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Three Part Question

In [children under 6 years old with mild or moderate croup] does [a single dose of oral prednisolone] as effective as dexamethasone in [reducing the symptoms and severity of croup]

Clinical Scenario

A 3 year old with croup presents to A&E with inspiratory stridor. You want to treat with a steroid, and know dexamethasone is commonly used. Having recently used prednisolone in asthma, you wonder if this would be as effective as dexamethasone.

Search Strategy

Embase and Ovid MEDLINE databases were checked in Jan 2011 using the following search strategy
prednisolone.af OR prednisone.af) AND (dexamethasone.af OR oradexon.af) AND (croup.af OR laryngotracheitis.af OR laryngotracheobronchitis.af).

Search Outcome

Ninety-nine papers were found, of which two were relevant. Scanning the article references or searching the Cochrane database, Clinical Evidence and SUMsearch, found a recent Cochrane review that incorporated these two studies.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Sparrow and Geelhoed, 2006, Australia	Convenience sample of 133 children presenting to a single emergency department with mild to moderate croup. Exclusion criteria included prior administration of steroids, non-English speakers and no access to telephone	Double-blind, randomised equivalence study. Patients received a single dose of 0.15 mg/kg dexamethasone or 1 mg/kg prednisolone	Primary outcome was reattendance to hospital following discharge..	Five out of 68 (7%) children who had received dexamethasone returned vs 19/65 children who had received prednisolone.	Included patients up to the age of 12 years, although very uncommon for older children to be affected
			Telephone follow-up after 7-10 days	No statistical difference between groups in terms of time spent in the emergency department, number admitted, use of epinephrine, duration of croup or viral symptoms
Fifoot and Ting, 2007. Australia	N = 99 Aged 6 months to 6 years (mean 1.7 years) Mild to moderate croup Excluded if: chronic respiratory disease, steroids contraindicated, recent treatment with steroids or adrenaline	Double-blind, randomised trial. Patients were randomised to receive 1 mg/kg prednisolone, 0.15 mg/kg dexamethasone or 0.6 mg/kg dexamethasone	Primary outcome was the magnitude and rate of reduction in Westley croup score, which was measured for up to 4 h	No significant difference between the three groups in magnitude or rate of Westley score reduction.	Small sample size. Large number of eligible patients not recruited. Primary outcome over short time period
			Follow-up by telephone interview at 7 days	No significant difference in admission rates, duration of symptoms or reattendances
Russell et al, 2011, International	Systematic review and meta-analysis incorporating the two papers listed above	Meta-analysis	Difference in change from baseline for two treatment groups.	No significant difference between treatment groups	Analysis based on two studies only
			Return visits and/or readmissions	RR 0.32 (95% CI 0.17 to 0.60) favouring dexamethasone

Comment(s)

The symptoms of acute viral laryngotracheobronchitis (croup) result from inflammation and oedema in the respiratory tract. The annual incidence is 3%, peaking in children aged 6-36 months during winter months. Most children are safely managed at home, although potential exists for increasing respiratory compromise.

The anti-inflammatory properties of glucocorticoids reduce the symptoms of airway obstruction as quickly as one hour after treatment for over 12 hours. They also reduce time in hospital, need for salvage therapy and re-presentation rates and increase rates of successful extubation. Care, however, must be taken in children with immune deficiencies or recent varicella exposure, due to immunosuppressive side-effects.

Oral dexamethasone is as effective as intramuscular dexamethasone and nebulised budesonide with advantages of cheaper cost and easier administration. Oral steroids are, therefore, the preferred treatment, although severe cases may require nebulised therapy, including adrenaline. Oral doses of 0.15mg/kg, 0.3mg/kg and 0.6mg/kg have the same clinical efficacy allowing the lowest dose to be given, minimising side-effects.

Despite both dexamethasone and prednisolone having proven efficacy in treating croup, dexamethasone has traditionally been used with prednisolone used in other paediatric diseases, including asthma exacerbations. Although having multiple drugs allows a wider choice, it also increases the risk of drug errors, especially in emergency settings. Therefore if prednisolone and dexamethasone are as efficacious in the treatment of croup, prednisolone could be adopted as the single steroid for use in all common conditions presenting to Emergency departments.

Both included studies had good validity with appropriate randomisation, double-blinding and over 85% follow-up with similar baseline characteristics between treatment groups. Recruitment was via the Emergency department and both included the most commonly affected ages. Both Westley and modified Taussig croup severity scores have been validated with good inter-rater reliability.

Dexamethasone and prednisolone were equally effective at reducing croup scores during the index visit, reducing length of stay and salvage therapy need. Fifoot and Ting did not distinguish between unscheduled re-attendances and planned reviews, making it difficult to accurately compare numbers with Sparrow and Geelhoed’s data of unscheduled visits only. Doctors may have planned more reviews if they knew children were enrolled in a study and parents may have been more likely to re-present if unsure of the trial drug’s effectiveness. However such effects should be seen across all treatment groups equally.

Prednisolone is up to six times less potent than dexamethasone with a shorter half life (12-36 hours vs 36-72) and less HPA axis suppression (1.5 days vs 2.5)[1]. This may account for the higher re-presentation rate, although the findings should be consistent across both studies. If true, a trial comparing a single dexamethasone dose to a 2 day prednisolone course should show no difference in re-attendance rates between groups, indicating a role for multiple-dose therapy with prednisolone. Soluble prednisolone is widely available, being cheaper than liquid dexamethasone. If treating a 12kg child, the prednisolone dose would cost £0.75 compared to £2.50 for 0.15mg/kg dexamethasone. Even if a 2 day course of prednisolone is given, it is still a 40% cost saving.

In summary, dexamethasone and prednisolone were equally effective at reducing croup severity when first given, so individual physicians or centres could choose either drug based on local cost and availability, administrative ease, palatability and clinical preference. However a consistent hospital-wide policy is recommended to avoid confusion. If using prednisone the child may be more likely to need a second dose during the same illness.

Clinical Bottom Line

Prednisolone (1mg/kg) and dexamethasone (0.15mg/kg), as a single dose, are equally effective in reducing croup symptoms during index presentation but patients receiving dexamethasone are significantly less likely to reattend

References

1. Sparrow A, Geelhoed G. Prednisolone versus dexamethasone in croup: a randomised equivalence trial. Arch Dis Child. 2006 ;91(7):580-3.
2. Fifoot AA, Ting JYS. Comparison between single-dose oral prednisolone and oral dexamethasone in the treatment of croup: a randomized, double-blinded clinical trial. Emerg Med Australas. 2007;19(1):51-8.
3. Geelhoed GC, Macdonald WBG. Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg. Pediatr. Pulmonol. 1995; 20: 362–8.
4. Russell K, Wiebe N, Saenz A et al. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011;(1):CD001955
5. Geelhoed GC, Macdonald WB. Oral and inhaled steroids in croup: a randomized, placebo-controlled trial. Pediatr Pulmonol. 1995 Dec;20(6):355-61.
6. Freezer N, Butt W, Phelan P. Steroids in croup: do they increase the incidence of successful extubation? Anaesth Intensive Care. 1990 May;18(2):224-8
7. Donaldson D, Poleski D, Knipple E et al. Intramuscular versus oral dexamethasone for the treatment of moderate-to-severe croup: a randomized, double-blind trial. Acad Emerg Med. 2003 Jan;10(1):16-21.
8. Parker R, Powell CV, Kelly AM. How long does stridor at rest persist in croup after the administration of oral prednisolone? Emerg Med Australas. 2004 Apr;16(2):135-8
9. Connors K, Gavula D, Terndrup T. The use of corticosteroids in croup: a survey. Pediatr Emerg Care. 1994 Aug;10(4):197-9