Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337

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Best Practice & Research Clinical

Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

Magnesium in obstetrics
M.F.M. James, MBChB, PhD, FRCA, Professor and Head *
Department of Anaesthesia, University of Cape Town Medical School, Anzio Road, Observatory 7925, Cape Town, South Africa

Magnesium is a critical physiological ion, and magnesium defi-

Keywords: ciency might contribute to the development of pre-eclampsia, to
magnesium impaired neonatal development and to metabolic problems
pharmacology extending into adult life. Pharmacologically, magnesium is
obstetrics a calcium antagonist with substantial vasodilator properties but
pre-eclampsia without myocardial depression. Cardiac output usually increases
tocolysis following magnesium administration, compensating for the vaso-
dilatation and minimising hypotension. Neurologically, the
inhibition of calcium channels and antagonism of the N-methyl-D-
aspartic acid (NMDA) receptor raises the possibility of neuronal
protection, and magnesium administration to women with
premature labour may decrease the incidence of cerebral palsy. It
is the first-line anticonvulsant for the management of pre-
eclampsia and eclampsia, and it should be administered to all
patients with severe pre-eclampsia or eclampsia. Magnesium is
a moderate tocolytic but the evidence for its effectiveness remains
disputed. The side effects of magnesium therapy are generally mild
but the major hazard of magnesium therapy is neuromuscular
weakness.
Ó 2009 Elsevier Ltd. All rights reserved.

Magnesium is the fourth most-prevalent cation in the body and is found predominantly in bone but
also substantially in muscle and neuronal tissue; less than 1% of the total body magnesium is found in
the plasma and red blood cells. Plasma magnesium (Mg2þ) is 62% ionised while the remainder is either
bound to albumin or complexed with ions such as citrate and phosphate. A variety of units are used in
the international literature to describe magnesium concentrations and these are summarised in
Table 1. The recommended dietary allowance (RDA) for magnesium is 350 mg per day for a male adult
and 280 mg per day for a female. The magnesium requirement is increased during pregnancy and
lactation (360–400 mg daily). Human milk containing about 30–40 mg l1 is believed to provide

* Corresponding author. Tel.: þ27 21 406 6143; Fax: þ27 21 447 5206.

1521-6934/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bpobgyn.2009.11.004
328 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337

Table 1
Equivalent magnesium concentrations in the three unit systems in common use.

mg dL1 mEq L1 mmol L1

Normal range 1.8–2.4 1.5–2.0 0.75–1.0
Therapeutic range 4.8–8.4 4–7 2–3.5
Neuromuscular toxic level >12 >10 >5

adequate magnesium for the growing infant.1 The main dietary sources of magnesium are green
vegetables, cereals, meat and drinking water.

Biochemistry and metabolism

Magnesium is vital for many biochemical processes, activating over 300 enzyme systems including
those involved in carbohydrate metabolism, protein synthesis, oxidative phosphorylation and the
synthesis of ATP, DNA and RNA. Magnesium is the physiologic calcium antagonist.
Magnesium regulation depends on renal excretion. The excretion capacity of the kidney ranges
widely depending on the plasma Mg2þ concentration. Excess plasma calcium (Ca2þ) or Mg2þ activates
a calcium receptor in the kidney that induces a diuresis increasing elimination of both ions. Hence,
infused magnesium tends to induce its own clearance, an important safety factor provided that renal
function is normal.

Magnesium deficiency

Magnesium deficiency has many consequences, including chronic fatigue states and delirium,
muscle weakness and tetany, disordered glucose metabolism, numerous myocardial arrhythmias,
vascular disorders and electrolyte disturbances, particularly of potassium. The generally accepted
normal range for total serum Mg2þ is 0.75–1.0 mmol l–1. However, since magnesium is primarily an
intracellular ion, whole body magnesium depletion may exist in the presence of normal or even
elevated plasma Mg2þ concentrations. Most Western diets are magnesium deficient.
Magnesium levels have been shown to decline during pregnancy, reaching their lowest point at the
end of the first trimester,2 due partly to dilution and expansion of the extracellular space and partly to
absolute magnesium deficiency. Magnesium deficiency may contribute towards placental insuffi-
ciency, and thus to the development of pre-eclampsia, as it contributes towards uterine artery spasm
and foetal growth retardation and has an essential regulatory role in prostaglandin synthesis. It has
also been suggested that magnesium supplementation during pregnancy can reduce maternal
morbidity and improve foetal outcome, but this study was too small and non-specific to indicate any
effect on the development of pre-eclampsia.3 Magnesium deficiency has also been associated with pre-
term labour and an increased incidence of leg cramps during pregnancy.4,5
Magnesium deficiency during pregnancy may result in permanent harm to the unborn child, with
animal evidence of growth retardation, an increased incidence of abnormal fat metabolism, insulin
resistance and diabetes.6 It has also been reported that magnesium deficiency during pregnancy may
be associated with the sudden infant death syndrome.4
The possible role of magnesium deficiency in the genesis of pre-eclampsia has been the subject of
considerable debate. Studies in ewes with pregnancy-induced hypertension demonstrated higher
arterial pressure and lower foetal weights in sheep fed on a magnesium-deficient diet.7 In a human
study of 568 women given magnesium aspartate or placebo from 16 weeks’ gestation or earlier, the
magnesium group had fewer hospital admissions, less frequent pre-term labour and fewer neonatal
intensive care unit (ICU) admissions.8 Kisters et al. studied the plasma and intracellular magnesium
concentrations in pre-eclamptic and normal pregnant women. Plasma Mg2þ concentrations were not
significantly different, but showed a greater scatter in the pre-eclamptic women. Both groups showed
lower red cell magnesium concentrations than normal non-pregnant values, and the pre-eclamptic
group had a significantly lower red cell concentration than the normal pregnant women. They
 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337 329

suggested that this decrease in intracellular magnesium might contribute to the vascular lesions of pre-
eclampsia.9 Standley and colleagues studied Mg2þ and Ca2þ concentrations in 31 normal pregnant
patients of whom nine eventually developed pre-eclampsia. All subjects showed a decrease in ionised
Mg2þ concentration with increasing gestational age. However, total Mg2þ concentrations were lower
and ionised Ca2þ/Mg2þ ratio increased in the second and third trimesters in those women who became
pre-eclamptic.10 A nuclear magnetic resonance spectroscopic study showed a lower brain and muscle
intracellular magnesium content in seven patients with pre-eclampsia.11
Conversely, Seydoux and colleagues were unable to demonstrate any effect of pre-eclampsia on
either plasma or intracellular magnesium concentrations and concluded that magnesium deficiency
had no causative role to play in the genesis of pre-eclampsia.12 Fong et al. studied serum and cere-
brospinal fluid (CSF) magnesium concentrations in normal pregnant patients and pre-eclamptic
patients presenting for caesarean section under spinal anaesthesia. There were no between-group
differences.13
There is, therefore, conflicting data regarding the possible contribution of magnesium deficiency to
the genesis of pre-eclampsia from which no firm conclusions can be drawn at present. However, it
would seem wise to offer magnesium supplementation to any pregnant woman who becomes
magnesium deficient. This may be particularly important in diabetic mothers as magnesium deficiency
is common in diabetics and may also worsen the pathology of the disease.14

Pharmacology of hypermagnesaemia

Hypermagnesaemia to control eclamptic convulsions was first reported by Lazard15 and pop-
ularised by Pritchard in 1955.16 Subsequently, it was used with some success as a tocolytic.17,18
Pharmacologically, magnesium is a calcium competitor that is effective, not only at the dihy-
dropyridine receptors, but also at other calcium channels unaffected by traditional calcium channel
antagonists. Magnesium is also an effective antagonist of the N-methyl-D-aspartic acid (NMDA)
receptor in the central nervous system.19 In order to achieve pharmacological plasma Mg2þ concen-
trations, parenteral administration is necessary as oral salts are poorly absorbed and renal excretion is
rapid. Magnesium toxicity is primarily a consequence of neuromuscular blockade with consequent
respiratory embarrassment. This occurs most readily in the presence of renal dysfunction, since renal
clearance is the only route of elimination of magnesium.

Magnesium and neuromuscular function

Hypermagnesaemia inhibits the release of acetylcholine at the motor end plate. Consequently,
magnesium therapy increases the sensitivity of the motor end plate to non-depolarising relaxants and
produces neuromuscular blockade in its own right at plasma Mg2þ concentrations above 5 mmol l1.
Clinically important neuromuscular block is unlikely to be seen at Mg2þ concentrations below 5 mmol l1;
the use of the patellar tendon reflex as a monitor of the degree of neuromuscular transmission block
has stood the test of time and is a useful measure of the danger of impending neuromuscular weakness,
but this may be misleading if epidural analgesia has been initiated. Patients with neuromuscular disorders,
including myasthenia gravis,20 Eaton–Lambert syndrome and myotonic dystrophy are at increased risk of
neuromuscular paralysis if exposed to magnesium.21

Magnesium and respiratory function

Several reports have characterised a decrease in respiratory volumes with magnesium infusions,
notably forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)22–24 all of which suggest
a reduction in mechanical ventilatory power, rather than respiratory depression. Magnesium has been
shown to limit respiratory muscle reserve in pre-eclamptic women at rather low plasma concentra-
tions.22 This should not be taken to imply that increases in PaCO2 are likely to occur in pregnant women
treated with magnesium sulphate (MgSO4), but may mean that women treated with magnesium may
be sensitive to increased respiratory work, although the ion has been used to assist in the management
330 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337

of severe, non-responsive asthma, especially in children. There is no evidence that magnesium affects
the CO2 response curve.

Magnesium and cardiovascular function

Magnesium is generally regarded as having little haemodynamic effect, since the changes seen in
blood pressure and heart rate in clinical settings are often minimal. However, magnesium has extensive
cardiovascular actions of clinical relevance.
Magnesium produces vasodilatation by both a direct action on the arterial blood vessels and an
interference with the action of a wide range of vasoconstrictor substances, notably alpha-adrenergic
inhibition.25 In animals, magnesium infusions induce a dose-related reduction in systemic vascular
resistance accompanied by sustained cardiac filling leading to increased cardiac output and stroke
volume. Consequently, at plasma magnesium concentrations below 5 mmol l1 only mild reductions in
arterial pressure occur despite substantial arterial dilatation.26,27 Whether or not this haemodynamic
effect contributes usefully to control of arterial pressure in pre-eclampsia has not been sufficiently
carefully studied to draw firm conclusions, although the improvements in tissue blood flow should be
beneficial. In an animal model of pre-eclampsia (using L-Nitro-Arginine Methyl Ester (L-NAME) to
induce hypertension in pregnant rats) magnesium infusions not only improved blood pressure control
but also enhanced foetal growth.28
Provided that respiratory failure and hypoxia are avoided, magnesium is remarkably safe from
a cardiac perspective with plasma Mg2þ concentrations as high as 12.5 mol l1 being required before
cardiac arrest occurs.29 Studies in animal models26 and pregnant women30 have failed to demonstrate
any myocardial depression and have reported an increase in cardiac output associated with raised
plasma Mg2þ concentrations. In dogs, magnesium enhanced inotropy and lusitropy with increased
cardiac output up to plasma concentrations of 6 mmol l1, and this level was described as ‘haemody-
namically safe’.27 Accidental overdose resulting in levels above 7 mmol l1 have been reported without
adverse cardiac events; in one case report, the patient suffered respiratory arrest, but made a rapid and
full recovery without cardiovascular difficulties following immediate institution of respiratory
support.31 Increased cardiac output and decreased systemic vascular resistance have been reported in
human subjects with pre-eclampsia whilst only mild effects were seen in patients receiving magnesium
infusions for pre-term labour.32 The evidence suggests that, at clinically used concentrations, magne-
sium infusions have no significant negative inotropic effects and may improve myocardial performance
through significant vasodilator actions in pre-eclamptic patients. However, the sympatholytic action of
magnesium may impair the haemodynamic response to haemorrhage.33 Consequently, it is important
that adequate fluid therapy is maintained in patients receiving magnesium treatment.

Calcium channel blockers

Some authors regard the interaction of magnesium with the calcium channel blockers as potentially
hazardous whilst others use the combination frequently for blood pressure control in severe pre-
eclampsia. In the isolated heart, magnesium potentiated the cardiac depressant effects of both verap-
amil and nifedipine,34 and it has been recommended that the combination be used with caution.35
However, a study of the haemodynamic effects of nifedipine in pre-eclamptic hypertensives who were
receiving magnesium failed to demonstrate any dangerous myocardial depression. On the contrary, at
mean plasma Mg2þ concentration of 2.5 mmol l1, cardiac index increased and peripheral resistance
decreased.32 No increase in adverse effects was seen in subjects given magnesium and nifedipine for the
management of severe pre-eclampsia compared with patients given magnesium alone.36 These reports
do not conclusively answer the question regarding the safety of the combination of calcium channel
blockers and magnesium in the obstetric patient but suggest that there might be less of a risk than the in
vitro experiments suggest, and the few reported adverse events might be an idiosyncratic response
rather than a predictable drug interaction. It has been suggested that the combination might increase
the risk of neuromuscular weakness than magnesium alone,37 but no such impairment was reported in
the Magpie trial,38 in which 1469 women assigned to receive MgSO4 also received nifedipine.39
Magnesium is a highly effective vasodilator and an alpha-adrenergic antagonist, reducing exces-
sively elevated blood pressure, particularly when that increase is due to catecholamine release. It
 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337 331

maintains cardiac filling and thus increases cardiac output. Consequently, only moderate reductions in
blood pressure occur in patients with pre-eclampsia, although tissue blood flow and cardiac output
probably improve significantly.

Magnesium and cerebral function

The control of convulsions by magnesium has been highly contentious since magnesium penetrates
the blood–brain barrier poorly and has no anaesthetic or major sedative actions when given paren-
terally, and is not an effective anticonvulsant against standard forms of epilepsy. The debate was
resolved by the Collaborative Eclampsia Study40 and subsequent meta-analyses, which concluded that
magnesium was significantly better than either phenytoin41 or diazepam42 for the treatment of
eclampsia. It has also been shown to be more effective in preventing the progress of pre-eclampsia to
eclampsia than other agents.43 Several possibilities for the mechanism of magnesium’s anticonvulsant
action in eclampsia have been suggested, including NMDA antagonism,44,45 calcium antagonism46 and
cerebral vasodilatation.47,48 Magnesium causes relaxation of arterial musculature from most organs,
including the brain,49 and increases cerebral blood flow in sheep.50 Reversal of vasospasm may,
therefore, be an important component of the anticonvulsant effect of magnesium in eclampsia. Other
possibilities include a reduction in pinocytosis and a down-regulation of aquaporin 4 in the cerebral
tissue, limited the opening of tight junctions through calcium antagonism (decreasing cerebral
oedema)51 and prevention of hypertensive encephalopathy through a reduction in cerebral perfusion
pressure.52
Whatever the mechanism, MgSO4 is the established drug of choice for the prevention of convulsions
in pre-eclampsia and eclampsia.

Magnesium and coagulation

Although reduction of the Ca2þ/Mg2þ ratio alters laboratory estimations of coagulation including
reduced platelet adhesiveness, no clinically significant abnormalities of coagulation have been
attributed to magnesium. Magnesium has only a small effect on thrombelastography in vitro.53
Increased bleeding time in pre-eclamptic patients from a mean of 6 min 31 s to 11 min 56 s after
magnesium infusion has been reported, but serum Mg2þ concentrations were not measured.54 A more
modest effect of magnesium infusion was reported at serum Mg2þ concentrations of 1.5 mmol l1 with
an increase of bleeding time from 8 to 11.8 min, although no other aspect of platelet function or
coagulation was altered. 55 It is not clear if this simply represents a correction of abnormal coagulation
to more normal values or indicates a real risk of increased bleeding. No increase in blood loss was
reported nor was there an increased requirement for blood transfusion in the magnesium-treated
groups in the Collaborative Eclampsia Trial.40 Magnesium might increase the risk of epidural hae-
matoma consequent to neuraxial block in pre-eclamptic patients, but there is no evidence that this has
ever happened in practice; the risk would appear to be, at worst, no greater than that related to aspirin
therapy.

Magnesium and the uterus

Magnesium has been used since 197717 to treat premature labour, especially in the United States.
Magnesium inhibits myometrial contraction as effectively as beta-agonists, but with a lower incidence
of side effects.56,57 Several publications have argued against the use of magnesium for this purpose,
citing absence of efficacy and a possible increase in side effects, particularly foetal death.58,59 A meta-
analysis of the data concluded that the only available randomised controlled trials were inadequate to
allow firm conclusions.60
Perhaps surprisingly, there is no evidence that MgSO4 therapy prolongs the duration of normal
labour.61–63 The effect on caesarean section rate is less clear, with some studies showing no increase in
the frequency of caesarean deliveries64,62 while a large meta-analysis found a significant increase in the
risk of caesarean section (relative ratio (RR) 1.21, 95% confidence interval (CI) 1.05–1.41) in magnesium-
treated women.43
332 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337

Magnesium and the foetus

Sporadic reports of neonatal hypotonia,65 respiratory depression and altered parathyroid hormone
function66 have led to concerns that magnesium might adversely affect the foetus, especially if
premature. Although the ion readily crosses the placental barrier, there is little hard evidence of
harmful effects.65 Foetal heart rate (FHR) variability is decreased by magnesium,67,68,18 but without
discernible harm to the neonate. However, this may make interpretation of FHR data difficult, and
necessitates some other means of assessing foetal health. Fewer babies born to magnesium-treated
pre-eclamptic mothers required intensive therapy than those whose mothers received either
phenytoin or diazepam, and Apgar scores of the infants were better in the magnesium group.61 Current
evidence in pre-eclampsia would suggest that there is no real concern for neonatal well-being.
However, the situation regarding premature infants born to mothers treated for early labour is less
clear with arguments that magnesium may be beneficial or harmful. Theoretically, the calcium and
NMDA antagonism of magnesium could protect the developing brain from hypoxia.69 FineSmith et al.
found that magnesium protected exposed neonates against developing cystic periventricular leuko-
malacia,70 but Canterino et al. found no benefit.71 Nelson and Grether noted an increased survival and
decreased incidence of cerebral palsy in very low-birth-weight infants whose mothers had received
MgSO4 either as a tocolytic or for pre-eclampsia,72 but subsequently, the same group failed to confirm
this effect in premature infants, although they concluded that magnesium did not increase the risk of
neonatal death.73 Other studies have tended to confirm the possible protection74 but have been
inconclusive. A retrospective study failed to demonstrate any association between magnesium therapy
and alterations in favourable or unfavourable outcomes in magnesium-exposed infants.75 Other
authors have suggested that magnesium in pre-term labour increased the risk of harm in very-low-
birthweight infants.76–78 Recently, however, two meta-analyses suggested that magnesium adminis-
tration to women at risk of delivery before 34 weeks of gestation reduced the risk of cerebral palsy,79
and one concluded ‘‘the neuroprotective role for antenatal MgSO4 therapy given to women at risk of
preterm birth for the preterm foetus is now established.’’80 Whilst these later studies are strongly
suggestive of a beneficial effect, neurologic protection of the pre-term foetus cannot be regarded as
firmly established at the present time, although the trend of current evidence seems to suggest
a possible benefit.

Clinical use of magnesium in obstetrics

Pre-eclampsia

While magnesium is now the agent of choice for the prevention of eclamptic convulsions, the
argument as to whether all pre-eclamptic patients should be given magnesium is not resolved.
Although magnesium is very safe, it is not entirely without risk, particularly in areas where
monitoring may be limited, and consideration has to be given to the benefit/risk ratio of using the
agent against the exposure of a large number of patients to a therapy which most of them do not
need. There are also risks attached to using an unfamiliar form of treatment in areas where severe
pre-eclampsia is infrequent.81 Most adverse effects are mild, but overdose may lead to respiratory
embarrassment and even death if not carefully managed. It can therefore be argued that magne-
sium should be administered selectively to patients at greatest risk of eclamptic convulsions. The
greatest risk/benefit ratio has been shown in countries with high perinatal mortality where severe
pre-eclampsia is common.38 Such patients are more likely to experience convulsions, and the
numbers needed to treat (NNTs) to prevent one eclamptic convulsion in this group of patients is 71.
In more developed countries, where mild pre-eclampsia predominates, the NNT is around 385, thus
requiring large numbers of patients to be exposed to magnesium to benefit only a small number.
Unfortunately, approximately 20% of eclamptic women do not have any premonitory signs or
symptoms before the onset of convulsions. In attempting to resolve this conundrum, one study
investigated the consequences of changing from a regimen of MgSO4 administration in all pre-
eclamptic women to one in which magnesium was only administered if mild pre-eclampsia pro-
gressed to severe disease.82 This change resulted in a 50% overall increase in the prevalence of
 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337 333

eclampsia and an increase in maternal and neonatal morbidity.83 There is no clarity as to the best
way to resolve the balance of risks and a randomised controlled trial to investigate this problem
would require vast numbers. Every woman with severe disease or who has had an eclamptic
convulsion should receive magnesium. Where to draw the line in patients with mild disease is
currently impossible to state. Related to this issue is the problem of when to stop therapy following
delivery. Again, there is no clarity, although current opinion generally recommends continuing the
magnesium infusion for 24 h after delivery although one, fairly small, study in which the infusion
was stopped at 12 h after delivery failed to demonstrate any increase in convulsions or progression
of disease.84
It is also not established whether or not magnesium is a good agent for controlling a patient who
is actually convulsing. Many authorities would recommend the use of diazepam as the first-line
agent to halt the convulsion and use magnesium thereafter to prevent further fits. However,
personal experience and that of others suggests that a bolus of 30–60 mg kg1 MgSO4 can be
rapidly effective in halting convulsions.39 The best choice remains open to question, and perhaps
the pragmatic approach of using the most readily available agent is the best route to follow at
present.

Dosage and administration

There are several dosage regimes for the use of magnesium in pre-eclampsia, largely dependent on
the availability of sophisticated delivery and monitoring systems. The main risk of magnesium infusion
is accidental massive overdose with neuromuscular blockade and respiratory failure.31 Intravenous
magnesium should be delivered using a syringe driver, rather than the far more risky approach of an
infusion through a drip set. Where such facilities are not available, the intramuscular route is
reasonably well tolerated and far less likely to produce dangerously high concentrations of plasma
magnesium.
Commonly used intravenous approaches for pre-eclampsia recommend a loading dose of 4–6 g
MgSO4 infused over 15–20 min. Giving this size of dose more rapidly (over 1–2 min) is unpleasant
in the awake patient, causing a burning sensation and nausea; in the unconscious, ventilated
patient, a rapid injection of 60 mg kg–1 may be safely given and repeated after 5 min for the control
of convulsions or to decrease excessively elevated arterial pressure. This is then followed by
a continuous infusion of 1–4 g h1. The target plasma concentration should be between 2 and
3.5 mmol l–1 and deep tendon reflexes should be monitored regularly. Monitoring of plasma
concentrations becomes important where tendon reflexes are absent or in the presence of renal
dysfunction. In the intramuscular regimen, bilateral 5 g intramuscular buttock injections are fol-
lowed by 5 g intramuscularly every 4 h thereafter. Some suggested approaches to magnesium
dosing are given in Table 2.

Tocolysis

A meta-analysis of tocolytics showed that all agents were more effective than placebo at
delaying labour at 48 h and at 7 days, but there were no other significant differences.85 This
analysis suggested that prostaglandin inhibitors provided the best combination of tolerance and

Table 2
Recommended MgSO4 dosage regimes. Maintenance should be continued for 24 hours after delivery or the last convulsion.

Indication Route Loading Dose Maintenance

Preeclampsia IV 4–6 g intravenously 1–2 g hr1 infusion
over 15–20 min
IM 5 g (10 mL) 50% MgSO4 into each buttock 5 g im every 4 hours
Combined 4–6 g intravenously 5 g im every 4 hours
over 15–20 min
Tocolysis IV 6 g intravenously 2–5 g hr1 infusion
over 15–20 min
334 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337

delayed delivery. Magnesium achieved a success rate of 82% at delaying labour by 48 h, superior to
all other agents other than the prostaglandin inhibitors85 but was less effective at 7 days. Part of
the difficulty in comparing the controversial evidence may lie in the variety of dosage regimes
employed. Lewis pointed out that dosage was crucial with low-dose regimens (4 g loading dose and
2 g h1 infusion) achieving less than 75% efficacy, while a higher dose (6 g loading dose and
>2 g h1) achieved over 85% efficacy.86 Elliott et al. suggested a dosage regimen for MgSO4 of a 6-g
loading dose followed by an infusion of 3–5 g h1.87 There seem, therefore, arguments both for and
against the use of magnesium for tocolysis, and the clinical choice should probably be influenced by
drug availability and familiarity until such time as convincing evidence of efficacy and safety for the
various agents is available. Where high-dose magnesium is to be used, it appears important that
adequate plasma levels are obtained, and this should be one area where therapy is guided by
measurements of plasma Mg2þ concentration with a lower limit of 2.5 mmol l1 and an upper limit
of 4 mmol l1 probably being advisable, but there are no studies to confirm these ranges.
Magnesium sulphate and nifedipine remain the most widely used first-line agents for tocolysis in
the United States at present.88

Anaesthesia and critical care

In patients receiving magnesium, lumbar epidural anaesthesia may cause modest hypotension with
minimal other haemodynamic changes.89 This reduction in afterload in pre-eclamptic patients is likely
to be beneficial. In pregnant ewes, magnesium infusions during epidural anaesthesia caused more
hypotension than epidural anaesthesia alone, but without adverse effects on uterine blood flow or on
foetal well-being.90 Magnesium was shown to attenuate the adverse effect of phenylephrine on uterine
vascular resistance in pregnant ewes and ephedrine was superior to either placebo or phenylephrine
for the treatment of hypotension after epidural anaesthesia in hypermagnesaemic, gravid ewes.91 If
these studies apply to women with pre-eclampsia, then ephedrine remains the vasopressor of choice
where magnesium is being used, although calcium is an effective magnesium antagonist and may be
the second option.
Given the well-established safety record of magnesium in pregnancy, the ion should be regarded
as the first-line agent to manage critical hypertensive events in pregnancy and during delivery.
Magnesium infusions have proven to be very effective in the management of patients undergoing
phaeochromocytoma excision including parturients.92–94 The established place of magnesium in
obstetric practice makes this agent ideal for the control of both pre- and intra-operative hyper-
tension. Similar considerations would apply to hypertensive crisis in any critically ill obstetric
patient where the ease of administration, rapid response and excellent safety margin make
magnesium the ideal first-line emergency drug. A dose of 40 mg kg1 intravenously (IV) given over
5 min should produce a rapid reduction in the peak arterial pressure and can be safely repeated
within 10 min.

Conclusions

Magnesium has widespread relevance to obstetric practice. Deficiencies may contribute to various
disease states, and correction of these deficits may improve maternal and child health. The ion is
undoubtedly the agent of choice for the prevention and control of eclamptic convulsions. The role in
tocolysis is less clear and is largely driven by individual experience and preference, rather than hard
evidence. Similarly, while current data suggest that it may protect against the development of cerebral
palsy in the premature infant, the risk/benefit balance is not yet clear. Finally, the ion has important
haemodynamic properties, which may be of use in the management of a variety of challenging clinical
circumstances.

Statement of conflict of interests

The author has no conflicts of interest to declare.

 M.F.M. James / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 327–337 335

Practice Points

 Magnesium is the drug of choice to prevent convulsions in pre-eclampsia and eclampsia, but
there is uncertainty as to which patients with mild disease need treatment.
 Magnesium may be of benefit in tocolysis, but the level of evidence is inadequate to make
firm recommendations.
 Magnesium treatment in pre-term labour may offer protection to the premature neonatal
brain, but the level of evidence is inadequate for firm recommendations.
 Magnesium therapy does not increase the risks of regional anaesthesia.
 Magnesium is an excellent adrenergic antagonist and is probably the agent of choice for the
management of hypertensive crisis in pregnant women.

Research Agenda

 The risk/benefit ratio of magnesium treatment in mild pre-eclampsia needs to be established.

 Confirmation of the possible protection against cerebral palsy should be obtained.
 The place of magnesium in tocolysis must be established.

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