Based on RT7-WK2 PICO

Clinical Scenario: 4 y/o F, with no PMHx, who presents to the ED for a dry cough x 3 days. Mother states that the patient’s cough has been waking her up at night. She also reports a sore throat, nausea, and vomiting. The patient is diagnosed with croup. You, as the clinician, are wondering whether to treat the patient with dexamethasone or prednisolone.

PICO Question: Is dexamethasone more effective than prednisolone in treating croup in children?

PICO Search Elements:

P	I	C	O
Children with croup	Dexamethasone	Prednisolone	Reduction of symptoms
Croup	Ozurdex	Omnipred	Decreased cough
Children with laryngotracheobronchitis			Symptom improvement
Laryngotracheobronchitis			Effectiveness

Search Strategy:

Google Scholar:

• Dexamethasone or prednisolone for croup – 6,450 results
  • Last five years – 1,310 results
• Dexamethasone versus prednisolone for children with croup – 5,800 results
  • Last five years – 1,230 results

ScienceDirect:

• Dexamethasone versus prednisolone for croup – 110 results
  • Last five years – 12 results
• Croup treatment with dexamethasone or prednisolone – 181 results
  • Last five years – 23 results
• Dexamethasone or prednisolone for laryngotracheobronchitis – 77 results
  • Last five years – 6 results

PubMed:

• Dexamethasone versus prednisolone for croup – 94 results
  • Last five years – 33 results
• Dexamethasone or prednisolone for croup – 130,020 results
  • Last five years – 61,285 results
• Dexamethasone versus prednisolone for laryngotracheobronchitis – 95 results
  • Last five years – 33 results

Cochrane:

• Dexamethasone versus prednisolone for croup – 6 results
  • Last five years – 3 results
• Dexamethasone versus prednisolone for the treatment of croup – 5 results
  • Last five years – 2 results

I found the articles below by first searching for articles within the last five years. I was not able to find the appropriate number of articles from within the last five years that were relevant to this topic, so I did have to use a few articles that were over five years old. I tried to find meta-analyses and systematic reviews when possible, but also included three randomized controlled trials. While one of the systematic reviews I included was a broad evaluation of glucocorticoids for croup and another looked at multiple drug comparisons for the treatment of croup, both did include a review on comparing dexamethasone and prednisolone from different randomized controlled trials, which is why I found it pertinent to include. Additionally, while two of the randomized controlled trials are from other countries, it is extremely pertinent to this topic. I reviewed the references of articles that I previously included to continue my research on this question, as my search results were not always providing new articles for me to read. After extensively researching, I found that I included the highest level of sources available with a Cochrane review, systematic reviews, and randomized controlled trials. I consistently found the same several articles on this topic, leading me to determine that I did the best research with the available articles on comparing dexamethasone and prednisolone for croup treatment in children. Because of the limited research on these two medications in comparison alone, I did include smaller randomized controlled trials. While the sample sizes were small, they directly addressed the search question and were double-blinded, which aided in reducing bias.

Articles Chosen:

Article 1:

Citation: Gates A, Gates M, Vandermeer B, et al. Glucocorticoids for croup in children. Cochrane Database Syst Rev. 2018;8(8):CD001955. Published 2018 Aug 22. Link: https://pubmed.ncbi.nlm.nih.gov/30133690/

Abstract: Background: Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011. Objectives: To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group’s Specialized Register, Ovid MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies. Selection criteria: We included randomized controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events. Data collection and analysis: One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta‐analysis. Two review authors independently assessed risk of bias for each study using the Cochrane ‘Risk of bias’ tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach. Main results: We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardized mean difference (SMD) ‐0.65, 95% confidence interval (CI) ‐1.13 to ‐0.18; 7 RCTs; 426 children; moderate‐certainty evidence), and the effect lasted for at least 24 hours (SMD ‐0.86, 95% CI ‐1.40 to ‐0.31; 8 RCTs; 351 children; low‐certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate‐certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference ‐14.90, 95% CI ‐23.58 to ‐6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children. Authors’ conclusions: Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.

Article 2:

Citation: Parker CM, Cooper MN. Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial. Pediatrics. 2019;144(3) Link: https://pubmed.ncbi.nlm.nih.gov/31416827/

Type of Article: Randomized Controlled Trial

Abstract: Objectives: The use of either prednisolone or low-dose dexamethasone in the treatment of childhood croup lacks a rigorous evidence base despite widespread use. In this study, we compare dexamethasone at 0.6 mg/kg with both low-dose dexamethasone at 0.15 mg/kg and prednisolone at 1 mg/kg. Methods: Prospective, double-blind, noninferiority randomized controlled trial based in 1 tertiary pediatric emergency department and 1 urban district emergency department in Perth, Western Australia. Inclusions were age >6 months, maximum weight 20 kg, contactable by telephone, and English-speaking caregivers. Exclusion criteria were known prednisolone or dexamethasone allergy, immunosuppressive disease or treatment, steroid therapy or enrollment in the study within the previous 14 days, and a high clinical suspicion of an alternative diagnosis. A total of 1252 participants were enrolled and randomly assigned to receive dexamethasone (0.6 mg/kg; n = 410), low-dose dexamethasone (0.15 mg/kg; n = 410), or prednisolone (1 mg/kg; n = 411). Primary outcome measures included Westley Croup Score 1-hour after treatment and unscheduled medical re-attendance during the 7 days after treatment. Results: Mean Westley Croup Score at baseline was 1.4 for dexamethasone, 1.5 for low-dose dexamethasone, and 1.5 for prednisolone. Adjusted difference in scores at 1 hour, compared with dexamethasone, was 0.03 (95% confidence interval −0.09 to 0.15) for low-dose dexamethasone and 0.05 (95% confidence interval −0.07 to 0.17) for prednisolone. Re-attendance rates were 17.8% for dexamethasone, 19.5% for low-dose dexamethasone, and 21.7% for prednisolone (not significant [P = .59 and .19]). Conclusions: Noninferiority was demonstrated for both low-dose dexamethasone and prednisolone. The type of oral steroid seems to have no clinically significant impact on efficacy, both acutely and during the week after treatment.

Article 3:

Citation: Elliott AC, Williamson GR. A Systematic Review and Comprehensive Critical Analysis Examining the Use of Prednisolone for the Treatment of Mild to Moderate Croup. Open Nurs J. 2017;11:241-261. Published 2017 Nov 30. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738747/

Type of Article: Systematic Review

Abstract: Background: Many randomized control trials and systematic reviews have examined the benefits of glucocorticoids for the treatment of croup in children, but they have reported mainly on dexamethasone as an oral treatment for croup. No systematic reviews have examined prednisolone alone.  Aim: To determine in a systematic review of the literature whether a single dose of oral prednisolone is as effective as a single dose of dexamethasone for reducing croup symptoms in children. Search Strategy: A detailed search was conducted on the following databases: CINAHL, MEDLINE EBSCO, MEDLINE, OVID, PubMed, The Cochrane Library, ProQuest, EMBASE, JBI, Sum search, and OpenGrey. Study authors were contacted. Selection Criteria: Randomized Controlled Trials, clinical trials or chart reviews which examined children with croup who were treated with prednisolone alone, or when prednisolone was compared to a dexamethasone treatment and the effectiveness of the intervention was objectively measured using croup scores and re-attendance as primary outcomes. Data Collection and Analysis: Following PRISMA guidelines for systematic reviews, relevant studies were identified. Scores were graded agreed by two independent reviewers using QualSyst. Main Results: Four studies met the inclusion criteria but were too heterogeneous to combine in statistical meta-analysis. The result suggests that although prednisolone appears as effective as dexamethasone when first given, it is less so for preventing re-presentation. Trial sample sizes were small, making firm conclusions difficult, however, a second dose of prednisolone the following day may be useful. More research including cost-benefit analysis is needed to examine the efficacy of prednisolone compared to dexamethasone.

Article 4:

Citation: Garbutt JM, Conlon B, Sterkel R, et al. The comparative effectiveness of prednisolone and dexamethasone for children with croup: a community-based randomized trial. Clin Pediatr (Phila). 2013;52(11):1014-1021. Link: https://pubmed.ncbi.nlm.nih.gov/24092872/

Type of Article: Randomized Controlled Trial

Abstract: Background: Although common practice, evidence to support treatment of croup with prednisolone is scant. Methods: We conducted a community-based randomized trial to compare the effectiveness of prednisolone (2 mg/kg/d for 3 days, n = 41) versus 1 dose of dexamethasone (0.6 mg/kg) and 2 doses of placebo (n = 46). Participants were children 1 to 8 years old with croup symptoms ≤48 hours, categorized as mild (42%) or moderate (58%). Results: There were no differences for those treated with dexamethasone or prednisolone for additional health care for croup (2% vs 7%, P = .34), duration of croup symptoms (2.8 vs 2.2 days, P = .63), nonbarky cough (6.1 vs 5.9 days, P = .81), nights with disturbed sleep for the parent (0.68 vs 1.21 nights, P = .55), and days with stress (1.39 vs 1.56 days, P = .51). Conclusion: There were no detected differences in outcomes between the 2 croup treatments for either child or parent.

Article 5:

Citation: Johnson DW. Croup. BMJ Clin Evid. 2014;2014:0321. Published 2014 Sep 29. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178284/

Type of Article: Systematic Review

Abstract: Introduction: Croup is characterised by the abrupt onset, most commonly at night, of a barking cough, inspiratory stridor, hoarseness, and respiratory distress due to upper airway obstruction. It leads to signs of upper airway obstruction, and must be differentiated from acute epiglottitis, bacterial tracheitis, or an inhaled foreign body. Croup affects about 3% of children per year, usually between the ages of 6 months and 3 years, and 75% of infections are caused by parainfluenza virus. Symptoms usually resolve within 48 hours, but severe upper airway obstruction can, rarely, lead to respiratory failure and arrest. Methods and outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in children with mild croup and moderate to severe croup? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results: We found 19 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids (dexamethasone, intramuscular and oral), nebulised budesonide, oral prednisolone, heliox, humidification, and nebulised adrenaline (racemate and L-adrenaline [ephinephrine]).

Article 6:

Citation: Sparrow A, Geelhoed G. Prednisolone versus dexamethasone in croup: a randomised equivalence trial. Arch Dis Child. 2006;91(7):580-583. Link: https://pubmed.ncbi.nlm.nih.gov/16624882/

Type of Article: Randomized Controlled Trial

Abstract: Background: Croup remains a common respiratory problem presenting to emergency departments. A single oral treatment of oral dexamethasone results in improved outcome. Prednisolone has similar pharmacokinetic properties and has a significant advantage in that it is commercially available in liquid preparations. Objective: To ascertain whether a single oral dose of prednisolone was equivalent to a single oral dose of dexamethasone (matched for potency) in children with mild to moderate croup. Design: A double blind, randomized, controlled equivalence trial. Setting: Tertiary pediatric emergency department. Patients: 133 children aged 3 to 142 months presenting with mild to moderate croup. Interventions: Children received either a single oral dose of dexamethasone 0.15 mg/kg or single oral dose of prednisolone 1 mg/kg. Outcome: The main outcome measure was unscheduled re-presentation to medical care as determined by telephone follow up at 7 to 10 days. Croup score, adrenaline (epinephrine) use, time spent in the emergency department, and duration of croup and viral symptoms were secondary outcome measures. Results: Children treated with prednisolone were more likely to re-present: 19 of 65 children (29%) reattended medical care compared with 5 of 68 (7%) from the dexamethasone group. The confidence intervals around this 22% difference in outcome were 8% to 35%, outside the 0% to 7.5% range of equivalence. There were no significant differences in other outcome measures. Conclusion: A single oral dose of prednisolone is less effective than a single oral dose of dexamethasone in reducing unscheduled re-presentation to medical care in children with mild to moderate croup.

Summary of the Evidence:

Author (Date)	Level of Evidence	Sample/Setting (# of subjects/ studies, cohort definition etc.)	Outcome(s) studied	Key Findings	Limitations and Biases
Gates, A. et al. (2018)	Systematic Review	– Cochrane Review with 43 studies from 1964 to 2013 with 4,565 children up to age 18 were included. – Only randomized controlled trials were included. – Inclusion criteria: children 0-18 years old with croup, pseudocroup or laryngotracheitis. Outpatients and inpatients were included. Studies with an intervention of more than one glucocorticoid were included in any administration route. – Exclusion criteria: if none of the treatment groups received one or more glucocorticoid and studies that did not include the primary or secondary outcomes outlined.	– Primary outcomes: change in croup score from baseline to 2, 6, 12 and/or 24 hours and return visits or admissions to the hospital. – Secondary outcomes included length of stay in the hospital or emergency department, patient improvement at the hour intervals above, use of additional treatments and adverse events.	– In one randomized controlled trial assessing 99 children with croup who visited the emergency department, there was no significant difference in reduction of croup score six hours after treatment with either dexamethasone or prednisolone. – In the three RCTs investigating these two medications with 306 children, dexamethasone significantly reduced the rate of return visits (13 out of 171 patients) for care in comparison to prednisolone (27 out of 135 patients). – There was no difference in length of stay between the two groups. – There was no difference in the use of additional treatments, such as epinephrine, for either group. 7 out of 133 patients treated with dexamethasone and 8 out of 99 patients treated with prednisolone required additional treatment. – Neither treatment group had serious adverse events.	– Assessed multiple results such as glucocorticoid efficacy in comparison to placebo or epinephrine, which was not the main outcome assessed in this search question. – Two of the authors in this systematic review were authors in some of the studies included in the review.  – While the authors of the review provided “risk of bias” assessments for each article included, it cannot be assumed it is exactly how the trial was conducted. Since many of the studies were published several years ago, it was not feasible to contact authors for more information regarding how trials were conducted. – Some of the studies were unclear on how they randomized participants.
Parker CM, Cooper MN (2019).	Randomized Controlled Trial	– Prospective double-blind randomized controlled trial that took place in two urban emergency departments in Australia with a total of 1,231 children. – Inclusion criteria: age over 6 months, English-speaking caregivers, and ability to contact patients by telephone. A limit of 20 kg of the child was included to limit the maximum dexamethasone dose to 12 mg. – Exclusion criteria: allergy to either medication, immunosuppressed, steroid therapy within the last two weeks, high suspicion of another diagnosis. – Children were assigned to either dexamethasone at 0.6 mg/kg, low dose dexamethasone at 0.15 mg/kg or prednisolone at 1 mg/kg and were randomized by a computer generator. Both staff and patients were blinded to the treatment. – WCS was assessed at baseline, 1 hour after treatment, 6 hours and at 12 hours if patients were still in the hospital.	– Primary outcomes: croup severity using the Westley Croup Score (WCS) and whether the patients followed up for continuous symptoms (during 7 days after treatment) – Secondary outcomes: length of hospital or ED stay, vomiting, need for additional treatment with epinephrine or additional steroid doses, intubation, and admission	– There was no statistically significant difference in the three groups WCS at one hour after treatment. – There was no statistical difference between the groups for following up in the 7 days after treatment. 17.8% for dexamethasone, 19.5% for low-dose dexamethasone and 21.7% for prednisolone. ED follow up was 5.9% for dexamethasone, 8.8% for low-dose and 7.5% for prednisolone. – Median length of stay for patients did not differ between treatment groups. – No difference between treatment groups for additional treatment with nebulized epinephrine.  – Additional steroid doses were given in 11.3% of dexamethasone patients, 15.1% of low-dose and 18.9% of prednisolone. – No difference in adverse events between treatment groups.	– The population studied in this trial was only from two institutions. – The number of participants screened for inclusion and those who were excluded or declined consent could not be recorded because data sheets were only kept from those who met enrollment criteria. – About 70% of families of patients were able to be contacted by phone, making follow-up limited and there is the possibility that the authors missed participants who returned to the emergency department or their primary care physician.
Elliott AC, Williamson GR (2017).	Systematic review	– Study used multiple databases to find studies that included prednisolone and dexamethasone usage for treatment of croup in children. – Inclusion: randomized controlled trials, case-controlled studies and cohort studies, studies in English, croup and treatment with prednisolone in comparison to dexamethasone in children, peer-reviewed. – Exclusion criteria: studies that did not include the treatments above, involved children with other illnesses or severely ill children. – Four studies were ultimately included for this review, three randomized controlled trials and one retrospective review.	– Primary outcome: change in clinical croup score from baseline to after treatment – Secondary outcomes: return or readmission visits	– One randomized controlled trial found that 7% (5/68) children who received dexamethasone and 29% (19/65) who received prednisolone returned for medical care. – Another randomized controlled trial found no significant difference in treatment of croup with dexamethasone, low-dose dexamethasone, or prednisolone both for initial treatment and at preventing readmission. – A third randomized controlled trial of children treated with either prednisolone for three days or one dose dexamethasone found no difference in self-reported scores of symptoms after treatment. However, this study did find that relapse and return visits were more common with prednisolone. Additionally, the prednisolone is administered for a longer duration than the one dose dexamethasone.	– Sample sizes of the articles included were small. – The four studies that were included were heterogenous, especially in their outcome measures and croup scoring method, making it difficult to draw firm conclusions. – The review is unable to determine the optimal dosages of each medication that is needed for symptom and clinical improvement.
Garbutt JM, Conlon B, Sterkel R, et al. (2013).	Randomized Controlled Trial	– Randomized double-blind controlled trial that was community based in ten primary care offices in St. Louis. – Inclusion criteria: One- to eight-year-old children diagnosed with croup – Exclusion criteria: Diagnosis of severe croup or respiratory failure, prior epinephrine or steroid treatment for the current croup, contraindication to systemic steroid use or if parent would not be available to participate in follow-up interviews on telephone or not English speaking – Children (87) were randomized to either be treated with prednisolone 2 mg/kg once a day for three days or one dose of dexamethasone 0.6 mg/kg followed by placebo for two days. 46 received dexamethasone and 41 received prednisolone.	– Primary outcome was if the children sought additional medical care within 11 days of randomization – Secondary outcomes: duration of symptoms, parental stress, and adverse events	– Croup symptoms persisted for 2.8 days with dexamethasone and 2.2 days with prednisolone. – No serious adverse events occurred in either group and each medication group had similar reports in side effects. – Parental stress was similar in each group, with no significant difference in either. – 42% of children taking dexamethasone and 33% taking prednisolone developed a new infection during follow-up, but many of these could not be verified. – Ultimately, this study found that dexamethasone and prednisolone were both effective in treating children with croup in outpatient settings. This study is unique in that it evaluates these treatments in primary care offices, where dexamethasone may not always be available.	– Small sample size of 87 children, the authors were unable to recruit their target of 200 patients. – The lack of firm conclusion may be due to the lack of power from the small sample size. – Conclusions drawn in this study may not be applicable to patients in different geographic locations.
Johnson DW (2014).	Systematic Review	– Multiple databases, such as Cochrane Database, Embase and Medline were used to select studies for this review. – Inclusion criteria: randomized controlled trials and systematic reviews in English that were published. Trials with use of corticosteroids such as dexamethasone and prednisolone had to have at least twenty participants. One systematic review and one RCT were used in the comparison of oral dexamethasone to oral prednisolone. – Exclusion: one randomized controlled trial where the children were described as having mild croup, but actually qualified as moderate. – This review evaluated multiple medications for croup, but the focus for this search question was on the dexamethasone versus prednisolone section.	– Outcomes included: symptom severity, specifically change in clinical severity over time, as well as need for additional medical intervention and adverse effects.	– In this review, one article, a systematic review of 99 children aged 6 months to 6 years, with moderate croup was evaluated in an outpatient setting. – The change in Westley Croup Score in the oral dexamethasone group was -2.16 in comparison to -2.35 in the oral prednisolone group. – The article above found 12/125 patients on oral dexamethasone had return visits or readmission in comparison to 28/94 in the oral prednisolone group. – The other article reviewed was a RCT, which found a 0.9 difference in mean croup score 1 day after treatment ended with oral dexamethasone followed by two days of placebo. In comparison, the mean croup score change was 1.0 for participants in the oral prednisolone for three days group. – The RCT found 1/46 participants had hospital admission on day 11 in the dexamethasone group and 0/41 in the oral prednisolone group.	– The two articles evaluating oral dexamethasone versus oral prednisolone were not standardized in their scoring methods, which can make it difficult to draw conclusions. – The sample sizes in each study were small, which limits the power of the conclusions. – The evidence from each were low-quality and therefore definitive conclusions could not be drawn.
Sparrow A, Geelhoed G. (2006)	Randomized Controlled Trial	– Double-blind randomized controlled trial conducted in the emergency department of a pediatric hospital in Australia. – Inclusion criteria: children diagnosed with mild to moderate croup by clinical symptoms at Taussig croup score, not already receiving steroids, and older than 3 months of age. – Exclusion criteria: Families that did not have a telephone for follow up or had limited English.  – Patients received either 0.15 mg/kg of dexamethasone or 1 mg/kg of prednisolone by computer generated randomization. – A total of 133 children with croup were included in this study with 68 receiving dexamethasone and 65 receiving prednisolone.	– Primary outcome: revisit/readmission to medical care. Duration of barking cough and other symptoms including fever and rhinorrhea were analyzed as well. – Secondary outcomes: duration of time spent in the emergency department and use of nebulized adrenaline.	– 19 out of 65 children who were treated with prednisolone had revisits for medical care in comparison to 5 out of 68 children who were treated with dexamethasone. Thus, children treated with prednisolone were more likely to receive additional medication attention. – Duration of croup symptoms were 26 hours in the dexamethasone group in comparison to 35 hours in the prednisolone group. – Duration of viral symptoms was 8 days and 7 days in dexamethasone and prednisolone groups respectively. – There was no difference found in time spent in the emergency department, duration of symptoms, or use of adrenaline. – No adverse events were reported in either group.	– This study included a small sample size of 133 children, which can limit the power of the conclusions. – The trial took place in Australia, so the results may not be applicable to patients outside of the geographic area represented. – Parents and/or families may have differing views on illness concerns of their child, therefore some parents may be prone to bring their child in for a revisit, while others may not be as concerned for similar symptoms. – This study was published in 2006, making it over ten years old (see reasoning behind inclusion below search terms in earlier section).

Conclusions:

Article 1: Gates et al. concluded that there was no significant difference in changes in croup score six hours following treatment of either prednisolone or dexamethasone, however dexamethasone did reduce the rate of revisits in comparison to prednisolone.

Article 2: Parker and Cooper concluded that there was no significant difference between dexamethasone and prednisolone Westley Croup Score one hour after treatment and seven days after treatment. Additionally, there was no significant difference in emergency department follow up for either group, however prednisolone had a higher percentage of return visits at 7.5% in comparison to 5.9% for dexamethasone.

Article 3: Elliott and Williamson concluded that prednisolone and dexamethasone have similar efficacy for acute treatment of croup. The authors also determined that prednisolone does not appear to be as effective at preventing revisits.

Article 4: Garbutt et al. concluded that dexamethasone and prednisolone were similar in efficacy for the treatment of croup in the duration of symptoms, parental stress, adverse events, and additional medical care in outpatient settings.

Article 5: Johnson determined that no definitive conclusion could be established from the evidence on oral dexamethasone versus oral prednisolone due to the low quality of evidence (small population sizes) of the articles available.

Article 6: Sparrow et al. concluded that prednisolone was less effective at preventing revisits in comparison to dexamethasone, but both treatments appear to be equally effective in the treatment of croup when first administered.

The overall conclusion from these articles is that dexamethasone and prednisolone are equally effective in initially treating the symptoms of croup in children. However, while the efficacy is similar during acute treatment, dexamethasone is more effective at reducing revisits/readmissions in comparison to prednisolone.

Clinical Bottom Line:

Weight of the Evidence:

I weighed article two the most even though it was a randomized controlled trial. While I had also had systematic reviews in my research, article two had a large population size of 1,231 participants that directly addressed the clinical question. In comparison, some of the systematic reviews also focused on other treatment options/comparisons, making the evaluation and discussions not as extensive as this article. The study also included the ability to contact the family by phone, allowing for adequate follow-up regarding severity and continuation of croup symptoms after treatment. The use of the Westley Croup Score was an additional strength as it provided a more standardize measure of croup severity.

I weighed article one next as it is a recent Cochrane Review from 2018 that evaluated glucocorticoids for croup in children. It is the newer review of a previously published one and included data not previously analyzed. A weakness is that only three randomized controlled trials in the review directly compared dexamethasone to prednisolone, however it still provided recent and thorough data on the question.

Article three was weighed third as it was a systematic review from 2017 of four studies, with three being randomized controlled trials. The review provided adequate insight into each of these trials and discussed the results and implications in depth. The authors were forthright with being unable to provide a meta-analysis with the trials included because they were too heterogenous.

Article five was weighed next as it is a systematic review. It is from over five years ago, however because it is a high level of evidence and more recent than the last two articles included, I decided to weigh it next. Unfortunately, no concrete conclusions could be drawn from this study due to the small sample size and lack of heterogeneity in scoring criteria, but just because no conclusion was drawn did not completely affect my decision to weigh it fourth.  

Article four was weighed fifth as it is a randomized controlled trial from 2013 that assessed dexamethasone versus prednisolone for the treatment of croup. This article was not from within the last five years and had a small participant size of only 87 children, making it weighed second to last in this evaluation.

The last article to be weighed was article six, which was another randomized controlled trial. This RCT was from 2006, making it beyond the five years that I initially wanted for this research. However, this was a study I found cited on multiple occasions, and one that directly researched the clinical question, which is why it was included. However, as stated previously, weaknesses of this study include the small sample size of 133 patients and being conducted in another country, making it possible that the results are not applicable outside the geographic area.

Magnitude of Effects:

Article 1: This article found no significant differences in reductions in croup score at any time point and no difference in effect by glucocorticoid at two hours. Compared to prednisolone, dexamethasone significantly reduced the rate of return visits to medical care (RR 0.39, 95% CI 0.19 to 0.79; P = 0.009). There was no significant difference in the reduction in croup score after six hours of treatment with either prednisolone or dexamethasone (MD 0.19, 95% CI ‐0.17 to 0.55; P = 0.30).

Article 2: This study found no statistically significant difference between the dexamethasone, low-dose dexamethasone, and prednisolone groups on the Westley Croup Score at one hour. The adjusted differences in scores at 1 hour was 0.03 (95% CI -0.09 to 0.15) for low-dose dexamethasone and 0.05 (95% CI -0.07 to 0.17) for prednisolone. Median length of stay did not differ significantly throughout the groups. The prednisolone group, relative to the dexamethasone group, WCS was 0.04 higher at two hours and three hours.

Article 3: This review found four studies assessing prednisolone versus dexamethasone for the treatment of croup. Narrative synthesis was performed, which suggested that both medications are effective for croup, but dexamethasone treatment is less likely to have revisits. Statistical analysis could not be performed on this review because the studies were too heterogenous.

Article 4: This trial found no difference in the prednisolone and dexamethasone groups in additional healthcare visits for croup following initial visit (dexamethasone, 2%, 95% CI, 0.0% to 11.5%; prednisolone 7%, 95%CI, 1.5% to 19.9%, p=0.34). Croup symptoms persisted for an average of 2.8 days with dexamethasone and 2.2 days with prednisolone (p=0.63). The two groups did not differ in side effects from the medications.

Article 5: This review could not adequately conclude on the effectiveness of oral prednisolone versus oral dexamethasone due to the low quality of evidence found. However, the systematic review included of 99 children found -2.16 change in WCS with oral dexamethasone versus -2.35 with oral prednisolone after six hours from treatment (WMD 0.19, 95% CI. -0.17 to +0.55, p=0.30). The RCT included found mean croup score was 0.9 with oral dexamethasone versus 1.0 with oral prednisolone (p = 0.42).

Article 6:  This randomized controlled trial found that 29% of children who received prednisolone revisited for medical care in comparison to 7% from the dexamethasone group, with confidence intervals were 8% and 35%. The difference of 22% was outside the expected range of 0-7.5%. 

Clinical significance:

The results found above are clinically significant as many of the articles found that neither dexamethasone nor prednisolone is superior for the treatment of croup. While not all articles found statistical significance, it shows that initial treatment for croup can be with either medication. Some of the studies could not draw conclusions, which enhances the need for further trials on the comparison between these two medications. Additionally, many of the studies found that while both are effective during acute treatment, dexamethasone treatment results in less revisits than prednisolone. This is important clinically because clinicians do not want patients to have additional visits due to persistent symptoms. Additional visits can affect the child’s immediate quality of life resulting in loss of school time or interaction with peers and can also cause increased parental stress due to having to watch a sick child or fear of the child’s health. No significant adverse effects were seen with either dexamethasone or prednisolone, and neither had worse adverse effects. Thus, it is reasonable to state that dexamethasone and prednisolone have similar efficacies for treating children with croup with minimal adverse events. However, dexamethasone, which has a longer half-life and has shown to result in less revisits or readmissions, may be more optimal in children with croup.

Other Considerations:

While the evidence retrieved for this clinical question did provide a reasonable conclusion, some of the articles could not establish adequate conclusions because of low quality evidence. This lack of evidence was mainly due to small sample sizes or studies being too heterogenous for statistical analysis. Beyond just more studies being needed that exclusively evaluate dexamethasone versus prednisolone for children with croup, studies need to use the same scoring criteria, such as the Westley Croup Score. This will provide an adequate measure of croup symptoms and severity and allow for determining the changes after treatment with either medication. The limited trials available were randomized controlled trials, which provide high level of evidence for this clinical question, however adequate insight into double-blind randomization will also allow for proper investigation into the quality of the study when systematic reviews or meta-analyses do occur. Additional research into dosages and forms of the two treatments should also be studied, as this can affect the efficacy of the medication. Other research into the need for additional treatment with epinephrine after using dexamethasone or prednisolone should be considered, as well as cost and availability of each of the drugs.