eMedicine Specialties > Pulmonology > Obstructive Airways Diseases
Status Asthmaticus: Treatment & Medication
Updated: Jun 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
After confirming the diagnosis and assessing the severity of the asthma attack, direct treatment toward controlling bronchoconstriction and inflammation.
- Bronchodilator treatment with beta-2 agonists
- The first line of therapy is bronchodilator treatment with a beta-2 agonist, typically albuterol.
- Handheld nebulizer treatments may be administered either continuously (10-15 mg/h) or by frequent timing (eg, q5-20min), depending on the severity of the bronchospasm.
- The dose of albuterol for intermittent dosing is 0.3-0.5 mL of a 0.5% formulation mixed with 2.5 mL of normal saline. Many of these preparations are available in a premixed form with a concentration of 0.083%.
- Studies have also shown an excellent response to well-supervised use of albuterol via an MDI with a chamber. The dose is 4 puffs, repeated at 15- to 30-minute intervals as needed. Most patients respond within 1 hour of treatment.
- The US Food and Drug Administration has approved the use of the R isomer of albuterol known as levalbuterol, for treating patients with acute asthma. This isomer has fewer effects on the heart rhythm (ie, tachyarrhythmia) and is associated with fewer occurrences of tremors, while having the same or greater clinical bronchodilator effects as racemic albuterol.
- The decreased prevalence of adverse effects with this new medication may allow physicians to use nebulizer therapy in patients with acute asthma more frequently with less concern over the adverse effects of other bronchodilators (eg, albuterol, metaproterenol). The dose of levalbuterol is either a 0.63-mg vial for children or a 1.26-mg vial for adults.
- These drugs, especially albuterol, are safe to use during pregnancy.
- Nonselective beta-2 agonists
- Patients whose bronchoconstriction is resistant to continuous handheld nebulizer treatments with traditional beta-2 agonists may be candidates for nonselective beta-2 agonists (eg, epinephrine [0.3-0.5 mg] or terbutaline [0.25 mg]) administered subcutaneously. However, systemic therapy has no proven advantage over aerosol therapy with selective beta-2 agents.
- Exercise caution in patients with other complicating factors (eg, congestive heart failure, history of cardiac arrhythmia).
- Intravenous isoproterenol is not recommended for the treatment of asthma because of the risk of myocardial toxicity.12
- Ipratropium treatment
- Ipratropium, which comes in premixed vials at 0.2%, can be synergistic with albuterol or other beta-2 agonists.
- Ipratropium is administered every 4-6 hours.
- Because children appear to have more cholinergic receptors, they are more responsive to parasympathetic stimulation than adults.
- Oxygen monitoring
- Monitoring the patient's oxygen saturation is essential during the initial treatment.
- ABG values are usually used to assess hypercapnia during the patient's initial assessment.
- Oxygen saturation is then monitored via pulse oximetry throughout the treatment protocol.
- Oxygen therapy
- Oxygen therapy is essential. It can be administered via a nasal canula or mask, although patients with dyspnea often do not like masks.
- With the advent of pulse oximetry, oxygen therapy can be easily titrated to maintain the patient's oxygen saturation above 92% (>95% in pregnant patients or those with cardiac disease).
- Glucocorticosteroids13
- Steroids are the most important treatment for status asthmaticus.
- The usual dose is oral prednisone at 1-2 mg/kg/d.
- In the authors' experience, methylprednisolone provides excellent efficacy when given intravenously at 1 mg/kg/dose every 6 hours.
- Some authorities report that pulse therapy with steroids at a high dose (eg, 10-30 mg/kg/d as a single dose) is associated with a more rapid response and shorter hospitalization and has similar adverse effects; however, this is not standard therapy. Adverse effects of pulse therapy, in the authors' experiences, are minimal and comparable to the traditional doses of intravenous steroids. The adverse effects may include hyperglycemia, which is usually reversible once steroid therapy is stopped; increased blood pressure; weight gain; increased striae formation; and hypokalemia. Long-term adverse effects depend on the duration of steroid therapy after the patient leaves the hospital.
- Steroid treatment for acute asthma is necessary but has potential adverse effects. The serum glucose value must be monitored, and insulin can be administered on a sliding scale if needed. Monitoring a patient's electrolyte levels, especially potassium, is essential. Hypokalemia can cause muscle weakness, which may worsen respiratory distress and cause cardiac arrhythmias.
- Nebulized steroids
- The use of nebulized steroids for treating status asthmaticus is controversial. Data comparing nebulized budesonide with prednisone in children suggest that the latter therapy is more effective for treating status asthmaticus.
- No good scientific evidence supports using nebulized dexamethasone or triamcinolone via a handheld nebulizer. In fact, in the authors' experiences, more adverse effects, including a cushingoid appearance and irritative bronchospasms, have occurred with these nebulizers.
- Fluid replacement: Intravenous fluids are administered to restore euvolemia.
- Antibiotics
- The routine administration of antibiotics is discouraged.
- Patients are administered antibiotics only when they show evidence of infection (eg, pneumonia, sinusitis).
- Aminophylline14
- Conflicting reports on the efficacy of aminophylline therapy have made it controversial.
- Starting intravenous aminophylline may be reasonable in patients who do not respond to medical treatment with bronchodilators, oxygen, corticosteroids, and intravenous fluids within 24 hours.
- Data suggest that aminophylline may have an anti-inflammatory effect in addition to its bronchodilator properties.
- The loading dose is usually 5-6 mg/kg, followed by a continuous infusion of 0.5-0.9 mg/kg/h.
- Physicians must monitor a patient's theophylline level. Traditionally, the level was targeted to the higher end of the local therapeutic range; however, many authorities suggest that the lower portion of the range (ie, > 5 but <10) may be preferable if the patient can obtain the benefits of the drug in the lower range.
- Adverse effects can include tachyarrhythmia, nausea, seizures, and anxiety.
- New therapy in patients with severe and resistant status asthmaticus despite mechanical ventilation
- Ketamine has been used in the management of status asthmaticus in a prospective trial in patients with respiratory failure who do not respond adequately to mechanical ventilation.15 Ketamine has been shown to improve airway resistance, particularly the lower airways, as well as improve lung compliance. Significant improvement in both oxygenation and hypercarbia has been reported, even after 15 minutes of the administration of ketamine.
- In patients with status asthmaticus, the use of deep anesthesia, such as with halothane or enflurane in combination with propofol or ketamine, may also be effective treatment as potent bronchodilators and in decreasing airway resistance, respectively.16,17
- Nitric oxide has also been used in a similar fashion in the treatment of status asthmaticus in isolated case reports and has also been effective when mechanical ventilation is not adequate.18,19
- Additionally, the use of nebulized lidocaine in combination with albuterol or levalbuterol is effective in helping the vocal cord dysfunction that may accompany status asthmaticus. This is an unpublished observation by the author in clinical practice.
- In 2007, Mikkelsen and colleagues20 reported the successful use of extracorporeal life support in patients with status asthmaticus and severe secondary asphyxia in any patient who otherwise was not responsive to aggressive pulmonary support.
- See New Guidelines Issued for Management of Asthma During Pregnancy for further information.21
Medication
Beta-agonists, steroids, and theophylline are mainstays in the treatment of status asthmaticus.
The usual first line of therapy is bronchodilator treatment with a beta-2 agonist, typically albuterol. This therapy may initially include handheld nebulizer treatments, either continuously or at frequent intervals (ie, q5-10min), depending on the severity of the bronchospasm. Most patients respond within 1 hour of treatment. The Food and Drug Administration has approved the use of levalbuterol (ie, the R isomer of albuterol) to treat patients with acute asthma. The advantage of levalbuterol is that it has fewer effects on the patient's heart rhythm (ie, tachyarrhythmia) and is associated with a less frequent occurrence of tremors. Levalbuterol has the same clinical bronchodilator effect as racemic albuterol.
Corticosteroids are essential in the treatment of patients with status asthmaticus. The mechanism of action of corticosteroids can include a decrease in mucus production, an improvement in oxygenation, a reduction in beta-agonists or theophylline requirements, and the activation of properties that may prevent late bronchoconstrictive responses to allergies and provocation. Corticosteroids can decrease bronchial hypersensitivity, reduce the recovery of eosinophils and mast cells in bronchioalveolar lavage fluid, and decrease the number of activated lymphocytes. Corticosteroids also help regenerate the bronchial epithelial cells.
The exact mode of corticosteroid action is not well understood. Their anti-inflammatory effect depends, at least partially, on inhibiting phospholipase A2, which can lead to prostaglandin inhibition and leukotriene synthesis. Corticosteroid action usually requires at least 4-6 hours from administration because it requires protein synthesis before it initiates anti-inflammatory effects. Because of this, patients with status asthmaticus must depend on other supportive measures (eg, beta-2 agonists, oxygen, adequate ventilation) in their initial treatment while awaiting the action of corticosteroids.
Theophylline preparations are also used in patients with status asthmaticus. Usually, theophylline is given parenterally, but it can also be given orally, depending on the severity of the attack and the patient's ability to take medications. This class of drugs can induce tachycardia and decrease the seizure threshold (especially in children); therefore, therapeutic monitoring is mandatory.
Typical theophylline levels range from 10-20 mcg/mL; however, adverse effects can occur even with therapeutic levels. A safer range is 10-15 mcg/mL, although seizures have occurred even with levels below 10 mcg/mL. Theophylline also has significant drug interactions with medications such as ciprofloxacin, digoxin, and warfarin (Coumadin). These interactions may decrease the rate of theophylline clearance by interfering with P-450 site metabolism. On the other hand, phenytoin (Dilantin) and cigarette smoking can increase the rate of metabolism of theophylline and, therefore, can decrease the therapeutic level of the drug.
Manage the theophylline dose in persons who previously smoked but quit fewer than 6 months ago as if they are still smoking. Patients who smoke or those on phenytoin require higher loading and maintenance doses of theophylline. Other adverse effects can include nausea, vomiting, and palpitations.
The usual loading dose of theophylline is 6 mg/kg, followed by maintenance doses of 1 mg/kg/h in the emergent setting. In patients who smoke, the maintenance dose may be higher and the loading dose may be slightly higher. Patients on phenytoin should also receive increased maintenance doses of theophylline. Patients with liver disease or elderly patients may require a maintenance dose as low as 0.25 mg/kg/h.
Theophylline can induce bronchodilation, stimulate the central respiratory cycle, reduce diaphragmatic muscle fatigue, and relax vascular smooth muscles. The mechanism of action includes an increased cyclic adenosine monophosphate concentration by the inhibition of phosphodiesterase; however, this usually occurs when the concentration of theophylline is toxic. Therefore, the true mechanism of action of theophylline is still unclear, but a possible explanation for the bronchodilatation may be related to adenosine antagonism. Theophylline is available in multiple preparations, both short- and long-acting. For patients with status asthmaticus, short-acting preparations are preferred; however, parental preparations are even better.
The addition of the anticholinergic ipratropium, which comes in premixed vials at 0.2%, sometimes results in additional bronchodilation beyond that achieved with albuterol.
Sevoflurane, a potent inhalation agent, has been successful in a single case report where it was used when conventional treatment failed in a 26-year-old woman.22
Beta-adrenergic agonists
Relieve reversible bronchospasm by relaxing smooth muscles of the bronchi.
Albuterol (Ventolin, Proventil)
Use for bronchospasms refractory to epinephrine. Relaxes bronchial smooth muscles by action on beta-2 receptors, with little effect on cardiac muscle contractility. First DOC because it can quickly reverse asthma bronchoconstriction. Available inhaled via MDI or HHN and orally for those too young to use nebulizer. Reserve oral dosing for preventative or longer-acting use.
Adult
PO: 2-4 mg PO tid/qid; not to exceed 32 mg/d
Inhaler: 1-2 puffs q4-6h; not to exceed 12 puffs/d
Nebulizer: Dilute 0.5 mL (2.5 mg) of 0.5% inhalation solution in 1-2.5 mL of NS; administer 2.5-5 mg q4-6h, diluted in 2-5 mL sterile saline or water
Pediatric
PO
<2 years: Not established
2-5 years: 0.1-0.2 mg/kg tid; not to exceed 12 mg/d
5-12 years: 2 mg tid/qid; not to exceed 24 mg/d
>12 years: Administer as in adults
Inhaler
<12 years: 1-2 puffs qid with tube spacer
>12 years: Administer as in adults
Nebulizer
<5 years: Dilute 0.25-0.5 mL (1.25-2.5 mg) of 0.5% inhalation solution in 1-2.5 mL NS and administer q4-6h in equally divided doses
>5 years: Administer as in adults
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders
Adverse effects include irritability, particularly in children; tachycardia (patients with baseline cardiac abnormalities have decreased threshold for tachyarrhythmia); and electrolyte abnormalities (eg, hypokalemia)
Ventilation of areas that are not well perfused may lead to ventilation-perfusion mismatch, which can be problematic in severe asthma
In outpatient setting, inappropriate use (ie, overuse of MDIs) can lead to paradoxical response of increased bronchial obstruction and may induce status asthmaticus
Levalbuterol (Xopenex)
Moderately selective beta2-receptor agonist. Active enantiomer of racemic albuterol and more potent than racemic mixture. Decreased occurrence of adverse effects may allow use of more frequent nebulizer therapy in patients with acute asthma with less concern over adverse effects of other bronchodilators (eg, albuterol, metaproterenol).
Adult
0.63-1.25 mg nebulized q6-8h; may be given more frequently during emergent situations
Pediatric
<12 years: Not established; however, if patient is albuterol intolerant and benefit outweighs risk, 0.63 mg may be used q6-8h
>12 years: Administer as in adults
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders
Adverse effects include irritability, particularly in children; tachycardia (patients with baseline cardiac abnormalities have decreased threshold for tachyarrhythmia); and electrolyte abnormalities (eg, hypokalemia)
Ventilation of areas that are not well perfused may lead to ventilation-perfusion mismatch, which can be problematic in severe asthma
In the outpatient setting, inappropriate use (ie, overuse of MDIs) can lead to paradoxical response of increased bronchial obstruction and may induce status asthmaticus
Mast cell stabilizers
These agents prevent histamine release from mast cells following stimuli by specific antigens.
Cromolyn (Intal)
Inhibits degranulation of sensitized mast cells following their exposure to specific antigens.
Adult
Powder in caps for use with Spinhaler: 20 mg inhaled qid at regular intervals
MDI: 2 puffs (800 mcg/puff) qid at regular intervals
Nebulizer: 20 mg inhaled qid at regular intervals
Once patient is stabilized, use lowest effective dose
Pediatric
Powder in caps for use with Spinhaler
>5 years: 20 mg inhaled qid at regular intervals
MDI
<5 years: Not recommended
>5 years: 2 puffs (800 mcg/puff) qid at regular intervals
Nebulizer
<2 years: Not established
2-12 years: 20 mg inhaled qid at regular intervals
>12 years: Administer as in adults
Once patient is stabilized, use lowest effective dose
None reported
Documented hypersensitivity; severe renal or hepatic impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use with severe renal or hepatic impairment; exercise caution when withdrawing drug because symptoms may recur
Corticosteroids
Maintenance medications that decrease inflammatory mediators to limit airway remodeling. Must be taken regularly to be beneficial. Glucocorticoids do not relieve acute bronchospasm, and short-acting bronchodilators must be available. Multiple formulations are available that are not equivalent on a per-dose or per-mcg basis. Inhaled corticosteroids are one of the most important developments in asthma management because they decrease inflammation. These agents are proven to improve lung function (FEV1 and airway hyperactivity) and decrease symptoms, exacerbation frequency, and the need for rescue inhalers.
Methylprednisolone (Solu-Medrol)
For treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. Other corticosteroids may be used in equivalent dosages.
Adult
Loading dose: 125-250 mg IV
Maintenance dose: 4 mg/kg/d IV divided q4-6h
Pediatric
Loading dose: 2 mg/kg IV
Maintenance dose: 4 mg/kg/d IV divided q6h
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use
Bronchodilators
Act to decrease muscle tone in both small and large airways in lungs, thereby increasing ventilation.
Theophylline (Aminophyllin)
Potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation. For bronchodilation, near toxic (>20 mg/dL) levels are usually required.
Adult
5.6 mg/kg loading dose (based on aminophylline) IV over 20 min, followed by maintenance infusion of 0.1-1.1 mg/kg/h
Pediatric
<6 weeks: Not established
6 weeks to 6 months: 0.5 mg/kg/h loading dose IV in first 12 h (based on aminophylline), followed by maintenance infusion of 12 mg/kg/d thereafter; may administer continuous infusion by dividing total daily dose by 24 h
6 months to 1 year: 0.6-0.7 mg/kg/h IV in first 12 h as loading dose, followed by maintenance infusion of 15 mg/kg/d; may administer as continuous infusion, as above
>1 year: Administer as in adults
Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon may increase effects
Documented hypersensitivity; uncontrolled arrhythmia, peptic ulcers, hyperthyroidism, uncontrolled seizure disorders
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in peptic ulcer, hypertension, tachyarrhythmia, hyperthyroidism, and compromised cardiac function; do not inject IV solution faster than 25 mg/min; patients diagnosed with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance
Anticholinergics
Thought to work centrally by suppressing conduction in vestibular cerebellar pathways. May have inhibitory effect on parasympathetic nervous system.
Regarding magnesium sulfate, more studies have not confirmed the effectiveness of intravenous administration of this agent.23,24 Its use is still controversial. However, inhaled magnesium sulfate has generated some interest in status asthmaticus when combined with beta-agonist use.25,26
Ipratropium bromide (Atrovent)
Synthetic ammonium compound very structurally similar to atropine. May provide additive benefit to inhaled beta-2 agonists when treating severe acute asthma exacerbations. Also may be alternative bronchodilator for patients unable to tolerate inhaled beta-2 agonists. Children may be more responsive to parasympathetic inhibition than adults because children appear to have more cholinergic receptors.
Adult
MDI: 2 puffs (18 mcg/puff) qid
Nebulizer: 500 mcg tid/qid
Pediatric
MDI
3-14 years: 1-2 puffs (18 mcg/puff) tid/qid
>14 years: Administer as in adults
Nebulizer
<3 years and neonates: 25 mcg/kg/dose tid
<14 years: 125-250 mcg tid/qid
>14 years: Administer as in adults
Very effective in children and usually given combined with beta-agonists
Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol may increase effects
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Not indicated for emergent episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction
Magnesium sulfate
Magnesium sulfate intravenously has been advocated in the past for the treatment of acute asthma. Usually 1 g or a maximum of 2.5 g during the initiation of therapy may be considered.
Adult
1-2 g IV
Pediatric
75 mg/kg IV, not to exceed 2.5 g; efficacy in children not established
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine
Documented hypersensitivity; heart block, Addison disease, myocardial damage, or severe hepatitis
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Magnesium may alter cardiac conduction leading to heart block in digitalized patients; respiratory rate, deep tendon reflex, and renal function should be monitored when electrolyte is administered parenterally; caution when administering magnesium dose since may produce significant hypotension or asystole; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be given as antidote for clinically significant hypermagnesemia
More on Status Asthmaticus |
| Overview: Status Asthmaticus |
| Differential Diagnoses & Workup: Status Asthmaticus |
 Treatment & Medication: Status Asthmaticus |
| Follow-up: Status Asthmaticus |
| References |
| Further Reading |
| « Previous Page | Next Page » |
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Further Reading
Asthma Resources from Medscape and eMedicine
Asthma News and Articles
Asthma Clinical Reference
Asthma CME
Keywords
status asthmaticus, asthma, asthma treatment, asthma children, acute asthma, hyperactive airway disease, asthma, asthma emergency, allergen exposure, respiratory tract infection, pollen, mold, animal dander, house dust mites, wheezing, chest tightness, progressive shortness of breath, dry cough, viral respiratory illness, underuse of anti-inflammatory therapy, allergic bronchopulmonary aspergillosis, Churg-Strauss vasculitis, beta-agonists, theophylline, bronchoconstrictive response, broncho-constrictive response, peripheral airway inflammation, bronchodilator therapy
