16
Vadim Gudzenko
M CLINICAL SIGNS AND SYMPTOMS
agnesium is an important ion that participates as a cofactor in
over 300 enzymatic reactions, especially in those involving
adenosine triphosphate (ATP). Hypomagnesemia is common
in critically ill patients and is associated with increased mortality.1
CELLULAR PHYSIOLOGY AND
METABOLISM OF MAGNESIUM
Magnesium is a divalent cation (Mg++) that is predominantly localized
to the intracellular compartment (99%). It is the second most abundant
intracellular cation after potassium and plays an important role in cel-
lular metabolism and homeostasis. At the cellular level, Mg++ influ-
ences membrane function by regulating ion transport; Mg++ is required
for sodium/potassium–adenosine triphosphatase (Na+/K+-ATPase)
activity, which maintains transmembrane gradients for Na+ and K+.2,3
Mg++ also regulates intracellular calcium (Ca++) flux by competing for
Ca++ binding sites and influencing intracellular Ca++ transport.2,3 It is
also an essential cofactor for most ATP-requiring processes. Intracel-
lular Mg++ is required for numerous critical biochemical processes,
including DNA synthesis, activation of gene transcription, initiation of
protein synthesis, and regulation of energy metabolism.2,3
Total body magnesium (21 to 28 g) is distributed in bone (53%),
muscle (27%), soft tissue (19%), and blood (0.8%).2 The normal con-
centration of total magnesium in serum is 1.5 to 2.3 mg/dL. Approxi-
mately 19% of circulating magnesium is bound to proteins, whereas
14% is complexed to plasma anions (citrate, phosphate, and bicarbon-
ate). The majority of magnesium in plasma exists in its ionized form
(67%), which represents the physiologically active species.2 Conse-
quently, the measurements of total serum magnesium may not accu-
rately reflect the relative abundance of circulating Mg++.1,2
Magnesium homeostasis is maintained by the small intestine,
kidney, and bone.2,4 Unlike calcium, there are no hormonal mecha-
nisms for regulating Mg++. Consequently, normal renal filtration and
the reabsorption of Mg++ represent important regulatory mechanisms
for Mg++ homeostasis.2,4 Non–protein-bound Mg++ is filtered by the
glomerulus. Under normal conditions, up to 95% of filtered Mg++ is
reabsorbed either in the proximal tubule (35%) or in the thick ascend-
ing loop of Henle (60%). Mg++ reabsorption in the loop of Henle is
linked to sodium chloride (NaCl) transport and is inversely related to
flow. Consequently, diuretic use and other conditions associated with
increased tubular flow result in decreased Mg++ reabsorption.2,4 Under
conditions of persistent Mg++ deficiency, the mobilization of Mg++ from
bone also represents a potential homeostatic mechanism.2
PREVALENCE AND ETIOLOGY OF
HYPOMAGNESEMIA IN PATIENTS
IN THE INTENSIVE CARE UNIT
The reported prevalence of hypomagnesemia in adult intensive care
unit (ICU) admissions ranges from 15% to 60% of cases.1,2 Most com-
monly, severe ionized hypomagnesemia in ICU settings is encountered
following liver transplantation and in patients with severe sepsis,1 but
many conditions encountered in ICU patients can be associated with
hypomagnesemia (Table 16-1). Hypomagnesemia is associated with an
increased risk of mortality.1
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Hypomagnesemia
OF HYPOMAGNESEMIA
Hypomagnesemia is frequently asymptomatic in critically ill patients
and is commonly identified through routine laboratory studies.4,5
However, the relationship between hypomagnesemia and intracellular
magnesium depletion is complex. Hypomagnesemia is most com-
monly seen in conjunction with hypokalemia, hypocalcemia, and/or
other electrolyte abnormalities. Consequently, determining the clinical
consequences of isolated hypomagnesemia has been difficult. In most
instances, symptoms were attributed to Mg++ deficiency only after
other electrolyte abnormalities had been corrected.2,4,5 As summarized
in Table 16-2, the clinical sequelae of Mg++ deficiency are most com-
monly related to the cardiovascular, metabolic, and neuromuscular
systems.
Hypomagnesemia is associated with electrocardiogram (ECG)
changes similar to those observed in patients with hypokalemia: flat-
tened T-waves, U-waves, and a prolonged QT interval. Magnesium is
a cofactor for Na+/K+-ATPase in cardiac tissue.2,4-6 Hypomagnesemia
is associated with a variety of dysrhythmias, including atrial fibrilla-
tion, multifocal atrial tachycardia, ventricular tachycardia, and tor­
sades de pointes.4-6 The administration of intravenous magnesium
sulfate (MgSO4) should be the initial therapy for torsades de pointes
and should be used as an adjunctive treatment for refractory ventricu-
lar dysrhythmias.2,4-6 Magnesium administration during acute myocar-
dial infarction is not recommended in the latest guidelines.7-9
Hypomagnesemia is commonly associated with both hypokalemia
and hypocalcemia.4 The medications and homeostatic changes that
affect magnesium handling often affect K+ handling as well. In
addition, hypomagnesemia promotes the renal losses of K+. Thus,
hypokalemia can be refractory to potassium supplementation unless
magnesium is replaced first.2,4 A somewhat similar condition is noted
for hypocalcemia because hypomagnesemia suppresses parathyroid
hormone release and activity.10 Consequently, hypocalcemia can be
refractory to Ca++ replacement unless Mg++ is replaced as well.2,4 Hypo-
magnesemia has been shown to be associated with an increased inci-
dence and degree of lactic acidosis.11
Magnesium produces a depressant effect on the nervous system
through its ability to cause presynaptic inhibition.2,4,6 It may also
depress the seizure threshold by its ability to competitively inhibit
N-methyl-d-aspartate receptors.2,4-6 The neurologic and neuromuscu-
lar manifestations of hypomagnesemia include coma, seizures, weak-
ness, and signs of muscular irritability. The supplementation of
magnesium might provide neuroprotective properties in patients with
traumatic brain injury and prevent cerebral vasospasm in patients with
aneurysmal subarachnoid hemorrhage.12,13 In addition, the administra-
tion of Mg++ therapy is commonly used in pregnant patients with
preeclampsia or eclampsia.4,5
Magnesium replacement has been used to treat bronchospasm in
patients with asthma.4,5 The proposed mechanism of action for the
therapeutic benefit of Mg++ in bronchospasm involves its relaxant
effects on smooth muscle. Some studies have demonstrated improved
forced expiratory volume in the first second of expansion (FEV1) fol-
lowing intravenous magnesium administration or improved peak flow
rates with nebulized magnesium, but these findings have not been
confirmed.5
59
60 PART 1 Common Problems

TABLE 16-1 Etiology of Hypomagnesemia in the ICU1,2,4-6

Decreased GI intake Magnesium-poor diet or total parenteral nutrition; malabsorption syndrome; short bowel syndrome
Increased GI losses Chronic diarrhea; intestinal and biliary fistulae; nasogastric suctioning; vomiting
Intrinsic renal losses Interstitial nephropathy; postrenal transplantation; postobstructive or postacute kidney injury diuresis
Drug-induced renal losses Loop and thiazide diuretics; aminoglycosides; amphotericin B; cyclosporine; cisplatin; granulocyte colony-stimulating factor
Endocrine and metabolic causes Hyperaldosteronemia; hyperparathyroidism; hyperthyroidism; SIADH; diabetic and alcoholic ketoacidosis; hypophosphatemia;
hypercalcemia; hypoalbuminemia
Magnesium redistribution Acute pancreatitis; administration of epinephrine, insulin; refeeding syndrome; massive blood transfusion
Other causes CRRT; CPB; severe burns

GI, gastrointestinal; SIADH, syndrome of inappropriate antidiuretic hormone; CRRT, continuous renal replacement therapy; CPB, cardiopulmonary bypass.

TABLE 16-2 Clinical Signs and Symptoms of Magnesium Deficiency

CARDIOVASCULAR METABOLIC NEUROLOGIC NEUROMUSCULAR

Atrial fibrillation, flutter Hypokalemia Seizures Chvostek sign
Ventricular tachycardia, esp. torsades de pointes Hypocalcemia Nystagmus Muscle cramps
Supraventricular tachycardia Hypophosphatemia Delirium Carpopedal spasm
ECG changes (↑ PR, wide QRS, ↑ QT) Insulin resistance Coma Muscle weakness
Hypertension Athetoid movements Muscle fasciculations
Risk of digitalis toxicity

ECG, electrocardiogram.

MgSO4 over 5 minutes is recommended. For the urgent treatment of

TREATMENT OF HYPOMAGNESEMIA
The management of hypomagnesemia should include the identifica-
tion and correction of underlying causes and the replacement of mag-
nesium. The degree of hypomagnesemia, severity of clinical symptoms,
associated electrolyte abnormalities, and renal function should be
assessed prior to initiating Mg++ therapy.
In general, intravenous administration of Mg++ is preferred in
symptomatic critically ill patients. However, caution must be used with
Mg++ replacement when renal dysfunction is present, since severe
hypermagnesemia may result. Current recommendations for Mg++
replacement therapies are of somewhat limited value owing to the lack
of adequately controlled studies. Magnesium may be administered
intravenously as MgSO4 (1 g = 4 mmol) or MgCl2 (1 g = 4.5 mmol)
and orally as magnesium gluconate (500 mg = 1.2 mmol) or magne-
sium oxide (400 mg = 6 mmol). When intravenous Mg++ replacement
is used, a bolus followed by continuous infusion or infusion alone is
preferred, since renal filtration and excretion may limit Mg++ retention.
For the management of torsades de pointes, 1 to 2 g of intravenous
hypomagnesemia, an intravenous bolus of 8 to 12 mmol of Mg++ (2-3 g
MgSO4), followed by an infusion of 40 mmol Mg++ (10 g MgSO4) over
the next 5 hours should be considered.
KEY POINTS
1. Hypomagnesemia is one of the most common electrolyte dis-
turbances encountered in ICU patients.
2. Hypomagnesemia is frequently asymptomatic; however, in ICU
patients it is associated with increased mortality.
3. Hypomagnesemia in ICU patients manifests as disturbances in
the cardiovascular, neuromuscular, and metabolic systems.
4. Aggressive intravenous administration of magnesium is indi-
cated in cardiac arrhythmias, including torsades de pointes,
preeclampsia/eclampsia, and status asthmaticus.

References for this chapter can be found at expertconsult.com.

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 CHAPTER 16 Hypomagnesemia 60.e1

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Descargado para Mario Fernando Castro Delgado (mariocastro301@icloud.com) en Pontifical Bolivarian University de ClinicalKey.es por Elsevier en agosto 09, 2019.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.