Status Asthmaticus

Etiology

Asthma is a chronic inflammatory disorder of the airways characterized by recurrent episodes of breathing difficulty resulting from airway inflammation and bronchospasm. The condition is associated with airway hyperreactivity to certain environmental stimuli and occurs more commonly in individuals with atopy.[1]

Two distinct patterns of asthma exacerbations can lead to status asthmaticus. Slow-onset asthma exacerbation involves a gradual worsening of peak expiratory flow rate (PEFR) over several days. Predisposing patient-related factors include inadequate inhaler regimens, suboptimal compliance, and psychological stressors. Sudden-onset asthma exacerbation presents as a rapid, severe decline within hours, often triggered by abrupt massive exposure to allergens, food particles, or sulfites.[2]

Approximately 80% to 85% of asthma-related fatalities result from slow-onset exacerbations, reflecting prolonged inadequate disease control. These patients typically exhibit extensive airway inflammation and mucus plugging, complicating acute management. In contrast, sudden-onset exacerbations generally involve clear airways with predominant bronchospasm.[3]

Epidemiology

Asthma prevalence varies by country, sex, ethnicity, and socioeconomic status. The overall worldwide prevalence of asthma is estimated at approximately 4%. According to the World Health Organization (WHO), the highest prevalence occurs in Australia, Sweden, the U.K., the Netherlands, and Brazil. China and Vietnam report some of the lowest asthma rates. Highly developed countries generally exhibit higher reported asthma rates, which may reflect better healthcare access and greater asthma awareness. Reported rates may also be artificially low in regions lacking robust reporting infrastructure.[4]

Centers for Disease Control and Prevention (CDC) data indicate that the prevalence of current asthma diagnosis in the U.S. ranges from 8% to 9% in adults and 6% to 7% in children younger than 18 years. (Sources: CDC Interactive Summary Health Statistics for Adults, 2025; CDC Interactive Summary Health Statistics for Children, 2025) Additionally, 10.4% of people with asthma in the U.S. live below the 100% poverty threshold. Black and American Indian (Alaska Native) populations have the highest prevalence rates, at 10.9% and 12.3%, respectively.

Certain populations face a higher risk of severe asthma and status asthmaticus. Multiple observational studies report increased incidence of status asthmaticus among women, African Americans, and individuals with asthma onset after 17 years of age.[5][6] Status asthmaticus is more prevalent in people with lower socioeconomic status, likely due to limited access to specialist care.[7] Individuals living alone are also disproportionately affected. An estimated 3% to 16% of hospitalized adult asthmatic patients develop respiratory failure requiring ventilatory support. Less than 1% of children with status asthmaticus in the U.S. require intubation and mechanical ventilation.

The mortality rate associated with status asthmaticus is decreasing in many regions worldwide. Advances in therapies, including tidal-volume ventilation standardization, avoidance of prolonged neuromuscular blockade, and implementation of assist-control mode ventilation, have contributed to reduced mortality. Older adults exhibit the highest mortality rates compared to other age groups.[8] Afessa et al reported approximately 10% mortality in patients with status asthmaticus admitted to intensive care units (ICUs).[9] Mortality rates for status asthmaticus in children remain below 1% in most regions.[10]

Pathophysiology

Asthma arises from chronic inflammation of the lower airways, which may be mediated by genetic, environmental, or microbial factors.[11] Inflammation can lead to expiratory collapse of small airways due to alterations in laminar flow and airway diameter. Premature airway closure during exhalation increases functional residual capacity and causes air trapping. The heterogeneous distribution of air trapping results in ventilation-perfusion mismatch, leading to hypoxemia, cellular anaerobic metabolism, and lactic acidosis. Respiratory alkalosis from tachypnea initially offsets the metabolic acidosis caused by cellular hypoxia. Respiratory acidosis may develop as the work of breathing decreases with fatigue.

Acute asthma consists of 2 physiological phases. The early bronchospastic phase occurs minutes after allergen or trigger exposure, involving mast cell degranulation and release of inflammatory mediators such as histamine, prostaglandin D2, and leukotriene C4. The latter inflammatory phase results in airway edema due to eosinophilic release of cationic and major basic proteins.[12] Type 2 inflammation appears to increase the risk of acute asthma exacerbation. This process involves the release of interleukins 4, 5, and 13 from T-helper type 2 cells and type 2 innate lymphoid cells. Non-type 2 inflammation, characterized by neutrophil involvement, also likely plays a significant role in asthma exacerbations.[13]

Cellular-level changes play a key role in the development of asthma symptoms. Destruction of cilia and epithelial denudation increase nerve ending irritability, resulting in hyperreactivity. Inflammation causes hypertrophy and hyperfunction of goblet cells and mucous glands, promoting mucus plugging within the airways. Dysregulated parasympathetic activity contributes to cellular pathology through pulmonary vagal branches and parasympathetic ganglia in small bronchi. Stimulation of postganglionic acetylcholine muscarinic receptors causes bronchoconstriction and hypersecretion. Dysfunction of inhibitory M2 receptors, commonly seen in individuals with atopy, sustained allergen exposure, viral infection, and chronic inflammation, further enhances parasympathetic activity.

Histopathology

Histopathological examination of the airways reveals inflammation, smooth muscle contraction, and airway hyperresponsiveness. Interactions among mast cells, T lymphocytes, and epithelial cells trigger a surge of inflammatory cells and cytokines that accumulate in lung tissue. Increased concentrations of histamines, leukotrienes, and platelet-activating factors are observed both locally and systemically. Lymphocytic and eosinophilic submucosal infiltrates in tracheal and bronchial biopsy specimens are associated with poorer outcomes in adult patients with asthma.[14]

History and Physical

Patients with an asthma exacerbation most often present with shortness of breath, cough, or chest tightness. Some report increased inhaler or nebulizer use within the preceding hours to days. Fever, upper respiratory tract infection symptoms, and chest pain may also occur. Key historical information includes comorbidities, current medications, known allergic or environmental triggers, and illicit substance use. Clinicians should determine whether the patient has ever required hospitalization or intubation for an asthma exacerbation.

Several risk factors predispose patients to status asthmaticus.[15][16] Poor perception of dyspnea and hypercapnia may delay treatment initiation, as may a blunted hypoxic ventilatory response from longstanding pulmonary disease or psychiatric illness.[17][18] Recurrent hospitalizations despite chronic oral steroid use, delayed presentation after symptom onset, altered mental status, and sleep deprivation during an exacerbation also increase the risk.

On physical examination, patients are typically tachycardic and tachypneic with increased work of breathing. Wheezing on pulmonary auscultation is often considered an indicator of bronchospasm but is unreliable in severe asthma exacerbations, as it may be absent when alveolar airflow is significantly impaired. The absence of wheezing should not be relied upon diagnostically, particularly in patients in extremis with a history of asthma.[19][20]

Tachycardia in the setting of asthma exacerbations may result from respiratory distress or β2-agonist administration. Sinus tachycardia is the most common rhythm, although supraventricular and ventricular arrhythmias have also been reported.

Brenner et al demonstrated that patients presenting with an asthma exacerbation who assumed an upright rather than supine position had significantly higher heart and respiratory rates than those who did not. Other findings in these patients included pulsus paradoxus, significantly lower arterial oxygen partial pressure (PaO2), and a lower PEFR. After initial treatment, diaphoresis, preference to sit upright, inability to speak in complete sentences, and accessory muscle use all suggest progression to status asthmaticus, which may result in progressive respiratory and mental status decline that eventually causes patients to rest supine. Patient positioning should not be relied upon alone for diagnostic or prognostic purposes.

Status asthmaticus causes marked respiratory-phase variation in pleural pressure that contributes to hemodynamic compromise. Increased inspiratory effort against an obstructed airway augments negative intrathoracic pressure, reducing left ventricular filling and cardiac output through the following mechanisms:

• Septal deviation to the left from right ventricular enlargement
• Increased left ventricular afterload
• Increased right ventricular afterload from elevated pulmonary arterial pressure

Obstructive shock may develop from bronchospasm and air trapping, which decrease venous return secondary to increased intrathoracic pressure. In addition to respiratory distress, affected patients may have altered mental status, cool skin with poor capillary refill, diminished peripheral pulses, and hypotension. Pulsus paradoxus, defined as a decrease in systolic blood pressure of at least 10 mm Hg during inspiration, may be present. In advanced stages, the magnitude of pulsus paradoxus may decline due to reduced respiratory effort.[21] Patients with preexisting cardiac disease may be unable to compensate for the hemodynamic dysfunction of status asthmaticus and are more likely to develop shock.

Evaluation

Patients should undergo continuous cardiac monitoring, pulse oximetry, and blood pressure monitoring. Vital signs should be recorded at least every 15 min during stabilization, as patients with status asthmaticus may rapidly deteriorate. Mental status should be monitored closely, since neurological decline indicates inadequate oxygenation and ventilation that may require mechanical support.

Airflow obstruction is best quantified by measuring PEFR and forced expiratory volume in 1 second (FEV1).[22] PEFR may be measured at the bedside in patients without altered mental status. A reduction in both values by 50% or greater from the patient's personal best indicates severe airway obstruction. An absolute PEFR less than 120 LPM and an absolute FEV1 less than 1 L indicate severe disease.[23]

Laboratory tests and imaging help identify treatable asthma triggers, assess disease severity, and evaluate alternative diagnoses. Initial blood tests may include a complete blood count (CBC), basic metabolic panel (BMP), and arterial blood gas (ABG) analysis. In status asthmaticus, CBC may show leukocytosis from inflammation with neutrophil demargination or superimposed infection. Marked neutrophilia is often associated with bacterial infection. Viral infections may present with leukocytosis or leukopenia, accompanied by lymphocytosis or mild lymphopenia. Infection may be confirmed with a nasopharyngeal swab, sputum test, or blood culture, depending on the suspected organism.

BMP evaluates electrolyte balance and kidney function. Dyspnea-related insensible fluid losses and poor oral intake can cause electrolyte abnormalities, dehydration, and prerenal acute kidney injury. Cardiac enzymes and electrocardiography (ECG) assess for primary or secondary acute cardiac pathology. Pulmonary obstruction may produce transient ECG signs of right heart strain, such as peaked P waves or right axis deviation. ECG may also show sinus tachycardia or dysrhythmias related to the underlying pathology or β2-agonist therapy.

Chest radiography may be normal or show lung hyperinflation with airway wall thickening in poorly controlled asthma or severe exacerbations (see Image. Asthma Radiography). X-rays may also reveal other causes of symptoms, including bronchiectasis, pneumonia, pleural effusion, pulmonary edema, or pneumothorax. Radiography should be considered in patients with poor treatment response or abnormal lung sounds such as rhonchi, rales, or absent breath sounds, which suggest alternative diagnoses.

Point-of-care ultrasound provides rapid bedside assessment of critically ill patients in respiratory distress. Severe asthma exacerbations may show reduced lung sliding. Lung and cardiac ultrasound can also identify pulmonary edema, consolidations, pleural or pericardial effusions, and abnormal cardiac wall motion, indicating other pathology. Ultrasound can assess fluid responsiveness and hemodynamic status in shock.[24]

ABG analysis yields essential information regarding oxygenation and ventilation, but should be interpreted alongside clinical appearance. Mild or moderate exacerbations typically cause respiratory alkalosis from tachypnea. Hypoxemia develops as severity increases. Carbon dioxide partial pressure (pCO2) may falsely normalize as fatigue reduces respiratory effort (see Table. Arterial Blood Gas Findings in Acute Asthma). Hypercarbia and hypoxemia indicate impending respiratory failure, and such patients may require mechanical ventilation.[25]

Table. Arterial Blood Gas Findings in Acute Asthma

Outpatient testing for patients with severe chronic asthma may include pulmonary function and allergen testing. Immunoglobulin E levels, skin tests, and radioallergosorbent tests are useful in evaluating patients with suspected allergen triggers. Identifying and avoiding allergens may improve long-term asthma control.

Treatment / Management

Pharmacological Interventions for Bronchoconstriction

Reducing bronchospasm and improving oxygenation and ventilation are the goals of asthma exacerbation treatment. Several classes of pharmacological agents are used to reduce lower airway obstruction.

β₂-agonists 

Short-acting inhaled β2-agonists are the 1st-line treatment for acute asthma exacerbations. Albuterol's β2 selectivity and duration of action make it the preferred agent in this class. Patient factors such as preexisting bronchoconstriction, airway inflammation, mucus plugging, and poor effort may reduce efficacy and duration of effect, particularly if patients cannot coordinate breaths with inhaler deployment. Larger and more frequent dosing may be necessary in the presence of these factors. Administration via nebulization or the use of a spacer with a metered-dose inhaler (MDI) can enhance medication delivery to the lungs.

The optimal delivery device of inhaled β2-agonists in patients without severe distress or altered mental status has, at times, been controversial. McIntyre and colleagues demonstrated that only 2.9% of a radioactive aerosol was deposited in the lungs when delivered by a small-volume nebulizer. The group advocated for the use of MDI via an adapter attached to the inspiratory limb of the ventilator circuit.

However, a subsequent study by Manthous and colleagues refuted these findings, demonstrating MDI's lesser effect on inspiratory flow-resistive pressure compared with nebulized albuterol.[26] Patients, nurses, and providers often perceive nebulizer treatments as more effective than MDIs despite evidence suggesting that they confer similar therapeutic benefits with proper use.[27]

Nebulization is often favored in emergency settings because it requires less supervision, patient breath coordination, and repeated instruction. This modality is also preferred in young children or other patients who cannot take deep breaths on command. Patients requiring invasive or noninvasive mechanical ventilation also typically receive albuterol via nebulization in line with the device circuit.

Initial nebulized albuterol treatment consists of 2.5 mg of albuterol (0.5 mL of a 0.5% solution in 2.5 mL normal saline) by nebulization every 20 min for 3 doses, followed by hourly treatments during the first several hours of therapy. This intervention may also be administered as hour-long or continuous nebulization treatments in severe exacerbations. Even in patients with severe disease, 4 puffs of albuterol (0.36 mg) delivered with an MDI and spacer may be as effective as a 2.5 mg dose by nebulization.

Some studies have shown a correlation between asthma mortality and inhaled β2-agonist use. This finding may reflect a paradoxical increase in airway hyperresponsiveness or the severity of underlying disease rather than adverse effects of the agents themselves.[28][29] Short-acting inhaled β2-agonists should not be withheld or underdosed during acute attacks, regardless of concerns about their long-term use. These agents remain the drugs of choice during acute asthma exacerbations.(A1)

Subcutaneous epinephrine (an α- and β-receptor agonist) and terbutaline (a selective β2-agonist) have fallen out of favor for routine use due to potential adverse effects and the efficacy of alternative treatments. Intramuscular or intravenous epinephrine may be considered when aerosolized albuterol is ineffective or cannot be administered, or when a severe allergen-triggered asthma attack occurs.[30][31] In such cases, 0.3 to 0.5 mg may be given intramuscularly, or 5 to 20 mcg intravenously every 2 to 5 min.

Patients with hypotension or symptoms refractory to other treatments may require an epinephrine infusion at 0.1 to 0.5 mcg/kg/min. Routine use of endotracheal epinephrine instillation is considered ineffective and unnecessary, given the availability of alternative routes of administration. Intravenous β2-agonists are not routinely recommended but have been tried with some success in younger patients with status asthmaticus unresponsive to inhaled therapy.

Methylxanthines

Aminophylline and theophylline are methylxanthine bronchodilators with immunomodulatory properties, acting through phosphodiesterase inhibition and adenosine receptor antagonism. Although these mechanisms may provide benefit, methylxanthines are associated with more adverse effects than β2-agonists and are rarely used in current practice. The narrow therapeutic index of these agents increases the risk of gastrointestinal distress, headaches, insomnia, cardiac dysrhythmias, seizures, and cardiac arrest. Use is limited to patients refractory to standard therapy, and those receiving these agents should be monitored closely for signs of toxicity.[32]

Corticosteroids

Evidence supports corticosteroid use in status asthmaticus in emergency settings. Expert recommendations favor initiating corticosteroid therapy concurrently with short-acting inhaled β2-agonists.[33] Corticosteroids reduce airway inflammation and mucus production, potentiate β2-agonist activity in smooth muscle, and mitigate β2-agonist tachyphylaxis in severe asthma. Optimal dosing in status asthmaticus is not well established, and oral and intravenous routes have similar efficacy.[34] Some patients may require a prolonged course after hospital discharge.(A1)

Anticholinergics

Anticholinergic agents produce variable responses in acute asthma exacerbations and exert bronchodilatory effects through antagonism of muscarinic smooth muscle receptors in the airways. These drugs also decrease airway secretions via antimuscarinic activity. The most commonly used agent is ipratropium bromide.

Anticholinergics may be useful in patients with β-blockade-induced bronchospasm or severe underlying obstructive disease with FEV1 less than 25% of the predicted value. Peak action may be delayed for 60 to 90 min. Therefore, these medications should be administered concurrently with the initiation of short-acting β2-agonists. Bryant and Rogers demonstrated that nebulization with 0.25 mg of ipratropium bromide plus 5 mg of albuterol produced greater FEV1 improvement than albuterol alone. The response time was also much faster than with corticosteroids, with a detectable FEV1 change within 19 min.

Nebulized glycopyrrolate is an alternative anticholinergic agent. However, this drug is rarely prescribed in the U.S. for this indication.

Magnesium sulfate

Magnesium inhibits calcium-mediated smooth muscle constriction, decreases acetylcholine release in the neuromuscular junction, and increases respiratory muscle force generation. Intravenous magnesium sulfate is a useful adjunct in cases of β2-agonist-refractory acute status asthmaticus.[35] The benefit does not appear limited to patients with low serum magnesium levels, although up to 50% of patients with acute asthma may have incidental hypomagnesemia.

Despite widespread use in emergency department settings, few studies have demonstrated statistically significant lung function improvement with magnesium in severe asthma exacerbations. The presumed benefits are largely extrapolated from experience with chronic obstructive pulmonary disease (COPD) exacerbations. However, magnesium is relatively inexpensive and safe when given as a 2-g intravenous infusion over 20 min in the setting of reactive airway disease.

Increased symptom responsiveness to magnesium among female patients may be due to estrogen's ability to potentiate magnesium's bronchodilator effects. Hypotension and hyporeflexia may occur at higher doses, and patients should be monitored for these adverse effects.

Supportive and Adjunctive Interventions

Managing severe asthma exacerbations often requires a multifaceted approach that extends beyond medication alone. The interventions discussed below target respiratory support and adjunctive care strategies to improve patient outcomes.

Heliox

Heliox is a 70:30 or 60:40 helium-oxygen mixture that decreases airway resistance and turbulence, work of breathing, and inspiratory muscle fatigue by enhancing laminar airflow. Routine use is limited by prohibitive cost, infrequent indication, and the need to recalibrate gas blenders and flow meters when used with mechanical ventilation.[36] In most areas, this modality is available only in specialized centers.(B3)

Noninvasive ventilation

Noninvasive positive-pressure ventilation (NIPPV) with continuous (CPAP) or bilevel (BiPAP) positive airway pressure may be used for ventilatory support in patients without significant encephalopathy or excessive secretions. The use of this intervention has increased despite stronger evidence for benefit in COPD exacerbations than in status asthmaticus. NIPPV may help keep smaller airways open that would otherwise collapse dynamically during expiration in asthma exacerbations. This treatment may also reduce the work of breathing by decreasing respiratory muscle use and preventing fatigue.

Prolonged NIPPV increases the risk of aspiration and facial pressure necrosis. Endotracheal intubation should be considered for patients requiring greater or prolonged ventilatory support.[37][38]

Evidence suggests that NIPPV may reduce bronchodilator requirements and shorten ICU and hospital stays in reactive airway disease exacerbations.[39][40] Studies have shown conflicting results regarding NIPPV's impact on the need for endotracheal intubation and mortality rates.[41][42] Other reports indicate that this therapy is safe, well-tolerated, and should be considered early if a patient presents in extremis but does not otherwise meet criteria for endotracheal intubation.[43](A1)

Mechanical ventilation and sedation 

The decision to intubate a patient with status asthmaticus is clinical. Immediate indications for intubation include the following:

• Acute respiratory or cardiopulmonary arrest
• Severe obtundation or coma
• Frank evidence of respiratory fatigue with gasping or inability to speak
• Persistent hypoxia despite multimodal treatment
• Worsening respiratory acidosis despite aggressive management

Individuals who do not meet these criteria but continue to deteriorate despite initial pharmacologic treatment require close bedside monitoring for possible intubation.[44] Clinical findings that favor intubation include the following:(B3)

• Increasing lethargy
• Increasing accessory muscle use
• Posture or speech changes
• Decreasing respiratory rate and depth

The choice of induction agent is critical for patients with status asthmaticus who require intubation. Ketamine is currently preferred for its sedative, analgesic, and bronchodilatory properties. The recommended dose is 1 to 2 mg/kg given intravenously at a rate of 0.5 mg/kg/min to provide 10 to 15 min of general anesthesia without significant respiratory depression. Bolus dosing yields inconsistent systemic effects and is not recommended. Adverse effects include hypertension and tachycardia from sympathetic stimulation, increased airway secretions, and a lowered seizure threshold. Ketamine should be avoided in patients with uncontrolled hypertension, preeclampsia, raised intracranial pressure, epilepsy, or liver dysfunction.

Proper postintubation sedation is critical to ensure patient comfort and avoid complications of mechanical ventilation. Overbreathing of ventilator settings may cause breath stacking and air trapping. Propofol is preferred in intubated patients with status asthmaticus for its rapid onset, titrability, sedative properties, and mild bronchodilatory effects. However, prolonged administration increases the risk of carbon dioxide retention by weakening the respiratory drive and reducing patient–ventilator synchrony. Propofol lacks analgesic properties. Thus, concurrent opioid administration may be necessary for pain control. Ketamine may also be considered for its combined bronchodilatory, sedative, and analgesic effects.

Outside of the initial intubation period, paralysis may be required to manage persistent ventilator asynchrony and minimize auto–positive end-expiratory pressure (auto-PEEP) or barotrauma. Commonly used agents in the U.S. include vecuronium, cisatracurium, and rocuronium. Vecuronium has less bronchoconstrictive potential than some alternatives and may be preferred. Atracurium can induce bronchoconstriction via histamine release and should be avoided. Prolonged paralytic infusions may cause critical illness myopathy and should be avoided when possible.[45] Paralytics should never be administered without sedation.(B3)

Ventilator settings for intubated patients with status asthmaticus require careful adjustment to minimize air trapping and prevent increases in intrathoracic pressure. Both pressure and volume control strategies may be used. Low-minute ventilation strategies with an inspiratory-to-expiratory (I:E) ratio of 1:4 or 1:5 reduce air trapping and lower the risk of hypotension and barotrauma.

Extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) may be considered when hypoxia and acidosis persist despite mechanical ventilation.[46][47] ECMO is a highly specialized intervention that requires significant resources and support and is unavailable in many centers. This modality carries risks of major hemorrhage, limb ischemia, and mechanical complications related to the circuit. Potential ECMO candidates should be discussed with appropriate specialists.[48][49](B2)

Antibiotics

Graham et al's randomized, double-blinded trial demonstrated that routine antibiotic use in status asthmaticus did not improve symptom scores, spirometry, or length of hospitalization. Antibiotics should be reserved for patients who show clinical signs of infection. Respiratory culture specimens should be obtained early if infection is suspected and antibiotics are administered.[50][51](A1)

Indications for Hospitalization and Intensive Care

Serial PEFR measurement is a practical and reliable predictor of exacerbation severity and the need for hospitalization. Stein and Cole found that the extent of PEFR improvement 2 hours after treatment predicted hospitalization, whereas initial PEFR on presentation did not. PEFR increased from 250 to 330 LPM in successfully treated patients. Rodrigo and Rodrigo demonstrated a similar pattern in FEV1 with treatment response, although FEV1 is challenging to measure at the bedside.[52][53][54] Overall, FEV1 or PEFR between 40% and 70% of the predicted value after initial emergency treatment is considered an inadequate response, indicating the need for further stabilization.(B3)

Favorable initial responses in status asthmaticus include visible symptom improvement sustained for at least 30 min after the last bronchodilator treatment and a PEFR greater than 70% of the predicted value. Less than 10% PEFR improvement or a PEFR below 40% of the predicted value indicates ongoing significant airway obstruction and warrants consideration for ICU admission. Intensive care should also be considered in the presence of respiratory fatigue, altered mental status, new or unstable arrhythmias, hypotension, need for NIPPV, and cardiac or respiratory arrest.

Patients who present with severe exacerbations and respond quickly to initial treatments may benefit from longer observation before final disposition. Kelsen and colleagues found that patients treated for 2 hours or less in a facility had a 50% symptom relapse rate and required additional treatment. In contrast, only a 4% relapse rate occurred in individuals observed for an additional 2 to 4 hours. While precise observation period recommendations vary, patients who initially present with respiratory distress should be closely monitored for several hours even after favorable initial treatment responses.

The ultimate disposition depends on both clinical and psychosocial factors. Hospitalization may be considered for patients with poor access to outpatient follow-up who might otherwise be candidates for discharge.

Differential Diagnosis

The differential diagnosis of status asthmaticus is broad. Many conditions can cause respiratory distress with or without wheezing. The following are important differential diagnoses with their key differentiating features:

• Pneumothorax may present with absent or asymmetric breath sounds. Tension pneumothorax may cause tracheal deviation and signs of obstructive shock.
• Pneumomediastinum usually presents with a mediastinal crunch or crepitus around the neck or chest on examination.
• Tracheal obstruction, tracheal stenosis, or angioedema may cause dyspnea and inspiratory stridor.
• Foreign body inhalation, mucous plugging, or focal atelectasis may present with localized rather than diffuse wheezing on auscultation.[55]
• Excessive dynamic airway collapse during positive pressure ventilation may cause wheezing.
• Pneumonia often presents with other adventitious sounds such as rhonchi or lobar crackles.
• Patients with COPD often have chronic dyspnea with or without productive cough, frequently accompanied by a history of excessive cigarette smoking.
• Acute heart failure may be differentiated by elevated cardiac enzymes, peripheral edema, and pulmonary edema on ultrasound or chest radiography.
• Allergic bronchopulmonary aspergillosis may be distinguished by a positive Aspergillus skin prick test, elevated immunoglobulin E levels, and characteristic imaging findings (see Image. Allergic Bronchopulmonary Aspergillosis on Computed Tomography).
• Vocal cord dysfunction may cause inspiratory stridor and wheezing.
• Inhalational injury may precipitate or mimic an asthma exacerbation due to airway inflammation.
• In neuromuscular diseases such as myasthenia gravis, a thorough neurological examination may demonstrate systemic neuromuscular weakness with shortness of breath due to diaphragm or respiratory muscle involvement.

A comprehensive history, physical examination, and judicious use of diagnostic tests can help distinguish these conditions from status asthmaticus.

Prognosis

Status asthmaticus has a good prognosis if recognized and treated promptly. Concurrent exacerbations of comorbidities such as congestive heart failure and COPD are associated with a worse prognosis. Patients with greater acidemia and carbon dioxide retention, as well as those requiring mechanical ventilation, have a poorer prognosis.[56] A study by Adnet et al found that neuromuscular blockade increases the risk of postintubation myopathy, ventilator-associated pneumonia, and prolonged ICU stay in patients with status asthmaticus.

Severe exacerbations and status asthmaticus can be fatal. Tens of thousands of people die from severe asthma each year worldwide. Mortality rates are higher among male patients, people with underlying cardiac or pulmonary pathology, older adults, and smokers. A history of near-fatal asthma requiring endotracheal intubation is the single greatest predictor of death from asthma. All-cause mortality in patients with asthma following a severe exacerbation peaks within the first month after the episode.[57]

Complications

Complications of status asthmaticus may be related to the underlying pathology or treatments rendered. Refractory exacerbations and sustained tachypnea, hypoxemia, or hypercapnia may result in electrolyte abnormalities, hypotension, dysrhythmias, and end-organ dysfunction.[58] Severe hypotension and respiratory acidosis may cause myocardial infarction, hypoxic encephalopathy, respiratory or cardiac arrest, and death.

Treatment side effects include tachycardia, arrhythmias, hypokalemia, and lactic acidosis from β2-agonists. Long-term corticosteroid use may cause weight gain, hyperglycemia, fluid retention, and adrenal insufficiency, particularly in critically ill patients with comorbidities. Chronic use of both short- and long-acting β2-agonists may be associated with increased airway hyperresponsiveness and mortality, possibly mediated by concurrent use of inhaled corticosteroids.

Dynamic hyperinflation from air trapping and auto-PEEP increases the risk of pulmonary barotrauma and obstructive shock due to elevated intrathoracic pressure and reduced venous return. This effect is worsened by invasive or noninvasive positive-pressure ventilation. Barotrauma may result in pneumothorax, tension pneumothorax, or pneumomediastinum. Patients receiving positive-pressure ventilation should be closely monitored for shock and barotrauma. Pneumothorax management in patients on NIPPV or mechanical ventilation requires tube thoracostomy to prevent tension physiology.

Patients manifesting with auto-PEEP should be transiently removed from mechanical ventilation circuits and have their chest walls compressed to empty the lungs of trapped air.[59] Ventilator exhalation time should be increased by reducing tidal volume or respiratory rate. Some patients may require deeper sedation or paralysis if over-breathing preset ventilator settings is contributing to air trapping. Ventilator-applied PEEP should be minimized to reduce the risk of barotrauma and obstructive shock. High peak pressure with stable plateau pressure should prompt airway and endotracheal tube clearance, as secretions may be thick and tenacious in severe asthma. A larger-lumen endotracheal tube (French 7.5 or 8) is preferred to reduce airflow resistance and facilitate bronchoscopy if needed.

Purposeful hypoventilation and permissive hypercapnia may be useful in status asthmaticus and seldom cause increased intracranial pressure or depressed myocardial function. Moderate hypercapnia reduces dynamic hyperinflation and ventilation-perfusion heterogeneity by preventing increases in alveolar dead space. Serum pH should be maintained above 7.15 rather than targeting a specific pCO2 value.