Research Article

Intravenous Magnesium Sulphate: An Effective Therapy for Acute Severe Attack of Bronchial Asthma

Muhammad Shahid Saeed1, Adeela Shahid2, Samia Jawed3, Muhammad Akram4, Irshad Hussain Qureshi5

1Assistant Professor of Physiology, King Edward Medical University, Lahore; 2Professor of Physiology, Shalimar Medical & Dental College, Lahore; 3Chairperson/ Professor of Physiology, King Edward Medical University, Lahore; 4Professor of Physiology, Poonch Medical College, Rawalakot, AJ&K; 5Registrar, KEMU, Professor & Head of East Medical Ward, KEMU/ Mayo Hospital, Lahore, Pakistan.

Received | January 02, 2016; Accepted | January 10, 2018; Published | April 28, 2018

*Correspondence | Dr. Shahid Saeed, King Edward Medical University, Lahore; Email: shahid.saeed1@hotmail.com

Citation | Saeed, M.S., A. Shahid, S. Jawed, M. Akram, I.H. Qureshi. 2018. Intravenous magnesium sulphate: An effective therapy for acute severe attack of bronchial asthma. Annals of King Edward Medical University, 24(1): 7-12.

DOI | https://doi.org/10.21649/akemu.v24i1.2364

Keywords | Asthma, I/V magnesium sulphate, FEV1, PEFR

Introduction

 

Bronchial asthma is chronic inflammatory conditions of respiratory tract, which inflames and narrows the airway passages. It is associated with recurrent attacks of wheezing and cough, which may vary from person to person (1). National Heart, Lung and Blood Institute (NHLBI) states “Bronchial asthma is a chronic inflammatory condition of the air passages in which a number of cells play an important role, especially eosinophils, neutrophils, T-lymphocytes, macrophages, mast cells and epithelial cells” (2).

There is a persistent increase in asthma patients among children around the world in last decade (3). According to the Center for Disease Control and Prevention (CDC), 9.5% of children and 8.2% adults had asthma in 2011 in the United States (4).

According to Global Initiative for Asthma (GINA), 250,000 patients succumbed due to asthma every year throughout the world (5). In Singapore, about 140,000 peoples are the sufferers of the disease and death toll is 100 per annum (6). The prevalence of asthma in Pakistan and central Asia is 4-5% (7).

The interaction between environmental and genetic components plays an important role in the pathogenesis of asthma (8,9,10). It has been observed that genetics of the person play a big role in development of asthma however it is effective only when environmental factors are helpful otherwise risk of disease is minimized (11).

The gold standard treatment is Salbutamol inhalation along with oxygen therapy aided by anticholinergic drugs and I/V steroids. It was observed that in some asthmatics, the effects of standard drugs were not up to the mark. In such patients, there was a need of different agents and in this search MgSO4 attracted the attention of researchers and practitioners. Magnesium (Mg++) is an important intracellular inorganic element and paly important roles in the body. The serum concentrations of Mg++may not precisely reflect the total body Mg++(12). It is involved in a number of metabolic reactions in the body by acting as a cofactor (13).

 

Materials and Methods

 

A total of 132 asthmatic subjects between 18-60 ages with FEV1 ≤ 30% predicted presented with acute attack in the Emergency Department (ED) of Mayo Hospital, Lahore. The study was approved by the Advance Study and Research Board of King Edward Medical University Lahore along with ethical permission and provision of funds. Patients with emphysema, chronic bronchitis, congestive cardiac failure chronic renal insufficiency, and pneumonia were excluded from the study.

It was a placebo-controlled, randomized, double blinded study.

Written informed consent to participate in the study was obtained from each subject. Patients with the FEV1 ≤ 30% predicted by Spirometry in the ED by Spirolab III were selected for study. A careful history of disease was taken covering present and past history along with family history of the illness. Complete general physical examination (GPE) was done, body weight (BW), height, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressures were determined according to the standard procedures (14). Intensity and severity of breathlessness was measured by modified Borg scale (15).

The study population was divided into two groups:

• Study group given I/V MgSO4 (n=66)
• Control group given placebo (n=66)

After spirometry, both groups received Salbutamol (2.5 mg) inhalation through nebulizer and followed by intravenous injection of 250 mg of IV hydrocortisone. The study group was given 2 gm of MgSO4 in 50 ml of 0.9% normal saline solution I/V slowly over 20 min and a placebo (50ml of 0.9% normal saline) was given to control group. This time was taken as 0 min. Spirometry was performed on emergency department arrival, at 30min and 180 min after giving I/V MgSO4 or placebo to check the response in two groups.

A total of 0.5 mL of 0.5% salbutamol (2.5 mg) via wet nebulizer with 100% oxygen inhalation was given again after 30 min. Clinical assessment of respiratory system was made and spirometry was performed prior to each treatment and again at 180 min and the results were recorded. The aim of spirometry was to determine the effects MgSO4 or placebo in the two groups. Any complaint of the patients was noted.

After treatment of 180 min, hospitalization or discharge the patients depended upon their condition. The criterion of hospitalization was if the patient’s FEV1 < 50% predicted, respiratory rate ≥ 22 breaths/min and there was no positive change in the condition of patient without any improvement in shortness of breath or wheezing.

The data collected was analyzed by SPSS version 17.0 (SPSS, Inc. Chicago, IL, USA). All the variables, which were quantitative, expressed as mean ± standard deviation (SD). General Linear Model test, one way Anova to compare different variables and finally Student’s t-test was applied to observe the differences between study and control groups. A p-value of < 0.05 was taken as significant statistically.

 

Results

 

A total of 132 patients were screened during this study. In the study group (I/V MgSO4) out of 66 patients, five were unable to complete the study protocol up to 180min. In the control group, 66 patients were included and three among those were unable to complete the protocol.

Mean respiratory rate was 22/min on arrival in ED in both groups. There was no significant difference (p>0.05, Table 1) in the respiratory rate between magnesium (study) group and placebo (control) group on arrival in ED (0 min). There was no significant decrease in respiratory rate after 30min in both groups. After 180 min, there was significant (p<0.05) decrease in the respiratory rate in the study group as compared to control group (Table 2 and 3). When magnesium group was compared at 0 min and 180 min, there was significant decrease in the respiratory rate 180 min after I/V Mg SO4 was given.

Borg scale was 7.5 on arrival in ED in both groups. There was no significant difference in the Borg scale at 0 min in ED arrival between study and control group (P>0.05, Table 3). There was significant decrease (p<0.05) in Borg scale after 30min and 180 min of treatment in magnesium treated group as compared to placebo (Table 2 and 3). There was significant decrease in the Borg scale at 0 min in ED and 180 min after magnesium treatment.

There was no statistically significant (p 0.54) difference in the FEV1 of both study and control groups at 0 min in ED arrival (Table 3 and 4). There was non-significant increase in FEV1 in magnesium treated group as compared to placebo after 30 min (p 0.72, Table 3). There was significant (p 0.004) improvement in FEV1 in magnesium treated group compared to placebo group as after 180 min (Table 4). There was 1.06 L increase in FEV1 in magnesium treated group after 180 min compared to 0.8 L in placebo group.

There was no significant (p>0.05) difference in the FEV1 % predicted of both study and control group at 0 min in ED arrival (Table 3 and 4). There was non-

 

Table 1: Clinical Parameters in two groups on ED arrival (0min), 30 min and 180 min after treatment

Variables	0 min		30 min		180min
	Placebo	Magnesium	Placebo	Magnesium	Placebo	Magnesium	P value
Respir atory rate/min	22.06± 2.29	22.33±2.38	21.43± 2.84	21.77±2.38	20.9± 2.25	17.85± 2.69*	<0.001*
Pulse rate/min	95.46± 4.9	95.5±5.23	98.95± 4.39	98.18±3.08	99.9± 3.59	99.82± 2.86	0.821
Systolic BP (mm Hg)	137.6± 7.44	137±5.29	136.9± 6.9	136.01±4.4	136.14 ±0.5	137±3.5	0.74
Diastolic BP (mm Hg)	85.05± 3.33	84.74±3.44	84.90± 3.93	85.03±4.21	84.43 ±4.38	83.93± 5.09	0.563
Borg scale	7.60± 0.79	7.59±0.99	5.65± 0.73	5.20±0.92*	3.45± 0.90	2.53± 0.45*	<0.001*

Data are presented as mean ± SD. Placebo and magnesium groups were compared at 0 min, 30 min and 180 minby‘t’ test. P* value <0.05 was statistically significant.

 

Table 2: Clinical Parameters in two groups on ED arrival (0 min) and 180 min after treatment

Variables	0 min			180min
	Placebo	Magnesium	P value	Placebo	Magnesium	P value
Respiratory rate/min	22.06±2.29	22.33±2.38	0.53	20.9±2.25	17.85±2.69	<0.001*
Pulse rate/min	95.46±4.9	95.5±5.23	0.887	99.9±3.59	99.82±2.86	0.821
Systolic BP (mm Hg)	137.6±7.44	137±5.29	0.955	136.14±0.5	137±3.5	0.74
Diastolic BP (mm Hg)	85.05±3.33	84.74±3.44	0.611	84.43±4.38	83.93±5.09	0.563
Borg scale	7.60±0.79	7.59±0.99	0.975	3.45±0.90	2.53±0.45	<0.001*

Data are presented as mean ± SD. Placebo and magnesium groups were compared at 0 min and 180 min by ‘t’ test. P* value <0.05 was considered statistically significant.

 

significant increase in FEV1 % predicted in study group as compared to placebo after 30 min (p 0.72, Table 3). The mean FEV1 at 180 min in the study group was 47.75 % predicted compared to 43.52% of predicted as in the placebo-treated group, which was statistically (p 0.004) significant (Table 4). There was 26.03% increase in FEV1 % predicted in magnesium treated group (from 21.72 % to 47.75%) after 180 min compared to 22 % (from 21.50% to 43.5%)in placebo group.

 

PEFR of both study and control group at 0 min in ED arrival was not significantly (p 0.58) different (Table 3 and 4). There was significant improvement in PEFR (160L/min) in magnesium treated group as compared to placebo (157L/min) at 30 min (p<0.05, Table 3 and 4). PEFR showed significant improvement in magnesium treated group (263L/min) as compared to placebo (227L/min) group at180 min (p 0.004), Table 4). There was improvement in PEFR of 124 L/min (from 139 L/min to 263L/min) after180 min in the magnesium treated group compared to the placebo group in which mean improvement in PEFR was 87L/min (from 140L/min to 227L/min)

PEFR % predicted of both study and control group at 0 min in ED arrival was not significantly (p 0.73) different (Table 3 and 4). There was significant increase in PEFR % predicted in magnesium treated group as compared to placebo at 30 min (p<0.05, Table 3 and 4). There was significant improvement in PEFR % predicted of magnesium treated group as compared to placebo group at 180 min (p 0.001, Table 4 and Figure 3).

 

Table 3: Pulmonary Function Test in two groups on ED arrival (0min), 30 min and 180 min after treatment.

Variables	0 min		30 min		180min
	Placebo	Magnesium	Placebo	Magnesium	Placebo	Magnesium
FEV1 (L)	0.78±0.08	0.77±0.06	0.98±0.15	1.01±0.19	1.58± 0.55	1.83±0.38*
FEV1% predicted	21.50±3.97	21.72±2.80	29.43±4.15	29.98±4.19	43.5± 4.2	47.75±3.20*
PEFR (L/min)	140±6.07	139±4.36	157±6.22	160±12.11*	227± 24.4	263±32.23*
PEFR % predicted	30.64±2.34	30.49±2.80	35.94±2.69	37.49±4.08*	48.78 ±8.01	59.87±7.45*

Data are presented as mean ± SD. Placebo and magnesium groups were compared at 30 min and 180 min by ‘t’ test. P* value <0.05 was statistically significant.

 

Table 4: Pulmonary Function Test in two groups on ED arrival (0min) and 180 min after treatment.

Variables	0 min			180 min
	Placebo	Magnesium	p- value	Placebo	Magnesium	P-value
FEV1(L)	0.78±0.08	0.77±0.06	0.54	1.58±0.55	1.83±0.38*	0.004*
FEV1 % predicted	21.50±3.97	21.72±2.80	0.72	43.5±4.2	47.75±3.20*	<0.001*
PEFR (L/min)	140±6.07	139±4.36	0.58	227±24.4	263±32.23*	<0.001*
PEFR % predicted	30.64±2.34	30.49±2.80	0.73	48.78±8.01	59.87±7.45*	<0.001

Data are presented as mean ± SD. Placebo and magnesium groups were compared at 0 min and 180 min by ‘t’ test. P* value <0.05 was considered statistically significant.

 

There was improvement in PEFR % predicted of 29.38% (from 30.49% to 59.87%) after180 min in the magnesium treated group compared to the placebo group in which mean improvement in PEFR% predicted was 18.14% (from 30.64% to 48.78%). When GLM model was applied, it further confirmed that independent of age and sex,the effect of I/V magnesium on pulmonary function (FEV1, FEV % predicted, PEFR, PEFR% predicted) and compared to placebo was significantly greater (p 0.004 ,0.001 .0.001 & 0.001, respectively) in patients at 180 min of the study protocol.

The overall hospital admission rate at 180 min was not significantly different in patients receiving magnesium (18 of 61 patients) or placebo (20 of 63 patients) group.

 

Discussion

 

In the present study, a total of 132 adult subjects with acute severe asthma were analyzed to determine the role of I/V Mg SO4 when given as an adjunct to standard asthma treatment on pulmonary function test. There was no statistically significant difference in the age, body weight, height, BMI, respiratory rate, pulse rate, SBP, DBP and Borg dyspnea scale on ED arrival between the magnesium treated group and placebo group in the present study.

It was found in the present study, that 2 g of IV MgSO4 when given as an adjunct to standard asthma treatment significantly improves pulmonary functions in adults. The results of previous studies investigating the role of IV MgSO4 in severe asthma have reported controversial results; data is available suggesting the use of magnesium in treating acute severe asthma (16.17). It has been reported in many studies to be useful in children (18,19,20), whereas available data in adults have revealed controversial results (21,22,23,24). There was no decrease in SBP and DBP in both groups in the present study; however respiratory rate and Borg dyspnea scale showed significant decrease in the present study in magnesium treated group at 180 min. There was increase in the pulse rate at 180 min as compared to the time in ED arrival in both groups, the increase in pulse rate might be due to repeated salbutamol nebulization at 0 min, 30min, 60 min, and 120 min in the present study.

A previous study has reported that when 2gm of I/V MgSO4 was given along with salbutamol nebulization, there was no significant improvement in PEFR and hospital admission rates in patients with acute asthma(22). Later on in another study, Tiffany et al (21) have reported that there was no significant improvement in PEFR and FEV1 when I/V MgSO4 was given in moderate to severe asthma, but surprisingly when given in severely ill patients there was a remarkable improvement in lung functions as compared to placebo.

The current study revealed significant improvement in PEFR after I/V MgSO4 was given along with salbutamol but no significant improvement was observed in placebo group. Similar results have been reported in a previous study, when 1.2 g of magnesium or placebo was given in patients with moderate-to-severe airway obstruction, significant improvement occurred in PEFR.  Whereas Aggrawal et al (23) have reported significant rise in PEFR in both groups i.e. magnesium treated group and placebo group with no significant difference in PEFR between these groups when magnesium was given along with conventional asthma treatment Another study reported that when 1.2 gm I/V MgSO4 was given it resulted in no improvement in % predicted PEF at 60 min and decrease in hospital admission rates in acute asthma (23). These differences in the results might be due to different doses of MgSO4 used in different studies.

In the present study, there was 1.06 L increase (from 0.78 to 1.83) in FEV1 in magnesium treated group at 180 min as compared to 0.8 L (from 0.7 to 1.58) in placebo group. Overall, patients receiving IV MgSO4 had a final FEV1 of 47% predicted (from 22% to 47.5%) compared to 43.5% (from 21.50% to 43.5%) predicted for patients receiving placebo. In the present study there was 26.03% increase in FEV1 % predicted in magnesium treated group at 180 min as compared to 22 % in placebo group (mean difference= 4.03%). Likewise, Singh et al (24) reported increase in percentage of FEV1 predicted (40.7+/-9.2% in magnesium groups 34.77+7.3% in placebo group) at 120 minutes in adults (mean difference= 6.07%).

The modified Borg scale for rating dyspnea decreased from 7.59±0.99 to 2.53±0.45 in the magnesium group after 180 min in the present study whereas the peak flow increased significantly. This finding indicated that there was a significant correlation between the change in modified Borg scale for rating dyspnea scores and the change in PEFR in the magnesium treated group. There was a significant improvement in PEFR from 139 + 4.36 to 263+ 32.23 a previous study has reported similar results with significant correlation between modified Borg scale for rating dyspnea and PEFR (25).

The finding of the present study that IV MgSO4 did not decrease hospital admission rates is in accordance with the previous report by Silverman et al (26), whereas Singh et al (24) have reported that IV MgSO4 decreased the hospital admission rates.

The present study reported definite role of I/V MgSO4 in asthmatic patients whereas Green and Rothrock have reported no improvement in the patients who received 2gm of I/V MgSO4 as adjunct in addition to conventional treatment. There was no decrease in SBP and DBP in both groups in the present study; however respiratory rate and Borg dyspnea scale showed significant decrease in the present study in magnesium treated group at 180 min. There was increase in the pulse rate at 180 min as compared to the time in ED arrival in both groups, the increase in pulse rate might be due to repeated salbutamol nebulization at 0 min, 30min, and 180 min, in the present study.

A previous study has reported that when 2gm of I/V MgSO4 was given along with salbutamol nebulization, there was no significant improvement in PEFR and hospital admission rates in patients with acute asthma. Later on in another study, Tiffany et al (21) reported that there was no significant improvement in PEFR and FEV1 when I/V MgSO4 was given in moderate to severe asthma, but surprisingly when given in severely ill patients there was a remarkable improvement in lung functions as compared to placebo.

The beneficial effects of I/V MgSo4 observed during attack of asthma proves the importance of the adjunct and effects are mediated by inhibition of Ca entry in the smooth muscles of bronchi. As far as level of MgSO4 in serum is concerned it does not match with true level inside the cells. Sometimes serum level is normal but still deficiency at cellular level. It is not confirmed that effects of MgSO4 are either due to replenish of deficiency or due to its known mechanisms of actions. In short it is proved by the study that there is a definite and confirmed role of MgSO4 in the treatment of asthma and it shows it’s effects through the improvement in lung functions.

 

Conclusion

 

Upon studying variables specially the pulmonary function test, a tremendous improvement in the study group as compared to the control was observed. Moreover the qualitative parameters such as breathlessness improved more in study group as compared to control group. On this basis, it can be concluded that use of intravenous MgSO4 along with conventional treatment may prove beneficial to the asthmatics.

 

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