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kg for the treatment of moderate to severe croup
International Journal of Pediatric Otorhinolaryngology (2007) 71, 473—477
www.elsevier.com/locate/ijporl
A randomized comparison of dexamethasone 0.15 mg/kg versus 0.6 mg/kg for the treatment of moderate to severe croup S. Chub-Uppakarn a, P. Sangsupawanich b,* a b
Pediatric Division, Hatyai Hospital, Songkhla 90110, Thailand Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hatyai 90110, Thailand
Received 7 September 2006; received in revised form 15 November 2006; accepted 17 November 2006
KEYWORDS Croup; Corticosteroids; Randomization
Summary Background: Although previous studies have shown that dexamethasone is useful in croup, the optimal dosage has not been clarified yet. The aim of this study was to investigate the effectiveness of dexamethasone 0.15 mg/kg single dose compared with the recommended dose of 0.6 mg/kg for treatment of hospitalized children with moderate to severe croup. Method: Forty-one children aged 6 months to 5 years admitted from March 2001 to October 2003 at the pediatric ward of Hatyai Hospital with moderate to severe croup were recruited for the study. After random allocation, each child received a single intravenous injection of either dexamethasone 0.6 mg/kg (maximum dose 12 mg) or 0.15 mg/kg (maximum dose 3 mg). All children were given a single dose of epinephrine nebulization at the beginning of the study. The croup scores were measured at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h after the dexamethasone injection. Results: One hour following the injection, the mean croup scores were significantly reduced from baseline values in both groups ( p < 0.01). There was no difference in the mean croup scores between the two groups at any time. Median times to croup scores equal or less than two in both high- and low-dose groups were 8 and 7.9 h, respectively. No patient required intubation or was removed from the study because of a rising croup score after enrollment. There was no significant adverse reaction from dexamethasone treatment in either group. Conclusion: Dexamethasone 0.15 and 0.6 mg/kg are equally effective in the treatment of moderate to severe croup. # 2006 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Tel.: +66 74 451250; fax: +66 74 212900. E-mail address: [email protected] (P. Sangsupawanich). 0165-5876/$ — see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2006.11.016
474
1. Introduction Croup (acute laryngotracheobronchitis) is a common cause of upper airway obstruction. The annual incidence ranges from 1.5% to 6% in children younger than 6 years of age [1]. From 1.5% to 31% of affected children are admitted to hospital [2] and 1—5% of hospitalized children with croup require mechanical ventilation [3]. The benefit of dexamethasone for treatment of croup has been well established [4—7]. However, although these studies have shown that dexamethasone is useful in croup, the optimal dosage has not yet been clarified. The earlier studies of dexamethasone treatment in croup mostly used a dose of 0.6 mg/kg [6] but the behavioral change was observed among croup patients during treatment with this recommended dose [7]. In a few studies, a smaller dose has shown efficacy superior to a placebo and no report of adverse events [8,9]. In an outpatient setting, oral dexamethasone 0.15 mg/kg significantly reduced the number of re-attending children for medical care with ongoing croup [8]. In hospitalized children, dexamethasone 0.15 mg/kg was as effective as a dose of 0.3 mg/kg [9]. However, no previous study has compared the efficacy of dexamethasone between doses of 0.6 and 0.15 mg/kg. Therefore, the aim of this study was to investigate the effectiveness of dexamethasone 0.15 mg/kg single dose compared with the recommended dose of 0.6 mg/kg for treatment of hospitalized children with moderate to severe croup.
S. Chub-Uppakarn, P. Sangsupawanich Table 1
Westley croup scoring system [10]
Indicator of disease severity
Score
Stridor None Only with agitation or excitement At rest with stethoscope At rest without stethoscope
0 1 2 3
Retraction None Mild Moderate Severe
0 1 2 3
Air entry Normal Decreased Severely decreased
0 1 2
Cyanosis None With agitation At rest
0 4 5
Level of consciousness Normal Altered mental status
0 5
Public Health. To establish a baseline assessment before treatment, we measured the Westley croup score, the respiratory and heart rates, and the oxygen saturation percentage while the children were breathing room air. Demographic information, associated symptoms, and the medical history were also documented.
2.2. Randomization
2. Material and methods 2.1. Study patients Enrollment occurred from March 2001 to October 2003 at the pediatric ward of Hatyai Hospital in the southern part of Thailand. Children aged 6 months to 5 years were eligible if they were admitted with moderate to severe croup (defined as 4—7 points on the validated croup scoring system of Westley et al. [10] in Table 1). Exclusion criteria were history of contact with chicken pox within the preceding 3 weeks, history of congenital or acquired stridor, chronic pulmonary disease, asthma, severe systemic disease or known immune dysfunction, treatment with corticosteroids within the preceding 2 weeks and treatment with epinephrine for respiratory distress before enrollment. Written informed parental consent was obtained for all children enrolled. The study was approved by the Scientific and Ethics Review Board of the Thai Ministry of
The computer-generated randomization scheme used random permuted blocks of four children. Codes were secured at the hospital pharmacy until enrollment and all decisions regarding data analysis had been finalized. Parents were unable to determine which preparation their child had received.
2.3. Study intervention The preparations of dexamethasone suspension consisted of 10 ml of dexamethasone phosphate injection in concentrations of 1.2 and 0.3 mg/ml. The preparations were packaged in identical containers by a hospital pharmacist and were not distinguishable by appearance. Each child received a single intravenous injection of 0.5 ml/kg of dexamethasone suspension which represented a single dose of either dexamethasone 0.6 mg/kg of body weight (maximum dose 12 mg) or 0.15 mg/kg (maximum dose 3 mg). At the time of dexamethasone injection, all patients
Comparison of dexamethasone 0.15 vs. 0.6 mg/kg for moderate to severe croup
475
received a single nebulization of epinephrine (1:1000) 1 ml in 0.9% saline 3 ml. Additional treatments, provided at the discretion of the attending physician, could include mist, antibiotics and oxygen.
data were analyzed with STATA software (version 7.0).
2.4. Outcome measures
During the study period, 47 patients were admitted and 41 met the inclusion criteria. The mean age of the studied patients was 17.2 months and 69% were male. Among the patients included in the randomization, 21 patients received 0.15 mg/kg and 20 patients received 0.6 mg/kg of dexamethasone. There were more males in the high dose dexamethasone group (Table 2). After 1 h of treatment, the mean croup scores in both groups were significantly reduced from baseline values ( p < 0.01). At no time was there a difference in the mean croup scores between the two groups. The mean croup scores for the selected times are given in Table 3. Median times to croup score equal or less than two in the high- and low-dose groups were 8 and 7.9 h, respectively (Fig. 1). After adjustment for sex by Coxproportional hazard regression, there was still no significant difference between the groups in terms of time until the croup scores were equal or less than two. No patient required intubation or was removed from the study because of a rising croup score after enrollment. There was no significant adverse reaction from dexamethasone treatment in either group. After the end of the study, all patients were discharged without relapse of croup symptoms.
We used the well-established and reliable Westley croup score to assess the clinical outcomes. The croup scores were measured at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h after the dexamethasone injection. The primary outcome was the difference of croup score at the end of the study and the secondary outcome was time to croup score equal or less than two. It was established that if a patient’s croup score rose more than two points from their baseline score, the enrollment would be terminated and the patient would be returned to routine croup treatment.
2.5. Statistical analysis A sample size of 16 patients in each group was required to achieve 80% power to detect a difference in mean croup score of 0.25 at the end of the study. Differences in baseline characteristics were assessed with Fisher’s exact test for proportional variables. Continuous data and mean croup scores at each observation time were compared with the Wilcoxon rank-sum test. Analysis of secondary outcomes (times to croup score equal or less than two) was based on survival analysis (Kaplan—Meier curve and log rank test). If there was an imbalance of baseline characteristics between the two groups after randomization, we adjusted its effect on the outcome by using Cox-proportional hazard regression. All statistical tests were two-tailed and p < 0.05 was considered significant. An intention-to-treat analysis was performed, in that all children who were randomly assigned to a treatment group were included in the full analysis. The
3. Results
4. Discussion We conducted a randomized, controlled clinical trial in order to compare the efficacy of dexamethasone 0.6 mg/kg versus 0.15 mg/kg for treatment of hospitalized children with moderate to severe croup. We found no difference in the croup scores between the two groups at
Table 2 Comparison of patient characteristics between low- and high-dose dexamethasone groups Characters
Dose of dexamethasone (mg/kg) 0.15 (n = 20)
0.6 (n = 21)
Percent of males Age (months) (mean S.E.) Percent of past illness with croup Duration of fever (days) (mean S.E.) Duration of rhinorrhea (days) (mean S.E.) Duration of hoarseness (days) (mean S.E.) Duration of dyspnea (days) (mean S.E.) Oxygen saturation (%) (mean S.E.)
55 16.9 2.0 10.0 2.1 0.2 1.6 0.3 1.2 0.2 1.4 0.2 95.6 0.7
86 18.8 2.6 9.5 2.3 0.3 1.7 0.4 1.9 0.4 1.5 0.1 96.6 0.4
p-Value 0.03 0.57 0.96 0.66 0.90 0.47 0.74 0.23
476
S. Chub-Uppakarn, P. Sangsupawanich
Table 3 Comparison of the croup scores between low- and high-dose dexamethasone groups Time (h) 0 1 2 3 4 6 8 10 12
Croup scores
p-Value
Dexamethasone 0.15 mg/kg (mean S.D.)
Dexamethasone 0.6 mg/kg (mean S.D.)
4.26 0.22 3.68 0.24 3.21 0.24 2.73 0.32 2.26 0.28 1.89 0.27 1.73 0.28 1.68 0.29 1.31 0.27
4.60 0.25 3.85 0.20 3.40 0.23 2.95 0.23 2.30 0.26 1.85 0.28 1.50 0.25 1.35 0.28 1.00 0.25
any time point. The onset of action of dexamethasone was rapid, within 1 h treatment, in both groups. Geelhoed and Macdonald [9] also reported that the croup scores of patients treated with corticosteroids improved within an hour. In addition, they found no difference of efficacy between high and low doses of dexamethasone, compatible with our results. However, the Geelhoed study compared three doses of dexamethasone in two trials (trial A: 0.6 mg/kg versus 0.3 mg/kg and trial B: 0.3 mg/ kg versus 0.15 mg/kg), and subsequently combined the results. Also, the two trials were conducted in different period, so the patients might have had different characteristics or co-interventions. To our knowledge, our study was the first study that directly compared dexamethasone doses of 0.6 and 0.15 mg/kg. The limitation of our study was an imbalance of the male/female ratio after randomization, but sex was not a significant determinant of croup score in Cox regression model. We limited the use of epinephrine to prevent co-intervention effect because epinephrine could reduce croup score significantly
Fig. 1 Kaplan—Meier plot of probability of children who had croup score >2 vs. time. There was no significant difference between the two groups by log rank test ( p > 0.05).
0.33 0.60 0.58 0.59 0.92 0.91 0.53 0.42 0.40
[11,12]. The rapid reduction of croup score in the first hour might reflect the dual therapeutic effects from both dexamethasone and epinephrine. However, no rising of croup score was detected after the epinephrine effect wore off. We conclude that dexamethasone 0.6 and 0.15 mg/kg are equally effective in the treatment of moderate to severe croup.
References [1] F.W. Denny, T.F. Murphy, W.A. Clyde, A.M. Collier, F.W. Henderson, Croup: an 11-year study in pediatric practice, Pediatrics 71 (1983) 871—876. [2] A. Marx, T.J. Torok, R.C. Holman, M.J. Clarke, Pediatric hospitalizations for croup (laryngotracheitis): biennial increases associated with human parainfluenza virus 1 epidemics, J. Infect. Dis. 176 (1997) 1423—1427. [3] J.S. Wagener, L.I. Landau, A. Olinsky, P.D. Phelan, Management of children hospitalized for laryngotracheobronchitis, Pediatr. Pulmonol. 2 (1986) 159—162. [4] D. Johnson, Croup, Clin. Evid. 14 (2005) 310—327. [5] F. Cetinkaya, B.S. Tufekci, G. Kutluk, A comparison of nebulized budesonide, and intramuscular, and oral dexamethasone for treatment of croup, Int. J. Pediatr. Otorhinolaryngol. 68 (2004) 453—456. [6] K. Russell, N. Wiebe, A. Saenz, S.M. Ausejo, D. Johnson, L. Hartling, T.P. Klassen, Glucocorticoids for croup, Cochrane Database Syst. Rev. 1 (2004) CD001955. [7] T.P. Klassen, W.R. Craig, D. Moher, M.H. Osmond, H. Pasterkamp, T. Sutcliffe, et al., Nebulized budesonide and oral dexamethasone for treatment of croup: a randomized controlled trial, JAMA 279 (1998) 1629—1632. [8] G.C. Geelhoed, J. Turner, W.B. Macdonald, Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial, BMJ 313 (1996) 140—142. [9] G.C. Geelhoed, W.B. Macdonald, Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg, Pediatr. Pulmonol. 20 (1995) 362— 368. [10] C.R. Westley, E.K. Cotton, J.G. Brooks, Nebulized racemic epinephrine by IPPB for the treatment of croup: a double-blind study, Am. J. Dis. Child. 132 (1978) 484— 487.
Comparison of dexamethasone 0.15 vs. 0.6 mg/kg for moderate to severe croup [11] S. Kristjansson, K. Berg-Kelly, E. Winso, Inhalation of racemic adrenaline in the treatment of mild and moderately severe croup. Clinical symptom score and oxygen saturation measurements for evaluation of treatment effects, Acta Paediatr. 83 (1994) 1156—1160.
477
[12] D. Fitzgerald, C. Mellis, M. Johnson, H. Allen, P. Cooper, P. Van Asperen, Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup, Pediatrics 97 (1996) 722—725.
www.elsevier.com/locate/ijporl
A randomized comparison of dexamethasone 0.15 mg/kg versus 0.6 mg/kg for the treatment of moderate to severe croup S. Chub-Uppakarn a, P. Sangsupawanich b,* a b
Pediatric Division, Hatyai Hospital, Songkhla 90110, Thailand Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hatyai 90110, Thailand
Received 7 September 2006; received in revised form 15 November 2006; accepted 17 November 2006
KEYWORDS Croup; Corticosteroids; Randomization
Summary Background: Although previous studies have shown that dexamethasone is useful in croup, the optimal dosage has not been clarified yet. The aim of this study was to investigate the effectiveness of dexamethasone 0.15 mg/kg single dose compared with the recommended dose of 0.6 mg/kg for treatment of hospitalized children with moderate to severe croup. Method: Forty-one children aged 6 months to 5 years admitted from March 2001 to October 2003 at the pediatric ward of Hatyai Hospital with moderate to severe croup were recruited for the study. After random allocation, each child received a single intravenous injection of either dexamethasone 0.6 mg/kg (maximum dose 12 mg) or 0.15 mg/kg (maximum dose 3 mg). All children were given a single dose of epinephrine nebulization at the beginning of the study. The croup scores were measured at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h after the dexamethasone injection. Results: One hour following the injection, the mean croup scores were significantly reduced from baseline values in both groups ( p < 0.01). There was no difference in the mean croup scores between the two groups at any time. Median times to croup scores equal or less than two in both high- and low-dose groups were 8 and 7.9 h, respectively. No patient required intubation or was removed from the study because of a rising croup score after enrollment. There was no significant adverse reaction from dexamethasone treatment in either group. Conclusion: Dexamethasone 0.15 and 0.6 mg/kg are equally effective in the treatment of moderate to severe croup. # 2006 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Tel.: +66 74 451250; fax: +66 74 212900. E-mail address: [email protected] (P. Sangsupawanich). 0165-5876/$ — see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2006.11.016
474
1. Introduction Croup (acute laryngotracheobronchitis) is a common cause of upper airway obstruction. The annual incidence ranges from 1.5% to 6% in children younger than 6 years of age [1]. From 1.5% to 31% of affected children are admitted to hospital [2] and 1—5% of hospitalized children with croup require mechanical ventilation [3]. The benefit of dexamethasone for treatment of croup has been well established [4—7]. However, although these studies have shown that dexamethasone is useful in croup, the optimal dosage has not yet been clarified. The earlier studies of dexamethasone treatment in croup mostly used a dose of 0.6 mg/kg [6] but the behavioral change was observed among croup patients during treatment with this recommended dose [7]. In a few studies, a smaller dose has shown efficacy superior to a placebo and no report of adverse events [8,9]. In an outpatient setting, oral dexamethasone 0.15 mg/kg significantly reduced the number of re-attending children for medical care with ongoing croup [8]. In hospitalized children, dexamethasone 0.15 mg/kg was as effective as a dose of 0.3 mg/kg [9]. However, no previous study has compared the efficacy of dexamethasone between doses of 0.6 and 0.15 mg/kg. Therefore, the aim of this study was to investigate the effectiveness of dexamethasone 0.15 mg/kg single dose compared with the recommended dose of 0.6 mg/kg for treatment of hospitalized children with moderate to severe croup.
S. Chub-Uppakarn, P. Sangsupawanich Table 1
Westley croup scoring system [10]
Indicator of disease severity
Score
Stridor None Only with agitation or excitement At rest with stethoscope At rest without stethoscope
0 1 2 3
Retraction None Mild Moderate Severe
0 1 2 3
Air entry Normal Decreased Severely decreased
0 1 2
Cyanosis None With agitation At rest
0 4 5
Level of consciousness Normal Altered mental status
0 5
Public Health. To establish a baseline assessment before treatment, we measured the Westley croup score, the respiratory and heart rates, and the oxygen saturation percentage while the children were breathing room air. Demographic information, associated symptoms, and the medical history were also documented.
2.2. Randomization
2. Material and methods 2.1. Study patients Enrollment occurred from March 2001 to October 2003 at the pediatric ward of Hatyai Hospital in the southern part of Thailand. Children aged 6 months to 5 years were eligible if they were admitted with moderate to severe croup (defined as 4—7 points on the validated croup scoring system of Westley et al. [10] in Table 1). Exclusion criteria were history of contact with chicken pox within the preceding 3 weeks, history of congenital or acquired stridor, chronic pulmonary disease, asthma, severe systemic disease or known immune dysfunction, treatment with corticosteroids within the preceding 2 weeks and treatment with epinephrine for respiratory distress before enrollment. Written informed parental consent was obtained for all children enrolled. The study was approved by the Scientific and Ethics Review Board of the Thai Ministry of
The computer-generated randomization scheme used random permuted blocks of four children. Codes were secured at the hospital pharmacy until enrollment and all decisions regarding data analysis had been finalized. Parents were unable to determine which preparation their child had received.
2.3. Study intervention The preparations of dexamethasone suspension consisted of 10 ml of dexamethasone phosphate injection in concentrations of 1.2 and 0.3 mg/ml. The preparations were packaged in identical containers by a hospital pharmacist and were not distinguishable by appearance. Each child received a single intravenous injection of 0.5 ml/kg of dexamethasone suspension which represented a single dose of either dexamethasone 0.6 mg/kg of body weight (maximum dose 12 mg) or 0.15 mg/kg (maximum dose 3 mg). At the time of dexamethasone injection, all patients
Comparison of dexamethasone 0.15 vs. 0.6 mg/kg for moderate to severe croup
475
received a single nebulization of epinephrine (1:1000) 1 ml in 0.9% saline 3 ml. Additional treatments, provided at the discretion of the attending physician, could include mist, antibiotics and oxygen.
data were analyzed with STATA software (version 7.0).
2.4. Outcome measures
During the study period, 47 patients were admitted and 41 met the inclusion criteria. The mean age of the studied patients was 17.2 months and 69% were male. Among the patients included in the randomization, 21 patients received 0.15 mg/kg and 20 patients received 0.6 mg/kg of dexamethasone. There were more males in the high dose dexamethasone group (Table 2). After 1 h of treatment, the mean croup scores in both groups were significantly reduced from baseline values ( p < 0.01). At no time was there a difference in the mean croup scores between the two groups. The mean croup scores for the selected times are given in Table 3. Median times to croup score equal or less than two in the high- and low-dose groups were 8 and 7.9 h, respectively (Fig. 1). After adjustment for sex by Coxproportional hazard regression, there was still no significant difference between the groups in terms of time until the croup scores were equal or less than two. No patient required intubation or was removed from the study because of a rising croup score after enrollment. There was no significant adverse reaction from dexamethasone treatment in either group. After the end of the study, all patients were discharged without relapse of croup symptoms.
We used the well-established and reliable Westley croup score to assess the clinical outcomes. The croup scores were measured at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h after the dexamethasone injection. The primary outcome was the difference of croup score at the end of the study and the secondary outcome was time to croup score equal or less than two. It was established that if a patient’s croup score rose more than two points from their baseline score, the enrollment would be terminated and the patient would be returned to routine croup treatment.
2.5. Statistical analysis A sample size of 16 patients in each group was required to achieve 80% power to detect a difference in mean croup score of 0.25 at the end of the study. Differences in baseline characteristics were assessed with Fisher’s exact test for proportional variables. Continuous data and mean croup scores at each observation time were compared with the Wilcoxon rank-sum test. Analysis of secondary outcomes (times to croup score equal or less than two) was based on survival analysis (Kaplan—Meier curve and log rank test). If there was an imbalance of baseline characteristics between the two groups after randomization, we adjusted its effect on the outcome by using Cox-proportional hazard regression. All statistical tests were two-tailed and p < 0.05 was considered significant. An intention-to-treat analysis was performed, in that all children who were randomly assigned to a treatment group were included in the full analysis. The
3. Results
4. Discussion We conducted a randomized, controlled clinical trial in order to compare the efficacy of dexamethasone 0.6 mg/kg versus 0.15 mg/kg for treatment of hospitalized children with moderate to severe croup. We found no difference in the croup scores between the two groups at
Table 2 Comparison of patient characteristics between low- and high-dose dexamethasone groups Characters
Dose of dexamethasone (mg/kg) 0.15 (n = 20)
0.6 (n = 21)
Percent of males Age (months) (mean S.E.) Percent of past illness with croup Duration of fever (days) (mean S.E.) Duration of rhinorrhea (days) (mean S.E.) Duration of hoarseness (days) (mean S.E.) Duration of dyspnea (days) (mean S.E.) Oxygen saturation (%) (mean S.E.)
55 16.9 2.0 10.0 2.1 0.2 1.6 0.3 1.2 0.2 1.4 0.2 95.6 0.7
86 18.8 2.6 9.5 2.3 0.3 1.7 0.4 1.9 0.4 1.5 0.1 96.6 0.4
p-Value 0.03 0.57 0.96 0.66 0.90 0.47 0.74 0.23
476
S. Chub-Uppakarn, P. Sangsupawanich
Table 3 Comparison of the croup scores between low- and high-dose dexamethasone groups Time (h) 0 1 2 3 4 6 8 10 12
Croup scores
p-Value
Dexamethasone 0.15 mg/kg (mean S.D.)
Dexamethasone 0.6 mg/kg (mean S.D.)
4.26 0.22 3.68 0.24 3.21 0.24 2.73 0.32 2.26 0.28 1.89 0.27 1.73 0.28 1.68 0.29 1.31 0.27
4.60 0.25 3.85 0.20 3.40 0.23 2.95 0.23 2.30 0.26 1.85 0.28 1.50 0.25 1.35 0.28 1.00 0.25
any time point. The onset of action of dexamethasone was rapid, within 1 h treatment, in both groups. Geelhoed and Macdonald [9] also reported that the croup scores of patients treated with corticosteroids improved within an hour. In addition, they found no difference of efficacy between high and low doses of dexamethasone, compatible with our results. However, the Geelhoed study compared three doses of dexamethasone in two trials (trial A: 0.6 mg/kg versus 0.3 mg/kg and trial B: 0.3 mg/ kg versus 0.15 mg/kg), and subsequently combined the results. Also, the two trials were conducted in different period, so the patients might have had different characteristics or co-interventions. To our knowledge, our study was the first study that directly compared dexamethasone doses of 0.6 and 0.15 mg/kg. The limitation of our study was an imbalance of the male/female ratio after randomization, but sex was not a significant determinant of croup score in Cox regression model. We limited the use of epinephrine to prevent co-intervention effect because epinephrine could reduce croup score significantly
Fig. 1 Kaplan—Meier plot of probability of children who had croup score >2 vs. time. There was no significant difference between the two groups by log rank test ( p > 0.05).
0.33 0.60 0.58 0.59 0.92 0.91 0.53 0.42 0.40
[11,12]. The rapid reduction of croup score in the first hour might reflect the dual therapeutic effects from both dexamethasone and epinephrine. However, no rising of croup score was detected after the epinephrine effect wore off. We conclude that dexamethasone 0.6 and 0.15 mg/kg are equally effective in the treatment of moderate to severe croup.
References [1] F.W. Denny, T.F. Murphy, W.A. Clyde, A.M. Collier, F.W. Henderson, Croup: an 11-year study in pediatric practice, Pediatrics 71 (1983) 871—876. [2] A. Marx, T.J. Torok, R.C. Holman, M.J. Clarke, Pediatric hospitalizations for croup (laryngotracheitis): biennial increases associated with human parainfluenza virus 1 epidemics, J. Infect. Dis. 176 (1997) 1423—1427. [3] J.S. Wagener, L.I. Landau, A. Olinsky, P.D. Phelan, Management of children hospitalized for laryngotracheobronchitis, Pediatr. Pulmonol. 2 (1986) 159—162. [4] D. Johnson, Croup, Clin. Evid. 14 (2005) 310—327. [5] F. Cetinkaya, B.S. Tufekci, G. Kutluk, A comparison of nebulized budesonide, and intramuscular, and oral dexamethasone for treatment of croup, Int. J. Pediatr. Otorhinolaryngol. 68 (2004) 453—456. [6] K. Russell, N. Wiebe, A. Saenz, S.M. Ausejo, D. Johnson, L. Hartling, T.P. Klassen, Glucocorticoids for croup, Cochrane Database Syst. Rev. 1 (2004) CD001955. [7] T.P. Klassen, W.R. Craig, D. Moher, M.H. Osmond, H. Pasterkamp, T. Sutcliffe, et al., Nebulized budesonide and oral dexamethasone for treatment of croup: a randomized controlled trial, JAMA 279 (1998) 1629—1632. [8] G.C. Geelhoed, J. Turner, W.B. Macdonald, Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial, BMJ 313 (1996) 140—142. [9] G.C. Geelhoed, W.B. Macdonald, Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg, Pediatr. Pulmonol. 20 (1995) 362— 368. [10] C.R. Westley, E.K. Cotton, J.G. Brooks, Nebulized racemic epinephrine by IPPB for the treatment of croup: a double-blind study, Am. J. Dis. Child. 132 (1978) 484— 487.
Comparison of dexamethasone 0.15 vs. 0.6 mg/kg for moderate to severe croup [11] S. Kristjansson, K. Berg-Kelly, E. Winso, Inhalation of racemic adrenaline in the treatment of mild and moderately severe croup. Clinical symptom score and oxygen saturation measurements for evaluation of treatment effects, Acta Paediatr. 83 (1994) 1156—1160.
477
[12] D. Fitzgerald, C. Mellis, M. Johnson, H. Allen, P. Cooper, P. Van Asperen, Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup, Pediatrics 97 (1996) 722—725.