancing the effectiveness of β2 agonists and avoiding tachyphylaxis to these agents. Aerosol treatments in intubated patients should be with double the amount normally recommended; this overcomes the increased deposition in the ETT. Sedation with IV propofol adds patient comfort and reduces the pressure needed to effectively mechanically ventilate. Propofol causes relaxation of the respiratory muscles, increasing the compliance of the chest wall; it also decreases cardiac output and causes vasodilation, which can lower the BP. This requires increased fluid administration. The use of safe pressures for MV may require an acceptance of a passive hypercapnia. Sedation helps the patient tolerate the feeling of the elevated PACO2. Intravenous magnesium sulfate may also help respiratory muscle strength. Careful attention to MV and ventilating the patient with the safest airways pressures are needed to avoid barotrauma and pneumothorax. Low-volume MV with a tidal volume (Vt) of 6 to 8 mL/kg of ideal body weight is needed to avoid unsafe high pressures. The pH should be maintained above 7.20 regardless of the PACO2 level as long as there is no hypoxia.

Overall, the national asthma prevalence rate is 10%, and has risen by 61% in the last 20 years. Patients are predisposed to a severe exacerbation from many different sources: allergen, exercise, infection (both viral and bacterial), cold air, emotional stress, gastroesophageal reflux (GERD), sinusitis, and post nasal drip. The underlying cause of asthma still remains unknown. Asthma accounts for about 2 million ED visits, 500,000 admissions, and 5 000 deaths per year in the United States and is the third leading cause of preventable admission. Asthma is responsible for 10 million lost school days each year at a cost of >$ 12 billion/y.

The mortality from asthma has not decreased over the last 2 0 years even with advancements in the treatment. An inflammatory process leads to airway obstruction, increased mucus production, and smooth muscle hypertrophy; these changes lead to airway narrowing and airflow obstruction during the expiratory phase. If uncontrolled, airway remodeling and irreversible airway obstruction develops.

The early and late phases of an allergic response contribute to airway inflammation and increased mucus production. The early response, occurring within 1 hour of allergen exposure, is marked by histamines and other mediators released and allergic symptoms such as sneezing, itchy eyes, and runny nose, and respiratory symptoms such as wheezing, coughing, and shortness of breath. The late-phase response, occurring 3 to 10 hours after exposure, can last for as long as 24 hours, and prolongs the asthma attack and results in more severe congestion and inflammation.

DIAGNOSIS

Patients presenting to the ED with asthma should be evaluated and triaged quickly to assess the severity and the need for urgent intervention, but assessment should not delay treatment. Clinicians should search for signs of life-threatening asthma and identify high-risk patients (Table 11-1) . Any of these conditions usually necessitate admission. Attention should be paid to factors that are associated with an increased risk of death from asthma, such as previous intubation or admission to an ICU, 2 or more hospitalizations for asthma during the past year, low socioeconomic status, and various coexisting illnesses.

MANAGEMENT

All patients should be treated with oxygen to achieve an arterial O2Sat exceeding 90%, with inhaled SABAs, and systemic corticosteroids. High-dose ipratropium bromide given in combination with SABAs has been shown to increase bronchodilation.

Oxygen, Compressed Air, and Heliox

Oxygen should be administered. Patients with chronic severe asthma and chronic hypercarbia should be carefully monitored, since excessive oxygen may lead to

increasing hypercarbia due to hypoventilation. The elbow of the oxyhemoglobin dissociation curve lies at 90% saturation, equivalent to a PAO2 of 60 mm Hg. Small decreases below this point leads to dramatic fall in oxygen delivery. PEEP, which is already increased intrinsically because of the reduced expiratory time, should be avoided. The use of 100% inspired oxygen (FIO2) is not uncommon. Oxygen can be toxic and is a potent oxidizing agent when used at high concentrations over prolonged periods of time. Heliox, which is a mixture of helium and oxygen with a density about one-third that of air, reduces airflow resistance in the bronchial tree where turbulent flow predominates. Heliox reduces airway flow resistance, eases the work of breathing, and improves the delivery of aerosolized medications. A heliox mixture can be used in severe cases. Since helium occupies some of the inspired volume, the higher the percent of helium used, the lower the maximum FIO2 that can be achieved. The roles of IV magnesium sulfate and heliox are controversial. The major benefit in their use may be avoiding the need for intubation.

Adrenergic Agents

SABAs should be administered immediately to a patient with an asthmatic exacerbation. The administration of SABAs can be repeated up to 3 times every 20 minutes via aerosols or by high-volume continuous nebulizer treatment. Rescue inhaler use of a SABA agent such as albuterol is the drug of choice. Levalbuterol, the R- isomer of albuterol, is effective at half the dose of albuterol, but trials have not consistently shown an advantage over racemic albuterol. Continuous high-dose inhalation of SABAs for acute rescue bronchodilation with the addition of ipratropium bromide adds a second but different short-acting bronchodilator. Should the patient need intubation, doubling the normal recommended dose of inhaled albuterol and ipratropium is advised, because of the increased deposition of these drugs in the ETT. Oral or parenteral administration of β2-adrenergic agonists is not recommended, and is associated with an increased frequency of side effects. In severe cases, parenteral use of a β2 agonist such as epinephrine (1/1000 solution) SC can be used with as many as 3 doses sq 20 minutes apart. This is generally reserved for younger patients with severe anaphylaxis with upper airway obstruction. Brethine in SC form or epinephrine IV may have a better side effect profile in these cases.

Anticholinergic Agents

When added to an inhaled β2-adrenergic agonist, ipratropium bromide improved symptoms and lung function equivalent to the addition of salmeterol, a long-acting inhaled β2-adrenergic agonist (LABA) . In poorly controlled asthmatics, the addition of tiotropium in once-a-day metered dose inhaler (MDI) form was superior to the doubling of the dose of an inhaled glucocorticoid and was equivalent to the addition of inhaled salmeterol, an LABA. Ipratropium or tiotropium added to an SABA caused a greater and longer lasting bronchodilator effect. The use of ipratropium together with an SABA in severe airflow obstruction, compared with an SABA alone, reduced the rate of hospitalization by 25%. Benefit of continuing ipratropium after hospitalization was seen in smokers or patients with a chronic bronchitis or COPD.

Glucocorticoids

Systemic corticosteroids are a cornerstone to successful treatment of most individuals with asthmatic exacerbations. Their use is associated with a faster improvement in lung function, fewer hospitalizations, and a lower rate of relapse after ED discharge. Although the optimal dose of corticosteroids is unknown, clinical trials have shown no added efficacy in doses of prednisolone exceeding 100 mg/d. The most recent guidelines recommend the use of 40 to 80 mg of prednisolone each day in 1 or 2 divided doses.

Inhaled Corticosteroids, Hydration

Evidence does not support the use of inhaled corticosteroids (ICS) for acute exacerbations of asthma. Aggressive hydration or mucolytic agents are not recommended in asthmatic exacerbations. Autopsy of asthmatics show impacted mucous in the airways. Elevation of the head of the bed (HOB) at 45 degree is important to prevent aspiration.

Leukotriene Antagonists

The efficacy of leukotriene antagonists (LTAs) in the acute setting is unclear. They are excellent agents with a favorable safe side effect profile in moderate and mild cases of asthma. A 20% improvement in PFTs and PEFR which is the same response expected due to the normal diurnal rhythm, may be accentuated in asthmatics.

Magnesium

Magnesium (Mg⁺) plays a role in neuromuscular function, and is more effective in relieving severe asthmatic exacerbations but less so in mild to moderate instances. Magnesium decreases muscle constriction via competition with calcium and pre, vents acetylcholine release, thereby decreasing cyclic GMP. Histamine release is also reduced. Magnesium is an important cofactor in many enzymatic reactions and there is evidence that IV magnesium can induce bronchodilation and reduce the neutrophilic burst of the inflammatory response. The effects of IV magnesium are rapid, within 5 to 1 0 minutes but the duration of action is also short. It has an excellent therapeutic-to-toxicity ratio at dosages of 2 to 4 g per hour as a continuous IV drip, and is widely used in asthmatics refractory to standard treatment. In children, intravenous magnesium sulfate has been shown to significantly improve lung function and reduce rates of hospital admission. A beneficial effect of nebulized magnesium sulfate is less substantiated.

Methylxathines and Antibiotics

Methylxanthines, once a standard treatment for asthma in the ED, are now rarely used because of their adverse effects (narrow therapeutic-to-toxic ratio ) and lack of proven efficacy. These agents ( theophylline, aminophylline ) are no longer recommended for routine use. Theophylline is still used in the most severe cases where any improvement is welcome. The main side effects of methylxanthines include tachycardia, cardiac arrhythmias, and nausea and vomiting. Serum levels should be targeted to about 8 μg/dL since this level is associated with maximum bronchodilator effect and minimum side effects.

Antimicrobial Agents

Antibiotics should not be used routinely, but rather reserved for patients in whom

a bacterial infection (eg, pneumonia or sinusitis ) seems likely. The majority of asthmatic

exacerbations are caused by viral infections, which can lead to a secondary

bacterial superinfection. The antibiotic chosen should be directed toward the most

likely pathogens (pneumococcus, Haemophilus influenzae, or mycoplasma).

Volatile Anesthetics

Volatile anesthetics are potent bronchodilators. Conventional tests of airway resistance demonstrate little difference between halothane, isoflurane, or enflurane (Ethrane) . Halothane appeared to be a more potent bronchodilator than isoflurane. ETI by itself can induce severe bronchospasm. Volatile anesthetics are useful in treating severe status asthmaticus when the patient is unresponsive to conventional treatments. Isoflurane may be the most appropriate choice of volatile anesthetics due to its minimal depressive influence on cardiovascular and arrhythmogenic potential. Increased cerebral flow, cerebral edema, and increased intracranial pressure may be associated with the use of volatile agents in hypercapnic patients who may have suffered a degree of hypoxic brain injury.

BiPAP, CPA P, and Positive Pressure Ventilation

Please refer to Chapter 1 2 on noninvasive ventilation.

Intubation and Mechanical Ventilation

The use of invasive ventilatory support can be life saving in patients with an asthmatic exacerbation. About 30% (range 2%-70%) of such individuals admitted to the ICU require intubation. The decision for MV is based on clinical judgment. Progressive hypercapnia, deterioration of mental status, exhaustion, and impending cardiopulmonary arrest strongly suggest the need for ventilatory support. Authorities agree that intubation should be considered before these signs develop. A physician who has experience with intubation and airway management should ideally be managing the MV. The high pressures encountered by MV should be attained with low tidal volumes of 6 to 8 mL/kg of ideal body weight and started in the assist control mode at a low rate of 8 to 1 0 breaths/minute to avoid high plateau pressures and auto-positive end expiratory pressure (auto-PEEP) . Plateau pressures should be kept <30 cm H2O when possible to avoid barotrauma. Passive hypercapnia with a pH of 7.20 or greater may be needed to attain safe ventilation pressures. Sedation with short-acting agents like propofol will assist the patient in tolerating this treatment. Bicarbonate therapy should be reserved for patients with arterial pHs lower than 7.20. Permissive hypercapnia is not uniformly effective, and consultation with or comanagement by physicians who have expertise in ventilator management is appropriate to avoid risks.

Quick access to chest tube placement in the case of pneumothorax should be available. Strategies to reduce auto-PEEP often result in hypoventilation. The ensuing hypercapnia, termed permissive hypercapnia, is well tolerated as long as it develops slowly and the carbon dioxide tension remains at 90 mm Hg or less. When necessary, the pH can be managed pharmacologically. Daily ABGs and chest x-rays should be performed. Sedation may be needed to keep the patient comfortable and breathing in synchrony with the MV. This can usually be achieved with benzodiazepines combined with opioids or propofol. Ketamine is an attractive agent because of its bronchodilating properties; however, its CNS effects, tachycardia, and hypertension limit its use. Switching to CPAP with PSV when possible will help the patient tolerate MV via better coordination with the MV. Patients should be kept at an elevation of the head of the bed of 45 degrees to avoid aspiration. Auto-PEEP is a common problem in patients receiving full or partial ventilatory support, especially those needing high pressures for ventilation or having short expiratory times.

Physicians should be alert for air trapping and take measures to reduce it, as it can have serious consequences. The clinician needs to fully understand the physiology of auto-PEEP so as to choose the appropriate ventilator settings. Some of these maneuvers should include arranging the longest expiratory time possible and avoiding high respiratory rates and tidal volumes. The recommended settings for initial ventilation are as follows: tidal volume of 6 to 8 mL/kg, respiratory rate of 11 to 14 breaths/minute, flow rate of 100 L/min, and PEEP of 5 . Allow the maximum possible time for exhalation by combining small tidal volumes with slow respiratory rates and short inspiratory times. Static end-inspiratory pressures (plateau pressures) levels of 30 cm H2O or greater correlate with hyperinflation and auto-PEEP. Auto-PEEP rises directly with minute ventilation. The lungs and chest walls become less elastic and work of breathing rises. Venous return, BP, and cardiac output fall. Paralyzing agents are associated with myopathy, which prolongs hospitalization by 1 day, and intubation increases this time to 4.5 days. Fatalities due to asthma in the ICU averaged 2.7% . In intubated patients, the rate rises to 8.1%. Deaths from acute exacerbations of asthma in general are reported in <0.5% of patients. Pulmonary lavage via flexible bronchoscope is used to remove mucous plugs frequently found in patients with severe asthma. This procedure carries some risk.

ADMISSION/DISCHARGE CRITERIA

The decision to admit or discharge a patient should be made within 4 hours after presentation to the ED. Patients may be discharged if the FEV1 or PEF after treatment is 70% or more of the personal best or predicted value. The initiation of therapy with ICS at the time of discharge reduces the risk of relapse. Discharging a patient who is on oral steroids and tapering the dosage schedule is needed only if steroids were used at high doses and for periods longer than 2 weeks. The patient should be free of symptoms at bedtime with a minimal need for rescue medication during the day. Patients should be educated about medications, inhaler technique, and reduce exposure to triggers of allergic reactions; they should have an asthma action plan and receive instructions for monitoring their symptoms and implementing their plan at home. A follow-up appointment should be scheduled with the treating physician 1 week after discharge.

To prevent readmission, discharge treatment should include rescue use of β2 agonist as needed, maintenance use of an ICS and an LABA combination, and LTA use such as monteleukast at bedtime. Additionally, if the patient has a history of smoking or chronic bronchitis, ipratropium bromide or oral steroids, or azithromycin (Zithromax) should be considered when an impending acute exacerbation occurs. Instruction of the appropriate use of MDI and home aerosol machines should be provided. Immunization with the influenza and pneumococcal vaccines should be given.

CONCLUSION

Severe asthmatic exacerbations remain an enormous challenge. Physicians have proven to be poor judges of the severity of an asthma attack, and it is essential to use objective criteria when triaging a patient to an unmonitored bed or an ICU bed. SABAs and early administration of systemic corticosteroids are the mainstays of treatment now with the additional benefit of an anticholinergic agent. When ventilatory support is needed, noninvasive ventilation can be attempted but not delay intubation and MV. Status asthmaticus carries significant complications, including death.

CLINICAL CASE CORRELATION

• See also Case 9 (Ventilator Management), Case 10 (Respiratory Weaning), and Case 12 (Noninvasive Methods of Ventilatory Support).

COMPREHENSION QUESTIONS

11.1 A 45-year-old man who is intubated because of a severe asthma exacerbation starts to show a significant decrease in BP, high RR, decreased expiratory time, and increased airway pressure on the MV. The O2 saturation reads 95% on the current settings. What should be performed to rule out auto-PEEP as a cause of deterioration?

A. Perform a stat arterial blood gas on present ventilator settings.

B. Disconnect the patient from the ventilator and see if there is rapid improvement.

C. Perform a stat chest radiograph.

D. Start the use of heliox mixture.

E. Insert a chest tube for probable pneumothorax.

11.2 A 22-year-old woman presents with a severe asthmatic exacerbation and respiratory distress. Which of the following would be the most important first step in her treatment?

A. A combination of ICS and long-acting inhaled β2-adrenergic agonists (LABA)

B. Intravenous (IV) corticosteroids

C. Heliox mixture

D. Magnesium infusion

E. Inhaled SABA therapy

ANSWERS TO QUESTIONS

11.1 B. Auto-PEEP occurs more frequently that previously thought. Decreased expiratory time results in air-trapping and increased intrathoracic pressure. Progressive vascular collapse ensues, decreasing preload resulting in hypotension with tachycardia. Auto-PEEP and dynamic hyperinflation cause significant discomfort and precipitate patient-ventilator asynchrony. Auto-PEEP increases the work of breathing, lowers gas exchange, and decreases cardiac output, which causes hypotension. Disconnecting the patient from the MV immediately alleviates the high intrathoracic pressure; a dramatic improvement in BP is strong confirmation that auto-PEEP was the cause of the hypotension.

11.2 E. Inhaled SABAs should be immediately administered when an asthmatic patient presents with an exacerbation. SABAs can be repeated every 20 minutes or used as a high-volume continuous nebulizer treatment. SABAs such as albuterol is the first drug of choice for relief of the bronchoconstriction. Levalbuterol, the R-enantiomer of albuterol, is effective at half the dose of albuterol; trials have not consistently shown a clinical advantage of levalbuterol over racemic albuterol. Continuous high-dose inhalation of SABAs and ipratropium bromide are an excellent treatment combination as acute rescue bronchodilators.

CLINICAL PEARLS

⯈ An  ETT should be greater than or equal to 8 mm to allow for suctioning and to decrease resistance during the MV of asthmatics. 

⯈ Vt of 6 to 8 mL/kg of ideal body weight should be used when MV to avoid barotrauma. 

⯈ Heliox and general anesthesia are beneficial in patients unresponsive to initial treatments. 

⯈ A quiet chest in an asthmatic exacerbation is a bad prognostic sign with decreased ventilation. 

⯈ Previous intubation, overuse of rescue medications, frequent nighttime awakenings are all high-risk signs of asthmatic exacerbation, need for admission, and aggressive treatment. 

⯈ Continuous high-dose inhalation of SABAs and ipratropium bromide is of great value for bronchodilation and in the acute treatment regimen. 

⯈ Intravenous magnesium and heliox can be used as adjunctive therapy. 

⯈ Complications from positive-pressure ventilation are common in asthmatic patients. 

References

Bordow RA, Ries AL, Morris TA. Manual of Clinical Problems in Pulmonary Medicine . 6th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005 . 

Deutschman CS, Neligan PJ . Evidence Based Practice of Critical Care. Philadelphia: Saunders; 2010. 

Lazarus S C . Emergency treatment o f asthma. N Engl ] Med . 2010;363 : 7 5 5 - 764. 

Toy EC, Simon B, Takenaka K, Liu T, Rosh A. Case Files Emergency Medicine. 2nd ed. McGraw-Hill Medical, 2009.

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