Transcript Magnesium Sulfate

Magnesium Sulfate in Obstetrics:
Indications and Complications
Siri L. Kjos, MD
Department of OBGYN, Harbor UCLA
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 toxicity—know 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
DTR’s
[10 mEq/L]
occur below1levels
or
Dosage for
seizure
prophylaxis:
g/hr of
orcardiac
2 g/hr:
respiratory
depression
•both doses
safe with normal renal function
–
monitorequally
high levels
but not(Magpie
to monitor
therapeutic
•1 Use
g/hrtoappears
effective
trial)
without
levels—brisk
reflexes do occur with anticonvulsant doses
serious
complications
[4-6 mEq/l]. Do not need to monitor levels for efficacy
– Monitorserum
DTR’s at[Mg]
least ~
every
2 hours serum [Mg]
•Neonatal
maternal
•AFI 4-6
levels
increase
with prolonged
infusion
secondary
• Load:
g over
15-30 minutes
→ Continuous
infusion
1-2 to
fetal renal excretion but fetal serum [Mg] do not increase
g/hr.
•Average
newborn
serum
[Mg]
3.7 mEq/dl
• Impaired
renal
function:
[Cr>1.0
mg/dl]
•No correlation of NN [Mg] and APGAR
– Rate 1.0 g/hr; Obtain [Magnesium]
•No evidence of cumulative effects on neonate from
• Calcium
Gluconate
(10ml of
10% solution given IV over 3
prolonged
magnesium
infusion
minutes)
Pharmacology of Magnesium Sulfate
• Volume distribution: beyond extracellular
fluid, enters bones and cells
• Circulates largely unbound to protein
• Exclusively excreted in the urine
– Reabsorbed in the proximal tubule, limited by
transport maximum (Tmax)
– Excretion increases as filtered load increases
above Tmax.
– T ½ time for excretion: 4 H (normal renal
function)
• Excretion prolonged in women with↓GFR
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
•
Percentage of eclamptic fits that occur intrapartum:
- UK 18% 3; Tennessee 19% 4; Scandinavia 29% 5
•
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. 1990; 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. 1994; 309:1395-1400.
4. Mattar F, Sibai BM. Eclampsia. Risk factors for maternal morbidity. Am J Obstet Gynecol. 2000; 182:307-312.
5. .Andersgaard, AB, et al. Eclampsia in Scandinavia: incidence, substandard care, and potentially preventable cases. Acta Obstetricia et Gynecologica.
2006; 85:929-36.
Frequency of symptoms preceding
Eclampsia
Symptom
Frequency ( %)
Headache
83
In the
US, prophylactic anticonvulsant
Hyperreflexia
80
therapy
Proteinuria
for all women meeting
80 criteria for
preeclampsia
Edema
is recommended
60
Clonus
46
Visual signs
45
Epigastric pain
20
Sibai BM. Obstet Gynecol 57:199-202, 1981
Intrapartum Management
Eclampsia: 1:300-1,000
Seizures are usually self-limited (1-2 minutes)
Prevent aspiration of gastric contents
Diazepam or Ativan only if sustained
Prolonged deceleration will recover after seizure
If possible, allow time for full fetal recovery
Cesarean only if vaginal birth not possible within a
reasonable time frame
Treatment of severe preeclampsia with Magnesium
sulfate is supported by level I evidence, ACOG (level A)
Author (year)
Seizure incidence
Magnesium Other
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 (level A)
Recurrent seizures
Magnesium
sulfate
Other
Agent
RR (CI)
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%)
Author (year)
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 symptoms3
1. Altman D, Lancet 359:1877-90, 2002 2. Alexander JM. Obstet Gynecol 108:826-32, 2006. 3.
Sibai BM. Obstet Gynecol 57:199-202, 1981
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 enrolled)
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
Seizure incidence
Magnesium Placebo
sulfate
All patients
0.8%
1.9%
Iminent
eclampsia*
1.0%
3.7%
Severe
preeclampsia
1.2%
2.8%
Non-severe
preeclampsia
0.7%
1.6%
RR
NNT
0.42
(0.3-0.6)
0.26
(0.1-0.6)
0.42
(0.2-0.8)
91
0.42
(0.3-0.7)
109
36
63
* 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 placebocontrolled trial. Lancet 2002; 359:1877-90.
The Magpie Trial
Conclusions
Magnesium
Placebo
RR
NNT
sulfate
•Women with severe preeclampsia, imminent eclampsia, and
High
PMR*
1.2%
0.42 to 63
those
with preeclampsia
in high PMR2.8%
countries, appear
>40/1,000
(0.2-0.8)
benefit the most.
Medium
PMR of Magnesium
0.7% sulfate in1.6%
0.42low PMR
109
• No benefit
countries with
20-40/1,000
(0.3-0.7)
•Magnesium sulfate is effective in reducing the risk of
Low
PMR in women with
0.5%
0.8%
0.67
N/A
eclampsia
preeclampsia:
(0.2-2.4)
<20/1,000 births
(4/778)
(6/782)
Eclampsia
* 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 2002; 359:1877-90
Placebo-controlled trials of Magnesium Sulfate in
mild preeclampsia*
Progression
to severe
AGOG Bulletin #33 January 2002
preeclampsia
“AlthoughMagnesium
there is no Placebo
unanimity of
opinion regarding
Magnesium
Author
Placebothe RR
Sulfate
prophylacticSulfate
use of magnesium sulfate
for the prevention of
(CI)
seizures in women
mild preeclampsia
or gestational
1.35
Witlin
0/67 with0/68
12%
9.1%
hypertension,
(0.5-3.7)
Seizures
Livingston
0/109
0/113
12.8%
16.8%
0.76
(0.4-2.4)
a significant body of evidence attests to the efficacy of
magnesium sulfate in women with severe preeclampsia or
0.90
Total
0/176
0/181
12.5%
13.8%
eclampsia.”
(0.5-1.5)
*Sibai BM. Magnesium sulfate prophylaxis in preeclampsia: lessons learned from recent trials. AM J Obstet Gynecol. 2004. 190: 1520-26.
Wtilin AG. The efect of magnesium sulfate therapy on the duration of labor in women with mild preeclampsia at term: A randomized, double-blind, placebocontrolled trial. Am J Obstet Gynecol. 1997; 176:623-27.
Livingston, JC. Magnesium sulfate in women with mild preeclampsia: a randomized control trial. Obstet Gynecol. 2003; 101:217-220.
When should Magnesium Sulfate Therapy be
initiated in preeclampsia?
Timing of Initiation in clinical trials
Author
Preeclampsia
Initiation of
MagSO4
MagSO4
regimen
Duration of
MagSO4
4g / 1g
Up to
24hrs
In clinical trials, in which the methods were clearly
Witlin ’97
Mild
Latent /
6g / 2g
11.4 +/described, Magnesium sulfate
(n=135)
Active was always initiated
10.6 hr
once the
decision
was/ Active
made for
Coetzee ‘98
Severe
Latent
4g delivery
/ 1g
(n=699)
Magpie ’02
Mild/
(N=10,141)
severe
Regardless
of
Latent /
Active
or
severe
mild
status, no
Livingston
’03 hasMild
/
6g the
/ 2g active
investigator
describedLatent
waiting
until
(N=222)
Active
phase of labor to start Magnesium sulfate
Belfort ’03
(n=1650)
Severe
Latent /
Active
6g / 2g
4g / 1g
-
Up to
24 hrs
Magnesium Sulfate: Duration of prophylaxis
Conclusion
Author
PreInitiation of MagSO4 Duration of
eclampsia limited
MagSO4
•Magpie trial ’02 (N=10,141)
Magnesium
sulfateMagSO4
to
regimen
24hrs.
Witlin ’97
Mild
Latent /
Active
6g / 2g
11.4 +/10.6 hr
•(n=135)
After 24hrs, if delivery had not occurred, the decision for
Coetzee ‘98treatment
Severe
Latent /
4g / 1g
continued
was physician-dependent
(n=699)
Active
•Magpie
Concluded
exceeding 24hr
limit
not
been proven
’02 that
Mild/severe
Latent
/ has4g
/ 1g
Up to
24hrs
safe
(N=10,141)
Active
Livingston ’03
Mild
Latent /
6g / 2g
(N=222)
Active
• Belfort
’03 (N=1650), also limited
Magnesium sulfate to
24hrs,
and’03
protocol called
unless/ delivery
imminent
Belfort
Severefor C/SLatent
6g / 2g
Up to
(n=1650)
Active
4g / 1g
24 hrs
Magpie Trial: Maternal Morbidity
Outcome
Magnesium
Sulfate
3.9%
Placebo
Respiratory depression
0.9%
0.5%
Pulmonary edema
0.6%
0.7%
Placental abruption
2%
3%
Use of >1 Anti-hypertensives
25%
27%
C-section (in labor)
17%
16%
EBL>500cc after delivery
17%
18%
Hospital stay
6d
6d
Admit to ICU
2%
2%
Any serious morbidity
3.6%
Magpie Trial: Perinatal morbidity
Conclusion
Outcome
Magnesium
Placebo
• Magpie trial concluded that there wasSO4
no difference in
maternal
perinatal morbidity in patients
receiving 24hrs
Perinatalordeath
11.4%
11.5%
Magnesium sulfate vs. placebo
Stillbirth
8.2%
8.6%
• There are no large clinical trials evaluating the effects of
Apgar <7 atsulfate
5min >24 hrs in preeclampsia
6%
6%
Magnesium
Intubated at delivery
4%
4%
• Earlier observational studies had suggested risks of:
Hospital stay
5d
5d
- postpartum hemorrhage
NICU >7d
19%
19%
- pulmonary edema
- respiratory depression
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
1.0%
0.5%
Major differences were in minor symptoms:
-Flushing, N/V, muscle weakness
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.
Magnesium Sulfate
How do we monitor for toxicity?
Many clinicians send level when concern for toxicity arises. However,
- When •levels
monitoring
toxicity need to realize:
>12 mEq/L are rare with proper infusion, and in the absence of renal
disease.
-Magnesium
is cleared by the kidneys in concentrationToxic levels:
dependent
manner
N/V, flushing, weakness:
9-12 mEq/L
Respiratory depression:
>14 mEq/L
- Usually, a higher Magnesium concentration leads to higher
Loss of tendon reflexes:
>12 mEq/L
excretion from the body
- However,
patients
witharrest:
oliguria, elevated
creatinine, and/or
Paralysis,
respiratory
15-17 mEq/L
chronic Cardiac
renal disease
(e.g. DM, CHTN)>25
should
be monitored very
arrest:
mEq/L
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, 2003) 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
•diuresis of >100ml/hr for >2hrs consecutive
Isler CM, et al. Postpartum seizure prophylaxis: Using maternal clinical parameters to guide therapy. Obstet Gynecol. 2003;
101:66-69.
Postpartum magnesium sulfate: using maternal
clinical parameters to guide therapy
Parameter
Mild Preeclampsia
Severe
Superimposed
PPreeclampsia preeclampsia value
Antepartum
MagSO4 (hr)
11
(1-55)
10
(1-83)
9
(1-68)
0.69
Postpartum
MagSO4 (hr)
3.5
(2-72)
4
(2-77)
3
(2-33)
0.06
Time to diuresis
(hr)
1
(1-18)
1
(1-13)
1
(1-12)
0.21
MagSO4
re-started
6.3%
5.7%
18.0%
0.02
3.1
3.2
3.0
0.69
Time to discharge
(d)
Isler CM, et al. Postpartum seizure prophylaxis: Using maternal clinical parameters to guide therapy. Obstet Gynecol. 2003;
101:66-69.
Postpartum magnesium sulfate: using maternal
diuresis to guide therapy
Study: (Fontenot , 2005). RCT to assess the use of diuresis as a
determinant of postpartum MgSO4 therapy in severe
preeclampsia
• Control group: MgSO4 2g/hr x 24 hrs
• Study group: MgSO4 until urine output >100 ml/hr x 2hrs
• Proposed that diuresis is indicative of diminishing vasospastic
response
Fontenot et al. A prospective randomized trial of magnesium sulfate in severe preeclampsia: Use of diuresis as a clinical
parameter to determine the duration of postpartum therapy. Am J Obstet Gynecol. 2005. 192:1788-94.
Postpartum magnesium sulfate: using maternal
diuresis to guide therapy
Study: (Fontenot , 2005). RCT to assess the use of diuresis as a
determinant of postpartum MgSO4 therapy in severe
preeclampsia
• Control group: MgSO4 2g/hr x 24 hrs
• Study group: MgSO4 until urine output >100 ml/hr x 2hrs
• Proposed that diuresis is indicative of diminishing vasospastic
response
Fontenot et al. A prospective randomized trial of magnesium sulfate in severe preeclampsia: Use of diuresis as a clinical
parameter to determine the duration of postpartum therapy. Am J Obstet Gynecol. 2005. 192:1788-94.
Postpartum magnesium sulfate: using maternal
diuresis to guide therapy
• Study wasVariable
underpowered
Control Study P-value
Groupin re-initation
Group of
•(powered to find a 20% difference
Antepartum
(hr)
19.3
19.4
0.99
magnesium MgSO4
sulfate therapy)
Cost
difference MgSO4 (hr)
Postpartum
24
8.5
<0.0001
•Difference
in cost
per day
in lower3.1
acuity nursing
Postpartum
hospital
stay
3.5 unit 0.15
(postpartum unit) is: $764
Eclampsia*
0
0
N/A
• Duration of treatment 65% less in study group
Re-intiation of MgSO4^
0
0
N/A
• Reduction in cost/patient: $495
*underpowered, to find a 2-fold difference would require 33,000 patients
• Total^Study
cost powered
(n=98):to $48,510
find 20% increased risk of re-initiation of MgSO4 therapy
Fontenot et al. A prospective randomized trial of magnesium sulfate in severe preeclampsia: Use of diuresis as a clinical
parameter to determine the duration of postpartum therapy. Am J Obstet Gynecol. 2005. 192:1788-94.
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 long-term
success 2
1. Cruikshank DP, et al. Breast milk magnesium and calcium concentrations following magnesium sulphate 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
• RCT’s 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
maternal / 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
Magnesium Sulfate for Tocolysis
Pharmocologic Therapy for Preterm Labor
Contraindications to Magnesium Sulfate
Contraindications
Hypocalcemia
Renal failure
Myasthenia gravis
Complications
Pulmonary edema
Respiratory depression
Cardiac arrest
Maternal Tetany
Profound Hypotension
Profound muscular
paralysis
Intravenous administration
Load:4-6 g; 1-4 g/H--titrate to response
Complications from Tocolysis with Magnesium
Sulfate
• Toxicity
– Inhibition of myometrial contractility (5-8 mg/dl)
– Loss of deep tendon reflexes (9-13 mg/dl)
– Respiratory depression (>13 mg/dl)
• Pulmonary edema (similar to -adrenergics)
–
–
–
–
 Twins (volume expansion);  Anemia
Urinary output (renal excretion)
Tocolysis >24 hours ( colloid oncotic pressure)
Fluid overload (overhydration)
• Careful attention to fluids decreases risk:
– Corticosteroids do not affect risk
Administration of Magnesium
Sulfate as a tocolytic
• Loading dose: 4-6 g in 10%-20% solution
– Give over 30 minutes
– 60 ml of 10% magnesium sulfate in D5NS
• Maintenance dose 2 g/hr
– 40g magnesium sulfate to 1 L D5NS @ 50 ml/hr
• Increase dose by 1g/hr until <1 U.C. per Hour
– Maximum: 4 g/hr
• Total fluids 125 ml/hr
Monitoring Tocolysis with Magnesium
Sulfate
• Hourly monitoring
of
Summary
– Fluid status (>30 cc/hr); DTR’s
“Magnesium
sulfate is arate
familiar agent but its tocolytic
– Vitals –respiratory
efficacy
poor.
• Magnesium levels
mayisbe
obtained
Maybe a useful choice if the diagnosis of preterm labor
–
If
suspected
toxicity
or
impaired
renal
status
is early and uncertain and in patients in whom other
([Cr]>0.9
mg/dl]
agents are
contraindicated (e.g. diabetes)”
– Reduce or stop infusion if respiration or urine
output declines
th Ed
Creasy
&
Resnik’s
Maternal-Fetal
Medicine
6
• Calcium gluconate readily available to reverse
effects of Magnesium sulfate
When to discontinue tocolysis with
Magnesium Sulfate
• When U.C.s decreased < 1 every 10-15
minutes or have ceased
• Magnesium sulfate sometimes continued to
arbitrary endpoint is reached (12 H after U.C.s
stopped or until steroid course completed)
– Not supported by data
Magnesium Sulphate
for Preventing PTB
Conclusion
Cochrane Meta-analysis 2002
Evaluated 23 RCTs: 9 RCTs included: Rx vs Control
“Magnesium Sulfate is ineffective at
delaying or preventing preterm birth
:
Primary outcome
RR (95% CI)
N
and its use is associated with
Preterm delivery
<48 Hr
0.85the
(0.58,
1.25)
881
increased
mortality for
infant.*”
Preterm delivery <37 weeks
0.91 (0.75, 1.11)
424
*one delivery
trial only,<34
subsequent
neuroprotective
Preterm
weeks RCTs
0.82 for
(0.45,
1.50)
80
haveinenrolled
>30 times subjects
without
Difference
GA@ delivery
-0.43 (1.72,
0.87)any 361
increased evidence of neonatal mortality/morbidity
Perinatal Death
2.82 (1.20, 6.62)
727
CVH
1.07 (0.56, 2.05)
495
Inconsistent evidence
Crowther CA, Hiller JE Doyle LW. Cochrane Collaboration 2002
A RCT (double-masked, placebo-controlled trial) of
Magnesium Sulfate for Prevention of Cerebral Palsy
Primary
RR (95% CI)
Conclusion
of outcome
RCT
:
“Fetal
exposure
Magnesium
before11.3%
anticipated
Composite
(CP orto
Death)
0.91Sulfate
(0.75, 1.11)
vs. 11.7%
Early
preterm deliver did not0.45
reduce
the combined risk
Moderate/severe Cerebral
(0.32, 0.87) 1.9% vs. 3.5%
of
moderate
severe cerebral palsy or death, although
Palsy
(> 2 y/o, or
among
the
rate of cerebral palsy was reduce in survivors.”
survivors)
Death (stillbirth or infant
1.12 (0.85, 1.47) 9.5% vs. 8.5%
<2 yrs)
May
be a role for prenatally administered magnesium
sulfate as a neuroprotectant to infants born <32 weeks.
Study: N= 2241, multi-center (20 sites), 22-31 weeks, 6 g load, 2 g/H
Creasy & Resnik’s Maternal-Fetal Medicine 6th Ed
Rouse DJ, et al. New Eng J Med 359:895-905
Magnesium Sulfate and Anesthesia
• General anesthesia
– Neuromuscular blocking agents used to facilitate
endotracheal intubation and relax abdominal musculature
for cesarean delivery
– Magnesium potentiates and prolongs the action of
depolarizing agents (succinylcholine) and non-deplorizing
agents (rocuronium, vecuronium, atracurium).
• Need lower doses of these agents
• Electronic monitoring of neuromuscular junction is helpful.
• End of surgery need to evaluate sufficient muscle
strength to sustain ventilation
• Discontinue Magnesium during general anesthesia as
drugs used during general anesthesia are
anticonvulsants