Comparison between single-dose oral prednisolone and oral dexamethasone in the treatment of croup: a randomized-controlled trial

Introduction:

Croup is a common respiratory illness in children, accounting for 15% of annual clinic and emergency department visits for pediatric respiratory tract infections. We aimed to compare single-dose oral prednisolone with single-dose oral dexamethasone in the treatment of croup in terms of mean change in the Westley Croup Score.

Setting:

Emergency Department of Children Hospital.

Duration:

Six months from December 2017 to June 2022.

Design:

Randomized-controlled trial.

Subjects and methods:

A total of 226 children with Westley Croup Score 2 or more were included in this study. Patients were randomized into two groups, 113 patients received a single dose of 0.15 mg/kg of oral dexamethasone, while 113 patients received a single dose of 1 mg/kg of oral prednisolone. Croup score and other clinical observations were repeated at 4 h and recorded in the questionnaire.

Results:

The average age of the patients was 2.88±1.17 years. There were 129 (57.1%) males and 97 (42.9%) females. At 4 h, a significant reduction in mean Westley Croup Score was observed in group dexamethasone as compared with group prednisolone (P=0.0005).

Conclusions:

Our trial demonstrated that oral dexamethasone at a dose of 0.15 mg/kg is effective in reducing the total croup score but there were no statistical differences in respiratory rate, pulse rate, and oxygen saturation between groups. Future studies are required to determine if these treatments differ in efficacy for severe croup and whether there is a role for multiple-dose corticosteroid therapy in some patients.

Introduction

Highlights

• This trial demonstrated that oral dexamethasone is effective in reducing the total croup score.

• Choice of corticosteroids might be based on local cost and availability, as well as clinician preference.

• Future studies should be conducted to assess the efficacy for severe croup, and whether there is a role for multiple-dose corticosteroid therapy in some patients

Croup is a common respiratory illness in children, accounting for 15% of the annual clinic and emergency department (ED) visits for pediatric respiratory tract infections. It is characterized by a hoarse voice, dry barking cough, inspiratory stridor, and a variable amount of respiratory distress that develops over a brief period of time1. There is a difference between a viral infection and a disease because certain viral infections are preclinical (i.e. symptomless, inapparent), while others cause a disease of varied severity that is often accompanied by recognizable clinical symptoms in the infected host. The result of the viral–host contact is mostly a function of the virulence of the getting infected virus and the vulnerability of the host, along with many other parameters that may also play a role.

It typically occurs in children 6 months to 6 years, and most commonly is caused by the parainfluenza virus. The disease occurs most often in late fall and early winter but may present at any time of the year. Croup places a large burden on healthcare systems because of frequent visits to doctors and accident and EDs and, when necessary, hospitalizations1.

Since the late 1980s, it has been recognized that glucocorticoids provide some clinical benefit for children with croup2. A systematic review published by the Cochrane Collaboration summarizes numerous studies that have evaluated the effectiveness of glucocorticoids in attenuating the clinical course of croup. Thirty-eight studies were included. Glucocorticoids were associated with an improved Westley score at 6–12 h. The length of time spent in accident and emergency, the intensity of viral croup symptoms, and the use of epinephrine decreased for children treated with a glucocorticoid. Fewer return visits and re-admissions occurred in participants treated with glucocorticoids2,3. Therefore, routine corticosteroid therapy is now provided to all children with croup.

The optimal type of corticosteroid, route of administration, and dose have remained unclear. Trials comparing parenteral, oral, and nebulized routes of steroid delivery in croup have demonstrated that intramuscular, intravenous, oral, and inhaled routes of administration of glucocorticoids are effective in croup of all levels of severity, including one randomized-controlled trial carried out in Iran4,5. For this reason, oral corticosteroids are the preferred route unless oral intake is not possible. Oral preparations have an advantage over intramuscular preparations in terms of ease of administration and noninvasiveness. The oral route is also preferred over nebulization because it is more effective, convenient, and less expensive than nebulization3.

The effectiveness and safety of corticosteroids for croup treatment have made them a standard medication for croup management in EDs, such as, at our own organization, all enrollments for croup. In patients of croup, steroid therapies have been proven to considerably reduce the number of hospitalization, length of stay in the hospital, follow-up appointments, admission to ICUs, and endotracheal intubation.

A single dose of orally administered dexamethasone (0.15–0.6 mg/kg) is the mainstay of treatment with the addition of nebulized epinephrine only in cases of moderate-to-severe croup3. Oral prednisolone has also proven efficacy in croup in comparison with placebo4. However, the use of prednisolone as an alternative to dexamethasone in the treatment of croup has been evaluated only in a limited number of studies4.

An ED-based trial done in Australia found no statistically significant difference in clinical outcome between single doses of oral prednisolone and oral dexamethasone used in the treatment of mild-to-moderate croup. This study’s primary outcome measure was the magnitude of change in the Westley Croup Score, which is a validated scoring system assessing different clinical criteria to classify the severity of croup. This trial found that at 4 h after the presentation, the mean change in croup score was 2.09 in the dexamethasone group and 2.35 in the prednisolone group4.

These treatments were equally effective at index presentation and at 1-week follow-up4. A subsequent randomized trial done compared oral dexamethasone with oral prednisolone in 87 children with mild or moderate croup who were treated as outpatients. There was no difference in the two groups in additional healthcare for croup in the 11 days following the index visit or for any of the other study outcomes6. Children having minor croup; often advises treatment at home. This usually entails taking paracetamol to relieve any discomfort brought on by the condition or may help reduce the temperature and fever of the child. It is uncommon for croup-related complications to arise. The respiratory strain that is very difficult to breathe and respiratory failure, in which the heart continues to beat despite the breathing failure.

In this study, we assess the effectiveness of a single-dose dexamethasone dosage versus an oral prednisolone dosage in treating children who report to the urgent care of a hospital with moderate-to-mild croup. Dexamethasone is extensively used, although it is expensive, frequently difficult to get, and children will vomit if administered orally. Prednisolone, in contrast, has higher tolerance, a good taste in liquid form, and is less expensive than oral dexamethasone. Thus, if oral prednisolone is shown to be similarly effective, it can be given preferred. For children experiencing acute asthma exacerbations, dexamethasone has been suggested as a treatment option comparable to prednisolone. With its extended half-life and history of safe usage in other acute pediatric diseases including croup, etc., a dexamethasone is an excellent option. Moreover, croup is a relatively common illness in our country, which affects infants and toddlers.

Subjects and methods

Randomized-controlled trial

This randomized-controlled trial was conducted in the ED from December 2017 to June 2022. A total sample size of 226 children was calculated using WHO Calculator keeping a confidence level: 5%, power of test: 90%, population group 1 (prednisolone) mean: 2.35⁴, population group 2 (dexamethasone) mean: 2.09⁴, and population average SD: 0.85. A nonprobability consecutive sampling technique was used.

CONSORT 2010 guidelines

Our study is fully compliant with the CONSORT 2010 guidelines7. A complete CONSORT 2010 checklist has been provided as a Supplementary File (Supplemental Digital Content 1, http://links.lww.com/MS9/A50). UIN researchregistry8482 (https://www.researchregistry.com/browse-the-registry#home/registrationdetails/636e06cf693cf0002170433f/) identifies our study in Research Registry. Our research adheres to the principles outlined in the Helsinki Declaration.

Inclusion criteria

Children above age 3 months till 6 years, with Westley Croup Score 2 or more.

Exclusion criteria

Chronic respiratory disease (including asthma), severe croup (defined as Westley Croup Score >8) or impending respiratory failure, known allergy to steroids, or a relative contraindication to steroids (varicella or exposure to varicella within previous 3 weeks, history of tuberculosis, diabetes or hypertension, or known immunodeficiency), or prior treatment with epinephrine or oral corticosteroids for this croup episode and symptoms or signs suggesting another cause of stridor.

Data collection procedure

Informed written consent was obtained from the parents or caregivers on the presentation of a child to the ED diagnosed clinically as having croup and fulfilling the inclusion criteria. The principal investigator and ED nursing staff recorded the Westley Croup Score, pulse rate, respiratory rate, and arterial oxygen saturation in the air. The patients were randomized using a lottery method into two groups: one received a stat dose of 0.15 mg/kg of oral dexamethasone dissolved in water, while the other group received a stat dose of 1 mg/kg of oral prednisolone available in syrup form in the ED.

Croup score and other clinical observations (pulse, respiratory rate, and saturation of oxygen) was repeated at 4 h and recorded in the proforma. Patients were discharged home at 4 h. Nebulized adrenaline was given at any time during the study if clinically indicated.

Data analysis procedure

Data was entered and analyzed using SPSS 16 software. Mean and SD was calculated for the quantitative variable, that is, age, respiratory rate, pulse, oxygen saturation, and change in Wesley croup score at 4 h. Frequency and percentage were calculated for sex, and previous history of croup.

Effect modifiers like age, sex, and previous history of croup was controlled through stratification. Poststratification, an independent sample t-test was applied and P-values less than 0.05 were considered significant.

Results

Data of patients

A total of 226 children with Westley Croup Score 2 or more were included in this study (Table 1). Patients were randomized into two groups, 113 patients received a single dose of 0.15 mg/kg of oral dexamethasone, while 113 patients received a single dose of 1 mg/kg of oral prednisolone. The average age of the patients was 2.88±1.17 years. Age distribution of the patients is shown in Figure 1.

Table 1.

Comparison of characteristics between groups

	Mean±SD
Variables	Group D (N=113)	Group P (N=113)	P
Baseline respiratory rate	36.78±1.66	36.46±1.89	0.167
At 4 h respiratory rate	32.78±1.66	32.46±1.89	0.182
Baseline pulse	115.3±11.99	112.56±11.57	0.182
At 4 h pulse	125.3±12.98	122.64±10.52	0.082
Baseline oxygen saturation	91.46±4.31	90.72±4.19	0.190
At 4 h oxygen saturation	95.11±4.27	95.84±1.93	0.095

Figure 1.

Age distribution of the patients.

The average age with respect to groups is also shown in Table 1. There were 129 (57.1%) male and 97 (42.9%) female. Sex distribution with respect to groups is also shown in Figure 2. History of croup was observed in 42.48% (48/113) in group D and 39.82% (45/113) in group P as shown in Figure 3.

Figure 2.

Sex distribution of the patients between groups.

Figure 3.

Previous history of croup between groups.

Average respiratory rate, pulse, and oxygen saturation was not statistically significant between groups at baseline and at 4 h as shown in Table 1. Baseline mean Westley Croup Score was not significant between groups, while at 4 h significant reduction in mean Westley Croup Score was observed in group D as compared with group P (P=0.0005). Stratification analysis was performed and it was observed that at 4 h, mean Westley Croup Score was not significant between groups in less than or equal to 1 year of children and above 3 years of age, while a significant reduction in mean Westley Croup Score was observed in group D as compared with group P (P=0.0005) in 1.1–3 years of age children as shown in Table 2.

Table 2.

Comparison of mean Westley Croup Score between groups having 1 year or less, 1.1–3 years, and above 3 years of age

	Mean±SD
Variables	Group D (N=113)	Group P (N=113)	P
Baseline Westley Croup Score	5.76±0.84	5.61±0.74	0.168
At 4 h Westley Croup Score	2.46±0.71	3.00±0.82	0.0005
Change (baseline−at 4 h) in Westley Croup Score	−3.3±1.10	−2.61±1.12	0.0005
Mean Westley Croup Score between groups for ≤1 year of age
Baseline Westley Croup Score	5.83±0.72	5.4±0.68	0.098
At 4 h Westley Croup Score	2.50±0.52	2.6±0.50	0.595
Change (baseline−at 4 h) in Westley Croup Score	−3.3±0.77	−2.8±0.89	0.097
Mean Westley Croup Score between groups for 1.1–3 years of age
Baseline Westley Croup Score	5.81±0.89	5.64±0.83	0.254
At 4 h Westley Croup Score	2.32±0.58	3.03±0.87	0.0005
Change (baseline−at 4 h) in Westley Croup Score	−3.49±1.03	−2.61±1.16	0.0005
Mean Westley Croup Score between groups for >3 years of age
Baseline Westley Croup Score	5.63±0.79	5.69±0.74	0.74
At 4 h Westley Croup Score	2.75±0.92	3.23±0.81	0.054
Change (baseline−at 4 h) in Westley Croup Score	−2.87±1.23	−2.46±1.17	0.201

Baseline mean Westley Croup Score was not significant between groups, while at 4 h Westley Croup Score was observed in group D as compared with group P (P=0.0005). Stratification analysis was performed and it was observed that at 4 h, mean Westley Croup Score was not significant between groups in less than and equal to 1.1 year and above 3 years age of children, while a significant reduction in mean Westley Croup Score was observed at 4 h in group D was higher than group P (P=0.027) for each sex as shown in Table 3.

Table 3.

Comparison of mean Westley Croup Score between groups for male and females

	Mean±SD
Variables	Group D (N=70)	Group P (N=59)	P
Mean Westley Croup Score between groups for male
Baseline Westley Croup Score	5.74±0.97	5.53±0.79	0.172
At 4 h Westley Croup Score	2.43±0.69	3.10±0.85	0.0005
Change (baseline−at 4 h) in Westley Croup Score	−3.31±1.26	−2.42±1.05	0.0005
Mean Westley Croup Score between groups for female
Baseline Westley Croup Score	5.79±0.60	5.70±0.76	0.544
At 4 h Westley Croup Score	2.51±0.74	2.89±0.79	0.018
Change (baseline−at 4 h) in Westley Croup Score	−3.27±0.76	−2.81±1.16	0.027

.

Baseline mean Westley Croup Score was not significant between groups, while at 4 h, significant reduction in mean Westley Croup Score was observed in group D as compared with group P (P=0.001). Previous history of croup absent Baseline Westley Croup Score was observed in group D as compared with group P (P = 0.659) in 4 years of age children was statistically significant (P = 0.0005) (Table 4).

Table 4.

Comparison of mean Westley Croup Score between groups for previous history of croup present and absent

	Mean±SD
Variables	Group D (N=48)	Group P (N=45)	P
Baseline Westley Croup Score	5.88±0.94	5.60±0.81	0.134
At 4 h Westley Croup Score	2.56±0.79	3.16±0.79	0.001
Change (baseline−at 4 h) in Westley Croup Score	−3.31±1.30	−2.45±1.01	0.001
Previous history of croup absent
Baseline Westley Croup Score	5.68±0.77	5.62±0.77	0.659
At 4 h Westley Croup Score	2.38±0.63	2.90±0.83	0.0005
Change (baseline−at 4 h) in Westley Croup Score	−3.2±0.93	−2.7±1.18	0.002

Discussion

The prevalence of comorbid congenital abnormalities (CAs) or if comorbid CAs may have a major impact on the use of children’s hospital resources are unclear. Comorbidity is regarded as existent when a condition is diagnosed either initially or afterward. Patients with either of the following two diagnoses often make up CA comorbidity groups: individuals who have a CA as the major diagnosis and also another condition as the secondary diagnosis; and patients who have a CA as the primary diagnosis and also another condition as the secondary diagnosis. Because it is unclear how the presence of a CA and also another medical problem affects the allocation of resources during pediatric hospitalization. It was our hypothesis that pediatric patients with CA comorbidities would use resources more often than pediatric patients without such conditions.

Corticosteroids improve symptoms of croup within 6 h and for at least 12 h after administration8. They also reduce the need for nebulized adrenaline, the length of ED and hospital stay, and the frequency of return visits and readmission.

Prednisone, cortisone, and hydrocortisone are corticosteroid medications. They are helpful in the treatment of asthma, inflammatory bowel disease, and rashes, among other ailments. Corticosteroids have become standard therapy in moderate-to-severe croup9,10. Although some controversy remains over corticosteroid use for mild croup11. Trials comparing parenteral, oral, and nebulized routes of steroid delivery in croup have demonstrated similar efficacy12. The possible long-term consequences on neurodevelopment from early exposure to corticosteroids in Asia are further brought to our notice by a recent comprehensive review and meta-analysis. In this analysis, a total of 30 articles were considered where the authors emphasized the risk of related neurocognitive, behavioral, and mental issues in preterm delivery with prenatal corticosteroid administration. According to the proposed theory, infants that are close to term are subject to both internal and external increases in cortisol from their mothers. External corticosteroids are given at an increased levels level, which might affect the brain’s development and the hypothalamic–pituitary–adrenal system. Single-dose oral dexamethasone is most widely preferred because of its proven efficacy, low cost, ease of administration, and patient acceptability13. Nebulized budesonide and intramuscular dexamethasone are alternatives for patients who do not tolerate oral preparation. The currently recommended dexamethasone dose in croup is 0.6 mg/kg9,14. There is some evidence that doses as low as 0.15 mg/kg might be equally effective15,16.

Oral prednisolone has proven efficacy in croup in comparison with placebo16,17. However, prednisolone has only once been compared with other corticosteroids in croup18,19. Despite the lack of published evidence that prednisolone is equivalent to dexamethasone in croup, some physicians routinely prescribe oral prednisolone (1 mg/kg) rather than oral dexamethasone for croup20,21.

In this study, the average age of the patients was 2.88±1.17 years. There were 57.1% male and 42.9% female. In Fifoot and Ting’s4 study, the mean age was 1.76±1.52 years.

Prednisolone is generally regarded as an alternative to dexamethasone in croup10, however, only one clinical trial has been published that directly compared prednisolone and dexamethasone in the treatment of croup. In that study, single-dose oral prednisolone was found to be less effective than single-dose oral dexamethasone in mild–moderate croup in reducing unscheduled re-presentation to medical care19.

In the present study, the baseline mean Westley Croup Score was not significant between groups, while at 4 h significant reduction in mean Westley Croup Score was observed in group D as compared with group P (P=0.0005).

In Fifoot and Ting’s study4, the study’s primary outcome measure was the magnitude of change in the Westley Croup Score, which is a validated scoring system assessing different clinical criteria to classify the severity of croup. This trial found that at 4 h after the presentation, the mean change in croup score was 2.09 in the dexamethasone group and 2.35 in the prednisolone group4.

No published data exist on whether multiple doses of corticosteroids provide greater benefit than a single dose in croup22 with most clinical trials using single-dose therapy23. A proportion of patients treated with single-dose corticosteroids re-present with persistent or recurrent croup symptoms and receive further corticosteroids. Prednisolone has a shorter biological half-life than dexamethasone24 so patients treated with prednisolone might be more likely to require additional steroid doses.

Although the purpose of our study was not to compare various treatment periods, it did show that patients who received a single dose of prednisolone were statistically more likely (P=0.06) than patients who received dexamethasone to get subsequent treatments of the steroid.

Dose comparison studies have attempted to determine the smallest dose of dexamethasone that retains the same clinical benefit as the historically standard dose of 0.6 mg/kg. Geelhoed and Macdonald16 found no difference in clinical efficacy between 0.15, 0.3, and 0.6 mg/kg of oral dexamethasone. Similarly, in the present study, oral dexamethasone 0.6 mg/kg was not more effective than 0.15 mg/kg, supporting the use of the lower dose in mild-to-moderate croup25.

Croup can be well treated with oral steroids and the type of steroid used appears to have no medically important impacts on how well it works, both immediately after therapy and for a week thereafter. Children who initially get prednisolone treatment are more likely to need further doses to endure the entire illness.

Conclusions

Our trial demonstrated that oral dexamethasone at a dose of 0.15 mg/kg is effective in reducing the total croup score but there were no statistical differences in respiratory rate, pulse rate, and oxygen saturation between groups. The choice of corticosteroids might be based on local cost and availability, as well as clinician preference. Future studies are required to determine if these treatments differ in efficacy for severe croup and whether there is a role for multiple-dose corticosteroid therapy in some patients.

Ethical approval

This study was approved by the Department of Children Hospital, PIMS, Islamabad.

Consent

Consent was obtained by all the parents for enrolling into the study using Helsinki’s declaration. All the authors approved the final version to be published

Sources of funding

No funding was received.

Author contribution

A.A. and A.T.: concept. S.Q., M.I., and R.Z.: manuscript writing. I.H. and H.M.: editing and review.

Conflicts of interest disclosure

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Research registration unique identifying number (UIN)

1. Name of the registry: Research registry

2. Unique identifying number or registration ID:researchregistry8482

3. Hyperlink to your specific registration (must be publicly accessible and will be checked):

4. https://www.researchregistry.com/browse-theregistry#home/registrationdetails/636e06cf693cf0002170433f

Guarantor

Hassan Mumtaz.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Supplementary Material

ms9-85-1379-s001.doc ^{(219KB, doc)}