Background
Methods
Search strategy
Inclusion criteria
Studies
Participants, interventions and comparisons
Outcomes
Study selection
Data extraction and management
Assessment of study quality/ risk of bias
Data synthesis and analysis
Results
Study selection
Evidence from randomised controlled trials
Comparison 1: magnesium sulphate versus placebo or no treatment
Outcome or subgroup | Studies | Participants | Method (I2(%))* | RR (95% CI) |
---|---|---|---|---|
Comparison 1: Magnesium sulphate versus placebo or no treatment
| ||||
1.1 Death
| 14662 | F (0) | 0.53 (0.26, 1.09) | |
1.1.1 Treatment of pre-eclampsia/eclampsia | 10795 | F (0) | 0.53 (0.26, 1.09) | |
1.1.2 Fetal neuroprotection | 3867 | F (NA) | No deaths | |
1.1.3 LD only | 1 [23] | 564 | F (NA) | No deaths |
1.1.4 LD and MD | 14098 | F (0) | 0.53 (0.26, 1.09) | |
1.1.5 4 g IV LD and MD | 11857 | F (0) | 0.53 (0.26, 1.09) | |
1.1.6 5–6 g IV LD and MD | 1 [25] | 2241 | F (NA) | No deaths |
1.1.7 1 g/hour IV MD | 7264 | F (0) | 0.41 (0.12, 1.43) | |
1.1.8 2–3 g/hour IV MD | 1 [25] | 2241 | F (NA) | No deaths |
1.1.9 IM MD | 1 [20] | 4593 | F (NA) | 0.61 (0.25, 1.48) |
1.2 Cardiac arrest
| 13977 | F (NA) | 0.80 (0.21, 2.98) | |
1.2.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 10110 | F (NA) | 0.80 (0.21, 2.98) |
1.2.2 Fetal neuroprotection | 3867 | F (NA) | No cardiac arrests | |
1.2.3 LD only | 1 [23] | 564 | F (NA) | No cardiac arrests |
1.2.4 LD and MD | 13413 | F (NA) | 0.80 (0.21, 2.98) | |
1.3 Respiratory arrest
| 13977 | F (NA) | 2.50 (0.49, 12.88) | |
1.3.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 10110 | F (NA) | 2.50 (0.49, 12.88) |
1.3.2 Fetal neuroprotection | 3867 | F (NA) | No respiratory arrests | |
1.3.3 LD only | 1 [23] | 564 | F (NA) | No respiratory arrests |
1.3.4 LD and MD | 13413 | F (NA) | 2.50 (0.49, 12.88) | |
1.4 Discontinuation due to adverse effects
| 13666 | F (0) |
2.77 (2.32, 3.30)
| |
1.4.1 Treatment of pre-eclampsia/eclampsia | 10245 | F (0) |
2.69 (2.18, 3.31)
| |
1.4.2 Fetal neuroprotection | 3265 | F (0) |
2.81 (2.01, 3.93)
| |
1.4.3 Tocolysis | 1 [18] | 156 | F (NA) |
17.88 (1.05, 304.57)
|
1.4.4 LD and MD | 13666 | F (0) |
2.77 (2.32, 3.30)
| |
1.4.5 4 g IV LD and MD | 11328 | F (0) |
2.75 (2.28, 3.31)
| |
1.4.6 5–6 g IV LD and MD | 2338 | F (0) |
2.94 (1.69, 5.12)
| |
1.4.7 1 g/hour IV MD | 1 [19] | 1062 | F (NA) |
2.74 (1.81, 4.15)
|
1.4.8 2–3 g/hour IV MD | 2494 | F (0) |
3.38 (1.97, 5.78)
| |
1.5 Given calcium gluconate
| ||||
1.5.1 Treatment of pre-eclampsia/eclampsia | 10795 | F (0) | 1.35 (0.63, 2.88) | |
1.5.2 4 g IV LD and MD | 10795 | F (0) | 1.35 (0.63, 2.88) | |
1.6 Intensive care unit admission
| 11172 | F (NA) | 0.97 (0.72, 1.30) | |
1.6.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 10110 | F (NA) | 0.97 (0.72, 1.30) |
1.6.2 Fetal neuroprotection | 1 [19] | 1062 | F (NA) | No admissions |
1.7 Any side effects
| 13322 | R (98) |
4.62 (2.42, 8.83)
| |
1.7.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 9992 | F (NA) |
5.26 (4.59, 6.03)
|
1.7.2 Fetal neuroprotection | 3265 | R (98) |
3.82 (1.38, 10.59)
| |
1.7.3 Tocolysis | 1 [22] | 65 | F (NA) |
26.71 (1.64, 435.03)
|
1.7.4 LD and MD | 13322 | R (98) |
4.62 (2.42, 8.83)
| |
1.7.5 4 g IV LD and MD | 11054 | R (99) |
3.52 (1.49, 8.32)
| |
1.7.6 5–6 g IV LD and MD | 2268 | F (5) |
6.28 (5.36, 7.35)
| |
1.7.7 1 g /hour IV MD | 6501 | R (98) |
3.31 (1.59, 6.88)
| |
1.7.8 2–3 g/hour IV MD | 2268 | F (5) |
6.28 (5.36, 7.35)
| |
1.7.9 IM MD | 1 [20] | 4553 | F (NA) |
5.84 (4.80, 7.09) |
1.8 Respiratory depression/other respiratory problems
| 14098 | F (29) |
1.41 (1.07, 1.86)
| |
1.8.1 Treatment of pre-eclampsia/eclampsia | 10677 | F (0) |
1.98 (1.24, 3.15)
| |
1.8.2 Fetal neuroprotection | 3265 | F (29) | 1.12 (0.79, 1.59) | |
1.8.3 Tocolysis | 1 [18] | 156 | F (NA) | 3.16 (0.13, 76.30) |
1.9 Absent or reduced tendon reflexes
| 11241 | F (0) | 1.01 (0.71, 1.44) | |
1.9.1 Treatment of pre-eclampsia/eclampsia | 10677 | F (0) | 1.00 (0.70, 1.42) | |
1.9.2 Fetal neuroprotection | 1 [23] | 564 | F (NA) | 1.94 (0.18, 21.32) |
1.10 Respiratory depression and absent reflexes
| ||||
1.10.1 Treatment of pre-eclampsia/eclampsia | 10899 | F (0) | 5.96 (0.72, 49.40) | |
1.11 Hypotension
| 1782 | F (0) |
1.52 (1.10, 2.11)
| |
1.11.1 Fetal neuroprotection | 1626 | F (0) |
1.51 (1.09, 2.09)
| |
1.11.2 Tocolysis | 1 [18] | 156 | F (NA) | 3.16 (0.13, 76.30) |
1.12 Tachycardia
| ||||
1.12.1 Fetal neuroprotection | 1 [19] | 1062 | F (NA) |
1.53 (1.03, 2.29)
|
1.13 Flushing and/or warmth
| 13956 | R (92) |
6.94 (4.19, 11.49)
| |
1.13.1 Treatment of pre-eclampsia/eclampsia | 10127 | R (91) |
6.39 (2.44, 16.74)
| |
1.13.2 Fetal neuroprotection | 3829 | R (94) |
7.55 (3.39, 16.85)
| |
1.14 Nausea and/or vomiting
| 13821 | R (92) |
5.50 (2.29, 13.22)
| |
1.14.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 9992 | F (NA) |
8.88 (5.46, 14.43)
|
1.14.2 Fetal neuroprotection | 3829 | R (92) |
4.60 (1.54, 13.73)
| |
1.15 Muscle weakness
| 10212 | F (0) |
15.81 (7.36, 33.96)
| |
1.15.1 Treatment of pre-eclampsia/eclampsia | 10056 | F (0) |
15.97 (7.23, 35.30)
| |
1.15.2 Tocolysis | 1 [18] | 156 | F (NA) | 13.68 (0.78, 238.67) |
1.16 Drowsiness or confusion
| 11189 | F (0) |
2.46 (1.83, 3.29)
| |
1.16.1 Treatment of pre-eclampsia/eclampsia | 10127 | F (0) |
2.26 (1.06, 4.85)
| |
1.16.2 Fetal neuroprotection | 1 [19] | 1062 | F (NA) |
2.49 (1.82, 3.42)
|
1.17 Headache
| 10556 | F (0) |
2.21 (1.27, 3.86)
| |
1.17.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 9992 | F (NA) |
2.12 (1.19, 3.76)
|
1.17.2 Fetal neuroprotection | 1 [23] | 564 | F (NA) | 3.89 (0.44, 34.57) |
1.18 Thirst or mouth dryness
| 11054 | R (42) |
2.38 (1.59, 3.56)
| |
1.18.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 9992 | F (NA) |
3.36 (1.72, 6.58)
|
1.18.2 Fetal neuroprotection | 1 [19] | 1062 | F (NA) |
2.11 (1.72, 2.59)
|
1.19 Dizziness
| 11054 | R (39) |
2.62 (1.63, 4.21)
| |
1.19.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 9992 | F (NA) |
3.70 (1.84, 7.42)
|
1.19.2 Fetal neuroprotection | 1 [19] | 1062 | F (NA) |
2.21 (1.53, 3.19)
|
1.20 Sweating
| ||||
1.20.1 Fetal neuroprotection | 3265 | R (95) |
6.37 (1.96, 20.65)
| |
1.21 Itching and/or tingling
| ||||
1.21.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 9992 | F (NA) |
14.98 (1.98, 113.38)
|
1.22 Blurred vision
| ||||
1.22.1 Fetal neuroprotection | 1 [19] | 1062 | F (NA) |
2.34 (1.32, 4.14)
|
1.23 Slurred speech
| ||||
1.23.1 Treatment of pre-eclampsia/eclampsia | 1 [26] | 135 | F (NA) | 3.04 (0.13, 73.42) |
1.24 Problems at the IV site or arm discomfort
| 8704 | R (92) |
6.34 (3.10, 12.98)
| |
1.24.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 5439 | F (NA) |
3.05 (2.15, 4.32)
|
1.24.2 Fetal neuroprotection | 3265 | F (NA) |
9.11 (7.18, 11.55)
| |
1.25 Problems at the IM site
| ||||
1.25.1 Treatment of pre-eclampsia/eclampsia | 1 [20] | 4553 | F (NA) |
1.49 (1.25, 1.79)
|
1.26 Caesarean section
| 14105 | F (0) |
1.04 (1.00, 1.08)
| |
1.26.1 Treatment of pre-eclampsia/eclampsia | 10096 | F (0) |
1.05 (1.01, 1.10)
| |
1.26.2 Fetal neuroprotection | 3853 | F (19) | 1.00 (0.93, 1.08) | |
1.26.3 Tocolysis | 1 [18] | 156 | F (NA) | 0.90 (0.45, 1.82) |
1.27 Postpartum haemorrhage
| 10535 | F (0) | 0.94 (0.87, 1.04) | |
1.27.1 Treatment of pre-eclampsia/eclampsia | 8909 | R (43) | 1.31 (0.39, 4.41) | |
1.27.2 Fetal neuroprotection | 1626 | F (0) | 0.84 (0.61, 1.15) | |
1.28 Pulmonary oedema
| 12787 | F (8) | 1.12 (0.72, 1.74) | |
1.28.1 Treatment of pre-eclampsia/eclampsia | 10560 | F (0) | 0.95 (0.60, 1.57) | |
1.28.2 Fetal neuroprotection | 1 [25] | 2227 | F (NA) | 2.80 (0.75, 10.53) |
Life-threatening adverse effects of treatment
Interventions to limit adverse effects
Adverse effects associated with treatment
Other outcomes
Subgroup analysis by indication for use
Subgroup analysis by regimen for administration
Comparison 2: lower dose versus higher dose IM maintenance: prevention or treatment of eclampsia
Outcome or subgroup | Studies | Participants | Method (I2(%))* | RR (95% CI) |
---|---|---|---|---|
Comparison 2: lower dose versus higher dose magnesium sulphate IM maintenance: treatment of pre-eclampsia/eclampsia
| ||||
2.1 Death due to 'toxicity’
| ||||
2.1.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) | 0.25 (0.01, 6.05) |
2.2 Stopped due to 'toxicity’
| ||||
2.2.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) |
0.05 (0.01, 0.39)
|
2.3 Deferred or skipped doses
| 176 | F (0) |
0.36 (0.20, 0.63)
| |
2.3.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) |
0.43 (0.23, 0.83)
|
2.3.2 'Dhaka’ regimen* versus 'Bhalla’ regimen~ | 1 [27] | 50 | F (NA) |
0.23 (0.07, 0.71)
|
2.4 Given calcium gluconate
| ||||
2.4.1 'Dhaka’ regimen* versus 'Bhalla’ regimen~ | 1 [27] | 50 | F (NA) | 0.25 (0.60, 1.06) |
2.5 Respiratory depression
| ||||
2.5.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) | 0.25 (0.01, 6.05) |
2.6 Absent tendon reflexes
| 176 | F (0) |
0.21 (0.10, 0.46)
| |
2.6.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) |
0.20 (0.08, 0.50)
|
2.6.2 'Dhaka’ regimen* versus 'Bhalla’ regimen~ | 1 [27] | 50 | F (NA) | 0.25 (0.06, 1.06) |
2.7 Gluteal abscess (pain, phlebitis, inflammation)
| ||||
2.7.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) | No gluteal abscesses |
2.8 Postpartum haemorrhage
| ||||
2.8.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) | 0.38 (0.03, 4.03) |
2.9 Pulmonary oedema
| ||||
2.9.1 4 g IV LD; 2 g/3 h IM MD versus Pritchard’s regimen^ | 1 [28] | 126 | F (NA) | 0.25 (0.01, 6.05) |
Comparison 3: magnesium sulphate IV maintenance versus IM maintenance: treatment of pre-eclampsia/eclampsia
| ||||
3.1 Death
| ||||
3.1.1 4 g IV LD; 0.75 g/hour IV MD versus Pritchard’s regimen^ | 1 [29] | 137 | F (NA) | 0.35 (0.04, 3.27) |
3.2 Discontinuation or modification of treatment
| 317 | F (0) | 1.46 (0.83, 2.58) | |
3.2.1 6 g IV LD; 2 g/hour MD versus Pritchard’s regimen^ | 1 [30] | 17 | F (NA) | 3.33 (0.15, 71.90) |
3.2.2 'Springfusor pump’ IV versus 'Standard’ IM regimen | 1 [31] | 300 | F (NA) | 1.41 (0.79, 2.52) |
3.3 Clinical signs of toxicity
| 154 | R (38) | 0.82 (0.05, 12.56) | |
3.3.1 4 g IV LD; 0.75 g/hour IV MD versus Pritchard’s regimen^ | 1 [29] | 137 | F (NA) | 0.21 (0.01, 4.27) |
3.3.2 6 g IV LD; 2 g/hour MD versus Pritchard’s regimen^ | 1 [30] | 17 | F (NA) | 3.33 (0.15, 71.90) |
3.4 Pain level 'acceptable’
| ||||
3.4.1 'Springfusor pump’ IV versus 'Standard’ IM regimen | 1 [31] | 300 | F (NA) |
4.93 (3.59, 6.78)
|
3.5 Caesarean section
| 154 | F (0) | 1.03 (0.78, 1.35) | |
3.5.1 4 g IV LD; 0.75 g/hour IV MD versus Pritchard’s regimen^ | 1 [29] | 137 | F (NA) | 0.99 (0.75, 1.32) |
3.5.2 6 g IV LD; 2 g/hour MD versus Pritchard’s regimen^ | 1 [30] | 17 | F (NA) | 1.50 (0.47, 4.76) |
3.6 Postpartum haemorrhage
| ||||
3.6.1 4 g IV LD; 0.75 g/hour IV MD versus Pritchard’s regimen^ | 1 [29] | 137 | F (NA) | 0.35 (0.04, 3.27) |
Comparison 4: short versus standard (24 hours) postpartum magnesium maintenance therapy: treatment of pre-eclampsia
| ||||
4.1 Toxicity
| 256 | F (NA) | 0.25 (0.06, 1.08) | |
4.1.1 Short (12 h) versus standard (24 h) | 1 [32] | 196 | F (NA) | No toxicity |
4.1.2 Short (based on clinical criteria) versus standard (24 h) | 1 [33] | 60 | F (NA) | 0.25 (0.06, 1.08) |
4.2 Side effects
| ||||
4.2.1 Short (based on clinical criteria) versus standard (24 h) | 1 [33] | 60 | F (NA) | 0.17 (0.02, 1.30) |
4.3 'Intolerance’
| ||||
4.3.1 Short (based on clinical criteria) versus standard (24 h) | 1 [33] | 196 | F (NA) | No intolerance |
Life-threatening adverse effects of treatment
Interventions to limit adverse effects
Adverse effects associated with treatment
Other outcomes
Comparison 3: IV maintenance versus IM maintenance: prevention or treatment of eclampsia
Life-threatening adverse effects of treatment
Interventions to limit adverse effects
Adverse effects associated with treatment
Other outcomes
Comparison 4: short versus standard (24 hour) postpartum maintenance therapy: prevention of eclampsia
Life-threatening adverse effects of treatment
Adverse effects associated with treatment
Comparison 5: lower dose versus higher dose IV maintenance: prevention of preterm birth
Outcome or subgroup | Studies | Participants | Method (I2(%))* | RR (95% CI) |
---|---|---|---|---|
Comparison 5: lower dose versus higher dose magnesium sulphate IV maintenance: tocolysis
| ||||
5.1 Cessation due to adverse effects
| 248 | F (NA) | No cessation | |
5.2 No side effects
| 248 | R (63) | 1.55 (0.94, 2.58) | |
5.2.1 4 g LD; 2 g/h MD versus 6 g LD; ≥ 2 g/h MD | 1 [34] | 100 | F (NA) | 1.17 (0.71, 1.91) |
5.2.2 4 g LD; 2 g/h MD versus 4 g LD; 5 g/h MD | 1 [35] | 148 | R (NA) |
1.96 (1.35, 2.84)
|
5.3 Flushing
| 248 | R (60) | 0.61 (0.33, 1.12) | |
5.3.1 4 g LD; 2 g/h MD versus 6 g LD; ≥ 2 g/h MD | 1 [34] | 100 | F (NA) | 0.87 (0.46, 1.63) |
5.3.2 4 g LD; 2 g/h MD versus 4 g LD; 5 g/h MD | 1 [35] | 148 | F (NA) |
0.46 (0.29, 0.73)
|
5.4 Nausea and vomiting
| ||||
5.4.1 4 g LD; 2 g/h MD versus 6 g LD; ≥ 2 g/h MD | 1 [34] | 100 | F (NA) | 0.79 (0.45, 1.37) |
5.5 Headache
| 248 | F (0) | 0.56 (0.30, 1.05) | |
5.5.1 4 g LD; 2 g/h MD versus 6 g LD; ≥ 2 g/h MD | 1 [34] | 100 | F (NA) | 0.80 (0.23, 2.81) |
5.5.2 4 g LD; 2 g/h MD versus 4 g LD; 5 g/h MD | 1 [35] | 148 | F (NA) | 0.50 (0.24, 1.03) |
5.6 Caesarean
| 248 | F (0) | 1.11 (0.73, 1.70) | |
5.6.1 4 g LD; 2 g/h MD versus 6 g LD; ≥ 2 g/h MD | 1 [34] | 100 | F (NA) | 1.31 (0.78, 2.21) |
5.6.2 4 g LD; 2 g/h MD versus 4 g LD; 5 g/h MD | 1 [35] | 148 | F (NA) | 0.88 (0.43, 1.80) |
5.7 Pulmonary oedema
| 260 | F (NA) | 0.21 (0.03, 1.76) | |
5.7.1 4 g LD; 2 g/h MD versus 6 g LD; ≥ 2 g/h MD | 1 [34] | 100 | F (NA) | No oedema |
5.7.2 4 g LD; 2 g/h MD versus 4 g LD; 5 g/h MD | 1 [35] | 160 | F (NA) | 0.21 (0.03, 1.76) |
Comparison 6: 'ready-to-use’ magnesium sulphate solution versus a reference drug requiring dilution: tocolysis
| ||||
6.1 Death
| 1 [36] | 46 | F (NA) | No deaths |
6.2 'Serious’ adverse events
| 1 [36] | 46 | F (NA) | No serious events |
6.3 Withdrawn from the study due to adverse effects
| 1 [36] | 46 | F (NA) | 0.67 (0.12, 3.62) |
6.4 Adverse events of 'severe intensity’
| 1 [36] | 46 | F (NA) | 0.67 (0.22, 2.05) |
6.5 1 or 2 injection site changes
| 1 [36] | 46 | F (NA) | 1.00 (0.28, 3.52) |
6.6 Poor general tolerability (physician assessed)
| 1 [36] | 43 | F (NA) | 3.14 (0.13, 72.96) |
6.7 Respiratory depression
| 1 [36] | 46 | F (NA) | 0.20 (0.10, 3.95) |
6.8 Warmth (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 0.84 (0.42, 1.69) |
6.9 Nausea and/or vomiting (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 0.536 (0.11, 2.56) |
6.10 Tiredness (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 1.18 (0.57, 2.45) |
6.11 Headache (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 0.92 (0.41, 2.06) |
6.12 Dry mouth (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 0.82 (0.38, 1.77) |
6.13 Dizziness (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 1.05 (0.30, 3.64) |
6.14 Sweating (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 1.31 (0.41, 4.20) |
6.15 Skin redness (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 1.75 (0.48, 6.38) |
6.16 Burning at injection site (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 0.42 (0.16, 1.12) |
6.17 Palpitations (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 1.58 (0.29, 8.46) |
6.18 Constipation (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 4.20 (0.51, 34.44) |
6.19 Dyspnoea (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | No dyspnoea |
6.20 Heart pain (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 0.35 (0.20, 8.10) |
6.21 Agitation (mild, severe, very severe)
| 1 [36] | 41 | F (NA) | 4.20 (0.51, 34.44) |
Life-threatening adverse effects of treatment
Interventions to limit adverse effects
Adverse effects associated with treatment
Other outcomes
Comparison 6: ready to use solution versus reference drug requiring dilution: prevention of preterm birth
Life-threatening adverse effects of treatment
Interventions to limit adverse effects
Adverse effects associated with treatment
Other outcomes
Evidence from non-randomised comparative studies with concurrent controls
Study | Participants and comparison | Adverse effect | Estimates | P-value or effect estimate (95% CI) |
---|---|---|---|---|
Magnesium sulphate versus no magnesium sulphate
| ||||
Ales 1987 [37] | 178 women. MgSO4 for H (n = 64) v no MgSO4 (n = 114) | Caesarean | 39.1 v 29.0% |
AOR 2.81 (1.99, 3.62)^
|
Caesarean (failure to progress) | 72.0% v 42.4% |
OR 3.49 (1.15, 10.62)
| ||
Seyb 1999 [38] | 1561 women. MgSO4 for PE (n = 54) v no MgSO4 (n = 1507) | Caesarean | 22.2% v 10.2% |
OR 2.53 (1.30, 4.91)
|
Caesarean |
AOR 2.18 (1.04, 4.55)*
| |||
Park 2006 [39] | 231 women. MgSO4 for PE (n = 29) v no MgSO4 (n = 202) | Failed induction of labour |
AOR 17.78 (1.62, 195.14)~
| |
Assaley 1998 [40] | 18 women. MgSO4 for PE (n = 15) v no MgSO4 (n = 3) | Significant ↑ in bleeding time with MgSO4 (v no significant change with no MgSO4) |
P < 0.0043
| |
Kynczl-Leisure 1996 [41] | 12 women. MgSO4 for PE (n = 9) v no MgSO4 (n = 3) | Significant ↑ in bleeding time with MgSO4 (v no significant change with no MgSO4) |
P < 0.01
| |
Ramanathan 1988 [42] | 16 women. MgSO4 for PE (n = 10) v no MgSO4 (n = 6) | Significant ↓ in pulmonary function (FVC (L), FEV1(L), MVV (L)) with MgSO4 (v no significant change with no MgSO4) |
P < 0.005; P < 0.01; P < 0.02
| |
Ramanathan 1988 [43] | 32 women. 1. Labour augmentation and MgSO4 for PE (n = 16) v 2. MgSO4 postpartum for PE (n = 6) v 3. Labour induction and no MgSO4 (n = 10) | Depression of neuromuscular transmission for Groups 1 and 2 (before MgSO4 to during MgSO4) v no changed for Group 3 (before and during induction, and postpartum) | ||
Poggi 2003 [44] | 66 women. Pulmonary oedema (n = 15) v no pulmonary oedema (n = 51) | Case (pulmonary oedema) v control MgSO4 exposure (for PE or PTL) | 93.3% v 62.7% |
P = 0.049
|
All women received magnesium sulphate: comparison based on antihypertensive agent received
| ||||
Magee 2005 [45] | 377 women who all received MgSO4 for PE. 1. Nifedipine (n = 162) v 2. Other antihypertensive (n = 32) v 3. No antihypertensive (n = 183) | Calcium gluconate given | 0.5% v 3.1% v 0.0% | P = 0.30 (1v2); P = 0.47 (1v3) |
Infusion stopped due to adverse effects | 1.2% v 3.1% v 4.9% | P = 0.42 (1v2); P = 0.05 (1v3) | ||
Infusion reduced due to adverse effects | 8.0% v 3.1% v 7.7% | P = 0.47 (1v2); P = 0.90 (1v3) | ||
Neuromuscular weakness | 53.1% v 53.1% v 44.8% | P = 0.99 (1v2); P = 0.13 (1v3) | ||
Absent deep tendon reflexes | 5.6% v 6.3% v 3.8% | P = 0.12 (1v2); P = 0.22 (1v3) | ||
Weakness | 15.4% v 28.1% v 10.9% | P = 0.99 (1v2); P = 0.26 (1v3) | ||
Respiratory depression | 9.9% v 9.4% v 6.6% | P = 0.99 (1v2); P = 0.45 (1v3) | ||
Neuromuscular blockade | 0.0% v 6.25% v 0.0% |
P = 0.03 (1v2); P = NA (1v3) | ||
Maternal hypotension | 41.4% v 31.3% v 53.0% | P = 0.33 (1v2); P = 0.04 (1v3)
| ||
Nausea/vomiting | 49.4% v 43.8% v 47.0% | P = 0.70 (1v2); P = 0.66 (1v3) | ||
Drowsiness/confusion | 45.7% v 37.5% v 38.3% | P = 0.44 (1v2); P = 0.16 (1v3) | ||
Dizziness | 28.4% v 25.0% v 20.8% | P = 0.83 (1v2); P = 0.10 (1v3) | ||
Flushing | 22.2% v 15.6% v 20.8% | P = 0.48 (1v2); P = 0.74 (1v3) | ||
Thirst | 20.4% v 21.9% v 7.1% | P = 0.81 (1v2); P < 0.001 (1v3)
| ||
Respiratory problems | 14.8% v 6.3% v 7.7% | P = 0.26 (1v2); P = 0.03 (1v3)
| ||
Dyspnoea | 8.6% v 0.0% v 4.9% | P = 0.13 (1v2); P = 0.17 (1v3) | ||
Pulmonary oedema | 2.5% v 0.0% v 1.1% | P = 0.99 (1v2); P = 0.57 (1v3) | ||
Oxygen required | 4.9% v 3.1% v 2.2% | P = 0.99 (1v2); P = 0.16 (1v3) | ||
Maternal tachycardia | 22.2% v 18.8% v 14.2% | P = 0.82 (1v2); P = 0.05 (1v3) | ||
Itchy/tingling | 14.8% v 18.8% v 15.3% | P = 0.60 (1v2); P = 0.90 (1v3) | ||
Tremulous | 6.8% v 9.4% v 2.7% | P = 0.27 (1v3) | ||
Minor bleeding | 4.9% v 6.3% v 0.0% | P = 0.67 (1v2); P = 0.002 (1v3)
| ||
Chest pain | 5.6% v 6.3% v 2.7% | P = 0.99 (1v2); P = 0.19 (1v3) |
Study | Participants and comparison | Adverse effect | Estimates | Effect estimate (95% CI) |
---|---|---|---|---|
Magnesium sulphate versus no magnesium sulphate
| ||||
Chowdhury 2000 [46] | 630 women (E). Low dose IV (4 g IV LD over 2–3 mins; 5 g/8 h IV MD) (n = 150) v Pritchard’s IM regimen (4 g IV and 10 g IM LD; 5 g/4 h IM MD) (n = 480) | Major adverse effects; respiratory depression | 0.0% v 0.0% | NA |
Absent knee jerks and oliguria; stopped dosing due to adverse effects | 0.0% v 3.2% | RR 0.10 (0.01, 1.71) | ||
Pain at injection site | 0.0% v 55.0% |
RR 0.01 (0.00, 0.10)
| ||
Mahajan 2007 [47] | 95 women (E). 1. (2 g IV and 4 g IM LD; 4 g IM/4 h) (n = 37) v 2. (2 g IV and 8 g IM LD; 4 g IM/4 h) (n = 58) | Respiratory depression | 0.0% v 0.0% | NA |
Absent knee jerks and MD omitted | 56.8% v 31.0% |
RR 1.83 (1.14, 2.94)
| ||
Young 1977 [48] | 144 women (PE or E). 1. (10 g IM LD; 2 g slow IV 'push’ with repeated doses every 1–2 h) (n = 97) v 2. (10 g IM LD; continuous IV 1 g/h) (n = 47) | Death | 0.0% v 0.0% | NA |
Heat and flushing | 92.8% v 0.0% |
RR 88.65 (5.62, 1397.80)
| ||
Respiratory effects (slowing respirations to complete apnoea) | 79.4% v 0.0% |
RR 75.92 (4.81, 1198.55)
| ||
Shoaib 2009 [49] | 100 women (severe PE). LD only (4 g IV and 10 g IM LD) (n = 50) v Pritchard’s IM regimen (4 g IV and 10 g IM LD; 5 g/4 h IM) (n = 50) | Death; respiratory failure or distress; cardiac arrest | 0.0% v 0.0% | NA |
Nausea and vomiting | 10.0% v 34.0% |
RR 0.29 (0.12, 0.74)
| ||
Warmth and flushing | 70.0% v 80.0% | RR 0.88 (0.70, 1.10) | ||
Dizziness | 20.0% v 56.0% |
RR 0.36 (0.19, 0.65)
| ||
Irritation at the injection site | 0.0% v 20.0% |
RR 0.05 (0.00, 0.79)
| ||
Caesarean | 12.0% v 30.0% |
RR 0.40 (0.17, 0.95)
| ||
Palmer 2009 [50] | 76 women (PE). New protocol (20% solution, separate LD and MD bags) (n = 29) v Old protocol (2-8% solution, same LD and MD bag) (n = 47) | Phlebitis; signs or symptoms of toxicity | 0.0% v 0.0% | NA |
Calcium gluconate (for hypocalcaemia) | 3.5% v 4.3% | RR 0.81 (0.08, 8.54) | ||
Errors (failure to reset pump after LD) | 0.0% v 4.3% | RR 0.32 (0.02, 6.44) | ||
Errors (change in drug order) | 3.5% v 2.1% | RR 1.62 (0.11, 24.92) | ||
Nassar 2006 [51] | 155 women (PTL). 1. Treatment for > 48 hours (n = 78) v 2. Treatment for < 48 hours (n = 77) | ≥ 1 adverse effect | 30.8% v 15.6% |
OR 2.41 (1.10, 5.26)
|
Discontinuation due to adverse effects | 6.4% v 0.0% | OR 11.60 (0.63, 213.47) | ||
Chest tightness | 19.2% v 11.8% | OR 1.80 (0.74, 4.40) | ||
Visual disturbances | 6.4% v 1.3% | OR 5.21 (0.59, 45.63) | ||
Vulvar oedema | 1.3% v 0.0% | OR 3.00 (0.12, 74.79) | ||
Pulmonary oedema | 6.4% v 2.6% | OR 2.57 (0.48, 13.66) | ||
Ileus | 3.8% v 1.3% | OR 3.04 (0.31, 29.89) | ||
Osteopenia | 2.6% v 0.0% | OR 5.07 (0.24, 107.25) | ||
Hypocalcaemia (< 8.5 mg/dl) | 24.6% v 15.6% | OR 1.77 (0.74, 4.21) |
Evidence from case series
Adverse effect | Mean (%) or effect | Median (%) | Range (%) | Women | Studies |
---|---|---|---|---|---|
Death | 0.14 | 0.00 | 0 to 0.41 | 285 | |
Cardiac arrest | 0.00 | 0.00 | NA | 21 | Adewole 2000* [53] |
Respiratory arrest | 0.41 | 0.42 | 0 to 0.82 | 983 | |
Discontinuation due to adverse effects | 9.53 | 9.52 | 1.75 to 20.78 | 532 | |
Given calcium gluconate | 0.70 | 0.70 | NA | 717 | Raman 1995* [56] |
'Toxicity’ | 3.17 | 2.04 | 0.0 to 8.60 | 182 | |
Need to adjust/skip dose due to adverse effects | 15.26 | 15.26 | 5.26 to 25.26 | 114 | |
Respiratory depression | 1.67 | 0.72 | 0 to 4.76 | 1363 | |
Absent or reduced deep tendon reflexes | 4.75 | 2.55 | 0 to 18.05 | 1789 | |
Any adverse effects | 13.39 | 14.29 | 6.76 to 19.11 | 826 | |
'Minor side effects’ | 1.75 | 1.75 | NA | 57 | Girard 2005* [58] |
Hypotension | 30.56 | 30.56 | NA | 72 | Hales 1995^ [69] |
Flushing or warmth | 52.88 | 52.88 | 4.55 to 100 | 27 | |
Nausea and/or vomiting | 47.37 | 38.46 | 3.66 to 100 | 373 | |
Generalised weakness | 23.08 | 23.08 | NA | 13 | Digre 1990^ [68] |
Drowsiness or confusion | 2.58 | 2.90 | 0.28 to 4.55 | 515 | |
Headache | 2.90 | 0.72 | 0.28 to 7.69 | 506 | |
Blurred vision | 46.30 | 46.30 | 0.28 to 92.31 | 368 | |
Diplopia | 30.77 | 30.77 | NA | 13 | Digre 1990^ [68] |
Photophobia | 30.77 | 30.77 | NA | 13 | Digre 1990^ [68] |
Visual signs | 76.92 | 76.92 | NA | 13 | Digre 1990^ [68] |
Abnormal visual acuity | 38.46 | 38.46 | NA | 13 | Digre 1990^ [68] |
Impaired concentration-confusion | 23.08 | 23.08 | NA | 13 | Digre 1990^ [68] |
Cardiac arrhythmias | 23.08 | 23.08 | NA | 13 | Digre 1990^ [68] |
Chest pain (and/or need for ECG) | 3.90 | 3.90 | 0.85 to 6.94 | 427 | |
Chest tightness | 0.28 | 0.28 | NA | 355 | Elliot 1983^ [57] |
Delayed recovery from anaesthesia | 0.14 | 0.14 | NA | 717 | Raman 1995* [56] |
Pulmonary oedema | 1.25 | 1.25 | 1.13 to 1.36 | 649 | |
Caesarean | 49.68 | 56.52 | 32.53 to 60.00 | 225 | |
Caesarean due to labour induction | 48.91 | 51.85 | 33.33 to 61.54 | 109 | |
'Transient nausea, vomiting, headache, flushing and palpitations’ | NA | NA | NA | 15 | Jirapinyo 1990^ [74] |
'Magnesium toxicity suspected’ | 2/49 deaths due to hypertensive disorders of pregnancy were attributed to magnesium | Dasari 2010* [61] | |||
Hospital errors in obstetric patients | 146 hospital errors in obstetric patients (3rd most common obstetric drug resulting in patient harm) | Kfuri 2008 ~ [75] | |||
10 class 2 errors (need for additional treatment/ hospitalisation) | Little 2001 ~ [76] | ||||
'Restrictive type of respiratory depression’ | Sig ↓ in FVC (L) | 18 | Bilgin 1994* [77] | ||
Decrease in respiratory function – 'generalised respiratory muscle weakness’ | Sig ↓ MIP (cm H2O), MEP (cm H2O), FEV1 (L) | 10 | Herpolsheimer 1991* [78] | ||
'Reduced attention and rapid information processing ability’ | Sig ↓ in SSS, PASAT, VAF, DSF scores | 15 | Ghia 2000^ [79] | ||
Increase in bleeding time ('clinical significance remains to be determined’) | Sig ↑ | 104 | |||
NS ↑ | 40 | Moghadas 2007^ [83] |
Evidence from case reports
Common theme and/or associated adverse effects | Studies |
---|---|
Iatrogenic overdose (16 studies)
| |
Death | |
Death or persistent vegetative state | Simpson 2004 (7 cases) [87] |
Cardiopulmonary arrest | |
Cardiac arrest | Cohen 1992 [85] |
Respiratory arrest | |
“Life-threatening situation” | Bruhwiler 1994 [97] |
Coma | Hayashi 2003 [98] |
Ventilatory impairment; failure to rouse from general anaesthesia | McDonnell 2010 [99] |
Need for additional monitoring | Buettner 2010 (2 cases) [100] |
Variety (not death or remaining in a persistent vegetative state) | Simpson 2004 (45 cases) [87] |
Rapid administration (1 study)
| |
Cardiac arrest | Richards 1985 [86] |
Unintended epidural or intrathecal administration (4 studies)
| |
Bilateral periumbilical pain | Dror 1987 [101] |
Inadequate pain relief | Goodman 2006 (2 cases) [102] |
Paralysis of lower extremities | |
Increased risk of adverse effects – neuromuscular junction disorders, myopathies and neuropathologies (8 studies)
| |
Weakness and/or temporary paralysis | |
Muscle pain and damage | Hosono 2001 [108] |
Acute respiratory insufficiently; ventilatory failure; respiratory depression | |
“Magnesium toxicity” | Moriarty 2008 [112] |
Increased risk of adverse effects – renal failure (3 studies)
| |
Decreased or absent deep tendon reflexes; prolonged QT interval | Archer 2010 [113] |
Muscle weakness | Chan 2008 [114] |
Progressive quadriparesis | Nethravathi 2007 [115] |
Drug interactions – agents used in general anaesthesia (10 studies)
| |
Cardiac arrest | Saitoh 1994 [116] |
Respiratory arrest | Baraka 1984 [117] |
Failure to achieve adequate ventilation | Nguyen 2001 [118] |
Numb; difficultly moving upper extremities | Fay 1996 [119] |
Prolonged neuromuscular blockade | |
Drug interactions – other agents (6 studies)
| |
Neuromuscular blockade – muscle weakness or paralysis | |
Extreme bradycardia | Pittman 2000 [129] |
Severe hypotension | |
Unusual/unexpected adverse effects (11 studies)
| |
Bilateral, progressive labial swelling (need for caesarean) | Awwad 1994 [132] |
Worsened clinical picture of appendicitis and cholecystitis | Basaran 2007 [133] |
Impaired lactogenesis | Haldeman 1993 [134] |
Severe paralytic ileus | Hill 1985 [135] |
Marked osteoporotic change (hips, knees, ankles) | Hung 2005 [136] |
Breast engorgement and galactorrhea | Lurie 2002 [137] |
Development of central pontine myelinolysis | Riggs 2000 [138] |
Urinary tract stone (magnesium ammonium phosphate) | Sameshima 1997 [139] |
Hyperkalaemia and hyponatremia (hyporeninemic hypoaldosteronism) | Spital 1991 [140] |
Left retinal detachment; partial right detachment | Roberts 1998 [141] |
Extensive urticarial rash | Thorp 1989 (2 cases) [142] |
Other adverse effects (16 studies)
| |
Severe hypotension | |
Hypothermia | |
Bradycardia (39-44/minute) | Hennessy 1999 [146] |
Asymptomatic atrial fibrillation (100-150/minute) | Oettinger 1993 [147] |
Absent deep tendon reflexes | Pritchard 1979 [148] |
Marked weakness; difficulty breathing | Pritchard 1979 [148] |
Sleepiness/fatigue; depressed/absent deep tendon reflexes | |
Chest pain; inverted T waves (ECG) (transient subendocardial ischemia) | Sherer 1992 [151] |
Pulmonary oedema | |
Bilateral hand contractures; tetany (serum hypocalcaemia) | Koontz 2004 (2 cases) [152] |
Diplopia; malaise; paresthesia; hoarseness; tetany (serum hypocalcaemia) | Mayan 1999 (2 cases) [153] |
Hypotension; cyanosis; tetany (serum hypocalcaemia) | Monif 1972 [154] |
Chest tightness and pain; prolonged QT interval (serum hypocalcaemia) | Nassar 2007 [155] |
Delirium with myoclonus (serum hypocalcaemia) | Ganzenvoort 2002 [156] |