Chest
Volume 119, Issue 5, May 2001, Pages 1480-1488
Journal home page for Chest

Clinical Investigations in Critical Care
Efficacy of IV The ophylline in Children With Severe Status Asthmaticus

https://doi.org/10.1378/chest.119.5.1480Get rights and content

Study objective:

To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV β-agonists, inhaled ipratropium, and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU (PICU).

Design:

A prospective, randomized, controlled trial. Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment.

Setting:

The PICU of an urban, university-affiliated, tertiary-care children's hospital.

Patients:

Children with a diagnosis of status asthmaticus who were admitted to the PICU for ≤ 2 h and who were in severe distress, as indicated by a modified Wood-Downes clinical asthma score (CAS) of ≥ 5.

Interventions:

All subjects initially received continuous albuterol nebulizations; intermittent, inhaled ipratropium; and IV methylprednisolone. The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 μg/mL. A CAS was tabulated twice daily.

Measurements and results:

Forty-seven children (median age, 8.3 years; range, 13 months to 17 years) completed the study. Twenty-three children received theophylline. The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group. All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion. Among the 41 subjects who were not receiving mechanical ventilation, those receiving theophylline achieved a CAS of ≤ 3 sooner than control subjects (18.6 ± 2.7 h vs 31.1 ± 4.5 h; p < 0.05). Theophylline had no effect on the length of PICU stay or the total incidence of side effects. Subjects receiving theophylline had more emesis (p < 0.05), and control patients had more tremor (p < 0.05).

Conclusions:

Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol, ipratropium, and methylprednisolone. The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined.

Section snippets

Materials and Methods

The Institutional Review Board of St. Louis University reviewed and approved this study at Cardinal Glennon Children's Hospital. Patients were enrolled after informed consent was obtained from their parents or guardians.

Patient Characteristics

Patients were enrolled in the study from October 1995 through January 2000. During this period, 4,520 patients were admitted to the PICU, including 320 in status asthmaticus. Forty-seven children in severe status asthmaticus, representing 49 separate admissions to the PICU, qualified and were enrolled in the study. Enrolled subjects ranged in age from 13 months to 17 years of age. One patient was enrolled on three occasions (two theophylline and one control assignment). Two other children were

Discussion

This is the first prospective, randomized, controlled trial of IV theophylline limited to children admitted to the PICU and receiving standard β-agonist, anticholinergic, and steroid therapy for severe status asthmaticus. We found that theophylline hastened the improvement of our nonintubated patients and shortened their observed recovery time from 31.1 ± 4.5 to 18.6 ± 2.7 h. Theophylline was associated with a greater fall in baseline respiratory rate than was seen in control subjects,

ACKNOWLEDGMENT

The authors express appreciation to the ED attendings, pediatric housestaff, PICU nurses, and respiratory therapists for their assistance. We are grateful to Doris Rubio, PhD, for her statistical consultation. A special thanks to Drs. James Kemp and Blakeslee Noyes for their review of the article.

References (46)

  • DA Van Der Windt et al.

    Clinical scores for acute asthma in pre-school children: a review of the literature

    J Clin Epidemiol

    (1994)
  • CH Fanta et al.

    Treatment of acute asthma: is combination therapy with sympathomimetics and methylxanthines indicated?

    Am J Med

    (1986)
  • R Vassallo et al.

    The ophylline: recent advances in the understanding of its mode of action and uses in clinical practice

    Mayo Clin Proc

    (1998)
  • J Mally et al.

    Potential role of adenosine antagonist therapy in pathological tremor disorders

    Pharmacol Ther

    (1996)
  • G Herrmann et al.

    Successful treatment of persistent extreme dyspnea “status asthmaticus”: use of the ophylline ethylene diamine (aminophylline, U.S.P.) intravenously

    J Lab Clin Med

    (1937)
  • TJ Gluckman et al.

    Management of respiratory failure in patients with asthma

    Curr Opin Pulm Med

    (2000)
  • WE Pierson et al.

    Double-blind trial of aminophylline in status asthmaticus

    Pediatrics

    (1971)
  • S Vozeh et al.

    The ophylline serum concentration and the rapeutic effect in severe acute bronchial obstruction: the optimal use of intravenously administered aminophylline

    Am Rev Respir Dis

    (1982)
  • D Murciano et al.

    Effects of the ophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease

    N Engl J Med

    (1984)
  • PA Easton et al.

    Ventilatory response to sustained hypoxia after pretreatment with aminophylline

    J Appl Physiol

    (1988)
  • Y Iikura et al.

    Antidiuretic hormone in acute asthma in children: effects of medication on serum levels and clinical course

    Allergy Proc

    (1989)
  • TH Rossing et al.

    Emergency therapy of asthma: comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline

    Am Rev Respir Dis

    (1980)
  • RW Katz et al.

    Safety of continuous nebulized albuterol for bronchospasm in infants and children

    Pediatrics

    (1993)
  • Cited by (70)

    • Asthma essentials

      2013, African Journal of Emergency Medicine
      Citation Excerpt :

      Thus their administration is not recommended as part of standard treatment for acute asthma exacerbation. In addition to other standard treatment, intravenous bronchodilators can be considered in paediatric status asthmaticus patients with impending respiratory failure, being mindful of their significant side effect profile.34 While in theory it may decrease airway resistance and oedema, there is insufficient evidence to support the routine use of epinephrine in the management of the critically-ill asthma patient.35

    • Pediatric Status Asthmaticus

      2013, Critical Care Clinics
      Citation Excerpt :

      This is caused in part by decreased bronchodilator effectiveness compared with β-adrenergic agonists and the small therapeutic window and their unfavorable side effect profile. However, they still may have a role in select patients with refractory status asthmaticus.51,52 Inhalational anesthetics, such as halothane and isoflurane, can cause bronchodilation through smooth muscle relaxation and have been used anecdotally to treat status asthmaticus in children refractory to conventional therapies.53–55

    • Anaesthetic management of the child with co-existing pulmonary disease

      2012, British Journal of Anaesthesia
      Citation Excerpt :

      Because of the fact that its effect is less than that of low-dose inhaled corticosteroids, it is seldom used as first-line therapy. It has proven effective as a rescue medication in status asthmaticus.18 Because theophylline has a very low therapeutic index, serum monitoring is essential.

    • Common Pediatric Respiratory Emergencies

      2012, Emergency Medicine Clinics of North America
      Citation Excerpt :

      IV β-agonists have not been shown to be beneficial in severe exacerbations, and carry significant side effects.3,67 Likewise, aminophylline has not been recommended, due to its considerable toxicity and lack of clear benefit,68 though a study has shown some effect in children with life-threatening asthma already receiving maximum doses of conventional therapy.69 However, in the setting of a status asthmaticus in extremis with no response to other therapies, guidelines still endorse consideration of their use as a last resort.2,3,9

    View all citing articles on Scopus

    Supported by Cardinal Glennon Children's Hospital.

    This study was presented, in part, at the 27th Educational and Scientific Symposium of the Society of Critical Care Medicine, San Antonio, TX, February 4–8, 1998.

    View full text