Justification for inclusion of magnesium sulphate as antihypertensive:
complementary listing, specifically for treatment of pre-eclampsia.
Pre-eclampsia is estimated to complicate 2-8% of pregnancies. The disorder is usually associated
with raised blood pressure and is a major cause of morbidity and mortality for the woman and her
child. Eclampsia is the occurrence of one or more convulsions superimposed on pre-eclampsia.
Anticonvulsant drugs have been used in women with pre-eclampsia in the belief that they reduce
the risks of seizure. Following a systematic review of existing trials of treatment, magnesium
sulphate was identified as the most promising agent to investigate in a large trial. The
MAGnesium sulphate for Prevention of Eclampsia (MAGPIE) trial was carried out and the
results were published in June 2002.
The MAGPIE trial was a trial in 10141 women carried out in 33 countries. Subjects were
included in the trial if they were pregnant or less than 24 hours post-partum, with blood pressure
 140/90 and proteinuria. There had to be clinical uncertainty about whether the patient should be
treated with magnesium sulphate. The outcomes measured were development of eclampsia and
death of the baby.
The formulation used as the basis for the magnesium treatment was 10mL ampoules of containing
5g magnesium sulphate heptahydrate (a 50% solution, approximately 2mmoL/mL). There were
two treatment regimens used in the trial:
1) 4g magnesium sulphate (8mL) diluted with normal saline and given iv over 10-15
minutes, followed by an infusion of 2ml/hr for 24 hours
2) 5g magnesium sulphate (10mL) given im into each buttock followed by 5g im every 4
hours for 24 hours
There were 5071 women randomised to magnesium sulphate and 5070 randomised to placebo.
The results for the primary outcomes were:
1) occurrence of eclampsia –
0.8% (40) compared to 1.9 % (96) in the placebo group; relative risk 0.42 (0.29 to
0.60); risk difference –1.1% (-1.6 to -0.7)
2) maternal death –
0.2% (11) compared to 0.4% (20) in the placebo group; relative risk 0.55 (0.26 to
1.14); risk difference –0.2 (-0.4 to 0.04)
3) death of the baby ( assessed in women randomised before delivery) –
12.7% (576) compared to 12.4% (558) in the placebo group; relative risk 1.02 (0.92
to 1.14); risk difference 0.3 (-1.1 to 1.6)
The authors of the trial noted that of all the secondary outcomes measured, the only notable
difference in maternal or neonatal morbidity was in the risk of placental abruption, which was
significantly reduced in the magnesium group.
The conclusion from the study is that magnesium sulphate halves the risk of eclampsia and
probably reduces the risk of maternal death. As there do not appear to be harmful effects, it is
therefore recommended that providing the regulatory issues (quality and availability) can be
satisfactorily resolved, the drug should be included in the EML as a complementary medicine,
specifically for the treatment of pre-eclampsia.
Suzanne Hill
March 13 2003