Magnesium Sulfate in

Obstetrics: Indications and

Complications
Siri L. Kjos, MD
Department of OBGYN, Harbor
UCLA
Oleh:
Rafsanjani
Fika Ariska
Pembimbing: dr. Tengku puspa Dewi, Sp.OG

Magnesium Sulfate in Obstetrics

Indications and Complications: Objectives

State mechanism of action on

muscles and cells
State the serum levels associated
with side effects and toxicityknow
how to monitor for toxicity
State benefits and risks of use in
preeclampsia and preterm labor

Seizure Prophylaxis in
Preeclampsia/Eclampsia

Magnesium Sulfate and Effect on

Musculature

Slows or blocks neuromuscular and cardiac conducting

system transmission
Inhibit release of acetylcholine from presynaptic
nerve terminal,
Depresses postjunctional membrane response
and response of underlying myofibrils
Result: Muscle weakness and respiratory
depression with overdose
Decreases smooth muscle contractility
Uterine smooth muscle: tocolytic
myocardial contractility, respiration

Depress central nervous system irritability

(anticonvulsant)
Little effect on Blood pressure in therapeutic ranges

Magnesium Sulfate and Effect on

Musculature
Depression
mEq/L] occur
below
Dosage
for DTRs
seizure[10
prophylaxis:
1 g/hr
or levels
2 g/hr:of

cardiac
or respiratory
depression
both doses
safe with normal
renal function

monitor
higheffective
levels but
not to
monitor
1Use
g/hr to
appears
equally
(Magpie
trial)
without
therapeutic
levelsbrisk reflexes do occur with
serious
complications
anticonvulsant doses [4-6 mEq/l]. Do not need
to monitor
levels
efficacy serum [Mg]
Neonatal
serum
[Mg]for
~ maternal

Monitor
atwith
least
every 2infusion
hours secondary to
AFI
levels DTRs
increase
prolonged
Load:
4-6 gexcretion
over 15-30
minutes
Continuous
fetal renal
but fetal
serum[Mg]
do not increase
infusion
g/hr. serum [Mg] 3.7 mEq/dl
Average1-2
newborn
No correlation
NN [Mg] [Cr>1.0
and APGAR
Impaired
renal of
function:
mg/dl]
No
evidence
of cumulative
effects on neonate from

Rate
1.0 g/hr;
Obtain [Magnesium]
prolonged magnesium infusion
Calcium Gluconate (10ml of 10% solution given IV
over 3 minutes)

Preeclampsia / Eclampsia
In the US, the frequency of eclamptic seizures in
preeclampsia is < 1%, with reported incidence in
the Western world of 1/2,000- 1/3,000 deliveries 1
Estimated < 1/200 for mild and 1/50 for severe
disease 2
Incidence of intrapartum eclampsia: < 1/600
(0.17%) of cases of mild preeclampsia

1.Sibai BM. Magnesium sulfate is the ideal anticonvulsant in preeclampsia-eclampsia. Am J Obstet. Gynecol. 2010;
162:1141-45.
2.Sibai BM. Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials. Am J Obstet Gynecol. 2004.
190:1520-26.
3. Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ. 2011; 309:1395-1400.
4. Mattar F, Sibai BM. Eclampsia. Risk factors for maternal morbidity. Am J Obstet Gynecol. 2008; 182:307-312.
5. .Andersgaard, AB, et al. Eclampsia in Scandinavia: incidence, substandard care, and potentially preventable cases. Acta
Obstetricia et Gynecologica. 2012; 85:929-36.

Intrapartum Management
Eclampsia: 1:300-1,000

Seizures are usually self-limited (1-2 minutes)

Prevent aspiration of gastric contents
Diazepam or Ativan
onlyif sustained
Prolonged deceleration will recover after seiz
If possible, allow time for full fetal recovery

Cesarean only if vaginal birth not possible within

reasonable time frame

Treatment of severe preeclampsia with

Magnesium sulfate is supported by level I
evidence, ACOG (level A)
Author (year)

Seizure incidence
Magnesiu Other
m sulfate

BP Agents

RR (CI)

Moodley (94)

1/112

0/116

Dihydralazine
Nifedipine

N/A

Chen (95)

0/34

0/34

Hydralazine,
Nifedipine

N/A

Belfort (97)

5/324

11/303

Nimodipine,
Hydralazine

0.43
(0.15-1.2)

Coetzee (98)
placebo RCT

1/345

11/340

Hydralazine,
Labetolol

0.09
(0.01-0.69)

Total

7/815
(0.9%)

22/793
(2.8%)

0.31
(0.13-0.72)

Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol.
1998; 92:883-9.

Treatment of eclampsia with

Magnesium sulfate
Supported by level I evidence, ACOG
Recurrent
(level A)

Author (year)

seizures
Magnesiu

Other

Agent

RR (CI)

m sulfate
Dommisse (90)

0/11

4/11

Phenytoin

N/A

Crowther (90)

5/24

7/27

Diazepam

0.8 (0.9-2.2)

Bhalla (94)

1/45

11/45

Cocktail

0.09 (0.01-0.7)

Friedman (95)

0/11

2/13

Phenytoin

N/A

Collaborative
Trial (95)

60/453
22/368

126/452
66/387

Diazepam
Phenytoin

0.48 (0.4-0.6)
0.33 (0.2-0.5)

Total

88/932
(9.4%)

216/935
(23.1%)

Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol.
1998; 92:883-9.

Magnesium Sulfate: Do women

with mild preeclampsia need
prophylaxis?
When does risk of Magnesium prophylaxis exceed
seizure risk?
Magpie Study1:
Magnesium safe and effective even in developing
countries
Most had severe preeclampsia (75% needed anti-hypertensive
Rx)

When Magnesium limited to severe disease 50%

in seizures2
Difficult to select which women with preeclampsia will
progress to eclampsia based on symptoms 3
1. Altman D, Lancet 359:1877-90, 2011
2. Alexander JM. Obstet Gynecol 108:826-32, 2008
3.
Sibai BM. Obstet Gynecol 57:199-202, 2010

Magnesium sulfate and Mild

Preeclampsia
Magpie Trial

Magpie Trial (n=10,141) 33 countries

involved
Double-blind, placebo RCT

Criteria: SBP 140 or DBP 90 (x2),

Proteinuria 1+
Magnesium sulfate vs. Placebo
* All patients from US (43), and 248/251
patients from Cuba, had mild
preeclampsia (severe cases not generally
The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium
sulphate? The Magpie Trial: a randomized placebo-controlled trial. Lancet 2010; 359:1877-90.

The Magpie Trial

Seizure incidence
Magnesiu Placeb
m sulfate
o

RR

NNT

All patients

0.8%

1.9%

0.42
(0.3-0.6)

91

Iminent
eclampsia*

1.0%

3.7%

0.26
(0.1-0.6)

36

Severe
preeclampsia

1.2%

2.8%

0.42
(0.2-0.8)

63

Non-severe
preeclampsia

0.7%

1.6%

0.42
(0.3-0.7)

109

* Two or more of the following: hyperreflexia, frontal headache, blurred

vision, epigastric tenderness (regardless of blood pressure and
proteinuria)

The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie
Trial: a randomized placebo-controlled trial. Lancet 2002; 359:1877-90.

The Magpie Trial

Conclusions
Magnesiu
Placebo
RR
NNT
m sulfate
Women with severe preeclampsia, imminent
High
PMR* and those
1.2%with preeclampsia
2.8%
0.42
eclampsia,
in high 63
>40/1,000
PMR countries, appear to benefit the (0.2-0.8)
most.
Medium
PMR of Magnesium
0.7%
1.6% in countries
0.42
109
No benefit
sulfate
20-40/1,000
(0.3-0.7)
with low PMR
Eclampsia

Low
PMR
0.5%
0.8%
0.67 the risk
N/A
Magnesium
sulfate
is effective
in reducing
(0.2-2.4)
<20/1,000
(4/778)with(6/782)
of eclampsia in women
preeclampsia:
births
* Perinatal mortality
rate

The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The
Magpie Trial: a randomized placebo-controlled trial. Lancet 2011; 359:1877-90

When should Magnesium Sulfate

Therapy be initiated in preeclampsia?
Timing of Initiation in clinical trials
tria
Author

Preeclampsia

Initiation of
MagSO4

MagSO4
regimen

Duration of
MagSO4

Mild/
severe

Latent /
Active

4g / 1g

Up to
24hrs

In clinical trials,
in which
the methods
were
Mild
Latent /
6g / 2g
11.4 +/described, Magnesium
sulfate 10.6
washr
Active
always
initiated
once
the decision
wasCoetzee
98
Severe
Latent
/ Active
4g / 1g
(n=699)
made for delivery
Witlin 97
clearly
(n=135)

Magpie 02
(N=10,141)

Livingston 03
Mild
Regardless
(N=222)

Latent /
6g / 2g
of mild
or
severe
status,
Active
no investigator
has described
waiting until
Belfort 03
Severe
Latent /
6g / 2g
Up to
the active phase of labor
(n=1650)
Active to start
4g / 1g
24 hrs
Magnesium sulfate

Magnesium Sulfate: Duration of

prophylaxis
Author

Conclusion

PreInitiation of MagSO4 Duration of

eclampsia
MagSO4
MagSO4
02
(N=10,141)
limitedregimen
Magnesium

Magpie trial
Witlin to
9724hrs. Mild
sulfate
(n=135)

Latent /
Active

6g / 2g

11.4 +/10.6 hr

After 24hrs, if delivery had not occurred, the

Coetzee 98
Severe
Latent /
4g / 1g
decision
for
continued
treatment
was
physician(n=699)
Active
dependent
Magpie 02
Mild/severe
Latent /
4g / 1g
Up to
24hrs
Active24hr limit has not
(N=10,141)
Concluded that exceeding

been
proven
safe
Livingston
03
Mild
(N=222)

Latent /
Active

6g / 2g

Belfort 03
Severe
Latent
/
6g
/ 2g
Up to
Belfort
03 (N=1650),
also
limited
Magnesium
Active
(n=1650)
24 hrs
sulfate
to 24hrs, and protocol
called 4g
for/ 1g
C/S unless
delivery imminent

Are Magnesium levels beneficial, or can we

rely on clinical symptoms to determine
Magnesium Sulfate toxicity?
Therapeutic dose
Zuspan initiated IV infusion : 4g load, and 1g/hr

Pritchard identified therapeutic range :

-serum magnesium 4.2-8.4 mEq/L
In study by Sibai, he found that with:
4g load, 1g/hr: 1.7% (2/115 ) in therapeutic range
4g load, 2g/hr: 5.1% (23/45 )in therapeutic range
6g load, 2g/hr: 100% within therapeutic range
Zuspan FP. Treatment of severe preeclampsia and eclampsia. Clin Obstet Gynecol. 1966;9:954-72.
Pritchard JA. The use of the magnesium ion in the management of eclamptogenic toxemias. Surg Gynecol Obstet 1955; 100: 131-140.
Sibai BM. Magnesium sulfate is the ideal anticonvulsant in preeclampsia-eclampsia. Am J Obstet Gynecol. 1990; 162:1141-45.

Magnesium Sulfate:
How do we monitor for toxicity?
Most physicians rely on clinical
signs/symptoms
In Magpie trial respiratory signs were
more telling than tendon reflexes:
Magnesium

Placebo

Reduced tendon reflexes

1.2%

1.2%

Respiratory depression
0.5%

1.0%

The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit
from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet
2002; 359:1877-90.

Major differences were in minor symptoms:

Magnesium Sulfate
How do we monitor for toxicity?
Many clinicians send level when concern for toxicity
- Whenarises.
monitoring
toxicity need to realize:
However, levels >12 mEq/L are rare with proper
infusion, and in the absence of renal disease.
-Magnesium
is cleared by the kidneys in
Toxic levels:
levels
concentration-dependent
manner
N/V, flushing, weakness:

9-12 mEq/L

Respiratory depression:

>14 mEq/L

- Usually, a higher Magnesium concentration leads

Loss of tendon reflexes:
>12 mEq/L
to higher excretion from the body
- However,
patients
with
oliguria, elevated
creatinine,
Paralysis,
respiratory
arrest:
15-17 mEq/L
and/orCardiac
chronic
renal disease (e.g.
DM, CHTN) should
arrest:
>25 mEq/L
be monitored very closely due to impaired excretion
Lindow SW. Magnesium sulphate: a review of clinical pharmacology applied to obstetrics. British
Journal of Obstetrics and Gynecology. 1998; vol.105:260-68.

Magnesium Sulfate
How long should we treat postpartum?
12-24 hr regimen postpartum followed in most
trials
27-65% of eclamptic seizures occur post-partum,
and 38-84% occur within 48hrs
However, studies on patients with eclampsia have
concluded that postpartum eclampsia is usually
self-limited and associated with decreased
morbidity
This has triggered desire to decrease post-partum
Magnesium sulfate
Mattar F, Sibai BM. Eclampsia: Risk factors for maternal morbidity. Am J Obstet Gynecol. 2000;
182:307-312.

Is postpartum magnesium sulfate

necessary?
Postpartum magnesium sulfate: using
maternal clinical parameters to guide
therapy

Study: (Isler, 2012) Prospective clinical trial

(n=503)

Gave Magnesium sulfate 2g/hr postpartum

until:
absence of persistent headache / visual
changes
absence of epigastric pain
greater than 50% BP readings <150/100
BP <160/110 preceding 2hrs

Isler CM, et al. Postpartum seizure prophylaxis: Using maternal clinical parameters to guide therapy.
Obstet Gynecol. 2012; 101:66-69.

diuresis of >100ml/hr for >2hrs

Postpartum Magnesium Sulfate and

Breastfeeding
Magnesium still elevated in colostrum
x24hrs after infusion, but the level is
considered safe in breastfeeding 1
The decision to treat mild preeclampsia
with magnesium sulfate, and the duration
of post-partum treatment in severe
preeclampsia can delay breastfeeding and
infant bonding
It is well studied that delayed initiation of
breastfeeding leads to lower rates of long1. Cruikshank DP, et al. Breast milk magnesium
and calcium concentrations following magnesium sulphate
2
term
success
treatment. Am J Obstet Gynecol. 1982; 143:685-88.
2.Yamauchi Y, Yamanouchi I. Breastfeeding frequency during the first 24 hours after birth in full-term neonates.
Pediatrics. 1990;86:171-75.

Summary: Magnesium sulfate

use in
preeclampsia/eclampsia
Magpie trial supports use of magnesium sulfate in
mild preeclampsia for countries with medium-high
PMR
RCTs show no benefit of magnesium sulfate in mild
preeclampsia in US and countries with low PMR
Magpie trial (N=10,141) concluded no difference in
perinatal morbidity between magnesium sulfate
and placebo (24hrs)
No clinical trial has been performed to evaluate the
initiation of magnesium sulfate in active labor, or to
evaluate its use >24hrs

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