Pediatric Status Asthmaticus Treatment & Management

According to the most recent guidelines available from the National Asthma Education and Prevention Program (NAEPP) Expert Panel, overall care for a child with asthma includes intensive outpatient treatment with medications and alteration of the environment.^[2] Admission to the hospital represents a failure of outpatient management. This discussion is limited to inpatient treatment for status asthmaticus.

• Oxygen

  • Supplemental oxygen generally must be provided in any patient who presents with status asthmaticus. Oxygen helps to correct V/Q mismatch. Oxygen can be provided via nasal cannula or face masks.
  • In the event of significant hypoxemia, nonrebreathing masks may be used to deliver as much as 98% oxygen. The goal of supplemental oxygen therapy is an oxygen saturation above 90%.
• Inhaled beta-agonists

  • Beta-agonist agents, typically albuterol or salbutamol, and terbutaline, are the mainstays of acute therapy in asthma. Levalbuterol is also used (see Medscape Viewpoints for a discussion on the use of levalbuterol). They act via stimulation of cyclic adenosine monophosphate (AMP)–mediated bronchodilation. The airway is rich in beta-receptors; the stimulation of these receptors relaxes airway smooth muscles, increases mucociliary clearance, and decreases mucous production.
  • Andrews et al conducted a randomized, double-blind trial to compare equipotent doses of racemic albuterol (RAC) with levalbuterol in children with severe asthma exacerbation who failed initial therapy in the emergency department with RAC and steroids.^[3] Patients received continuous nebulized RAC at 20 mg/h (n = 40) or levalbuterol (n = 41). Results did not significantly vary between the groups for median time for continuous therapy (RAC for 18.3 h vs levalbuterol for 16 h), asthma severity scores, individual clinical measures, or time to discharge (RAC for 45 h vs levalbuterol for 46 h).
  • The nebulized inhaled route of administration is generally the most effective route of delivery, though some patients with severe refractory status asthmaticus may benefit by the addition of beta-agonists delivered intravenously. Beta-agonists are generally most effective in the early asthma reaction phase. However, patients who present with status asthmaticus despite frequent use of beta-agonists at home may have tachyphylaxis and resistance to these agents. Similar issues may be seen in patients on chronic long acting beta agonists. Therefore, these patients may not respond as well when these agents are given in the hospital. Inhaled beta-agonists can be administered intermittently or as continuous nebulized aerosol in a monitored setting.
• Corticosteroids

  • Corticosteroids, such as methylprednisolone prednisolone or prednisone, are critical in the therapy of status asthmaticus and are used to decrease the intense airway inflammation and swelling in asthma.^[4] In addition, corticosteroids potentiate the effects of beta-agonist agents and improve capillary leak. Therefore, corticosteroids affect the late asthma reaction phase.
  • Corticosteroids may be administered intravenously or orally. Although most practitioners administer corticosteroids intravenously during status asthmaticus, some studies indicate that early administration of oral corticosteroids may be just as effective.
• Anticholinergics

  • Anticholinergic agents act via inhibition of cyclic guanosine monophosphate (GMP)–mediated bronchoconstriction. They may also decrease mucus production and improve mucociliary clearance
  • Ipratropium bromide (Atrovent), a quaternary amine that does not cross the blood-brain barrier, is the recommended sympathomimetic agent of choice. Atropine, a tertiary amine, may also be used and nebulized but may cause CNS effects because it may enter the CNS. In patients with severe airflow obstruction, the combination of ipratropium and albuterol can provide better bronchodilatation than albuterol alone.
• Further therapy: Although not as well investigated in large-scale, randomized, controlled trials, other therapies may be helpful when the standard combination of oxygen and intermittent or continuous beta-agonists (ie, albuterol), intermittent inhaled anticholinergics (ie, ipratropium bromide), and corticosteroids are insufficient in relieving significant respiratory distress in severe acute asthma. These include the following:

  • Magnesium sulfate
    • Magnesium can relax smooth muscle and hence cause bronchodilation by competing with calcium at calcium-mediated smooth muscle binding sites.
    • The published doses used range from 25-75 mg/kg infused over 20 minutes or less, with a maximum of 2-2.5 g/dose.
    • One double-blind placebo-controlled study reported a significant increase in peak expiratory flow, FEV₁, and forced vital capacity in children who had asthma and were treated with a single 40-mg/kg dose of magnesium sulfate (MgSO₄) infused over 20 minutes, along with steroids and inhaled bronchodilators, compared with control subjects who received saline placebo.^[5] In addition, patients who received intravenous magnesium (8 of 16 patients) were significantly more likely to be discharged home from the presenting ED than control subjects (0 of 14 patients; P = .002).
    • No data regarding duration of effect or efficacy with repeated doses are available, and no guidelines describe the monitoring of serum magnesium levels if more than an initial magnesium dose is administered. In one small study of 4 children who received 40-50 mg/kg MgSO₄, serum magnesium levels were all less than 4 mg/dL, whereas ECG changes are generally not seen until levels exceed greater than 4-7 mg/dL. Adverse effects may include facial warmth, flushing, tingling, nausea, and hypotension.
  • Intravenous beta-agonists
    • Some patients with refractory status asthmaticus may respond to intravenous administration of beta-agonists. Intravenous albuterol and salbutamol may be administered where available but are not available in the United States. Intravenous terbutaline is most commonly used in the United States.^[6] Historically, isoproterenol has been used, but its potent beta1 stimulation may lead to significant tachycardia and inotropy, which has caused myocardial infarction in adults. Reported doses for intravenous terbutaline have ranged from 0.4-10 mcg/kg/min in children.
    • The dose administered should be titrated to effect and adverse cardiac effects (tachycardia, arrhythmias, ECG changes). Some practitioners advocate monitoring cardiac enzyme levels in patients who receive prolonged significant infusions of intravenous beta-agonists. Small studies in children have shown that enzymes such as troponin I may be elevated during terbutaline infusion, although these levels normalize as terbutaline is discontinued. The clinical significance of such enzyme elevation remains unclear.^{[7, 8]}
  • Ketamine
    • Ketamine is a short-acting pentachlorophenol (PCP) derivative that exerts bronchodilatory effects because it leads to an increase in endogenous catecholamine levels, which may bind to beta-receptors and cause smooth muscle relaxation and bronchodilation.
    • Case reports have also described the use of ketamine as a sedative to reduce anxiety and agitation that can exacerbate tachypnea and work of breathing and potentially obviate further respiratory failure in small children with status asthmaticus.
  • Methylxanthines
    • The role of methylxanthines, such as theophylline or aminophylline, in the treatment of severe acute asthma has been diminished since the advent of potent selective beta-agonists and their use at higher doses.^[9] At therapeutic doses, methylxanthines are weaker bronchodilators than beta-agonists and have many undesirable adverse effects, such as frequent induction of nausea and vomiting. Furthermore, most studies have failed to show additional benefit when methylxanthines are administered to patients who are already receiving frequent beta-agonists and steroids.
    • Nevertheless, several recent prospective, randomized, controlled studies in children with refractory status asthmaticus have reexamined the role of the methylxanthines theophylline and aminophylline and demonstrated improvement in the clinical asthma scores when compared with placebo control. One study compared intravenous theophylline with intravenous terbutaline in critically ill children with refractory asthma and demonstrated equal therapeutic efficacy but significantly lower costs associated with theophylline use.^[10] Among the theophylline effects that are important in managing asthma are bronchodilatation, increased diaphragmatic function, and central stimulation of breathing.
• Other potential therapies

  • Helium
    • Helium is an inert gas that is less dense than nitrogen. The administration of a helium-oxygen mixture (heliox) reduces turbulent airflow across narrowed airways, which can help to reduce and, thus, relieve the work of breathing. This, in turn, can result in improved gas exchange and improve pH and clinical symptoms.^{[11, 12]} It does not improve the caliber of the narrowed airways. Some data suggest that nebulized-size particles may be more uniformly distributed in the distal airways when nebulization treatments are administered via heliox than with a standard oxygen-nitrogen mixture.^[13]
    • Heliox can be administered via a well-fitting face mask at flows high enough to prevent entrainment of room air. The effectiveness of heliox in reducing the density of administered gas and improving laminar airflow depends on the helium concentration of the gas; the higher the helium concentration, the more effective the result. Therefore, an 80:20 mixture of helium-oxygen is most effective, and heliox loses most of its clinical utility when the FiO₂ is greater than 40%, reducing the percentage of helium to less than 60%. Therefore, the limitation to the use of heliox is the amount of supplemental oxygen the patient requires to maintain an adequate oxygen saturation. Heliox has also been used to drive mechanical ventilation with lower dynamic peak inspiratory pressures.
  • Inhaled anesthetic agents: Inhaled anesthetic agents, such as halothane, isoflurane, and enflurane, have been used with varying degrees of success in refractory intubated patients with severe asthma. The mechanism of action is unclear but they may have direct relaxant effects on airway smooth muscle.
  • Extracorporeal membrane oxygenation (ECMO): Some case reports describe instances of ECMO being successfully used in extreme cases of refractory status asthmaticus in which maximum standard pharmacotherapy and mechanical ventilation was unsuccessful, often involving significant pneumothoraces and hypoxia.^[14]

Status asthmaticus is generally managed by means of medical therapy, with some exceptions.

• Thoracentesis or thoracostomy is indicated in pneumothoraces.
• Some children may have asthma that is primarily exacerbated by gastroesophageal reflux disease (GERD). Some can be treated with a combination of antireflux and histamine 2 (H2)–receptor antagonist agents; however, surgery, such as Nissen fundoplication, is occasionally required.
• Anesthesia support is needed if inhaled anesthetic agents are considered for refractory severe intubated status asthmaticus.
• If all other support modalities fail and ECMO is required, surgical support for cannula placement at an established pediatric ECMO center should be performed as a life-saving therapy.

• Consult allergists or pulmonologists because these specialists can provide comprehensive follow-up care with the appropriate therapy; allergy testing, if indicated; control of environmental factors; and consistent follow-up testing and manipulation of medications as required. Admission to hospital for asthma should be considered a failure of outpatient management. Better outpatient therapy is necessary to prevent subsequent admissions.
• Consultation with a surgeon may be required if the child can benefit from fundoplication.
• Consultation with a member of social services can provide support in the complex management of a chronic illness.
• Adolescents who have severe uncontrolled asthma and are nonadherent or have depression or significant behavioral issues may require the services of a psychiatrist or psychologist.

Some children with asthma may have episodes triggered by food allergies. Consultation with a nutritionist may be necessary to provide appropriate dietary management.