ORIGINAL ARTICLE

The efficacy of nebulized salbutamol, magnesium sulfate,and salbutamol/magnesium sulfate combinationin moderate bronchiolitis

Mehmet Kose & Mehmet Adnan Ozturk &Hakan Poyrazolu & Tuba Elmas & Duygu Ekinci &Filiz Tubas & Tuba Kurt & Mehmet Akif Goktas

Received: 28 January 2014 /Revised: 24 March 2014 /Accepted: 24 March 2014 /Published online: 2 April 2014# Springer-Verlag Berlin Heidelberg 2014

Abstract The aim of this paper is to compare the effect ofnebulized magnesium sulfate to nebulized salbutamol andsalbutamol/magnesium sulfate on successful discharge fromthe emergency department. A total of 56 infants were includedin this double-blinded, prospective study. Infants weregrouped according to the nebulized treatment they received:group 1salbutamol/normal saline, group 2magnesiumsulfate and normal saline, and group 3salbutamol plusmagnesium sulfate. Heart beat, bronchiolitis, clinical severity

scores (CSS), and oxygen saturation of the patients weredetermined before and after nebulization (0, 1, 4 h). Thepatients were monitored for adverse reactions. Post-treatment mean CSS results were significantly lower thanpre-treatment scores in all groups at 4 h with no significantdifference within groups. CSS scores were lower in thesalbutamol/magnesium sulfate group when compared withthe magnesium sulfate and salbutamol groups (3.4 (2.44.3),4.7 (3.85.7), 4.0 (3.24.3)). CSS were significantly lowerthan those from the magnesium sulfate group. Conclusion:Nebulized magnesium sulfate plus salbutamol may have ad-ditive effects for improving the short-term CSS.

Keywords Magnesium sulfate . Salbutamol . Bronchiolitis

AbbreviationsCSS Clinical severity scoresSaO2 Oxygen saturation

Introduction

Bronchiolitis is a disorder of the lower respiratory tract thatoccurs most commonly in young children and is caused byinfection with seasonal viruses, such as respiratory syncytialvirus (RSV). Bronchiolitis is the leading cause of infant hos-pitalization in the world [16]. The role of bronchodilators inthe treatment of bronchiolitis has been the subject of manystudies. In general, no single treatment modality has proveneffective in controlling the disease.

Magnesium is an important cofactor in many enzymaticreactions and is linked to cellular homeostasis [10]. Studiesdemonstrated that magnesium inhibits the contraction ofsmooth muscle, acetylcholine release, and histamine release.Thus, both intravenous and nebulized magnesium sulfate has

Communicated by Peter de Winter

M. Kose (*)Department of Pediatric Pulmonology, Erciyes University Faculty ofMedicine, Pediatric Pulmonology Unit, Kayseri 38000, Turkeye-mail: mhmtkose@yahoo.com

M. A. OzturkDepartment of Pediatric Emergency Medicine, Erciyes UniversityFaculty of Medicine, Kayseri, Turkeye-mail: adozturk@erciyes.edu.tr

H. Poyrazolu : T. Elmas :D. Ekinci : F. Tubas : T. Kurt :M. A. GoktasDepartment of Pediatrics, Erciyes University Faculty of Medicine,Kayseri, Turkey

H. Poyrazolue-mail: mhpoyraz@erciyes.edu.tr

T. Elmase-mail: tubaelmas84@hotmail.com

D. Ekincie-mail: belduya610@gmail.com

F. Tubase-mail: filizhafo@yahoo.com

T. Kurte-mail: drtubakurt@hotmail.com

M. A. Goktase-mail: makifgoktas@yahoo.com

Eur J Pediatr (2014) 173:11571160DOI 10.1007/s00431-014-2309-3

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become a treatment option in acute asthma in adults andchildren [1, 2, 6, 1113]. The effect of magnesium has notbeen fully studied in acute bronchiolitis in children (PubMed).

The aim of our study was to determine short-term effects ofnebulized salbutamol, magnesium sulfate, and salbutamol/magnesium sulfate measured by clinical severity scores(CSS) in infants with acute moderate bronchiolitis.

Material and methods

This double-blinded, prospective clinical trial was conductedbetween October 2012 and March 2013 in the short-stay unitof the Pediatric Emergency Department of Erciyes Universityhospital. Erciyes University Children Hospital is a 200-beddedtertiary hospital in Central Anatolia, Kayseri, Turkey. Thishospital is a referral center serving a population of approxi-mately 3 million along with the surrounding cities. The outpa-tient administration number is approximately 175,000 per year.

Inclusion criteria were as follows: age of 124 months, ahistory of preceding viral upper respiratory infection followedby wheezing and crackles on auscultation, first wheezingepisode, and a clinical severity score (CSS) of 48 on admis-sion. Viral respiratory infection was diagnosed on clinicalgrounds. The CSS was defined based on four parametersincluding respiratory rate, degree of wheezing, degree ofaccessory muscle use, and general condition, as describedpreviously by Wang et al. [15]. A single point was given topatients with a respiratory rate of 3145 breaths/min, wheez-ing at terminal expiration using a stethoscope, intercostalretraction, and normal general condition. Two points weregiven to patients with a respiratory rate of 4660 breaths/min, wheezing during the entire expiration or audible onexpiration without stethoscope, tracheosternal retractions,and stable general conditions. Three points were given topatients with a respiratory rate of >60 breaths/min, inspiratoryand expiratory wheezing without stethoscope and severe re-traction with nasal flaring and a general condition of irritabil-ity, lethargy, and poor appetite [15].

Exclusion criteria were as follows: infants with CSS 8, oxygen saturation (SaO2)

4 h were better in all groups when compared with baselinescores (P

The contraction and dilation of smooth muscles of thebronchi are a result of phosphorylation and dephosphorylatingof the myofibrillar proteins conducted by specific enzymesand regulated by intracellular calcium concentration. Thephosphorylation and dephosphorylation reactions are carriedout by two enzymes: myosin kinase and myosin phosphatase.Myosin kinase phosphorylates myosin chains and depends onmagnesium. Myosin phosphatase phosphatases the lightchains of myosin and depends on calcium. In bronchialsmooth muscle, magnesium decreases intracellular calciumby blocking its entry and its release from the endoplasmicreticulum and by activating sodiumcalcium pumps [4, 7, 10].Magnesium makes competition with calcium at certain bind-ing sites on troponin-C and myosin. Therefore, magnesiumhas direct effects to myosin kinase and indirect effects tomyosin phosphatase which leads to reduction of muscle ten-sion development [4, 7]. Interestingly magnesium may de-crease bronchoconstriction due to pilocarpine and histamine,or increase FEV1 in histamine-, methacholine-, andbethanechol-induced bronchoconstriction. In cholinergic mo-tor nerve terminals, magnesium depresses muscle fiber excit-ability by inhibiting acetylcholine release. Magnesium stimu-lates nitric oxide and prostacyclin synthesis [3, 14]. Theseproperties have additional bronchodilatation effects on bron-chial smooth muscles. Magnesium also stabilizes T cells andinhibits mast cell degranulation, leading to a reduction ininflammatory mediators. Recent studies suggest that it hasanti-inflammatory effects and mitigates lung injury [8, 9].These properties have beneficial effects with salbutamol ininfants with bronchiolitis in terms of their short-time clinicalscores.

No adverse reaction was observed in the three groups.Also, the hypotension, arrhythmias, and loss of deep tendonreflexes noted in the literature during intravenous magnesiumsulfate administration [2, 48] were not observed in our study.Heart rates were decreased in the magnesium sulfate andmagnesium sulfate/salbutamol groups at 1 and 4 h of the studyand did not change in the salbutamol group. The 4-h heartrates in the magnesium sulfate and magnesium sulfate/salbutamol groups were significantly lower when comparedwith baseline values. However, in the three groups, the 4-hheart rates were tachycardiac. Our preliminary results alsoindicated that two doses of nebulized magnesium sulfatewas not associated with any side effect in the short-termfollow-up of children under 2 years of age, a finding whichis reported for the first time in the English medical literature.The limitations of our study are as follows: the number ofchildren in the study group was limited; no placebo group wasincluded because we did not find it ethical not to treat patientswith moderate bronchiolitis. We excluded children with se-vere bronchiolitis because of ethical considerations. A poweranalysis was not done. Unfortunately, this is a limitation of our

study. We administered only two doses of magnesium sulfateand magnesium sulfate/salbutamol because there are notenough data in the literature about the dosage, duration, andadverse reactions of nebulized magnesium sulfate in this agegroup. In conclusion, nebulized magnesium sulfate plussalbutamol treatment may have a beneficial effect in infantswith bronchiolitis in emergency departments. Further studiesare needed to provide more data on this subject.

Conflict of interest None of the authors have conflict of interest.

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1160 Eur J Pediatr (2014) 173:11571160

The efficacy of nebulized salbutamol, magnesium sulfate, and salbutamol/magnesium sulfate combination in moderate bronchiolitisAbstractIntroductionMaterial and methodsResultsDiscussionReferences