# Green et al. 1992 Intravenous Magnesium for Acute Asthma: Failure to Decrease Emergency Treatment Duration or Need for Hospitalization Annals of Emergency Medicine (217 prior to exclusion) 120 participants (58 in magnesium group and 62 in control group) Description: Patients presenting with acute exacerbation of asthma to ED. Exclusion Criteria: Atherosclerotic heart disease, angina, chest pain, uncontrolled hypertension, congestive heart failure, heart block, metastic cancer, renal disease, temperature above 38.3 degrees celsius, systolic BP < 120mm Hg, pregnancy, radiographic evidence of pulmonary disease, requiring mechanical ventilation in ED, or hospitalization. Age = 40.0 IV mag, 39.8 control, Gender = 79% female IV mag, 74% female control, Ethnicity = 59% white IV mag, 64% white control, 33% hispanic IV mag, 21% hispanic control, 5% black IV mag, 10% black control. Standard of Care: Oxygen, 125 mg IV methylprednisolone, albuterol. Treatment: Patients on odd days given 2g magnesium sulfate diluted in 50mL D5W IV over 20 minutes - given immediately after methyl-prednisolone administration and within 45 minutes of treatment initiation. Alternative Therapy: Other therapy (E.g. theophylline, injectable B- agonists or EP) up to physician. Outcome Design Hospitalization Days in Hospital ED Treatment Time (min) Absolute Change in PEF (L/min) Relative Change in PEF (%) 22% in Magnesium group (95%CI 13-32), 17% in control (95%CI 10-26), p = 0.523 Prospective Randomized Clinical Trial 1) Physicians were not blinded to patient randomization but patients and respiratory therapists were unaware that a study was being performed (-1) No Deductions No Deductions No Deductions No Deductions Moderate (3) 2.4 +/- 1.5 IV mag, 2.1 +/- 0.7 control, p = 0.525 " " " " " " " " " " " " Moderate (3) 224 +/-75 IV mag (95%CI 208-240), 228 +/- 90 control (95%CI 209-247), p = 0.832 " " " " " " " " " " " " Moderate (3) 122 +/- 75 IV mag (95%CI 106-138), 133 +/- 82 control (95%CI 116-150), p = 0.419 " " " " " " " " " " " " Moderate (3) 103 +/- 91 IV mag (95%CI 83-123), 123 +/- 26 control (95%CI 101-145), p = 0.272 " " " " " " " " " " " " Moderate (3)
Skobeloff et al. 1989 # Intravenous Magnesium Sulfate for the Treatment of Acute Asthma in the Emergency Department JAMA (40 - prior to exclusion) 38 entered in study (19 in each group) Description: Patient presenting to ED with acute asthma exacerbation. Exclusion criteria: Rectal temperature > 38 degrees celsius, SBP < 120mmHg, history of kidney disease, purulent sputum, infiltrate on chest roentgenogram, pregnancy, average PEFR over 200L/min. Age = 39.9+/-12.4 IV mag, 36.2+/-11.5 control, Gender = unclear, Ethnicity = 89% black, 0% white for both IV mag and control. Moderate to Severe Asthma Standard of Care: Patients (PEFR < 200 L/min) given nebulized metaproterenol sulfate (0.3 ml in 3.0mL of saline) or albuterol sulfate (0.5mL in 2.5mL of saline) based on physician decision as well as 125 mg of methylprednisolone intravenously. Theophylline (0.5mg/kg/hr maintenance infusion). Post 1st nebulization, 45-60min later 2nd nebulization given. 15min later obtained PEFR. Patients who did not double their PEFR = poor responders and were randomized. Treatment: Infusion 1.2g of magnesium sulfate in 50mL of saline over 20min. Control: Saline placebo in 50mL of saline over 20min. Outcome Design Peak Expiratory Flow Rate Admission Figure 1 - Significant results however difficult to quantify - may need to contact author. Significant difference (0.043), main effects with time (p<0.001), group by interaction (p<0.05) Randomized, doubleblind, placebo-controlled trial No Deductions Low dose of Ivmag compared to norm (1.2g vs. 2.0g) (-1) No Deductions Few participants (19) (-1) No Deductions Low (2) 15/19 of placebo group required admission whereas only 7/19 for IV mag. (p<0.01) " " " " " " " " " " " " Low (2)
# Bloch et al. 1995 Intravenous Magnesium Sulfate as an Adjunct in the Treatment of Acute Asthma Chest (149 - prior to exclusion) 135 in final analysis (67 in mg, 68 in placebo) Description: Patients presenting to ED with acute asthma and FEV-1 < 75% predicted before/after albuterol. Exclusion Criteria: History of congestive heart failure, diabetes mellitus, angina, chronic renal insufficiency, temperature >38 degrees celsius, pneumonia, pregnant, requiring intubation, unable to perform spirometry, unable to give informed consent, FEV1 was >/= to 75% predicted, on presentation/post-albuterol. Age = 36+/-12.7 Mg, 38.6+/-13.2 placebo, Gender(%female) = 73% Mg, 71% placebo, Ethnicity = N/A Severe = < 25% predicted FEV1, Moderate = 25-75% predicted FEV1 Standard of Care: Nebulised albuterol (2.5mg in 2.5ml). Given 125mg methylprednisolone if % predicted FEV1 <40% or those who had received oral prednisone within 6 months of study. Treatment: At 30min, randomized to 2g IV magnesium sulfate or 50ml Saline IV (placebo). Outcome Design Admission rates 35.3% in the placebo group and 25.4% in the MgS04 group p = 0.21 Double Blind, randomized control trial " " " " " " " " " " High (4) % predicted FEV1 at 120min 56% placebo, 55% MgS04; p=0.92 " " " " " " " " " " " " High (4) Admission rates - severe group % predicted FEV1 at 120min - severe group Admission rates - moderate group % predicted FEV1 at 120min - moderate group Side effects 78.6% in the placebo group and 33.3% in the MgS04 group p = 0.009 " " " " " " " " " " " " High (4) Fig 1 - deemed to be significant impact in favor of MgSO4 " " " " " " " " " " " " High (4) 22.4% in the placebo group and 22.2% in the MgS04 group p = 0.98 " " " " " " " " " " " " High (4) Fig 1 - deemed to be non-significant in favor of MgSO4 " " " " " " " " " " " " High (4) No life-threatening noted, 58% of MgSO4 patients noted minor side-effects " " " " " " " " " " " " High (4)
# Ciarallo et al 1996 Intravenous magnesium therapy for moderate to severe pediatric asthma: of a randomized, placebo-controlled trial The of Pediatrics 31 patients, 15 in Ivmag, 16 in placebo Description: Patients (6-18 yo) with acute asthma presenting to ER with PEFR < 60% predicted following 3 B-agonist nebuliser treatments. Exclusion Critieria: PEFR > 60% predicted post 3 b-agonist nebulizer treatments. T > 38.5 C, systolic BP < 25th percentile for age, history of cardiac, renal or pulmonary disease, pregnancy, or recent theophylline. Age = 10.8+/-3.6 for IVmag, 11.9+/-3.6 placebo, Gender(% male) = 46.6% IVmag, 43.8% placebo, Ethnicity =N/A Standard of care: Patients given oxygen, nebulized beta-agonists (0.15mg/kg in 3ml of saline). About 75% received intravenous methylprednisolone. Treatment:IV magnesium sulfate, 25mg/kg (maximum 2g) over 20min, Control: equal volume of saline solution over 20 min. Outcome Design % of improvement in PEFR 80min post Ivmag 46% Ivmag, 16% placebo (p = 0.05) Randomized, doubleblind, placebo-controlled, clinical trial No Deductions No Deductions No Deductions Few participants (-1) No Deductions Moderate (3) % of improvement in PEFR 110min post Ivmag 59% Ivmag, 20% placebo (p = 0.05) " " " " " " " " " " " " Moderate (3) PEFR <60% predicted at end of observation period IV mag 4/15, placebo 11/16 (p=0.02) " " " " " " " " " " " " Moderate (3) FEV1 improvement at 50min 34% Ivmag, -1% placebo; p = 0.05 " " " " " " " " " " " " Moderate (3) FEV1 improvement at 80min FEV1 improvement at 110min FVC improvement at 80min Fig. 2 -Values difficult to deduce, in favor of Ivmag; p = 0.01 " " " " " " " " " " " " Moderate (3) Fig. 2 - Values difficult to deduce, in favor of Ivmag; p = 0.01 " " " " " " " " " " " " Moderate (3) Values difficult to deduce, in favor of Ivmag; p = 0.05 " " " " " " " " " " " " Moderate (3) Rate of Discharge from the Hospital 27% Ivmag, 0% placebo; p = 0.03 " " " " " " " " " " " " Moderate (3) Hospital Stay No significant difference - values not given " " Mean serum magnesium concentration Lack of outcomes given (-1) " " " " " " " " Low (2) 1.3mmol/L Ivmag, 0.7mmol/L placebo; p=0.001 " " No Deductions " " " " " " " " Moderate (3)
# Silverman et al. 1996 Magnesium Sulfate as an adjunct to standard therapy in acute severe asthma (abstract) Academic Emergency Medicine 249 patients were randomized (127 placebo and 122 MgS04) Description: Acute asthma patients (18-60 years) presenting with % predicted FEV-1 </= 30 to ER.. Median Age = 34 years, Gender = 52% female. Ethnicity = N/A Standard of care: Oxygen, nebulized inhaled albuterol (2.5mg) at 0, 30, 60, 120, and 180 minutes. IV 125mg methylprednisolone administered at t=0. Treatment: 2 gm of IV magnesium sulfate at 30min. Control: 50cc of saline at 30min. Outcome Design Median FEV1 at 240 minutes Median FEV1 - last recorded Baseline - 23% placebo, 23.5% Ivmag; 240min - Placebo-controlled, doubleblind, 39.5% predicted in placebo group, 46% predicted in the Ivmag group; p = 0.007 randomized clinical trial No Deductions No Deductions No Deductions No Deductions No Deductions High (4) 39.5% predicted in placebo group, 46% predicted in the Ivmag group; p = 0.025 " " " " " " " " " " " " High (4)
# Tiffany et al. 1993 Magnesium Bolus or Infusion Fails to Improve Expiratory Flow in Acute Asthma Exacerbations Chest 48 asthmatic patients - 21 placebo, 15 bolus, 12 infusion Description: Patients (18-60 yo) with initial PEFR < 200L/min - failed to double their initial PEFR post 2 albuterol treatments. Exclusion Criteria: PEFR > 200 L/min pre-treatment, first episode of wheezing, history of chronic bronchitis/emphysema, oral temperature > 38.2C, history of renal failure or congestive heart failure, or requiring tracheal intubation. Age = 36.2 placebo, 42.9 bolus, 41.4 infusion, Gender (% male) = 52.3 placebo, 53.3 bolus, 16.7 infusion, Ethinicity = N/A Standard of care: Nebulised albuterol (2.5 IV every 30 minutes), standardized aminophylline (serum levels at 15mg/l) and IV methylprednisolone (125 mg ). Treatment: 2 methods of administration: 1) loading dose of IVmag, 2g over 20 minutes followed by 2g/h over 4 hours (infusion) or 2) MGS04, 2g over 20 minutes folllowed by placebo infusion (bolus). Control: saline. Outcome Design PEFR FEV1 No significant differences - values difficult to estimate Randomized, doubleblind, placebo-controlled trial No Deductions Dose of 2g + 2g/h for 4 hours much greater than standardized dose (-1) No Deductions Few Participants (-1) No Deductions Low (2) No significant differences - values difficult to estimate " " " " " " " " " " " " Low (2)
# Devi et al. 1997 Intravenous Magnesium Sulfate In Acute Severe Asthma Not Responding to Conventional Therapy Indian Pediatrics 47 children, 23 placebo, 24 Ivmag Description: Children (1-12 yo), presenting to ED with severe asthma & poor response to initial therapy. Exclusion Criteria: T > 38.0C (axillary), BP < 50% for age and gender. Mean age = 36.7 SD 3.62 IVmag, 6.75 SD 3.5 placebo, Gender (%Male) = 19/24 IVmag, 17/23 placebo. Severity: mild, moderate, severe based on a rating sytem from the National Heart, Lung and Blood Institute (USA) Standard of Care: Nebulised salbutamol (0.15mg/kg/dose) every 20 minutes for 1h. IV/po corticosteroids, aminophylline infusion, oxygen and +/- subcutaneous epinephrine. Treatment: 0.2ml of 50% MgS04 in 30ml (100mg/kg) in 5% dextrose over 35 minutes Control: normal saline in 30ml of 0.25 saline in 5% dextrose over 35 minutes. Outcome Design Median Clinical Asthma Scores 1h postivmag 10 placebo, 9 Ivmag; p <0.01 Randomized, doubleblind, placebo-controlled trial No Deductions No Deductions No Deductions Few Participants (-1) No Deductions Moderate (3) Median Clinical Asthma Scores 2h postivmag 10 placebo, 8 Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) Median Clinical Asthma Scores 3h postivmag 10 placebo, 7 Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) Median Clinical Asthma Scores 11h postivmag 7 placebo, 6 Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) PEFR at 30 minutes postivmag PEFR at 1 hour postivmag PEFR at 2 hour postivmag PEFR at 3 hour postivmag PEFR at 7 hour postivmag Values difficult to estimate; significantly higher in Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.01 " " " " " " " " " " " " Moderate (3) PEFR >70% post-ivmag 8/15 Ivmag, 2/16 placebo; p<0.05 " " " " " " " " " " " " Moderate (3) SaO2 30 minutes postivmag SaO2 1 hour postivmag SaO2 2 hour postivmag SaO2 3 hour postivmag SaO2 7 hour postivmag Values difficult to estimate; significantly higher in Ivmag; p<0.05 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.05 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.05 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.05 " " " " " " " " " " " " Moderate (3) Values difficult to estimate; significantly higher in Ivmag; p<0.05 " " " " " " " " " " " " Moderate (3) Hospital Stay 13.6+/-6.8h Ivmag, 18.9+/-7.7h; p<0.05 " " " " " " " " " " " " Moderate (3) Serum Magnesium Concentration pre to postinfusion in Ivmag patients 0.61+/-0.15mmol/L to 1.71+/-0.21mmol/L p <0.001 " " " " " " " " " " " " Moderate (3) Serum Magnesium Concentration pre to postinfusion in Placebo patients 0.69+/-.20mmol/L to 0.71+/-0.23mmol/L " " " " " " " " " " " " Moderate (3) Side effects 12.5% epigastric warmth, 16.6% pain, 12.5% tingling and numbness at site of infusion " " " " " " " " " " " " Moderate (3)
# Boonyavorakul et al. 2000 Intravenous magnesium sulfate in acute severe asthma Respirology 34 patients before exclusion. 33 remains (17 Mg, 16 placebo) Description: Patients (15-65 yo) with acute severe asthma attack (severity scores > 4). Exclusion Criteria: History of heart disease, hypertension, diabetes mellitus, chronic renal disease, infection, pregnancy (suspected or confirmed) and FISCHL index of 4+. Mean Age = 42.88+-2.99 SD Mg group, 35+-3.03 SD placebo group, Gender (%Male) = 11.76% Mg, 12.50% placebo, Ethnicity = N/A Standard Treatment: 5mg IV dexamethasone, 2.5mg nebulized salbutamol at 0, 20, 40, and 60min, and oxygen via mask (if necessary). Treatment: Randomly allocated patients received either 2g IV MgSO4 or placebo, sterile water as an adjunctive medication. Medication diluted in 50ml of 0.9% saline. Outcome Design Admission Rates 17.65% MgS04; 25% placebo; RR 071 (95%CI 0.19-2.67). Risk Ratio 0.71 (95%CI 0.19-2.67) not significant Randomized double-blind placebo controlled trial No Deductions No Deductions No Deductions Few Participants (-1) No Deductions Moderate (3) Mean Severity Scores - Between subjects Mean Severity Scores - Within subjects Treatment - SS 0.41, DoF 1, MS 0.41, Adjusted F-ratio 0.33, p-0.571; Error - SS 39.04, DoF 31, MS 1.26 " " " " " " " " " " " " Moderate (3) Time - SS 17.92, DoF 3*0.763, MS 5.97, Adjusted F-ratio 0.000; Treatment*time - SS 0.4, DoF 3*0.763, MS 0.15, Adjusted F-ratio 1.04, p-value 0.366; Error - SS 13.29, DoF 93*0.763, MS 0.14 " " " " " " " " " " " " Moderate (3)
# Ciarrallo et al. 2000 Higher-Dose Intravenous Magnesium Therapy for Children with Moderate to Severe Acute Asthma Arch Pediatr Adolesc Med 38 enrolled - 30 remained post-exclusion (16 Ivmag, 14 placebo) Description: Patients (6 to 17.9 yo) with acute exacerbation needing 3 nebulized bronchodilating treatments (albuterol or ipratropium bromide or a combination). Exclusion Criteria: Body temperature > 38.5 degrees C, theophylline use (<1 week), history of cardiac, renal or pulmonary disease (exc. asthma). Mean Age = 10.9+-0.9 IVmag, 12.0+-1.0 placebo; Gender (Male %) = 68% IVmag, 50% placebo, Ethnicity= N/A Standard of Care: 3 nebulized bronchodilating treatments (albuterol or ipratropium bromide or a combination). After enrollment, intravenous methylprednisolone (2mg/kg - max 100g) was given (patients who had not gotten corticosteroids). Treatment: Patients randomized: 1) magnesium sulfate 40mg/kg - max 2g in 100ml normal saline or 2) equivalent volume of saline (placebo). Outcome Design PEFR % predicted - 20minutes Fig 1 - contact author for values - p<0.001 Randomized double-blind placebo-controlled trial No Deductions No Deductions No Deductions Few Participants (-1) No Deductions Moderate (3) PEFR % predicted - 50minutes Fig 1 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) PEFR % predicted - 110minutes Fig 1 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) FEV1 % predicted - end of infusion Fig 2 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) FEV1 % predicted - 30minutes post-infusion Fig 2 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) FEV1 % predicted - end of study period Fig 2 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) FVC % predicted - end of infusion Fig 3 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) FVC % predicted - 30minutes post-infusion Fig 3 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) FVC % predicted - end of study period Fig 3 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) % improvement from Baseline - PEFR - 20min Fig 4 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) % improvement from Baseline - PEFR - 110min Fig 4 - contact author for values - p<0.001 " " " " " " " " " " " " Moderate (3) Admission 50% Ivmag (8/16), 100% placebo (14/14); p=0.02 " " " " " " " " " " " " Moderate (3) Clinical Asthma Scores - 95min 1.4 Ivmag, 2.5 placebo; p<0.001 " " " " " " " " " " " " Moderate (3) Clinical Asthma Scores - 110min 1.1 Ivmag, 2.4 placebo; p<0.001 " " " " " " " " " " " " Moderate (3) Discharge 8/16 Ivmag, 0/14 placebo; p=0.002 " " " " " " " " " " " " Moderate (3)
# Scarfone et al. 2000 A Randomized Trial of Magnesium in the Emergency Department Treatment of Children With Asthma Ann Emerg Med 62 eligible (8 refused) 54 children (24 Ivmag, 30 placebo) Description: Children (1-18 yo) with moderate to severe asthma exacerbation presenting to ED. Exclusion Criteria: Less severe (PI score </= 7) or more severe (PI score >/= 14) ill children. Corticosteroid use (last 72h), concurrent bronchiolitis, lobar pneumonia, croup, suspected foreign body aspiration, history of cystic fibrosis, bronchopulmonary dysplasia, congenital heart disease, liver disease, renal disease, sickle cell anemia, or pregnancy. Mean age = in months (SD): 81+-44 IVmag, 58+-39 placebo, Gender (%Male) = 58% IVmag, 47% placebo, Ethnicity = 58% black IVmag, 63% black placebo. Standard of Care: Nebulized albuterol treatment (0.15mg/kg) and methylprednisolone (1mg/kg). Treatment: Post standard-of-care randomly assigned to receive 75mg/kg of magnesium sulfate (max 2.5 g) or placebo. Post-randomization, all patients treated with nebulized albuterol (structured protocol). Outcome Design PI Scores Mean PI scores for all 7 assessment times (0, 20min, 30min, 40min, 60min, 80min, and 120min) showed significant improvement - in each group (p<0.001); Randomized, double-blind placebo-controlled trial No Deductions 2.5g of Ivmag max vs. standard of 2.0g (-1) No Deductions Few Participants (-1) No Deductions Low (2) Mean change in PI from baseline to 120min 2.83 (SD=+-2.44) Ivmag; 2.66 (SD=+-2.65). " " " " " " " " " " " " Low (2) Mean differences in PI scores- Ivmag vs. placebo T=0min 0.41 (95%CI -.59 to 1.40) " " " " " " " " " " " " Low (2) Mean differences in PI scores- Ivmag vs. placebo T=20min (-)0.33 (95%CI -1.45 to 0.80) " " " " " " " " " " " " Low (2) Mean differences in PI scores- Ivmag vs. placebo T=30min 0.30 (95%CI -0.89 to 1.49) " " " " " " " " " " " " Low (2) Mean differences in PI scores- Ivmag vs. placebo T=40min 0.65 (95%CI -0.56 to 1.86) " " " " " " " " " " " " Low (2) Mean differences in PI scores- Ivmag vs. placebo T=60min 0.85 (95%CI -0.54 to 2.24) " " " " " " " " " " " " Low (2) Mean differences in PI scores- Ivmag vs. placebo T=80min 0.80 (95%CI -0.62 to 2.22) " " " " " " " " " " " " Low (2) Mean differences in PI scores- Ivmag vs. placebo T=120min 0.74 (95%CI -0.83 to 2.31) " " " " " " " " " " " " Low (2) Physician determination of need of hospitalization after 150min 11/24 (46%) Ivmag; 16/30 (53%) placebo " " " " " " " " " " " " Low (2)
# Bijani et al. 2002 Intravenous Magnesium Sulfate As an Adjunct in the treatment of severe asthmatic patients non-responding to conventional therapy The Internet of Asthma, Allergy and Immunology 81 subjects (48 Ivmag, 33 control) Description: Asthma patients (12-85 yo) with acute exacerbation (PEFR <200L/min with bronchodilators, corticosteroids and assisted ventilation). Age: 12-85 range Ivmag, 15-80 range placebo. Gender (%male): 54.2% Ivmag, 51.5% placebo, Ethnicity: N/A Standard of Care: Oxygen, nebulized salbutamol, IV aminophyllin and corticosteroids. Treatment: Randomized to receive MgS04 (25mg/kg) or saline (100ml normal saline) placebo given as infusion (over 30-45min). Outcome Design PEFR - at 30min after infusion Baseline - 31.46+-5.6 Ivmag, 30.00+-5.9 placebo; 30min - 62.81+-6.7 Ivmag, 46.52+- 8.3 placebo Randomized, doubleblind, placebo-controlled trial No Deductions No Deductions No Deductions No Deductions No Deductions Moderate (3) PEFR - at 3h after infusion Clinical Asthma Score Baseline - 31.46+-5.6 Ivmag, 30.00+-5.9 placebo; 3h - 82.60+-5.8 Ivmag, 47.8+-8 placebo; p<0.002 " " " " " " " " " " " " Moderate (3) Ivmag showed significant improvement (p<0.0005) at 30min and 3h " " Did not state values (-1) " " " " " " " " Low (2) Mean (+SEM) increase in PEFR at 30min 62.81+-6.7 Ivmag; 46.52+-8.3 placebo " " No Deductions " " " " " " " " Moderate (3) # of Breaths % Diaphoresis % Cyanosis % Using of Respiratory Accessory Muscles Baseline - 34.38 Ivmag, 35.1 placebo; 30min 27.21 Ivmag, 33.20 placebo; 3h 24.42 Ivmag, 30.22 placebo " " " " " " " " " " " " Moderate (3) Baseline - 29.2% Ivmag, 30.3% placebo; 3h - 2.1% Ivmag, 12.1% placebo; p=0.02 " " " " " " " " " " " " Moderate (3) Baseline - 35.4% Ivmag, 22.7% placebo; 3h - 2.10% Ivmag, 12.1% placebo " " " " " " " " " " " " Moderate (3) Baseline - 100% Ivmag, 40.9% placebo; 3h - 22.9% Ivmag, 18.2% placebo; p=0.06 " " " " " " " " " " " " Moderate (3)
# Porter et al. 2001 Intravenous magnesium is ineffective in adult asthma, a randomized trial European of Emergency Medicine 55 met inclusion criteria - 42 patients: 18 Ivmag, 24 placebo Description: adult asthma patients (18-55 yo) presenting to ED (PEF of <100 L/min or <25% of predicted flow). Exclusion Criteria: SSx pneumonia, congestive heart failure, renal insufficiency, previous myocardial infarction, hypertension on therapy and hypertension/hypotension (SBP >180 or <110mmHg), pregnancy, or patients with high likelihood of endotracheal intubation. Age = 32+-13 IVmag, 38+-15 placebo, Gender (%Male) = 50% IVmag, 25% placebo, Ethnicity = N/A Standard of Care: 2.5mg albuterol sulphate via nebulizer, 125mg methylprednisolone IV, oxygen as needed. Treatment: Patients given either 2.0 grams of MgS04 or placebo. All received inhaled bronchodilators and IV steroids Outcome Design PEF - at 60min 174L/min Ivmag; 212L/min Placebo; p (bivariate)=0.038; p(multivariable) 0.132 Randomized, doubleblind, placebo-controlled trial No Deductions No Deductions No Deductions Few Participants (-1) No Deductions Moderate (3) Median PEF t=60min 140 Ivmag, 200 Placebo " " " " " " " " " " " " Moderate (3) Final PEF 211+-104L/min Ivmag, 252+-108L/min Placebo; p(bivariate) = 0.28, p(multivariable) 0.073 " " " " " " " " " " " " Moderate (3) Median final PEF 200 Ivmag, 240 Placebo " " " " " " " " " " " " Moderate (3) Mean BDS at t=60min 2.2 Ivmag, 1.6 Placebo; p(bivariate) = 0.682, p(multivariable) = 0.563 " " " " " " " " " " " " Moderate (3) Median BDS at t=60min 2.0 Ivmag, 1.0 Placebo " " " " " " " " " " " " Moderate (3) Mean final BDS 1.3 Ivmag, 0.9 Placebo; p(bivariate) =0.807, p(multivariate) 0.109 " " " " " " " " " " " " Moderate (3) Median final BDS 1.0 Ivmag, 1.0 Placebo " " " " " " " " " " " " Moderate (3) Admission rate 5/18 (28%) Ivmag, 5/24 (21%) Placebo; p(bivariate) = 0.72 " " " " " " " " " " " " Moderate (3)
# Silverman et al. 2002 IV Magnesium Sulfate in the Treatment of Acute Severe Asthma: A Multicenter Randomized Control Trial Chest 254 were randomized - (6 were enrolled 2times) 248 Description: Patients (18 to 60 yo) presenting to ED with acute asthma (FEV1 </= 30% predicted). Exclusion Criteria: History of COPD or other chronic lung disease, diabetes mellitus, renal insufficiency, or hypertension on medication, temperature was >38.9C, or suspected pneumonia, pregnancy, requiring intubation or unable to perform spirometry, congestive heart failure, coronary artery disease, requiring intubation. Age = 36.5(11.4) placebo, 36.4(11.1) IVmag, Gender (%female) = 49% placebo, 55 IVmag, Ethnicity = 38% black placebo, 39% black IVmag; 43% hispanic placebo, 43% hispanic IVmag; 11% white placebo, 14% white IVmag, 8% other placebo, 4% other IVmag. Standard of Care: Nebulized albuterol at regular intervals and IV methylprednisolone. Treatment: 2g of IV magnesium sulfate or placebo 30min after ED arrival. Outcome Design Pulse rate (beats/min) at baseline to 240min Baseline - 104 placebo, 100 Ivmag; 240min - 102 (15) placebo; 96(15) mag; p<0.05 Placebo-controlled, double blind, randomized clinical trial No Deductions No Deductions No Deductions No Deductions No Deductions High (4) Mean difference (95%CI) at 240 min - pulse rate (beats/min) (-)5.9 (-10 to -2.0) " " " " " " " " " " " " High (4) FEV1, L at baseline to 240min Baseline - 0.75 placebo,.76 Ivmag; 240min - 1.42 (0.66) placebo; 1.60 (0.69) mag; p<0.05 " " " " " " " " " " " " High (4) Mean difference (95%CI) at 240 min - FEV1 L 0.17 (0.02 to 0.34) " " " " " " " " " " " " High (4) FEV1, % predicted at baseline to 240min Baseline - 22.7 (5.7) placebo; 23.1 (4.9) mag; 240min - 43.5 (18.7) placebo; 48.2 (18.1) mag; p<0.05 " " " " " " " " " " " " High (4) Mean difference (95%CI) at 240 min - FEV1 % predicted 4.7 (0.29 to 9.3) " " " " " " " " " " " " High (4) PEFR L/min at baseline to 240min At baseline - 144 (73) placebo; 141 (74) mag; 240min - 236 (123) placebo; 272 (144) mag; p<0.01 " " " " " " " " " " " " High (4) Mean difference (95%CI) at 240 min - PEFR L/min 36.0 (8 to 64) " " " " " " " " " " " " High (4) PEFR % predicted at baseline to 240min Baseline - 32.0 (14.0) placebo; 32.2 (18.0) mag; 240min - 53.1 (20.9) placebo; 62.7 (24.3) mag; p<0.001 " " " " " " " " " " " " High (4) Mean difference (95%CI) at 240 min - PEFR 9.6 (3.7 to 15.4) " " " " " " " " " " " " High (4) Hospital Admission Rate at 4h 39/122 Ivmag, 41/126 Placebo, 32% in both groups " " " " " " " " " " " " High (4)
# Bradshaw et al. 2008 Intravenous magnesium sulphate provides no additive benefit to standard management in acute asthma Respiratory Medicine 150 before exclusion (129 in final analysis) 62 Ivmag, 67 placebo Description: Patients (16+ yo) presenting with acute asthma attack (PEF <75%), and past asthma diagnosis wrt BTS guidelines. Exclusion Criteria: COPD ( or other chronic lung disease), pneumonia, congestive heart failure, coronary artery disease, renal insufficiency, hypertension (w/ medication), inability to perform spirometry, pregnancy. Age = 36(18-73) mg, 38.8(17-73) placebo, Gender (% male) = 39% mg, 45% placebo, Ethnicity = N/A Standard of Care: 35% oxygen, 5mg nebulised salbutamol, 500mcg nebulized ipratropium and 200mg IV hydrocortisone. Treatment: Patients were randomized to receive 1.2g MgSO4 in 50ml saline or placebo consisting of 50ml normal saline over 15min. Outcome Design Life Threatening Group (12 Mg; 17 placebo) Double-blind, randomized, placebo-controlled trial No Deductions Low Drug Dose (1.2g vs. 2.0g) (-1) No Deductions No Deductions No Deductions Moderate (3) Difference in % predicted PEF at T=60 43.4 cf Ivmag, 42.5 cf placebo " " " " " " " " " " " " Moderate (3) Mean difference in % predicted PEF at T=60 1.0 (95%CI -10.3 to 12.3) p=0.85 " " " " " " " " " " " " Moderate (3) Changes in % predicted PEF over time Fig 2 - p=0.92 " " " " " " " " " " " " Moderate (3) Admission 100% mg; 88% placebo; p=0.50 " " " " " " " " " " " " Moderate (3) " " " " " " " " " " " " Moderate (3) Severe Group (30mg; 31 placebo) " " " " " " " " " " " " Moderate (3) % predicted PEF at endpoint 63.7 cf mag; 61.6 cf placebo; " " " " " " " " " " " " Moderate (3) Mean difference in PEF at endpoint 2.1 (95%CI -6.7 to 11.0); p=0.63 " " " " " " " " " " " " Moderate (3) Changes in % predicted PEF over time Figure 3 - p=0.93 " " " " " " " " " " " " Moderate (3) Hospital Admission Rates 70% Ivmag; 84% placebo; p=0.32 " " " " " " " " " " " " Moderate (3) " " " " " " " " " " " " Moderate (3) Moderate Group (20 Ivmag; 19 placebo) " " " " " " " " " " " " Moderate (3) Admission Rates 80% Ivmag; 58% placebo; p=0.18 " " " " " " " " " " " " Moderate (3) PEF % predicted at t=60 81.1 mg, 82.9 placebo " " " " " " " " " " " " Moderate (3) Mean difference % predicted PEF at t=60 (-)1.8 (95%CI -10.6 to 6.7) p=0.67 " " " " " " " " " " " " Moderate (3) Change in % predicted PEF over time No difference; p=0.99 " " " " " " " " " " " " Moderate (3) " " " " " " " " " " " " Moderate (3) Adverse Events " " " " " " " " " " " " Moderate (3) Systolic BP Mg - trend to decrease SBP at t=60, (t=0, 133cf. T=60 123.5) p=0.09 " " " " " " " " " " " " Moderate (3) Difference in SBP T=60; Mg 123.5 cf; Placebo 134.6; p=0.06 " " " " " " " " " " " " Moderate (3)
# Gurkan et al. 1999 Intravenous magnesium sulphate in the management of moderate to severe acute asthmatic children nonresponding to conventional therapy European of Emergency Medicine 20 (10 Ivmag, 10 placebo) Description: Patients with acute asthma exacerbation (PEFR <60% predicted) post 3 b2-agonist nebulizer treatments (0.15mg/kg/dose, max 5mg/dose of salbutamol solution in 3ml normal saline). Exclusion Criteria: Fever, systolic blood pressure (less than 25th percentile of age), theophylline (recent use), history of cardiac, renal or pulmonary diseases. Mean age: 10.8+-2.8 years, Gender (% male) = 55%, Ethnicity: NA Standard of Care: Intravenous infusion of methylprednisolone (2mg/kg; max 100mg) with first nebulizer. Treatment: 40mg/kg doses (2g max) or equivalent volume of normal saline solution. Outcome Design Mean % of improvement from baseline in PEFR 30min post-iv mag infusion Mean % of improvement from baseline in PEFR at end of observation (post-iv mag infusion) Mean Clinical Asthma Score -30min from baseline -Ivmag 43.0+-6.3% Ivmag; 14.6+-3.7% placebo; p=0.0002 Randomized, double blind, placebo, controlled-trial No Deductions No Deductions No Deductions Few Participants (-1) No Deductions Moderate (3) 58.4+-2.9% Ivmag; 21.8+-4.5% placebo; p=0.0001 " " " " " " " " " " " " Moderate (3) Baseline: 4.0+-0.5, 30min - 5.8+-0.4; p=0.004 " " " " " " " " " " " " Moderate (3) Mean Clinical Asthma Score -30min from baseline - Placebo Baseline - 5.5+-0.5; 30min - 5.7+-0.5; p>0.05 " " " " " " " " " " " " Moderate (3) % individuals at end of observation with PEFR <60% predicted 30% (3) Ivmag; 70% (7) placebo " " " " " " " " " " " " Moderate (3)
Cheuk et al. 2005 A meta-analysis on intravenous magnesium sulphate for treating acute asthma Arch. Dis. Child # Studies Included: Ciarallo 1996, Devi 1997, Gurkan 1999, Ciarallo 2000, Scarfone 2000. Inclusion Criteria: Controlled clinical trials of Ivmag of any dose, age <18 years. Treatment: No limitation on treatment, predominantly 2g max of Ivmag, except for Scarfone 2000 which used a 2.5g max. Outcome Design OR of hospitalization Pooled point estimate = 0.290 (95%CI 0.143-0.589) p=0.0006; Qtest of heterogeneity pvalue=0.13 (df=3) Aggregated Data OR of persistent PEFR <60% Difference in % improvement of PEFR at end of study Difference in clinical symptom score at end of study Pooled point estimate = 0.155 (95%CI 0.057 to 0.422) p=0.0003; Qtest of heterogeneity pvalue=0.97 (df=2) " " Pooled point estimate = 8.58 (95%CI 0.94 to 16.22) p=0.028; Qtest of heterogeneity pvalue<0.0001 (df=2) " " Pooled point estimate = 1.33 (95%CI 0.31 to 2.36) p=0.011; Qtest of heterogeneity pvalue=0.0001 (df=3) " "
Mohammed et al. 2007 Intravenous and nebulised magnesium sulphate for acute asthma: systematic review and meta-analysis Emerg. Med. J. # Studies Included: Bijani 2002, Silverman 2002, Porter 2001, Bilaceroglu 2001 (not analyzed), Boonyavorakul 2000, Scarfone 2000, Ciraallo 200, Gurkan 1999, Devi 1997, Cirallo 1996, Bloch 1995, Matusiewicz 1994 (not analyzed), Tiffany 1993, Green 1992, Skoboleff 1989. Age = range 1-85, Gender (% female) = range 23%-88%, Ethnicity = N/A Moderate-severe to severe Treatment: Predominantly 2g max of Ivmag, except Scarfone 2000 (2.5g max), Skobeloff (1.2g max), Mastusiewicz (1.2g max). Outcome Design Effects of Ivmag on respiratory function - adult SMD (random) 0.25 (95%CI -0.01 to 0.51); test for heterogeneity x2=27.20, df=8 (p=.0007), i2=70.6^; Test for overal effect z=1.92 (p=0.05) Aggregated Data Effects of Ivmag on respiratory function - children Effects of Ivmag on respiratory function - total Effects of Ivmag on hospital admission - adult Effects of Ivmag on respiratory function - children Effect of Ivmag on hospital admission - total SMD (random) 1.94 (95%CI 0.80-3.08); Test for heterogeneity: x2=19.26, df=3 (p=0.0002), i2=84.4%; Test for overall effect: z=3.34 (p=0.0008) " " SMD (random) 0.61 (95%CI 0.26 to 0.96); Test for heterogeneity: x2=76.66, df=12 (p<0.00001), i2=84.3%; Test for overall effect: z=3.46 (p=0.0005) " " RR (random) 0.87 (95%CI 0.70 to 1.08); Test for heterogeneity: x2=9.99, df=7 (p=0.19), i2=30.0%; Test for overall effect: z=1.23 (p=0.22) " " RR (random) 0.70 (95%CI 0.54-0.90); Test for heterogeneity: x2=2.16, df=2 (p=0.34); i2=7.3%; Test for overall effect: z=2.81 (p=0.005) " " RR (random) 0.81 (95%CI 0.67-0.97); Test for heterogeneity: x2=16.02, df=10 (p=0.10), i2=37.6%; Test for overall effect: z=2.30 (p=0.02) " "
Rowe et al. 2000 Magnesium sulfate for treating exacerbations of acute asthma in the emergency department The Cochrane Database of Systematic Reviews # Studies Included: Bloch 1995, Ciarallo 1997, Devi 1997, Green 1992, Skobeloff 1989, Silberman 1996, Tiffany 1993. Inclusion Criteria: RCT/quasi-RCT, children or adult patients presenting to EDs for acute asthma therapy/management Treatment: Patients randomized to receive Ivmag or placebo in ED treatment. Co-interventions/therapies: beta-agonist (all studies), theophyllie administration up to physician (except for in two studies), ICS therapy common in studies (Bloch 1995 providing ICS in most severe cases). Outcome Design Admission to hospital OR 0.31 (95%CI 0.09-1.02); significant heterogeneity - chi-squared=19.53, df=5; p<0.05 Aggregated Data Admission to hospital - severe asthma subgroup OR 0.10 (95%CI 0.04 to 0.27); heterogeneity - chi-sqaured =0.26; df=3; p>0.1 " " Admission to hospital - mild-moderate asthma OR 1.36 (94%CI (stated as 94%) 0.72-2.55) " " Improvement in PEFR % predicted FEV-1 WMD 29.4 (95%CI -3.4 to 62) statistically significant heterogeneity: chi-sqaured =9.7, df=4, p<0.05) " " WMD 4.3 (95%CI - -2.3 to 10.9) statistically significant heterogeneity: chi-squared = 7.47; df=2, p<0.01 " "
# Santana et al. 2001 Controlled study on intravenous magnesium sulfate or salbutamol in early treatment of severe acute asthma attack in children of Pediatria 50 patients (17 Mg; 17 salbutamol; 16 placebo) Description: Children (>2 yo), with severe acute asthma admitted for observation. Exclusion Criteria: Other pulmonary or cardiac pathology on admission, known family history of supraventricular tachycardia, diabetes mellitus, glucose intolerance, collection delay of pre-established laboratory exams, delayed study drug administration, significant deterioration (transfer to ICU), immediate endotracheal intubation, no consent. Mean age = 4.5, Gender = 53% female, Ethnicity = N/A Standard of Care: Oxygen, corticosteroids, beta-adrenergics (all given equal dosages at equal intervals). Treatment: 3 options - 1) IVMg (2.5mg/kg/min for 20min - 2gmax) 2) intravenous salbutamol (1ug/kg/min) c) saline solution. Outcome Design Length of Stay at hospital Oxygen therapy (# days) Use of corticosteroids (# days) Length of stay in Pediatric Intensive Care Unit 6.12+-2.47 Mg; 4.65+-3.10 sal; 6.56 +-3.67 placebo; p=0.19 Randomized, double-blind placebo-controlled trial No Deductions No Deductions No Deductions Few Participants (-1) No Deductions Moderate (3) 4.24+-2.22 Mg; 2.71+-1.19 sal;4.44+-2.34 placebo; p=0.04 " " " " " " " " " " " " Moderate (3) 5.88+-2.34 Mg; 4.06+-2.25 sal; 5.81+-2.83 placebo; p=0.06 " " " " " " " " " " " " Moderate (3) 2.71+-2.57 Mg; 1.71+-1.86 sal; 2.88+-3.12 placebo; p=0.37 " " " " " " " " " " " " Moderate (3)
# Berstein et al. 1995 Lack of Effectiveness of Magnesium in Chronic Stable Asthma Arch Intern Med 15 patients with chronic stable asthma, 10 nonasthmatics Description: Patients (18-45 yo) with chronic stable asthma/normal subjects. Exclusion Criteria: Treatment with steroids (<2 weeks prior to study), treatment with tapering doses of steroids, renal dysfunction. Mean age = 30.3+-2.2 Mg, 30.7+-1.7 normal, Gender = 46.6% male Mg; 90% male normal, Ethnicity = N/A Design: Day 1 - spirometry and albuterol challenge to confirm asthma via ATS definition; Day 2 - subjects received Ivmag (2g) or placebo, Day 3 - subjects crossed to receive other drug Outcome Design Improvements in FEV1 in asthmatic/normal subjects Figure 1; not significant; p=0.6336 Randomized, double blind, placebo-controlled crossover trial No Deductions No Deductions No Deductions Few Participants (-1) No Deductions Moderate (3) Improvements in FVC in asthmatic/normal subjects Figure 2; not significant; 0.1993 " " " " " " " " " " " " Moderate (3) Improvements in Maximum FEF in asthmatic/normal subjects Figure 3; not significant; p=0.9792 " " " " " " " " " " " " Moderate (3)
New Table for IV Magnesium Treatment for Asthma # Singh et al. 2008 A Randomized Controlled Trial of Intravenous Magnesium Sulphate as an Adjunct to Standard Therapy in Acute Severe Asthma Iran J Allergy Asthma Immunol 75 patients screened (15 excluded) 60 participants (30 IV magnesium sulphate) (30 control) Description: Patients presenting to ER with acute asthma. Inclusion Critieria: physician diagnosed demonstrating 12% reversibility, and on medication last 6 months, FEV1 <30% predicted when presenting to ED, fulfilled most of the GINA criteria for a severe asthmatic exacerbation. Exclusion Criteria: History of COPD or other chronic lung disease or cardiac, renal or hepatic abnormalities, pregnant or lactating, requiring intubation or unable to perform spirometry. Age = Treatment group 34.79 (8.05), control group 35.9 (8.76), Gender = Treatment group 47% male, control group 50% male, Ethnicity =N/A Standard of Care: 100mg of IV hydrocortisone, a nebulizing solution consisting of 2.5mg of B2-agonist, 1.5ml of ipratropium bromide and 2.5 ml of normal saline, 100% oxygen at 0, 20, and 40 minutes after admission into protocol. Treatment: At 30 min, 2g of magnesium sulphate in 250 ml normal saline given over 20 minutes. Control: At 30 min, placebo in 250 ml normal saline solution. Outcome Design Indirectness of FEV1 % predicted Hospital Admission at 2 hours At arrival - 22.0(SD 5.1) placebo, 22.07 (SD 4.77) IV mag; At 120 minutes (Discharge) - 56.70 (SD 6.20) placebo, 62.84 (SD 10.02) IV mag; Mean difference between groups (95%CI) = 6.07 (1.87-10.62); p=0.01 Prospective Randomized Control Trial Single-blinded trial (-1) No Deductions No Deductions Few Participants (- 1) No Deductions Low (2) 9/30 Placebo; 2/30 IV MgSO4; p=0.011; OR for admission (IVMag vs. Placebo) OR=0.16 CI 0.05-0.77, p<0.05 " " " " " " " " " " " " Low (2)
Articles/Abstracts Not Analyzed: 1) Bilaceroglu S, Akpinar M, Tiras A, et al. Intravenous magnesium sulphate in acute asthma. Annual Thoracic Society 97th International Conference. San Francisco, 18-23 May, 2001 2) Matusiewicz SP, Cusack S, Greening AP, et al. A double blind placebo controlled parallel group study of intravenous magnesium sulphate in acute severe asthma. Eur Respir J 1994; 7(Suppl 18): 14s