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Vil 32 no. 1, 2008.pmd

BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 10-16 Comparative Efficacy of Nebulized L-adrenaline versus Salbutamol
in Infants with Acute Bronchiolitis
Background: Bronchiolitis is one of the most prevalent diseases of infancy for which
large number of infants need hospitalization, particularly during winter period. RSV
(Respiratory syncitial virus) is the principal causative pathogenic organism. Reliving
symptoms are the main aim of management though none of the treatment modalities
is specific. Bronchodilators like salbutamol, adrenaline, anti-cholinergic drugs,
ipratropium bromide and saline nebulization have been used with varying results.

Methods: This prospective study included 52 infants (2-12 months, male:female ratio 2:1)with bronchiolitis (with 1st episode of wheeze, previously healthy baby, physical findingswith cough, running nose, fever, coryza and inflation of lungs) to understand comparativeefficacy of nebulized salbutamol with adrenaline in bronchiolitis. The cases wererandomized into nebulized salbutamol group (n=25) and nebulized adrenaline group (n=27).
After randomization three nebulization were given at the interval of 20 minutes. Outcomeof therapy was evaluated by respiratory rate, MRDAI (Modified Respiratory DistressAssessment Instrument) score and O saturation before and after therapy.
Results: Study cases in both the groups presented with cough (100%), respiratorydistress (100%), feeding difficulty (90.3%), running nose (98%) and wheeze (100%).
Majority of the cases live in urban area and mostly from non-smoker family. Insalbutamol group respiratory rate, MRDAI score and O saturation (before nebulization
RR-67.5±6.1, MRDAI score-14.6±1.3, SaO 93.9±1.6 and after nebulization RR- 52.5±4.9, MRDAI score-6.4±1.7, SaO -97.1±1.5) significantly improved after 3 nebulizations. In adrenaline group respiratory rate, MRDAI score and O saturation (before nebulization RR-64.9±5.9, MRDAI score-15.0±0.8, SaO 94.1±1.4 and after nebulization RR-50.0±2.9, MRDAI score-7.7±1.0, SaO -97.9±1.5) also significantly improved after 3 nebulizations. Improvement was more significant in adrenaline group.
Heart rate in both groups were increased (salbutmol group-151.8±10.6 and in adrenalinegroup-160.2±10.1) but more in adrenaline group. When comparative efficacy evaluated,it was observed that nebulized adrenaline therapy was significantly superior to nebulizedsalbutamol therapy in reliving symptoms (p=.004).
Conclusion: The study concluded that both nebulized salbutamol and l-adrenalineare effective and nebulized l- adrenaline is significantly superior to nebulized salbutamolin infant with bronchiolitis in reliving symptom. Key words: Nebulized l-adrenaline, nebulized salbutamol, acute bronchiolitis.
virtually all children become infected during first 3 year Bronchiolitis is an acute viral inflammatory lesion of of life1. Bronchiolitis occurs most commonly in male small airways. More than 70% cases are due to infants who have not been breastfed and live in respiratory syncytial virus (RSV), other pathogens are crowded condition. The source of viral infection is Parainfluenza virus, Adenovirus, Rhinovirus, Influenza usually a family member with minor respiratory illness.
virus and Mycoplasma pneumonae. The occurrence Infants whose mothers smoke cigarette are more likely is highest in mid winter to late spring. The peak to acquire bronchiolitis than infants of non-smoking incidence of bronchiolitis is 2-6 months of age and mother. The occurrence is more observed where a 1. OSD, Department of Paediatrics, BSMMU, Shahbag, Dhaka heavy smoker stays with children2. In USA >90,000 2. Professor of Paediatric Pulmonology, BICH, Dhaka Shishu hospital admissions yearly are due to bronchiolitis, Correspondence: Dr. AKM Amirul Morshed
the majority of infants younger than 90 days3.
Comparative Efficacy of Nebulized L-adrenaline versus Salbutamol BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 11 Variation in the management of bronchiolitis has been After selecting the cases relevant history and physical documented. Hospitalized patients receive a variety of examination finding were recorded in a pretested treatment modalities with uncertain efficacy such as questionnaire. Heart rate, respiratory rate and the bronchodilator, ribavirin, steroids and antibiotics. These severity of illness were assessed by using a variant modalities of treatment significantly impact the combination of MRDAI score (Modified Respiratory cost and adverse events associated with hospitalization4.
Distress Assessment Instrument) (Table-1) and O2 saturation. Oxygen saturation was measured non- Bronchodilators are often used in the treatment of invasively using pulse oxymeter, and those with values bronchiolitis but data on efficacy are conflicting. Most less than 92% were designated as having significant studies have shown no beneficial effect on lung mechanics. JD Kellner et al done an evidence based studywhere they commented that bronchodilator produce The cases were then randomly (one case to salbutamol modest short term improvement in clinical scores5.
group and next case to adrenaline group) assignedinto two groups designated as A (salbutamol group) In an article, Arivolli Verappan and Ashir Kumar and B (adrenaline group). Group A (salbutamol group) described that any form of steroid is effective inbronchiolitis, specially nebulized budesonide 1000 received salbutamol in a dose of 0.15 mg/kg body micro-gram/dose. They also comment that L- weight (minimum dose 1 mg)7 diluted in normal saline epinephrine was effective as well as less costly in to make a total volume of 3 ml. Cases in group B treatment of bronchiolitis6. Ribavirine a broad (adrenaline group) received nebulization with 0.1 ml/ spectrum anti viral agent is the only specific therapy kg body weight of 1 in 10,000 solution of adrenaline (1 for RSV infection in infant1. Ray and Singh concluded ampoule 1:1000 injection diluted with 9 ml of normal in a recent study that both nebulized epinephrine and saline to make it 1 in 10000 solution) 7. The drug was salbutamol caused significant improvement in mean further mixed with normal saline to make a total volume symptom score and oxygenation. However the of 3 ml. Nebulization in each groups were given at 20 epinephrine group showed a significantly better minutes intervals. Pulse oxymetry (NBP-40, Nellcor- improvement in study parameters than salbutamol Puritan Benett, Ireland) was done during this period group. They concluded by saying “Adrenaline is more and SaO values were recorded before and after effective than salbutamol and is thus a better, nebulization. No other drugs like antibiotics, steroids, inexpensive and relatively safe alternative”7.
intravenous fluids, etc were given during this period.
Bertrand P et al had been done a prospective study on In febrile cases only hydrotherapy was given.
efficacy of nebulized epinephrine versus salbutamol in Ten minutes after administration of the last dose, hospitalized infants with bronchiolitis. They commented respiratory rate, MRDAI score and oxygen saturation that nebulized epinephrine decreased the baseline (by pulse oxymetry) were evaluated again to assess clinical score of bronchiolitis faster than salbutamol.
the response to therapy. The decision for further They also concluded that nebulized epinephrine is more management was taken on the basis of this evaluation.
effective agent than salbutamol in the initial treatment Children who showed a sustained decrease in of bronchiolitis and is equally safe8.
tachypnea and respiratory distress (wheezing and The study was conducted to understand the retractions), and were accepting well orally after an comperative efficacy of nebulized salbutamol versus observation period of 1 hour, were sent home with oral nebulized l-adrenaline in reliving in acute bronchiolitis.
medication. Children who did not improve admitted inhospital for further management.
Materials and Methods
The study was a prospective, randomized,
Supportive measures like propped up positioning, fluid, interventional study conducted at Dhaka Shishu feeding and antibiotics (whenever indicated) and (Children) Hospital from July 2002 to December 2003.
counseling was done. MRDAI score was chosen to Previously healthy infants (2-12 months) having first assess the clinical outcome of nebulized salbutamol episode of wheeze accompanying physical findings and adrenaline because it is clinically relevant and of viral infection i.e., coryza, cough, fever, etc and has undergone validation and reliability measurement evidence of hyperinflation of the lungs clinically and in randomized controlled trials involving patients with radiologically were included in this study. The patients with evidence of similar previous attack, asthma,previous use of corticosteroid and history of atopy or Data was analyzed by using SPSS statistical software allergy and presence of congenital heart disease and employing appropriate statistical tests like paired and BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 12 Respiratory distress assessment instrument9 Twenty cases (20/25; 80%) in salbutamol group and The study included 52 cases, 25 (male-15, female- 23 cases (23/27; 85%) in adrenaline group live in urban 09) in nebulized salbutamol group, 27 (male-17, area and 05 cases (5/25; 20%) in salbutamol group female-10) in nebulized adrenaline group. Most of the and 4 cases (4/27; 15%) live in rural area. Majority of cases (salbutamol group-25, adrenaline group-24) in the cases (salbutamol group-19/25; 76% and both the groups were born at term and 42 (salbutamol adrenaline group-23/27; 85%) live in normal group-21, adrenaline group-21) infants were delivered environment. Minority of the cases (salbutamol group- normally. Body weight of the cases ranged from 4.5 6/25; 24% and adrenaline group-4/27; 15%) lives in crowded environment. Majority of the cases(salbutamol group-21/25; 84% and adrenaline group- Majority in salbutamol (17/25; 68%) and adrenaline 24/27; 89%) lives in well-ventilated rooms. Ventilation group (17/27; 63%) were exclusively breastfed up to of the rest of the families was poor. In salbutamol 4 months of age. Only 2 cases in both groups had group 12 (11/25; 44%) family members were smokers combined breast feeding and complementary feeding.
while it was 6 (6/27; 22.2%) in adrenaline group.
Only complementary feeding was given to 6 cases Majority of the family members 34(13/25; 52% in (6/25; 24%) in salbutamol group versus 8 cases (8/ salbutamol group and 21/27; 77.8% in adrenaline Table-II
Residence of the family, crowded living and ventilation status distribution Comparative Efficacy of Nebulized L-adrenaline versus Salbutamol BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 13 Table-III
(97.1±1.5) and RDAI score (6.4±1.7) had significantly improved in comparison to respiratory rate (67.5±6.1), oxygen saturation (93.9±1.6) and RDAI score (14.6±1.3) of before nebulization (p=<.001 in all parameter). Heart rate also significantly increased after nebulization (151.8±10.6 After nebulized adrenaline therapy mean respiratory rate (50.0±2.9), oxygen saturation (97.9±0.8), RDAI score (7.7±0.1) had also significantly improved in comparison to respiratory rate (64.9±5.9), oxygen saturation (94.11±2.9) and RDAI score (15.04±0.8) All the cases presented with cough but 98% of the before nebulization (p=<.001 in all parameter). Mean cases presented with running nose (salbutamol group- heart rate was significantly increased after 24/25; 96% and adrenaline group-27/27; 100%).
nebulization (160 ±10.1 versus 105, ±10.04) Difficulty of feeding was a presenting feature in 21 (84%) patients of salbutamol group and 26 (96%) patients in adrenaline group. Only in 16 cases in both In comparison between two modalities of treatment, groups (salbutamol group-16/25; 64% and adrenaline adrenaline was found to be significantly more group-16/27; 59%) presented with fever (98ºF -103ºF).
efficacious than salbutamol in every parameter except All the cases were presented with wheeze and in MRDAI score after nebulization where p value was 0.08. But in respiratory rate (p=.03), oxygen saturation On examination of the lungs, 33 (63.5%) patients had (p=.03) and MRDAI score reduction (.004) was no significant auscultatory finding and spleen was significantly better in adrenaline group after 3rd palpable in 10 (19.2%) patients. Asthma, eczema and allergic rhinitis (atopic conditions) were present in only We have done RSV antigen of nasal swab in 25 (48%) patients of both groups and found only 4(16.0%) patients were positive for RSV antigen. Here group respiratory rate (52.5±4.9), oxygen saturation Table-IV
Comparison of response to therapy with nebulized salbutamol versus adrenaline BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 14 Discussion
60% of cases had RSV positive antigen in their nasal The present study included 52 cases, 25 (male-15, female-09) in nebulized salbutamol group, 27 (male- Comparing nebulized salbutamol with adrenaline there 17, female-10) in nebulized adrenaline group. Male was significant improvement of respiratory rate and infants are predominantly affected with bronchiolitis O saturation and difference of improvement between in both the groups7,10. Most of the cases in both the the two groups after 3rd nebulization was statistically groups were born at term and delivered normally. Body significant. One study in neighbouring country also weight of the cases ranged from 4.5 kg to 13 kg (mean- observed significant improvement by nebulized 6.5 kg). In an Indian study mean age was 5.6 months7.
salbutamol and adrenaline therapy and the efficacy of Majority cases in both salbutamol and adrenaline nebulized adrenaline was significantly superior to groups were exclusively breast-fed up to 4 months.
salbutamol7. Menon et al observed no significant Only 2 cases in both the groups had mixed feeding.
difference between nebulized salbutamol and Only complementary feeding was given to 6 cases in salbutamol group versus 8 cases in adrenaline group.
Though breast feeding has a protective effect against In the present study (Table-IV) mean O saturation infection the present study showed that breast fed before nebulization were 93.9% and 94.1% in babies also suffer with bronchiolitis. Twenty cases salbutamol and adrenaline group respectively. After (80%) in salbutamol group and 23 cases (85.2%) in nebulization mean oxygen saturation raised upto adrenaline group live in urban area and few cases live 97.1% and 97.8% in salbutamol and adrenaline group in rural area. Here urban infants are affected more respectively, which is statistically significant. In and it is established inference for bronchiolitis2.
another Indian study SaO before nebulization was Majority of the cases live in normal environment and 91.1% and 90.6% in salbutamol and adrenaline group in well-ventilated rooms. Though living in well-ventilated respectively and after nebulization these score raised room, majority of the cases had attack of bronchiolitis.
to 93.9% and 98.0% respectively7, similar to our study.
Forty-seven mothers are housewives and only 4 In a canadian study there was no significant mothers work outside home. In salbutamol group only improvement in O saturation when compared with 12 family members were smokers versus 6 in before and after nebulization salbutamol versus adrenaline group. Majority of the family members of adrenaline14. Ainiune AA et al compared the efficacy both the groups were non-smokers. Though smoking of nebulized adrenaline with nebulized normal saline is a recognized risk factor for bronchiolitis, particularly and concluded that adrenaline is not superior to normal saline13. An earlier trial on croupy infants had revealedthat the peak effect of nebulized epinephrine appeared In the present study running nose, cough, wheeze, in 30 minutes and lasted for 60-90 minutes15. In this fever and feeding difficulty were predominant presenting study even though the continued effect of the drugs features in both the groups (Table-III). All the cases was seen after the third dose, the maximal change in (100%) of the present study presented with cough SaO appeared in both groups after the second and 94% cases presented with running nose. Difficulty of feeding was a presenting feature in 75% cases in nebulization, i.e., about 30 minutes after the onset of salbutamol group and almost all cases in adrenaline nebulization. This may perhaps explain why certain group. Only 16 cases in both the groups presented authors who used only a single dose of adrenaline with fever (up to 1030F). One study in Bangladesh failed to observe any significant improvement16.
observed that clinical presentations were almost similar MRDAI (Respiratory Distress Assessment Instrument) to our study10. L kabir et al found that spleen was score reduction in our study was 6.1 and 7.3 in palpable in 42% cases while it was only 19% in present salbutamol and adrenaline group respectively, which is statistically significant. Reduction of MRDAI score We tested only 25 samples of nasal swabs out of in adrenaline group is significantly better than total 52 cases for RSV where only nasal swabs of 4 salbutamol group in our study which was also shown patients had RSV antigen positive. A previous study by a previous Indian study where mean score reduction in Bangladesh showed 45.0% anti RSV antibody (IgM) was 8.8 and 5.9 in adrenaline and salbutamol groups positive cases10. A study in England reported that respectively7. A study in Canada, MRDAI score Comparative Efficacy of Nebulized L-adrenaline versus Salbutamol BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 15 reduction was 7.5 and 6.6 in salbutamol and adrenaline be safely used in reliving of symptoms in bronchiolitis groups respectively, which did not have any statistical without any major side effects. Larger, multicentre, significance14. Ainine AA has also shown no significant double blind, randomized controlled trials are required difference regarding RDAI score reduction between adrenaline and saline nebulization13.
In our study, we have used a combination of MRDAI score and oxygen saturation to assess the respiratory Advances in Treatment. Indian J Pediatr 1996; functional status and degree of distress. These score are non-invasive, have low inter-observer variation and Orenstein DM. Bronchiolitis. In: Behrman RE, can be easily evaluated in the OPD set-up. Arterial oxygen saturation by pulse oxymetry has suggestedbeing the best objective criterion to assess degree of Textbook of Pediatrics. 17th ed. Philadelphia: WB Analysis of the present study also revealed that the children in both the groups had similar clinical profile Byington CL. Sepsis evaluation in hospitalizedinfants with bronchiolitis. Pediatr Infect Dis J during the time of inclusion in the study. After nebulization for three times consecutively, within 20minutes interval both the adrenaline and salbutamol Klassen TP, Rowe CP, Sutclife T, Roop LJ, groups showed significantly improvement which was more marked in the adrenaline group in comparison salbutamol in acute bronchiolitis. J Pediatr 1991; to salbutamol group in all parameters. Not only the mean score and mean SaO levels were better in the adrenaline group but also more proportion of patients EEL. Bronchodilator therapy in Bronchiolitis.
significantly improved both in clinical scores as well as oxygen saturation in adrenaline group comparedto salbutamol group (p< 0.03).
Verappan A, Kumar A. Role of steroid in croupand beta agonist in Bronchiolitis. Indian Pediatr The cardiac side effects of drugs used were also assessed because the chronotropic action ofadrenegric agents on the heart is often a matter of concern. Both salbutamol as well as adrenaline showed a significant increase in heart rate that was associated respiratory tract infection in infants.
more in case of adrenaline group. However, this study did not have any adverse clinical effects like increased Bertrand P, Aranibar H, Castro E, Sanchez I.
irritability, tremors, facial blanching, arrhythmia, congestive heart failure and none of the children required drug withdrawal or intervention for tachycardia Bronchiolitis. Pediatr Pulmon 2001; 31: 28.
Lowell DI, Lister G, Von Koss H, MacCarthy P.
Bronchodilator, both specific (β agonist e.g, salbutamol) and nonspecific agonist (adrenaline) are epinephrine. Pediatrics 1978; 79: 939-45.
useful in relieving symptoms and improving 10. Kabir ARML, Haq N, Hoque M, Ahmed F, Amin R, Hossain A, et al. Evaluation of hospital infantsand young children with Bronchiolitis - a Conclusion
multicentre study. Mymensingh Medical Journal The study concluded that both salbutamol and l- adrenaline are useful in relieving symptoms andimproving oxygenation in bronchiolitis. When Mc Connochie, Roghman KJ. Parental Smoking, comparative efficacy was evaluated it was observed presence of older siblings and familly history of that nebulized l-adrenaline was superior to nebulized asthma increase risk of asthma. Am J Dis Child salbutamol in bronchiolitis. Nebulized adrenaline can BANGLADESH J CHILD HEALTH 2008; VOL 32 (1) : 16 12. Mc Connochie, Roghman KJ. Bronchiolitis as a randomized double blind study comparing L- possible cause of wheezing in childhood. New epinephrine and racemic epinephrine aerosols evidence. Pediatrics 1984; 74: 1-10.
in the treatment of laryngotracheitis (croup).
Pediatrics 1992; 89: 302-06.
13. Ainiune AA, D Leyf. Short term effect of Adrenaline in Bronchiolitis: a randomized 16. Lenney W, Milner AD. Alpha and beta adrenergic controlled trial. Arch Dis Child 2002; 86: 276-79.
stimulants in bronchiolitis and wheezy bronchitisin children under eighteen months of age. Arch 14. Menon K, Sutcliff T, Klassen TP. A randomized trial comparing the efficacy of epinephrine withsalbutamol in the treatment of acute bronchiolitis.
17. Henerson FE, Clyde WA, Collier AM, Denny FW, Senior RJ, Sheaffer CT, et al. The etiology andepidemiologic spectrum of bronchiolitis in 15. Waisman Y, Klein BL, Boenning DA, Young GM, pediatric practice. J Pediatr 1979; 86: 95-100.
Chamkerlain JM, O’Donnel R, et al. Prospective



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