Efficacy of Salbutamol-Ipratropium bromide nebulization compared to salbutamol alone in children with mild to moderate attacks.

Paediatr Indones, Vol 52, No.4, July 2012

Oleh: Samuel Arifin Siemarga

Pembimbing Kasus: Dr. Andrew Sitepu, SpA

Pembimbing Internship: Dr. Agrina Dr. Yeni

Background
Asthma is global health problem in children, and is

increasing in prevalence. Rahajoe et al. reported asthma prevalence to be 6.7% in Indonesia The addition of ipratropium bromide for patients with asthma attacks has been controversial. Beta2 agonist are potent bronchodilators, but multiple or large doses may cause adrenergic side effects,Ipratropium bromide in an anticholinergic bronchodilator with a slower onset, longer duration of action, and less adrenergic effect. Previous studies shown a combination of salbutamol and ipratropium in patients with severe asthma attacks improve lung function and clinical score, and has superiority in patients with moderates attacks, while its use in patients with mild asthma attacks has been few.

 Salbutamol-ipratropium nebulization has commonly

been given to patients with mild to moderate asthma attacks, although only one Indonesian study to date has been published on this subject. This journal aimed to compared the efficacy of salbutamol-ipratropium nebulization with salbutamol alone in pediatric patients with salbutamol alone in pediatric patients with mild-moderate asthma attacks.

Methods
Single blind, randomized Clinical trial performed from September 2010-March 2011

at the Community Health Center of Tebet District, ED Cipto Mangunkusumo, MH Thamrin Salemba Hospital. Use table generated by block randomization of six
Included Excluded

Age 5-18 years, with

mild- moderate asthma, classified according to Schuhs asthma clinical score

Respiratory failure Need of Intensive Care Management Heart Abnormality Pneumonia Other respiratory disorders altering lung function Ocular Disorder Hypersensitivity to ipratropium or salbutamol Received Ipratropium treatment within 36 hours prior to enrollment

Subjects were given either 2.5 mg Salbutamol with 0.5mg Ipratropium bromide or 2.5 mg Salbutamol nebulization in 3-5ml Saline
Subjects were given two doses, 10 minutes each nebulization, and 20 minutes interval between treatment Data Collected Data Measured

Demographic characteristic ( Age, sex, nutritional status ) Asthma history Treatment History Schuhs clinical score Vital sign

Asthma comorbidities
Duration of current symptoms Asthma severity

PFR
Oxygen Saturation

Schuhs clinical score

Score

Accessory Muscle Score

Wheeze score

Dyspnea score

0
1

No retractions
Intercostal retractions Intercostal and suprasternal retractions Nasal flarinf

No wheeze and moving Dyspnea absent air well

End expiratory wheezes Panexpiratory + inspiratory wheezes Wheezes audible without stethoscope Normal activity and speech; minimal dyspnea Decreased activity;5-8 words sentences, moderate dyspnea Concentrate on breathing; <5 word sentences; severe dyspnea

Mild attack : total score 1-3 Moderate attack : total score 4-6 Severe attack : total score 7-9

Parameters Mean age, years (SD) Male gender, n Obese, n Onset of Asthma > 5 years ago, n Asthma severity : infrequent attacks episodes, n Asthma attack severity : mild attack, n Median duration of current symptomps, days ( range ) Previous prophylaxis, n Current non-steroid, non-ipratropium inhalant use, n Current steroid use, n Asthma comorbidities ( allergic rhinitis and or sinusitis),n Median initial clinical score (range) Median initial peak flow rate, liters/min (range) Median initial oxygen saturation, % ( range ) Mean initial respiratory rate, x/min (SD)

Control (n=23) 11.39 (2.56) 12 1 13 14 16 2 (1-7) 2 10 2 8 2 (1-4) 175(50-350) 97 (96-99) 28.76 (6.24)

Experimental (n=23) 11.07 (3.29) 11 2 13 15 16 1 (1-7) 3 7 2 5 3 (1-6) 100(50-300) 98 (96-99) 29.42(7.11)

Table 3. Comparative median/mean decreases in clinical score Decrease in clinical score Subjects Time at evaluation Control(n=23) Experimental (n=23) median (range) median(range) 20 minutes 2 (1-4) 2 (1-4) Mild to moderate 40 minutes 2 (1-5) 3 (1-6) attack 60 minutes 2 (1-5) 3 (1-6) 120 minutes 2 (1-5) 3 (1-6)

P 0.56 0.775 0.524 0.414

20 minutes Moderate attack only 40 minutes 60 minutes 120 minutes

Control(n=7) median (SD) 2.14 (0.90) 3.57 (0.98) 3.71 (0.95) 3.71 (0.95)

Experimental (n=7) median(SD) 2.43 (0.98) Statistical analysis was not 4.14 (1.07) performed due to 4.86 (1.07) inadequate number of 5.29 (0.76) subjects

Table 4. Comparative median PFR percentage increase Control(n=21) Experimental (n=19) Subjects Time at evaluation %increase, (range) %increase, (range) 20 minutes 14.28(0-100) 33.33(8.33-200) Mild to moderate 40 minutes 25(7.14-100) 50(8.33-200) attacks 60 minutes 25(11.1-100) 50(8.33-300) 120 minutes 25(11.1-100) 50(8.33-200)

P 0.012 0.114 0.115 0.115

Mild attacks only

20 minutes 40 minutes 60 minutes 120 minutes

Control(n=16) %increase, (range) 13.39(0.57-14) 22.5(7.14-60) 25(11.11-100) 25(11.11-100) Control(n=5) %increase, (range) 16.7 (0-100) 50(16.7-100) 50(16.7-100) 50(16.7-100)

Experimental (n=14) %increase, (range) 29.16(8.33-100) 50(8,33-100) 50(8.33-200) 50(8.33-200)

P 0.058 0.234 0.531 0.531

20 minutes Moderates attacks 40 minutes only 60 minutes 120 minutes

Experimental (n=5) P %increase, (range) 66.7(20-200) Statistical analyses was 100(20-200) not performed due to lack 166.7(60-300) of subjects 166.7(60-300)

Table 5. Comparative proportions of PFR reversibility (defined as PFR increase >12 % from baseline) Control(n=21) Experimental (n=19) Reversibility at P Mild to moderate attacks 20 minutes 40 minutes 60 minutes 120 minutes 13 19 20 20 17 17 17 17 0.069 1 0.596 0.596

Control(n=16) 20 minutes 40 minutes 60 minutes 120 minutes 10 14 15 15 Control(n=5) Moderates attacks only 20 minutes 40 minutes 60 minutes 120 minutes 3 5 5 5

Experimental (n=14) 12 12 12 12 Experimental (n=5) 5 5 5 5

P 0.226 1 0.586 0.586 P Statistical analyses was not performed due to lack of subjects

Mild attacks only

Table 6. Comparative median respiratory rate decrease Control(n=23) Experimental (n=23) Time at evaluation Mild to moderate attacks 20 minutes 40 minutes 60 minutes 120 minutes 4 (2-18) 6 (4-20) 6 (4-20) 6 (4-20) Control(n=7) Moderates attacks only 20 minutes 40 minutes 60 minutes 120 minutes 4 (4-16) 6 (4-16) 6 (4-18) 6 (4-18) 4 (0-8) 8 (1-16) 8 (1-16) 8 (1-16) Experimental (n=7) 8 (4-8) 10 (8-12) 12 (8-12) 12(8-12)

P 0.907 0.585 0.602 0.602 P Statistical analyses was not performed due to lack of subjects

Table 7. Comparative proportion hospitalization Control(n=23) Experimental (n=23) Hospitalization No hospitalization 2 21 0 23

Discussion
Limitations : single-blinded Demographic and clinical parameters similar in the

two groups. Greater decrease in clinical score in the experimental group than in the control group (mean difference 1.58), further statistical analyses could not be performed due to insufficient subjects. Previous studies by Schuh et al, Sharma et al, Kartiningsih et al, Qureshi et al demonstrated a larger decrease in clinical score in their experimental groups. No significant difference in decreased Respiratory rates between two groups, Studies by Sharma et al and Qureshi et al reported a greater decrease in respiratory rate in subjects with moderate attacks and subjects with severe attacks. Our contrasting results may be due to the smaller number of subjects with moderate attacks in our study.

 Theres a 19% difference in PFR between the groups

at 20 minutes, beyond 20 minutes, theres differences of 25% but they were not significant. This result due to the slower onset of ipratropium bromide compare to salbutamol, Sharma et al also found a higher PFR increase percentage in the experimental group at 30 minutes to 4 hours after nebulization. minutes in the experimental group ( 27% ), in contrast to previous studies which showed better efficacy at the end of the observation periods. This study included mostly patients with mild attacks and less bronchoconstrictions, the proportion of reversibility did not further increase because maximal bronchodilatation had already occurred at 20 minutes.

Theres a greater proportion of PFR reversibility at 20

 Kartininingsih et al and Qureshi et al found significant

differences in oxygen saturation between subjects with moderate and severe attacks. In contrast, most of subjects had mild attacks with high oxygen saturation (96-99%) at base line. Ducharme et al also reported no significant difference in oxygen saturation in subjects with mild to moderate attacks. Theres a small difference in hospital admission, but it was not statistically significant. Its due to the sample size was too small to detect any differences in hospitalization rates. But in many previous studies on subjects with moderate to severe attacks reported lower hospital admission rates in the iporatropium bromide groups.

Conclusion
Salbutamol-ipratropium bromide nebulization

showed better efficacy compared to salbutamol alone in patients with mild to moderate asthma attacks.