Magnesium Sulphate
Magnesium sulphate (heptahydrate) is a white crystalline
powder or brilliant, colourless crystals. It effloresces in warm
dry air. Each g of magnesium sulphate (heptahydrate) repre-
sents approximately 4.1 mmol of magnesium. Magnesium
sulphate (heptahydrate) 10.1 g is approximately equivalent to
I g of magnesium. Soluble I in 0.8 of water and I in 0.5 of
boiling water: freely but slowly soluble I in I of glycerol;
sparingly soluble or practically insoluble in alcohol. A 5%
solution in water has a pH of 5.0 to 9.2. .
Dried magnesium sulphate is a white odourless or almost
odourless powder, prepared by drying magnesium sulphate
(heptahydrate) at 100Β° until it has lost about 25% of its
weight, it contains 62 to 70% of MgSO4. Freely soluble in
water; more rapidly soluble in hot water.
Adverse Effects
Excessive parenteral administration of magnesium
salts leads to the development of hypermagnesae-
mia, important signs of which are loss of deep
tendon reflexes and respiratory depression, both due
to neuromuscular blockade. Other symptoms of hy-
permagnesaemia may include nausea, vomiting.
flushing of the skin, thirst, hypotension due to pe-
ripheral vasodilatation, drowsiness, confusion, mus-
cle weakness, bradycardia, coma and cardiac arrest.
Hypermagnesaemia is uncommon after oral admin-
istration of magnesium salts except in the presence
of renal impairment. Ingestion of magnesium salts
may cause gastro-intestinal irritation and watery
diarrhoea.
Effects on the gastro-intestinal tract. Although oral
magnesium salts stimulate peristalsis, paralytic ileus has oc-
curred in a woman receiving an intravenous infusion of mag-
nesium sulphate for premature labour; magnesium
concentrations were within the normal range. See also Preg-
nancy. under Precautions, below.
Hypenensitivity. Hypersenstivity reactions characterised
by urticaria have been described in 2 women after receiving
magnesium sulphate intravenously.
Treatment of Adverse Effects
A patient with supralethal hypermagnesaemia was success-
fully treated using assisted ventilation, calcium chloride ad-
ministered intravenously, and forced diuresis with mannitol
infusions.
Precautions
Parenteral magnesium salts should generally be
avoided in patients with heart block or severe renal
impairment. They should be used with caution in
less severe degrees of renal impairment and in pa-
tients with myasthenia gravis. Patients should be
monitored for clinical signs of excess magnesium
(see above), particularly when being treated for con-
ditions not associated with hypomagnesaemia such
as eclampsia. An intravenous preparation of a calci-
um salt should be available in case of toxicity. When
used for hypomagnesaemia. serum-magnesium con-
centrations should be monitored.
Magnesium crosses the placenta. When used in
pregnant women, fetal heart rate should be moni-
tored and administration within 2 hours of delivery
should be avoided.
Oral magnesium salts should be used cautiously in
patients with impaired renal function. Administra-
tion with food may decrease the incidence of diar-
rhoea. Chronic diarrhoea due to long-term
administration may result in electrolyte imbalance.
Hepatic disorders. Severe hypermagnesaemia and hyper-
calcaemia developed in 2 patients with hepatic encephalopa-
thy following the administration of magnesium sulphate
enemas: both patients died. one during and one after asystole.
It was recommended that patients with liver disease who
might develop renal impairment, or in whom renal failure is
established, should not be presented enemas containing mag-
nesium for treatment of hepatic encephalopathy as serious
magnesium toxicity can occur, which may contribute to
death.
Pregnancy. The meconium-plug syndrome (abdominal dis-
tention and failure to pass meconium) has been described in 2
neonates who were hypermagnesaemic after their mothers
had received magnesium sulphate for eclampsia. It was be-
lieved that the hypermagnesaemia may have depressed the
function of intestinal smooth muscle. See also Effects on the
Gastro-intestinal Tract, above.
In a study in 12 women with pre-eclampsia there was a de-
crease in short-term fetal heart rate variability when women
were administered intravenous magnesium sulphate; howev-
er although variability is considered a sign of fetal well-
being
the decrease was considered clinically insignificant.
Interactions
Parenteral administration of magnesium sulphate
potentiates the effects of neuromuscular blockers
such as tubocurarine, suxamethonium. and vecuro-
nium . The neuromuscular blocking effects
of parenteral magnesium and aminoglycoside anti-
bacterials may be additive. Similarly, parenteral
magnesium sulphate and nifedipine have been re-
ported to have additive effects .
Oral magnesium salts decrease the absorption of tet-
racyclines and bisphosphonates, and administration
Pharmacokinetics
Approximately one third to one half of magnesium
is absorbed from the small intestine following oral
administration and even soluble magnesium salts
are generally very slowly absorbed. The fraction of
magnesium absorbed increases if magnesium intake
decreases. In plasma, about 25 to 30% of magnesi-
um is protein bound. Parenterally administered
magnesium salts are excreted mainly in the urine,
and orally administered magnesium salts are elimi-
nated in the urine (absorbed fraction) and the faeces
(unabsorbed fraction). Small amounts are distribut-
ed into breast milk. Magnesium crosses the placen-
ta.
Human Requirements
Magnesium is the second most abundant cation in
intracellular fluid and is an essential body electro-
lyte which is a cofactor in numerous enzyme sys-
terns.
The body is very efficient in maintaining magnesi-
um concentrations by regulating absorption and
renal excretion and symptoms of deficiency are rare.
It is therefore difficult to establish a daily require-
ment.
Foods rich in magnesium include nuts, unmilled
grains, and green vegetables.
In the United Kingdom dietary reference values (DRV)' and
in the United States recommended daily allowances (RDA)Z
have been published for magnesium. In the UK the estimated
average requirement (EAR) is 200 mg (or 8.2 rnmol) daily for
adult females and 250 mg (or 10.3 mmol) daily for adult
males; the reference nutrient intake (RNI) is 270 mg (or
10.9 mmol) daily for adult females and 300 mg, (or
12.3 mmol) daily for adult males; no increment is recom-
mended during pregnancy but an increment of 50 mg (or
2.1 mmol) daily in the RNI is advised during lactation. In the
USA under the new dietary reference intakes an EAR of 330
to 350 mg daily has been set in adult males and 255 to 265 mg
daily in adult females: the corresponding RDAs are 400 to
420 mg and 310 to 320 mg daily.' An increase in RDA to 350
to 360 mg is recommended during pregnancy but the standard
RDA is considered adequate during lactation.
Uses and Administration
Magnesium salts have a variety of actions and uses.
Many are given as a source of magnesium ions in the
treatment of magnesium deficiency and hypomag-
nesaemia . Doses may be expressed in
terms of mmol or mEq of magnesium, mass (mg) of
magnesium, or mass of magnesium salt (for com-
parative purposes, see Table 2. below).
In simple deficiency states magnesium salts may be
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Table 2. Some Magnesium salts and their magnesium content
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Magnesium content per g
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Magnesium salts mg mmol mEq
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Magnesium acetate (tetrahydrate) 113 4.7 9.3
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Magnesium ascorbate (anhydrous) 65 2.7 5.3
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Magnesium aspartate (tetrahydrate) 67 2.8 5.5
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Magnesium chloride (hexahydrate) 120 4.9 9.8
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Magnesium gluceptate (anhydrous) 51 2.1 4.2
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Magnesium gluconate (anhydrous 59 2.4 4.8
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Magnesium glycerophosphate (anhydrous) 125 5.1 10.3
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Magnesium lactate (anhydrous) 120 4.9 9.9
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Magnesium phosphate (pentadrous) 207 8.5 17.0
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Magnesium pidolate (anhydrous) 87 3.6 7.1
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Magnesium sulphate (heptahydrate) 99 4.1 8.1
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magnesium daily adjusted according to individual re-
quirements. Salts that are. or have been. employed
include magnesium aspartate. magnesiurrl chloride.
magnesium gluceptate, magnesium gluconate. mag-
nesium glycerophosphate, magnesium lactate, mag-
nesium laevulinate. magnesium orotate. and
magnesium pidolate. In acute or severe hypomagne-
saemia. magnesium may be given parenterally most
usually as the chloride or sulphate. A suggested reg-
imen is to administer 35 to 75 mmol of magnesium
by slow intravenous infusion (in glucose 5%) on the
first day followed by 25 mmol daily until the hy-
pomagnesaemia is corrected; up to a total of
160 mmol may be required. Alternatively, magnesi-
um sulphate has been given by intramuscular or
slow intravenous injection. Careful monitoring of
plasma-magnesium and other electrolyte concentra-
tions is essential. Doses should be reduced in renal
impairment. Other salts which are. or have been,
used parenterally include magnesium acetate, mag-
nesium ascorbate, magnesium aspartate hydrochio-
ride. magnesium laevulinate, and magnesium
pidolate.
Several magnesium salts such as the carbonate, hy-
droxide, oxide, and trisilicate are widely used for
their antacid properties . Magnesium salts
also act as osmotic laxatives ,the salts generally used for this
purpose are,magnesium sulphate (an oral dose of 5 to lOg in
250 mL of water being administered for rapid bowel
evacuation) and magnesium hydroxide .
Parenterally administered magnesium sulphate has
some specific uses. It is used for the emergency
treatment of some arrhythmias such as torsade de
pointes and those associated with hypo-
kalaemia . The usual dose is 2 g of magne-
sium sulphate (8 mmol of magnesium) administered
intravenously over 10 to 15 minutes.
Parenteral magnesium sulphate is also used for the
prevention of recurrent seizures in pregnant women
with eclampsia (see below). A variety of dosage
regimens have been used and debate continues as to
which is most appropriate. Typically an intravenous
loading dose of 4 g of magnesium sulphate
(16 mmol of magnesium) is administered over up to
20 minutes. This is then followed by either an infu-
sion of I g(4 mmol magnesium) per hour or deep
intramuscular administration of 5 g (20 mmol mag-
nesium) into each buttock then 5 g intramuscularly
every 4 hours. Should seizures recur under either
regimen, then an additional intravenous dose of 2 to
4 g can be administered. It is essential to monitor for
In signs of hypermagnesaemia. and to stop magnesium
administration should this occur. Doses should be
reduced in renal impairment.
The use of magnesium sulphate in acute myocar-
dial infarction and premature labour is discussed
below.
Dried magnesium sulphate has been used in the
form of Magnesium Sulphate Paste (BP 1998) as an
application to inflammatory skin conditions such as
boils and carbuncles, but prolonged or repeated use
may damage the surrounding skin.
Anaesthesia. Magnesium sulphate has been used to prevent
the undesirable haemodynamic response sometimes associat-
ed with intubation .
Eclampsia and pre-eclampsia. For many years magnesi-
sulphate has been the preferred treatment in the USA for
seizures associated with eclampsia and studies have
shown it to be more effective than phenytoin" or diazepam
as well as causing fewer adverse effects.
A commentary on 2 of these studies thought that magnesium
sulphate offered considerable advantages. It produced a rapid
effect and did not cause sedation in-the mother or the infant.
It was also considered to have a wide safety margin with the
added security of calcium gluconate being an easily available
antidote should overdose occur. Subsequently a meta-
analysis of 9 randomised trials reinforced this favourable
view. Thus many in the UK now consider magnesium sul-
phate to be the preferred drug for the treatment of eclampsia.
Magnesium sulphate may also be used for prophylaxis in pre-
eclampsia, but some uncertainty remains about the degree of
benefit, nonetheless, it appears to be more effective than
phenytoin. (For a recent study that raised some concerns
about the effects of early use of magnesium sulphate on the
fetus. see Premature Labour, below).
Hypokalaemia. Potassium and magnesium homoeostasis
are linked, and hypokalaemia with increased urine potassium
excretion may occur in patients with hypomagnesaemia. In
this situation, correction of potassium deficit usually
requires
concomitant magnesium administration. Administration of
magnesium sulphate at doses greater than those required to
correct hypomagnesaemia has been associated with greater
improvements in potassium balance than doses just sufficient
to correct hypomagnesaemia.
Myocardial Infarction. Magnesium has an important phys-
iological role in maintaining the ion balance in muscle includ-
ing the myocardium. Administration of magnesium might
have an antiarrhythmic effect and might protect the myocar-
dium against reperfusion injury including myocardial stun-
ning (delayed recovery of myocardial contractility function).
Intravenous magnesium salts have been used for cardiac
arrhythmias and in an overview of studies in patients with
suspected myocardial infarction their administration, general-
ly within 12 hours of (he onset of chest pain. had reduced
mortality. The beneficial effect on mortality appeared to be
confirmed by the LIMIT-2 study2 in which 8 mmol of magne-
sium was given by intravenous injection before thrombolysis
and followed by a maintenance infusion of 65 mmol over the
following 24 hours. Benefit was confirmed at follow-up an
average of 2.7 years later~ however, there was no evidence of
an antiarrhythmic effect. These beneficial effects were not
borne out by the larger ISIS-4 study and although there were
slight differences in the magnesium regimen and its timing
which might have played a part in these contradictory results.
at present the routine use of magnesium in myocardial infare-
tion cannot be recommended.
Patients with acute myocardial infarction may have magnesi-
um deficiency and long-term treatment with oral magnesium
has been tried, but in one study was associated with an in-
creased risk of adverse cardiac events and could not be rec-
ommended for secondary prevention?
Porphyria. Magnesium sulphate is one of-the drugs that has
been used for seizure prophylaxis in patients with porphyria
who continue to experience convulsions while in re-
mission.
Premature labour. Magnesium sulphate has been given in-
travenously to suppress initial uterine contractions in the
management of premature labour and has been found
possess similar efficacy to beta2 agonists (sec Salbutamol)
Other magnesium salts have also sometimes been given
en by mouth. Retrospective observational studies have also
found a lower incidence of cerebral palsy in children with
birth weights of less than 1500 g when mothers were treated
with magnesium sulphate for pre-eclampsia. Eclampsia or
premature labour. However, increased total paediatric mor-
tality was noted in an interim analysis of a recent trial
was subsequently discontinued. Although they considered the
safety of magnesium sulphate well established in gestation at
term, the authors cautioned against the use of magnesium sul-
phate in very preterm labour.
Pulmonary hypertension of the newborn. Preliminary
studies have suggested that intravenous magnesium sulphate
may be effective in treating persistent pulmonary hyperten-
sion of the newborn.
Respiratory disorders. Magnesium sulphate, administered
intravenously over 20 minutes in doses of 1.2 g to patients
with acute exacerbations of chronic obstructive pulmonary
disease who had received inhaled salbutamol, appeared to have
moderate efficacy.
Infusion or inhalation of magnesium has been reported to
of benefit in some patients with asthma but results
have been conflicting.