Comparative Efficacy of Nebulized Magnesium Sulphate in Combination with Beta2 Agonist versus Beta2 Agonist Alone for Managing Acute Severe Asthma in Children: A Single-Blinded Randomized Clinical Trial

TITLE:

Comparative Efficacy of Nebulized Magnesium Sulphate in Combination with Beta2

Agonist versus Beta2 Agonist Alone for Managing Acute Severe Asthma in Children:

A single-Blinded Randomised Clinical Trial

 Introduction:

Asthma is a major non communicable disease(NCD),affecting both children and adults and

its most common chronic disease among children. Inhaled medication can control asthma

symptoms &allow people with asthma to lead a normal active life. Most asthma related

deaths occur in low &lower middle income population where under diagnosis & under

treatment is a challenge.1Magnesium sulphate has been proposed as a possible additive

treatment in acute asthma & has been shown to be effective in severe acute asthma when

given intravenously.2It has been shown to relax smooth muscle by inhibiting calcium ion influx 3

, it also inhibits acetylcholine &histamine release from cholinergic motor nerve terminals &mast cells 4. Promotes nitric oxide synthesis 5. Brochodilation & vasodilation is stimulated by Prostacyclin 6. As magnesium ions have an anti inflammatory role, attenuatingneutrophil activation in children with asthma 7

  Objectives:

1. Evaluate and compare the therapeutic effectiveness of nebulised magnesium Sulfate

in conjunction with beta 2 agonists against the use of beta2 agonist Alone in the

management of moderate to severe asthma in children.

2. Investigate the safety profile and tolerability of nebulised magnesium Sulfate when

administered alongside beta2 agonists in the treatment of moderate to severe asthma

in children.

3. Assess the long term impact of the combined nebulised magnesium sulphate & beta 2

agonist treatment on the frequency and severity of asthma exacerbations in children.

 study design:

The study is Randomized controlled study involving two treatment group

The study participants of children age group between 5-18 years of both sex were randomly allocated to two treatment groups

Group A: Magnesium sulphate in addition to Beta 2 agonist

Group B: Beta2 agonist alones, will be conducted in Chettinad hospital and research institute ,chennai.

 sample size:

SPSS (Statistical Package For Social Sciences) version 20. (IBM SPASS statistics [IBM corp. released 2011] will be used to perform the statistical analysis

total sample size is 94& each group  is 47.

study procedure:

All children who meets the inclusion &exclusion criteria will be taking into the study after taking an informed assent& written consent  from the parents &participants . Detailed history will be taken & thorough physical examination will be done.

 STUDY METHODOLGY:

The study will be conducted after ethical committee approval. The eligible participants  with clinical features of  asthma will randomized into

Group A: Magnesium sulphate in addition to Beta 2 agonist

Group B: Beta2 agonist alone by using simple randomization technique.

Randomisation will be done using a computer generated simple randomization technique.

Each participant from each group will receive nebulization of 2.5ml of salbutamol & other group will receive 1ml of mgso4(1ml=50mg) + 3ml of sterile water+1.5 ml of salbutamol nebulization with tight fitting mask. the nebulization will be given by the investigator or by trained staffs with 8-10 litres of oxygen /minute. Nebulization will be continued till the child improves symptomatically. participants will receive the standard supportive treatment, such as supplemental oxygen, maintenance of hydration, and antipyretics as required. The clinical data (ASS,HR,oxygen saturation with pulse oximeter& need for supplemental oxygen)will be measured &recorded.in this study length of hospital stay &improvement in the asthma severity score will be considered as the primary outcome measure. it will be calculated as the number of days between the first dose of nebulization to the time at which the patient fulfilled the study discharge criteria, the discharge criteria includes child orally feeding well, no need for supplemental oxygen and intravenous fluids, absence of accessory muscle use or normal respiratory rate,and oxygen saturation>95% on room air.secondary outcomes include HR,oxygen saturation with pulse oximeter,need of supplemental oxygen &adverse events such as tachycardia>200, hypoxia, trembling, drop in saturation&dry mucosae.

 STUDY OUTCOME:

primary outcome measure: it will be calculated as the number of days between the first dose of nebulization to the time at which the patient fulfilled the study discharge criteria, the discharge criteria includes child orally feeding well,no need for supplemental oxygen and intravenous fluids,absence of accessory muscle use or normal respiratory rate,and oxygen saturation>95% on room air.

 secondary outcomes: include HR,oxygen saturation with pulse oximeter,need of supplemental oxygen &adverse events such as tachycardia>200, hypoxia,trembling,drop in saturation&dry mucosae.

  Ethical consideration:

once the child is clinically diagnosed with acute severe asthma, the parents will be explained regarding usage of mgso4 or salbutamol nebulization its mechanism of action ,side effects.after getting their informed written consent , their children will be enrolled in my study to compare the efficacy of nebulized mgso4 with beta 2 agonist &beta 2 agonist alone.

 REFERENCE:

1 Sarhan HA, El-Garhy OH, Ali MA, Youssef NA. The efficacy of nebulized magnesium

sulfate alone and in combination with salbutamol in acute asthma. Drug design,

development and therapy. 2016 Jun 9:1927-33.

2 Knightly R, Milan SJ, Hughes R, Knopp‐Sihota JA, Rowe BH, Normansell R, Powell

C. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database of

Systematic Reviews. 2017(11).

3 Gourgoulianis KI, Chatziparasidis G, Chatziefthimiou A, Molyvdas PA. Magnesium as

a relaxing factor of airway smooth muscles. Journal of aerosol medicine. 2001 Sep

1;14(3):301-7.

4 Del Castillo J, Engbaek L. The nature of the neuromuscular block produced by

magnesium. The Journal of physiology. 1954 May 5;124(2):370.