Dexamethasone for mild croup

March 2005

The most recent Pharmacology Consult discussing corticosteroid treatment of croup (2004) concluded that dexamethasone is an effective therapy. Since this column appeared, an additional controlled study of dexamethasone has been published. This trial provides data on an important aspect of the therapy of croup: treatment of mild illness. This month’s Pharmacology Consult will update the use of dexamethasone in the treatment of croup.

Data from published trials have demonstrated the benefits of using corticosteroids for croup. Most studies have evaluated subjects with moderate or severe illness. Demonstrated benefits include reductions in the need for epinephrine, time spent in the emergency department, the need for hospitalization and the need for ICU admission or intubation. Dexamethasone is the most commonly used corticosteroid to be evaluated, although budesonide given by nebulization has also been demonstrated to be effective.

Traditionally, dexamethasone has been given intramuscularly as a single dose of 0.6 mg/kg (equivalent in anti-inflammatory effects to 4 mg/kg of prednisone). However, several studies have evaluated oral dosing, and they have demonstrated efficacy of this route of administration. The pharmacokinetic profile of dexamethasone includes good oral absoprtion. Several dosage forms of dexamethasone are available commercially, including parenteral and oral dosage forms. Oral dosage forms include two concentrations of liquid products, 0.5 mg/5 mL and 1 mg/mL, as well as several strengths of tablets (Table). Studies evaluating orally administered dexamethasone have employed crushed tablets mixed with flavored syrup and jelly and concentrated solution mixed with flavoring syrup. These have generally been well tolerated. Oral administration may offer a benefit over intramuscular administration in a child with croup, especially when fear of the needle may further aggravate the child’s symptoms.

What has not been as well defined in croup therapy is the efficacy of doses less than 0.6 mg/kg and the demonstrated benefit of dexamethasone for mild croup. Doses of 0.15 mg/kg and 0.3 mg/kg given orally have been evaluated in two small studies and found to be effective for moderate croup. Additional larger studies are needed to clarify the role of lower doses, as adverse effects from 0.6 mg/kg dosing have been infrequent. As some clinicians have expressed concerns for the potential of adverse immunosuppressive effects of dexamethasone, a clearer demonstration of the efficacy and safety of smaller doses may be useful.

Mild croup

Most children with croup have mild symptoms, but most published studies have evaluated children with more severe illness. Until the publication of the latest trial, only two studies had evaluated dexamethasone orally for mild croup, and these trials have been criticized for ill-defined inclusion criteria and the potential inclusion of children with more severe illness.

The most recent study evaluating orally administered dexamethasone was published in September 2004, evaluating children with mild croup (Bjornson). This large trial evaluated a single oral 0.6 mg/kg dose of dexamethasone or placebo in 720 children with mild croup in randomized, double-blind fashion. The setting was four pediatric emergency departments in Canada. Mild croup was defined by a score of 2 or less (maximum 17) on the Westly croup scoring system. The primary outcome measure was a return to a health care provider for croup within seven days of treatment. Other outcome measures included the presence of ongoing croup symptoms on days 1 to 3, hours of sleep missed by the child secondary to croup symptoms and parental stress because of the child’s illness. A parenteral dosage form of dexamethasone added to cherry-flavored syrup was used for oral administration.

Primary outcome data were available for 354 children in each group enrolled, dexamethasone and placebo. Of the 354 children receiving placebo, 54 (15.3%) returned for care within seven days, as compared with 26 (7.3%) children receiving dexamethasone ( P < .05). In the first 24 hours after treatment, children who had received placebo were more ill than children who had received dexamethasone were. At day 3, most children in both groups (> 75%) were improved and asymptomatic, and there was no difference between the groups. Of the children returning for care, 30 (six of 26 in the dexamethasone group, 24 of 54 in the placebo group) were treated with corticosteroids, and this difference between the groups was not significant ( P > .05). There was a significant difference between the groups for sleep lost due to croup symptoms: 2.9 hours lost (dexamethasone) vs. 4.2 hours lost (placebo), and this difference was greatest on day 1 after treatment. Using a Likert scale, parents rated their level of stress secondary to their child’s illness. Although small, there was a significant difference in parental stress between the groups (less in the dexamethasone group), but only on day 1 of treatment. Dexamethasone was well tolerated, as no child experienced bacterial tracheitis, complicated varicella or gastrointestinal bleeding.

Two additional studies have evaluated oral dexamethasone in children with croup (Luria, Geelhoed). Although these studies state that children enrolled had mild croup, the loose inclusion criteria likely allowed children with more severe illness to be enrolled. Both of these studies concluded that a single oral dose of dexamethasone was effective at reducing the necessity for additional medical care.

With the publication of the large, well-done trial by Bjornson, there is now evidence of the efficacy of a single oral dose of dexamethasone in children with mild croup. Benefits demonstrated in this study include reduction in the need for additional medical care, decreased illness within 24 hours of administration, less sleep lost and less parental stress.

Dexamethasone is commercially available in several oral dosage forms – liquid and tablet (Table). The Bjornson trial used an injectable formulation mixed with cherry syrup, and this was well tolerated. However, use of this dosage form may be more difficult and impractical in other medical settings. Other studies have employed tablets crushed and mixed with jelly or oral solutions mixed with flavoring syrups (although flavoring syrups may have been used to equate dexamethasone and placebo doses for blinding). The concentrated dexamethasone commercial product (1 mg/mL) would require a 6-mL dose for a 10-kg child receiving a 0.6 mg/kg dose. Flavoring syrups may be beneficial for the child who does not initially tolerate the product’s taste.

The benefits and efficacy of lower doses of dexamethasone have not been fully evaluated to allow recommendation of their use at this time. Adverse effects with 0.6 mg/kg dosing have not been common enough to prompt concerns, and it is not known if lower doses are less likely to result in fewer adverse effects.

For more information:

• Bjornson CL. A randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J Med. 2004;351:1306-1313.
• Luria JW. Effectiveness of oral or nebulized dexamethasone for children with mild croup. Arch Pediatr Adolesc Med. 2001;155:1340-1345.
• Geelhoed GC. Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double-blind placebo controlled clinical trial. BMJ. 1996;313:140-142.

• Edward Bell, PharmD, BCPS, is an associate professor of pharmacy practice at Drake University College of Pharmacy, and a clinical specialist at Blank Children’s Hospital, Des Moines, Iowa.