Study

Severity of asthma exacerbation

Diagnosis based on

Population (adult/mixed/paediatric)

MgSO₄ and SABA and Ipratropium bromide versus SABA and Ipratropium

Ashtekar 2008

Severe

BTS definition clinical features

Paediatric (2 to 16)

Drobina 2006

Unclear

PEF and clinical signs

Adults

Gallegos‐Solórzano 2010

Moderate to severe

FEV1 < 60%

Adults >18

Gaur 2008

Severe

FEV1 < 30%

Adults (18 to 60)

Goodacre 2013

Severe

BTS definition

Adult (≥ 16)

Hossein 2016

Moderate to severe

PEF < 70% and clinical signs

Adult (> 16)

Powell 2013

Severe after conventional treatment

BTS definition

Paediatric (2 to 16)

MgSO4 and SABA versus SABA

Abreu‐Gonzalez 2002

Moderate

FEV1 and PEF at baseline

Adults

Aggarwal 2006

Severe and life threatening

BTS definition clinical features and PEF

Mixed (13 to 60)

Ahmed 2013

Severe

PEF

Not documented

Alansari 2015

Moderate to severe

Clinical score

Paediatric (2 to 14)

Badawy 2014

Unclear

N/A

Adult

Bessmertny 2002

Moderate to severe

PEF between  40% to 80%

Adults (18 to 65)

Dadhich 2005

Severe

PEF < 50%

Adults

Hughes 2003

Severe

FEV1 < 50%

Adults (16 to 65)

Khashabi 2008

Unclear

Clinically defined as respiratory distress

Paediatric (mean age 3.55 years)

Kokturk 2005

Moderate to severe

Clinical scores and PEF

Adults (18 to 60)

Mahajan 2004

Moderate to severe

FEV1 between 45% and 75%

Paediatric (5 to 17)

Mohammedzadeh 2014

Moderate to severe

GINA definition

Paediatric (5 to 14)

Nannini 2000

Severe

PEF < 50%

Adult (> 18)

Sarhan 2016

Unclear

PEF < 300L/min

Mixed (11 to 70)

Turker 2017

Moderate

Not described

Children (3 to 15)

MgSO₄ versus SABA

Dadhich 2005

Severe

PEF < 50%

Adults

Mangat 1998

Moderate to severe

PEF < 300 L/Min

Mixed (12 to 60)

Meral 1996

Moderate to severe

PEF < 75%

Paediatric

Neki 2006

Severe

FEV1 < 40% or PEF < 300 L/Min

Adult (15 to 60)

Sarhan 2016

Unclear

PEF < 300L/min

Mixed (11 to 70)

Study

Presentation to which department?

Origin

Primary outcome(s)

Total n randomised

Side effects (patients in study)

Pharmaceutical exclusions

Other Interventions

MgSO₄ and SABA and Ipratropium bromide versus SABA and Ipratropium

Ashtekar 2008

Children’s Assessment Unit after GP referral

Cardiff, Wales

ASS (Yung)

17

1 tingling in fingers and 1 transient hypotension

None stated

All management followed the BTS/SIGN guidelines; all children received 2 mg/kg prednisolone

Drobina 2006

ED

USA

PEF, admissions

110

No comment on side effects in paper

Not stated

All subjects received 50 mg of oral prednisone at the onset of the treatment

Gallegos‐Solórzano 2010

ED

Mexico City, Mexico

% change FEV1,

O₂ post treatment, admission rates

112

Dry and bitter mouth (MgSO₄ group 1), dizziness (MgSO₄ 1; placebo 1)

Use of steroids prior to presentation

All participants received one IV dose of 125 mg methylprednisolone at admission and 1 mg/kg/day for 10 days prednisolone,on discharge. Other treatments were administered according to the treating physician

Gaur 2008

ED

Delhi, India

FEV1

60

None reported

None stated

All participants received IV hydrocortisone on arrival

Goodacre 2013

ED

UK

Admission within 7d, visual analogue scale for breathlessness at 2 h

703

AEs (41 MgSO₄/salbutamol; 36 placebo/salbutamol)

MgSO₄ in the past 24 h

All participants were managed according to BTS/SIGN guidelines (consisting of
oxygen, nebulised salbutamol (5 mg), nebulised ipratropium (500 μg), and oral prednisolone administered during recruitment, followed by up to 5 mg salbutamol added to each trial nebuliser. Other treatments were provided at the discretion of the clinician

Hossein 2016

ED

Tehran, Iran

PEFR improvement, admission rate

50

No serious side effects reported

None stated

All participants received 50 mg oral prednisolone

Powell 2013

ED and children's assessment units

UK

Yung asthma severity score

508

47 in MgSO₄ group and 59 in control group

None

Hospital‐defined conventional treatment

MgSO4 and SABA versus SABA

Abreu‐Gonzalez 2002

‐

Tenerife Spain

FEV1, PEF

24

None reported

None stated

Not stated

Aggarwal 2006

ED

New Delhi India

PEF

100

Palpitations (MgSO₄/salbutamol 13; salbutamol/placebo 11) and tremors (7; 7).

None stated

Clinicians free to administer steroids, salbutamol, IV hydrocortisone if judged to be required

Ahmed 2013

‐

Mymensingh, Bangladesh

PEF

120

None reported

None stated

Not stated

Alansari 2015

Paediatric emergency centre

Doha, Qatar

Time to readiness for discharge

400

Chest tightness and facial rash (MgSO₄/salbutamol 191), excessive cough (placebo/salbutamol 174)

None stated

All participants received methylprednisolone 1 mg/kg IV every 12h and additional nebulised albuterol at clinicians' discretion

Badawy 2014

Outpatient department and ED

Sohag, Egypt

Exacerbations post intervention, delivery outcome, post‐partum health status

60

None reported

None stated

All participants received 100 mg hydrocortisone IV, 500 mg aminophylline IV

Bessmertny 2002

ED

Brooklyn, USA

FEV1 (% pred)

74

No SAEs reported

No theophylline or anticholinergics 2 h prior to presentation

Intravenous hydrocortisone, 2 mg/kg
every 6 h, was administered to patients who failed to show an adequate improvement of pulmonary function after 3 initial doses of albuterol

Dadhich 2005

ED

Ajmer India

PEF

71

"Side effects were self limiting"

Not stated

Not stated

Hughes 2003

ED

Wellington New Zealand

FEV1

52

None reported

None

All participants received 100 mg hydrocortisone IV

Khashabi 2008

‐

Urmia, Iran

Reduced mean duration of O₂ therapy in MgSO₄ group,

no change in Respiratory Distress Score)

40

No side effects

Not stated

Not stated

Kokturk 2005

ED

Gazi, Turkey

PEF difference

26

Transient hypotension (1 MgSO₄), palpitation (1 salbutamol)

None

All participants received 1 mg/kg prednisolone. Theophylline, anticholinergics and salbutamol given at clinicians discretion

Mahajan 2004

ED

Detroit, USA

% change in FEV1

62

No side effects

Steroids, ipratropium or theophylline in the last 3 days.

All participants received 2 mg/kg of prednisone

Mohammedzadeh 2014

‐

Babol, Iran

Pulmonary index, PEFR, adjusted PEFR

80

‐

Corticosteroids; steroids, theophylline or ipratropium use within last 72 h

Not stated

Nannini 2000

ED

4 hospitals in Argentina

PEF, admissions

35

None reported

Oral or parenteral steroids in the last 7 days

No other medications were permitted during the study except
supplemental oxygen; if the patient’s condition worsened, a 2.5 mg dose of nebulized salbutamol was administered at the discretion of the treating physician

Sarhan 2016

Chest and ED

Minia, Egypt

Clinical improvement, PEFR

30

None severe enough to warrant withdrawal

Bronchodilators in last 6 h, steroids in last 12 h

Nebulised salbutamol, IV hydrocortisone, IV aminophylline at clinicians' discretion

Turker 2017

ED

Turkey

Modified pulmonary index score

100

"No side effect caused by magnesium was observed in any of the patients in the study"

Not stated

Nebulised salbutamol (0.15 mg/kg), methylprednisolone 1 mg/kg IV; Oxygen was given to patients with SaO2≤ 95%

MgSO₄ versus SABA

Dadhich 2005

ED

Ajmer India

PEF

71

"Side effects were self limiting"

Not stated

Not stated

Mangat 1998

ED

St John’s College, India

PEF, Fischl index score, admissions

33

Transient self limiting hypotension (1) palpitation (1) tremors (2) all in control group and only 1 transient hypotension in MgSO₄ group (33)

Oral parenteral bronchodilators (6 h) steroids (last 12 h)

All participants received 100 mg hydrocortisone IV

Meral 1996

‐

Izmir, Turkey

% change in PEF

ASS (Davies Leffert, Dabbous score)

40

No side effects

Beta2‐agonists or theophylline in the last 12 h

No other medication given

Neki 2006

‐

Amritsar Punjab

PEF, RR, Fischl index

40

‐

Oral, inhaled or parenteral steroids in last 12 h

All participants received 100 mg hydrocortisone IV

Sarhan 2016

Chest and ED

Minia, Egypt

Clinical improvement, PEFR

30

None severe enough to warrant withdrawal

Bronchodilators in last 6 h, steroids in last 12 h

Nebulised salbutamol, IV hydrocortisone, IV aminophylline at clinicians' discretion

Study (N)

Magnesium sulfate

Control

Dose

N

Co‐interventions

Dose

N

Co‐interventions

MgSO₄ and SABA and Ipratropium bromide versus SABA and Ipratropium

Ashtekar 2008

2.5 mL isotonic MgSO₄ (151 mg /dose)

7

500 mcg Ipratropium bromide

2.5 mg salbutamol or 5 mg salbutamol (depending on age) 3 times per h

2.5 mL of isotonic saline)

10

Same as for MgSO₄ group

Drobina 2006

150 mg MgSO₄ (0.3 mL of 50% MgSO₄ heptahydrate)

60

Albuterol sulfate (0.5%) 5 mg/mL) and 0.5 mg ipratropium bromide (0.02% inhalation solution) (frequency*)

No placebo so volume will be less: i.e. blinding may be an issue)

50

Same as for MgSO₄ group

Gallegos‐Solórzano 2010

3 mL (333 mg) of 10% isotonic MgSO₄ (1 g/10 mL)

60 (30 withdrawals)

2.5 mg albuterol and 500 mcg ipratropium 3 doses per hour

3 mL isotonic saline

52 (22 withdrawals)

Same as for MgSO₄ group

Gaur 2008

3 mL (3.2 g%)

isotonic MgSO₄

30

Salbutamol and ipratropium (dose*, frequency*)

Saline

30

Same as for MgSO₄ group

Goodacre 2013

2 mmol MgSO₄

339 (7 withdrawal)

7.5 mL 0.9% NaCl nebulised, 3 doses; 100 mL 0.9% NaCl IV once, BTS/SIGN standard treatments plus others at clinicians' discretion

7.5 mL 0.9% saline nebulised, 3 doses, 100 mL 0.9% NaCl IV once

364 (7 withdrawal)

BTS/SIGN standard treatments plus others at clinicians' discretion

Hossein 2016

3 mL (260 mmol/L) MgSO4

25

2.5 mg salbutamol, 0.5 mg ipratropium nebulised every 20 to 60 minutes, 50 mg oral prednisolone (once*)

3 mL 0.9% NaCl

25

Same as for MgSO₄ group

Powell 2013

2.5 mL 250 mmol/L MgSO₄

252 (13 withdrawals)

3 doses every 20 min. Hospital‐defined conventional treatment

2.5 mL isotonic saline

256 (10 withdrawals)

Same as for MgSO₄ group

MgSO4 and SABA versus SABA

Abreu‐Gonzalez 2002

2 mL MgSO₄ (isotonic)

13

400 mcg salbutamol

(once*)

2 mL of a physiological serum of an inhaled form

11 patients

11

400 mcg salbutamol

Aggarwal 2006

1 mL of 500 mg/mL MgSO₄

50

1 mL salbutamol (dose*, 8 mL distilled water, (295 mOsml/kg) 3 times per h

ultrasonic nebuliser

7.5 mL normal saline

50

1 mL salbutamol (dose*),

1.5 mL distilled water

(287 mOsml/kg) 3 times per h

Ahmed 2013

MgSO₄ (dose* frequency*)

60

Not recorded

Normal saline (dose* frequency*)

60

Not recorded

Alansari 2015

800 mg (15 mL) MgSO₄

208 (17 withdrawals)

5 mg albuterol, divided into 3 doses over 1 h. Methylprednisolone 1 mg/kg IV every 12 h. 3 doses nebulized 1 mL albuterol (5 mg/mL), 250 mcg ipratropium, 2 mL normal saline before trial doses started

15 mL 0.9% NaCl

192 (18 withdrawals)

Same as for MgSO₄ group

Badawy 2014

500 mg (1mL) MgSO₄

30

1 mL salbutamol solution (dose*), 8 mL 0.9% NaCl, max 3 doses with 20 mins apart. 100 mg hydrocortisone IV, 500 mg aminophylline IV (once*)

1 mL 0.9% NaCl

30

Same as for MgSO₄ group

Bessmertny 2002

MgSO₄ (384 mg)

37 (3 withdrawals)

Followed by ( i.e. not mixed) albuterol 2.5 mg/mL 3 times per h

Normal saline (no volume documented)

37 (3 withdrawals)

Same as for MgSO₄ group

Dadhich 2005

MgSO₄

26

No doses in any group or co‐interventions described

Not stated

24

No doses in any group or co‐interventions described

Hughes 2003

2.5 mL isotonic MgSO₄ (250 mmol/L 151 mg)

28 patients

28

2.5 mg salbutamol 3 times per

30 minutes

2.5 mL normal saline

24

Same as for MgSO₄ group

Khashabi 2008

Isotonic MgSO₄

(dose*, frequency*)

*

Salbutamol (dose*)

2.5 mL normal saline (frequency*)

*

Same as for MgSO₄ group

Kokturk 2005

Isotonic MgSO₄ (2.5 mL)

14

Salbutamol (dose*) 3

times per h then 1 per h for 3 h

2.5 mL normal saline

12

Same as for MgSO₄ group

Mohammedzadeh 2014

3 mL 7.5% MgSO₄

40

0.15 mg/kg salbutamol 3 doses, every 20 min

3 mL normal saline

40

Same as for MgSO₄ group

Mahajan 2004

2.5 mL Isotonic (6.3%) MgSO₄ solution

31

Albuterol 2.5 mg 1 dose

2.5 mL normal saline

31

Same as for MgSO₄ group

Nannini 2000

3 mL isotonic MgSO₄

(286 mOsml, 7.5%, 225 mg)

19

0.5 mL 2.5 mg salbutamol

1 dose*

3 mL normal saline

16

Same as for MgSO₄ group

Sarhan 2016

2.5 mL MgSO4 (100 mg), 0.5 mL salbutamol (2.5 mg)

10

4 doses at 20 min intervals. If needed: additional nebulised salbutamol, IV hydrocortisone, IV aminophylline

2.5 mL isotonic saline

10

Same as for MgSO4 group

Turker 2017

1 mL magnesium sulfate (15%) + 1.5 mL isotonic saline

50

3 doses at 20 min intervals. Also nebulised salbutamol (0.15 mg/kg), methylprednisolone 1 mg/kg IV; Oxygen was given to patients with SaO2 ≤ 95%

1.5 mL isotonic saline

50

Same as for MgSO₄ group

MgSO₄ versus SABA

Dadhich 2005

MgSO₄

21

No doses in any group or co‐interventions described

Not stated

24

No doses in any group or co‐interventions described

Mangat 1998

3.2% solution MgSO₄ = 95 mg)

16

4 doses every 20 minutes

3 mL (2.5 mg) salbutamol

17

Four doses every 20 minutes

Meral 1996

2 mL MgSO₄ (280 mmol/L)

20

1* dose given over 10 to 15 minutes

Salbutamol 2.5 mg in 2.5 mL

20

1 dose* given over 10 to 15 minutes

Neki 2006

20 patients

3.2 G % MgSO₄

20

4 doses every 20 min

3 mL of 25 mg* salbutamol (likely decimal point missing)

20

Same as for MgSO4 group

Sarhan 2016

3 mL (100 mg) MgSO4

10

4 doses at 20 min intervals. If needed: additional nebulised salbutamol, IV hydrocortisone, IV aminophylline

0.5 mL salbutamol (2.5 mg)

10

Same as for MgSO₄ group

TOTAL: 2907 randomised to comparisons of interest. 130 withdrawn, 2777 completed

TOTAL: 1476 randomised, 70 withdrawn = 1406 completed intervention

TOTAL: 1431 randomised, 60 withdrawn = 1371 completed control

Study ID (author, date of publication)

Review primary outcomes

Review secondary outcomes

FEV1

PEF

Clinical severity scores

Hospital admissions

Duration of symptoms

Vital signs

Adverse effects

MgSO₄ and SABA and Ipratropium bromide versus SABA and Ipratropium

Ashtekar 2008

N

N

Y

N

N

N

Y

Drobina 2006

N

P

N

N

N

N

P

Gallegos‐Solórzano 2010

Y

N

N

N

N

N

Y

Gaur 2008

Y

N

N

N

N

N

N

Goodacre 2013

N

Y

N

Y

N

Y

Y

Hossein 2016

N

Y

Y

Y

N

Y

N

Powell 2013

N

N

Y

P

N

N

Y

MgSO4 and SABA versus SABA

Abreu‐Gonzalez 2002

Y

Y

N

N

N

N

N

Aggarwal 2006

N

Y

N

Y

N

Y

Y

Ahmed 2013

N

P

N

N

N

N

N

Alansari 2015

N

N

Y

P

N

N

Y

Badawy 2014

Y

Y

N

N

N

Y

N

Bessmertny 2002

P

N

N

N

N

N

Y

Dadhich 2005

P

P

N

N

N

N

Y

Hughes 2003

Y

N

N

Y

N

N

Y

Khashabi 2008

N

N

N

N

N

N

N

Kokturk 2005

N

Y

P

Y

N

N

Y

Mahajan 2004

Y

N

N

Y

N

N

Y

Mohammedzadeh 2014

N

Y

Y

N

N

N

N

Nannini 2000

N

Y

N

Y

N

N

Y

Sarhan 2016

N

Y

Y

N

N

Y

N

Turker 2017

N

N

Y

Y

N

N

Y

MgSO₄ versus SABA

Dadhich 2005

P

P

N

N

N

N

Y

Mangat 1998

N

Y

N

Y

N

N

Y

Meral 1996

N

Y

N

N

N

N

Y

Neki 2006

N

Y

N

N

N

Y

N

Sarhan 2016

N

Y

Y

N

N

Y

N