Original Article. T Akter 1, N Islam 2, MA Hoque 3, S Khanam 4, HA khan 5, BK Saha 6. Abstract:

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1 Fridpur Med. Coll. J. 214;9(2):61-67 Originl Article Nebuliztion by Isotonic Mgnesium Sulphte Solution with Provide Erly nd Better Response s Compred to Conventionl Approch ( Plus Norml Sline) in Acute Excerbtion of Asthm in Children. Abstrct: T Akter 1, N Islm 2, MA Hoque 3, S Khnm 4, HA khn 5, BK Sh 6 Asthm ttcks re serious respirtory problem tht cn be lethl when not treted ppropritely. Till tody the min sty of therpy is short cting ß2-gonist. Unfortuntely in cute sthm episodes this is not enough to relieve the bronchospsm nd reduce dyspne. The shortcoming of ß2-gonist therpy hs resulted in the use of vriety of other tretment in the mngement of cute sthm. The use of mgnesium sulphte is one of the recent tretment options. This study ws done to compre the efficcy of nebulized with mgnesium sulphte versus with norml sline in the tretment of cute excerbtion of sthm in children. This rndomized controlled tril ws crried out mong 6 ptients with cute excerbtion of bronchil sthm fulfilling the inclusion criteri, dmitted in the deprtment of Peditrics, Mymensingh Medicl College Hospitl over period of one yer from Jnury 29 to December 29. They were distributed rndomly, 3 ptients received nebulized (.15mg/kg; minimum dose 2.5mg) with 2. ml of isotonic mgnesium sulphte solution nd nother 3 ptients received the sme dose of with 2. ml of norml sline on 3 occsions t 2 minute intervls. With single dose of nebuliztion in the mgnesium group, by 2 minute lmost ll 26 (86.7%) ptients chieved t lest 6% of predicted PEFR. Within 2 minute from control group none could chieve 6% of predicted PEFR. After second dose of nebuliztion control group strted chieving 6% of predicted vlue. Regrding response criteri, with second dose of nebuliztion, t 4 minute 16 (53.3%) ptient from mgnesium group showed good response (PEFR>7% predicted). But within the first 4 minutes, none could show good response in control group. With 3rd dose of nebuliztion ll from mgnesium sulphte group showed good response but even t 6 minute, 5 (16.7%) ptients in control group filed to be included s good responder. In conclusion, nebuliztion by isotonic mgnesium sulphte solution with provide erly nd better response s compred to conventionl pproch ( plus norml sline) in cute excerbtion of sthm in children. Key words: Asthm, Mgnesium sulphte,, PEFR Introduction: Asthm is n importnt chronic disorder of the irwys with significnt morbidity nd mortlity. Around 3 million people in the world currently hve sthm. It is estimted tht there my be dditionl 1 million people with sthm by During the lst few decdes, the prevlence of sthm in childhood hs incresed worldwide. 1) Dr. Thmin Akter, MD (Peditrics) Asst. Prof. of Peditrics, 2) Professor Dr. Md. Nzrul Islm, FCPS (Peditrics), Prof of Peditrics, Community Bsed Medicl College, Mymensingh. 3) Dr. Mohmmd Azizul Hoque, FCPS (Peditrics), Associte Professor of peditrics, Mymensingh Medicl College, Mymensingh. 4) Dr. Sury Khnm, DGO, Asst Prof. of Gyne nd Obstetrics, 5) Dr. Husne Ar Khn, FCPS (Peditrics), Junior Consultnt of peditrics, Chokori, Cox's Bzr. 6) Dr. Bijoy Kumr Sh, MBBS, Registrr, Dept. Of peditrics, Address of correspondence : Dr. Thmin Akter, MD (Peditrics) Asst. Prof. of Peditrics, Mobile: Emil: shelly21stssmc@gmil.com 61 Asthm is the commonest cuse of hospitliztion other thn infection, in children under 15 yers in USA. Children with sthm commonly seek cre for cute excerbtion in the Emergency Deprtment (ED). Urbn children often use the ED s primry source of sthm cre. Children ged -17 yers hd over 867, ED visits nd n ED visit rte ws 124 per 1, 2. In Bngldesh bout 7 million people (5.2% of the popultion) re suffering from current sthm nd 7.4% of the peditric popultion in our country is suffering from sthm 1. Currently cornerstone of therpy for cute excerbtion of sthm is rpid reversl of irwy obstruction. The min sty of therpy is short cting ß2-gonist therpy. Despite the effectiveness of ß2-gonists, s mny s 3% of ptients presenting to the emergency deprtment fil to respond dequtely to these medictions nd require hospitl dmission 3. In ddition to ß2-gonist inhltion, nticholinergic drugs ct s ntibronchoconstrictors by blocking muscrinic receptors, which cuse tightening of smooth muscle in

2 Nebuliztion by Isotonic Mgnesium Sulphte Solution with Provide Erly nd Better Response s Compred to Conventionl Approch ( Plus norml Sline) in Acute Excerbtion of Asthm in Children. T Akter et l. nd round irwys. But the onset of ction of nticholinergic drugs is slow with mximum effect fter pproximtely 3-6 minutes 1. Xnthine derivtives re bronchodiltor medicines tht open irwys by relxing the muscles in nd round the irwys tht tighten during sthm episodes nd fcilitte diphrgmtic movement during inspirtion. They lso hve some nti inflmmtory properties 1. Xnthine derivtives hve nrrow therpeutic rnge, individul differences in metbolic clernce nd re ssocited with dverse effects t usul therpeutic doses. There is miniml evidence for dded benefit to optiml doses of inhled ß2-gonist. They re not generlly recommended for excerbtion of sthm 4. All these fcts stress the need for the emergency bsed intervention. Therefore, n gent tht could help reverse bronchoconstriction erly in the ttck would be of gret benefit. An efficient sthm djunct is needed to help bridge the time to onset of corticosteroid therpy effects specilly in subpopultion of ptient with cute sthm. This idel drug should be fst cting, sfe nd effective. In ptients with cute sthm excerbtion, the use of isotonic mgnesium s vehicle for nebulized produced significntly greter increse in pek expirtory flow compred with in sline. The more severe the bseline obstruction the greter the response to the combined mgnesium sulphte nd, which supports the observtion tht mgnesium is prticulrly effective in cute excerbtion of sthm 5. Most of the studies 6 mesured 1st outcome t 1 minute fter completion of the nebuliztion. Some study lso mesured 1st outcome t lest 3 minute fter completion of nebuliztion. In some study, it is found tht mgnesium sulphte hs better response s compred to norml sline. But no known study completed recommended schedule of 3 doses of nebuliztion. This study ws done to compre the efficcy of nebulized with mgnesium sulphte versus with norml sline in the tretment of cute excerbtion of sthm in children. Mterils nd Methods: This rndomized controlled tril ws crried out mong 6 ptients with cute excerbtion of bronchil sthm dmitted in the deprtment of Peditrics, Mymensingh Medicl College Hospitl over period of one yer from Jnury 29 to December 29. Children of either sex with cute excerbtion of sthm, ge rnging from 6 to 12 yers nd those who were cpble of mesuring PEFR were included nd ny evidence of respirtory trct infection or suppurtive lung disese, ny history or evidence of crdic, renl or heptic dysfunction, use of short cting bronchodiltors within 8 hours or long cting bronchodiltors within 24 hours & use of steroid within seven dys were excluded from the study. A totl 6 ptients were tken s smple size. Thirty ptients were in nebulized mgnesium sulphte with group nd the rest 3 were in nebulized with norml sline i.e., control group. Study procedure: Preprtion of isotonic mgnesium sulphte solution. Mgnesium sulphte solution 7.5% (w/v) is isotonic (286 mosm). In Inj G-MAG SULPH ; 2.47g mgnesium sulphte contined in 5 ml. So 7.5g mgnesium sulphte contined in ml/2.47 =15.18 ml (pproximtely). In sterile mber coloured glss bottle, ml of inj G-MAG SULPH tken nd then sterile distilled wter dded to mke the totl volume 1 ml. This isotonic mgnesium sulphte solution. Preprtion for rndomized controlled tril: Step-1: 6 sets of identicl eppendorf tube (ech set contining 3 eppendorf tube) were tken nd lbeled serilly from 1 to 6. In ny set ll the eppendorf tube hd the sme lbel number. Step-2: Every odd number of eppendorf tubes re filled with isotonic mgnesium sulphte solution nd every even number of eppendorf tube re filled with norml sline solution. In ny set ech eppendorf contin 2. ml of sme fluid (either isotonic mgnesium sulphte or norml sline solution). Clinicl procedure: Step-1: As ny ptient presented to the Peditric Deprtment of Mymensingh Medicl College Hospitl indoor with respirtory distress, he/she ws ssessed with view to estblish the dignosis nd severity of excerbtion of sthm. Step-2: On the bsis of inclusion nd exclusion criteri, ptients were enrolled in the study. Step-3: Clinicl exmintions of the ptients were done with regrds to vitl signs of cute ttck s well s the chest findings s per requirements of the study. Step-4: Questionnire-cum-dt sheet filled in. 62

3 Fridpur Medicl College Journl Vol. 9, No. 2, July 214 Step-5: Objective mesurement of irwy obstruction ws recorded with pek flow meter. The procedure of using the pek flow meter ws demonstrted to the ptient. Dt nlysis: Dt were nlyzed mnully nd by computer. Results were expressed s men ±SD. The primry end point ws reltive chnges in pek expirtory flow rte. Initilly the bse lines between the two groups were compred. Then the improvement in pek flow, respirtory rte. Pulse rte nd SO 2 were compred t 2, 4 nd 6 minutes from the strt point. Most of the nlyses were done by SPSS 14. for Windows (Sttisticl pckge for socil science) softwre. Unpired student's "t" test ws used to compre mens between two groups. Chi-squre nlysis ws done to compre distribution of ge, sex, fmily history of sthm, history of smoking, mediction nd presenting symptoms nd signs. Confidence intervl ws set t 95% level. Results were considered to sttisticlly significnt t <.5. When <.1, ws considered s highly significnt. Observtion nd Results: In the isotonic mgnesium group 14 ptients were femle nd 16 ptients were mle, On the other hnd in the control () group 12 ptients were femle nd 18 ptients were mle. Tble I: Bseline chrcteristics of ptients. Mgnesium sulphte with, men ±SD Age (yers) 1.6±1.7 Height (inch) 51.17±2.46 Weight (kg) 26.4±3.2 Durtion of sthm (yers) 2.23±1.19 (control) group (n=3) men ±SD 9.4± ± ± ±.88 Tble I shows the bseline chrcteristics of ptients of two groups. Age of the ptients in mgnesium sulphte with group ws 1.6±1.7 yers wheres in (control) group it ws 9.4±1.65 yers. In mgnesium nd control group height ws 51.17±2.46 inches nd 5.63±2.83 inches respectively. Weight of the ptients in mgnesium nd control group ws 26.4±3.2kg nd 25.93±4.79kg respectively. The durtion of sthm ws 2.23±1.19 yers in the mgnesium group nd 2.1±.88 yers in the control group. In ll cses the differences between the groups were not sttisticlly significnt. Tble II: Presenting symptoms nd sign Symptoms Brethlessness during Tlking Resting Physicl exhustion Yes No Tlks in Phrses Words Mgnesium Signs Wheeze Loud Very loud Use of ccessory muscle No Yes Prominent Pulse (per minute) 1-16 PEFR (%) 4-6 SO 2 94%-9% <9% (Control) group (no=3) ns Tble II shows tht ll cses pulse rte ws within 1-16 per minute nd PEFR ws 4-6 percent of predicted vlue. In mgnesium nd control group 28 nd 27 ptients respectively were brethless during tlking while 2 nd 3 ptients were brethless during resting. Only 2 ptients from mgnesium group nd 1 from control group were 63

4 Nebuliztion by Isotonic Mgnesium Sulphte Solution with Provide Erly nd Better Response s Compred to Conventionl Approch ( Plus Norml Sline) in Acute Excerbtion of Asthm in Children. T Akter et l. exhusted during presenttion. Twenty seven ptients tlked in phrses nd 3 in words in the mgnesium sulphte plus group wheres 28 ptients tlked in phrses nd 2 in words in the control group. In the mgnesium group. Loud nd very loud wheeze present in 26 nd 4 ptients respectively while in the control group they were found in 25 nd 5 ptients. The differences were not sttisticlly significnt in ll the prmeters in both the group. Tble III: PEFR (L/min) sttus t different times. Mgnesium Men±SD (control) Group(n=3) Men±SD Predicted min/bse line ± ± ± ±2.72 Men percent of predicted 2 min/bse line 49.47± ±3.41 Men percent chnge from ± ±25.59 <.1* min Men percent of predicted 27.41± ± min/bse line 63.3± ±1.36 Men percent chnge from min ± ±27.42 <.1* Men percent of predicted 41.99± min/bse line Men percent chnge from 7.25± ± ±1.39 min Men percent of predicted ± ±32.42 <.1* 55.19± ± ± ±1.56 Tble III shows bseline ( minute) pek expirtory flow rte (L/min) between the groups both in bsolute vlue nd percent of predicted were similr. Absent vlue men±sd for mgnesium group ws ±15.13 L/min nd for control group ws 12.±2.72 L/min. ws reched by Unpired students' 't' test nd ws >.1 which ws not significnt. Men of percent predicted vlue for mgnesium nd control group 49.47±3.52 nd 48.55±3.41 respectively nd the differences were lso non significnt <P vlue >.1) At 2 minute, men expirtory flow rte, men percent chnge from minute (bseline) nd men percent of predicted vlue for mgnesium nd control groups respectively were ±22.3 nd141.96±25.59 ( <.1); 27.41±7.25 nd 18.29±6.36 ( <.1); 63.3±1.74 nd 57.44±1.36 ( <.1) respectively. So t 2 minute, there re significnt differences between the groups regrding pek flow rte (bsolute vlue), percent improvement from bse line nd improvement in percent predicted vlue. Similr type of results were founds up to 6 minute of the study period. Tble IV: Comprison of ptients chieving t lest 6% of predicted vlue At min PEFR At 2 min PEFR At 4 min PEFR At 6 min PEFR Mgnesium (Control) group (no=3) Tble IV shows, t presenttion, ll the ptient hd PEFR <6% predicted vlue. In mgnesium sulphte with group t 2 minute from the strt point 26 ptients chieved t lest 6% of predicted PEFR. So with single dose of nebuliztion lmost ll children (26 out of 3) chieved t lest 6% predicted PEFR in mgnesium group. Within this 2 minute, in the control group none could chieve PEFR t lest 6% of the predicted vlue. >.1ns A 64

5 Fridpur Medicl College Journl Vol. 9, No. 2, July 214 Immeditely fter recording dt s per schedule, second dose of nebuliztion done t 2 minute from strt point. After nother 2 minute t 4 minute from the strt point 3 nd 28 ptient from mgnesium nd control group respectively chieved t lest 6% of predicted vlue. At 6 minute ll ptient from both the group chieved PEFR t lest 6% predicted. Tble VI: Comprison of outcome t different times PEFR% predicted Group A 49.47±3.52 min Group B Respirtory rte/min 34.33± ± ±1.34 Pulse rte/min ± ±4.57 SO ± ±.95 Tble V: Comprison of responses t different times Mgnesium At 2 min PEFR Good response Incomplete response Poor response At 4 min PEFR Good response (Control) group (no=3) Group A 2 min Group B Group A 4 min Group B Group A 63.3± ± ± ± ± ± ±1.36 <.5* 24.93± ±1.16 <.1* 22.93± ± ± ± ± ± ± ±o ± ±.97 <.5* 95.73±.91 Incomplete response Poor response At 6 min PEFR Good response 3 1 Incomplete response Poor response <.5* 6 min Group B 71.8± ± ± ±.85 <.5* Group A: Treted with mgnesium sulphte plus, Group B: Treted with (control group) Good response : PEFR >_ 7% of predicted vlue. Incomplete response : PEFR 5% to < 7% of predicted vlue Poor response : PEFR < 5% of predicted vlue Tble V shows tht within 2 minutes, none could show the good response. Second dose of nebuliztion done t 2 minute fter tht t 4 minutes 16 (53.3%) ptients in the mgnesium group showed good response. Despite of using two doses of nebuliztion, within this 1st 4 minutes time from control group none could show good response (PEFR >_7% of predicted). Immeditely fter recording dt t 4 minutes 3rd dose of nebuliztion done. At 6 minute, 3 (1%) ptient from mgnesium group showed good response nd 5 (16.7%) ptient from the control group filed to show good response. Tble VI show in ddition to PEFR, respirtory rte, pulse rte nd SO 2 were lso recorded t, 2, 4, nd 6 minute. At minute regrding ll the prmeters, differences between two groups were not significnt. From 2 to 6 minute, differences of men PEFR percent of predicted were lwys significnt between the groups. ( <.1). Respirtory rte t minute ws similr in both groups nd from 2 up to 6 minute, respirtory improvement were significntly different. Pulse rte differences were not sttisticlly significnt up to 4 minutes. Only 2 ptient (1 in mgnesium group nd 1 in control group) hd SO 2 89% (within <9% rnge) t presenttion, SO 2 ws >_ 9% in ll cses. Men oxygen sturtion t presenttion ws not significntly different. But from 2 minute up to 6 minute, improvement in men SO 2 ws significntly different nd mgnesium group showed superiority. 65

6 Nebuliztion by Isotonic Mgnesium Sulphte Solution with Provide Erly nd Better Response s Compred to Conventionl Approch ( Plus Norml Sline) in Acute Excerbtion of Asthm in Children. T Akter et l. Discussion: This study reveled tht combining nebulized isotonic mgnesium results in erly nd better response in pek flow s compred with the stndrd pproch ( plus norml sline) for nebuliztion in the initil tretment of cute excerbtion of sthm in children. The effect ws evident t 2 minute nd mintined up to 6 minute from the strt point. This finding is consistent with tht of Mollick (23). PEFR expressed s percentge predicted vlue eliminted gender, ge. Weight nd height bis nd men percent improvement in PEFR from bseline ( minute) eliminted the bis introduced by difference in the degree of initil irflow obstruction. Men percent of predicted PEFR detected in both group t, 2, 4 nd 6 minutes. Results in both groups t bse line ( minute) were similr but from 2 minute up to 6 minute, the vlues were significntly different. Men percent improvement in PEFR from bseline ws lwys significntly different from 2 up to 6 minutes nd mgnesium group (Tble III) showed superiority which is lso consistent with findings of Nninni et l, (2). In this study, in the mgnesium group t 2 minute from the strt point 26 out of 3 ptients chieved t lest 6% of predicted PEFR. Following 1st dose of nebuliztion t minute, within this 1st 2 minute from the control () group none could chieve PEFR t lest 6% of the predicted vlue. Second dose of nebuliztion done t 2 minute nd fter nother 2 minute from strt point 3 (1%) nd 28 (93.3%) ptient from mgnesium group nd control group respectively chieved t lest 6% of predicted vlue. From 6 minutes ll ptient from both the group chieved PEFR t lest 6% predicted. In cute excerbtion of sthm, to reduce likelihood of relpse nd hospitliztion rte, chieving s rpidly s possible sfe vlue for the percentge predicted pek flow bout 6% is needed which is suggested s the cut off point between dischrge from emergency deprtment nd dmission into the hospitl6. According to GINA (25), ptient with post tretment lung function (FEVi/PEF) in the rnge of 4%-6% of predicted vlue cn potentilly be dischrged, ssuming dequte follow up is vilble in the community nd complince is ssured. Ptients with objective evidence of lung function 6% predicted or greter cn usully be dischrged 7. 2 minute fter 2nd dose of nebuliztion t 4 minute only 16 (53.3%) ptients in the mgnesium sulphte with group showed good response (PEFR _>7% predicted). Despite of using two doses of nebuliztion, within this 1st 4 minutes from control group none could show good response. With three doses of nebuliztion, t 6 minute, 3 (1%) ptients from mgnesium group nd 25 (83.3%) ptient in the control group showed good response. Finlly 5 (16.6%) ptient in the control group filed to be included s good responder (Tble V). This finding consistent with Hqq et l, (26) 8. In the present study, ll ptient of mgnesium sulphte with group chieved 7% PEFR fter 3 dose of nebuliztion. Nninni et l 6 conducted study with ptient ged 18 yers nd over found significnt benefit fter single dose of nebuliztion with isotonic mgnesium sulphte. But the effect is much better in the present study. Hughes et l., (23) undertken double blind plcebo controlled study nd found significntly greter improvement in FEV1 with nebulized plus isotonic mgnesium sulphte solution thn plus norml sline. In tht study 3 doses of nebuliztion were done nd observtions were mde t 3 minute intervl nd the response ws similr s 2 minute intervl in the present study. Mollick 7 crried out prospective controlled study in dult popultion nd lso found the similr response fter 1 minute of completion of tretment. The current recommendtion for initil tretment of cute sthm in 3 doses of nebuliztion t 2 minute intervl for 1 hour but most of the studies 6,7 did not follow. Though intrvenous mgnesium sulphte cn be used s n djunct to conventionl nebuliztion nd other therpy but if nebuliztion of with isotonic mgnesium sulphte cn exert the sme effect, use of this combintion nebuliztion my be convenient both for the physicin nd for the ptient. So the nebuliztion mgnesium sulphte is preferble to IV mgnesium 9. Acute excerbtion of sthm requires strt of tretment even t home nd in the protocol of home mngement of sthm, oxygen dministrtion is not recommended 5. Acute hypoxi hs no effect on short cting ß2 gonist () induced bronchodilttion in ptients with sthm 9. Improvements in Oxygen sturtion following bronchodiltor dministrtion documents the presence of reltive preexisting hypoxi which is reversed to some degree with bronchodiltors 1. In our study, oxygen sturtion lso rised to sfe vlue in ll ptients (Tble VI). 66

7 Fridpur Medicl College Journl Vol. 9, No. 2, July 214 Following current recommendtion for initil tretment of cute excerbtion of sthm, In this study, nebuliztion ws done s one dose every 2 minutes for 1 hour nd found tht ptient gets comfort erlier if nebuliztion done with isotonic mgnesium sulphte solution. Conclusion: This study concludes tht combining isotonic mgnesium sulphte solution 2.ml with for nebuliztion results in erly response nd greter improvement in pek expirtory flow rte s compred with the nebuliztion with norml sline in the initil tretment of cute excerbtion of sthm in children. Ptient treted by nebulized isotonic mgnesium sulphte solution with quickly chieves sfe vlue for the percentge predicted pek flow nd t the end of initil tretment shows good response. References : 1. Ntionl guidelines: Asthm, Bronchiolitis, COPD. Asthm ssocition, Bngldesh Mhjn P, Hritos D, Rosenberg N, et l. Comprison of nebulized mgnesium sulphte plus lbuterol to nebulized lbuterol plus sline in children with cute excerbtions of mild to moderte sthm. J Emerge Med 24; 27: Bessmertn O, DiGregorio RV, Cohen H, et l. "A rndomized clinicl tril of nebulized mgnesium sulphte in ddition to lbuterol in the tretment of cute mild to moderte sthm excerbtion in dults". Ann Emerge Med, 22; 39: Expert pnel report-2: Guidelines for the dignosis nd mngement of sthm, Ntionl institutes of Helth, Ntionl institutes of Helth, Ntionl Hert, Lung nd Blood Institute, USA Nnnini LJ Jr, Pendino JC, Corn RA, et l. Mgnesium sulphte s vehicle for nebulized in cute sthm. Am J Med 2; 18: Sntn JC, Bretto SSM, Piv JP, et l. Controlled study on intrvenous mgnesium sulphte or in erly tretment of severe cute sthm ttck in children. J Peditr (Rio) 21;77: Mollick MKA. Comprison of nebulized mgnesium sulphte plus vs sline plus in the tretment of cute sthm. Thesis (MD), Ntionl institute of Diseses of the Chest nd hospitl, Mohkhli, Dhk, Bngldesh, GINA. Globl strtegy for sthm mngement nd prevention. 25. Avilble t: 9. Hqq A, Rhmn H, Khnm S, et l. Efficcy of nebulized mgnesium sulphte in the tretment of cute excerbtion of sthm in children. Bngldesh J Phrmcol 26; 1: Ymmmoto LG, Wiebe RA, Rosen LM, et l. Oxygen sturtion chnges during the peditric emergency tretment of wheezing. Am J Emerge Med 1992; 1: