• Magnesium (Mg²⁺) is a vital and abundant cation that plays a role in enzyme function, ATP synthesis, potassium balance, bone stability, and neurotransmission. Consequently, abnormalities can manifest as a variety of pathophysiologic scenarios.
• Hypomagnesemia commonly presents in the perioperative period with non-specific signs and symptoms. Furthermore, it is associated with several pathologic processes (hypokalemia, arrhythmias, mitral valve prolapse, migraines, anxiety and psychiatric disorders, fibromyalgia, diabetes, hearing loss, osteoporosis, dysmenorrhea, asthma, and allergies).
• Hypermagnesemia's clinical presentation ranges from hyporeflexia to respiratory depression to cardiac arrest. It often results from exogenous replacement for the treatment of arrhythmias, hypokalemia, asthma, and preeclampsia, as well as hemolysis, or impaired renal function.

• Mg²⁺ is the fourth most common cation in the body and the second most common intracellular cation (following potassium) (1).
• Distribution: Similar to potassium, magnesium is unevenly distributed throughout the body. It has been described as a physiologic calcium antagonist (regulates entry into the cell and intracellular action). Intracellularly, it is bound to ATP and enzyme complexes (1).
  • Bone (contains approximately 50% of total body stores). Functions to provide physical structure or scaffolding and regulates calcium and phosphorus. By binding to vitamins B6, D, and K, it regulates the absorption of calcium into bone. Thus, it is necessary for mineralization. Bone also serves as a "storage" site that can be drawn upon during times of low concentration.
  • Muscle (contains approximately 25% of total body stores). Plays a role in relaxation by blocking calcium influx.
  • Nerve cells
  • Nucleic acid synthesis
  • Energy metabolism
  • Red blood cells: Hemolysis may falsely elevate serum measurements.
• Extracellular or serum (contains approximately 0.3% of total body stores). Present in ionized form, attached to anions, and bound to protein. Free Mg²⁺ is physiologically active. Similar to potassium, serum levels do not necessarily reflect total body stores. Furthermore, plasma levels are the major regulators of urinary Mg²⁺ excretion.
• Absorption is via dietary oral intake and gastrointestinal absorption (primarily in the ileum and colon).
• Excretion: Renally cleared.
• Regulation: primarily renal. Serum magnesium is filtered at the glomerular level into the renal tubule. Reabsorption occurs along the tubule to regulate serum levels. Its control is complex and at this time, no single hormone has been implicated in this process. It is known, however, that calcium and potassium levels affect reabsorption (2).

• Hypomagnesemia (<1.4 mEq/L). Recently, the incidence of hypomagnesemia has increased, and may be attributed to changes in modern diets. Studies have shown that up to 11% of hospitalized patients and up to 65% of ICU patients may have Mg²⁺ deficiency.
• Causes of hypomagnesemia. In addition to reduced intake, levels can also be reduced by gastrointestinal or renal loss.
  • Gastrointestinal losses can result from small bowel disorders including acute and chronic diarrhea, malabsorption, volume expansion (decreases passive transport), and gastric bypass surgery.
  • Renal losses can result from inhibition of sodium reabsorption or defects in Mg²⁺ reabsorption. Sodium reabsorption drives magnesium transport within the tubular segments. Thus loop and thiazide diuretics may enhance the deficiency.
• Signs and symptoms of hypomagnesemia are non-specific and can be confused with signs and symptoms of hypokalemia, hypocalcemia, and metabolic alkalosis. They can manifest clinically as neuromuscular hyperexcitability, cardiac arrhythmias, and co-existing electrolyte abnormalities (hypokalemia, hypocalcemia).
  • Neuromuscular abnormalities: Excitability is manifest as tremor, twitching, tetany, and positive Chvostek and Trousseau signs. In the CNS, Mg²⁺ normally blocks NMDA receptors which function in excitation. Thus, it may result in generalized convulsions.
  • Cardiac arrhythmias: Mg²⁺ is necessary for all reactions involving ATP, including the Na⁺-K⁺-ATPase pump. Hypomagnesemia impairs function by impeding K⁺ efflux and increasing the resting membrane potential (less negative). This decreases the excitation threshold for an action potential. Additionally, the reduced intracellular K⁺ levels hinder repolarization. This results in increased irritability (ventricular arrhythmias: Ectopy, ventricular tachycardia and fibrillation, and Torsades de pointes) as well as conduction disturbances. EKG manifestations include widening of the QRS complex along with peaking of the T wave. Severe deficiency can flatten the T wave and may impair myocardial contractility.
  • Electrolyte derangements
    • Hypokalemia: As previously mentioned, Mg²⁺ is necessary for proper Na⁺-K⁺-ATPase function and hypomagnesemia can result in reduced intracellular K⁺ levels. Additionally, hypomagnesemia is associated with renal potassium wasting in the loop of Henle (3).
    • Hypocalcemia: Mg²⁺ is necessary for the release of parathyroid hormone (PTH); thus, a deficiency results in low PTH and calcium levels (3).
• Association with other disease processes (does not imply causation) include: Mitral valve prolapse, fibromyalgia, diabetes, asthma, allergies, osteoporosis, and dysmenorrhea.
• Hypermagnesemia (>2.5 mEq/L) results from excessive exogenous intake/therapy, hemolysis, or impaired renal excretion/function. Hemolysis may increase levels due to increased intracellular stores.
• Signs and symptoms of hypermagnesemia include weakness, hypotension, respiratory distress, arrhythmias, cardiac arrest, and coma.
  • Neuromuscular: Hypermagnesemia inhibits pre-synaptic acetylcholine release in skeletal muscles (manifests as weakness, hyporeflexia, and respiratory depression). In smooth muscle, Mg²⁺ antagonizes calcium and results in urinary retention and ileus. In the CNS, it can excessively block NMDA receptors which are involved in excitation.
  • Cardiac: Vascular smooth muscle dilation causes hypotension (Mg²⁺ antagonizes calcium). In the myocardium, it may hyperpolarize the cell membrane and cause sinus bradycardia, SA and AV nodal blocks, and cardiac arrest.

• Hypomagnesemia can be present in patients presenting for surgery. Signs and symptoms are often non-specific, or are overshadowed by hypokalemia or hypocalcemia. It may clinically manifest as ventricular and neuromuscular excitability.
  • Patients on certain medications (warfarin, birth control pills, lithium, laxative use), who are diagnosed with asthma, allergies, MVP, migraines, congestive heart failure, acute coronary events, psychiatric illness, or have had massive blood transfusions (citrate rich blood products), may have hypomagnesemia. Serum levels should be assessed.
  • Hypomagnesemia carries an increased risk for perioperative arrhythmias and resistance to neuromuscular blockade.
  • Treatment depends on the severity of clinical manifestations. In urgent and emergent situations such as Torsades de pointes, magnesium 1–2 grams IV contains 8–15 mEq and can be administered over 15 minutes followed by 1 g/h until serum levels have been normalized (4).
• Hypermagnesemia can result from exogenous therapy, renal dysfunction, or hemolysis. It has several perioperative effects that the anaesthetist must be able to identify and treat appropriately.
  • Sedative effects of anesthetic drugs and volatiles may be compounded.
  • Hypotension (from reduced intracellular calcium levels in smooth muscle) can be compounded by anesthetics that directly vasodilate or reduce sympathetic discharge.
  • Muscle weakness (from inhibited release of synaptic neurotransmitters) may be compounded by neuromuscular blocking drugs (NMBD). Furthermore, the calcium antagonist effects of magnesium may potentiate NMBD.
  • Respiratory depression from muscle weakness may be compounded by anesthetics such as opioids, benzodiazepines, and volatiles.
  • Local anesthetic effects may be potentiated.
• Preeclampsia: Magnesium is administered to parturients to reduce the incidence of eclampsia. Seizures are believed to be due to the excessive release of the excitatory neurotransmitter glutamate, which activates the NMDA receptor and leads to massive neural activity. Mg²⁺ competitively antagonizes glutamate (5).
  • Therapeutic levels are 5–7 mg/dL and are followed by physical exam (monitoring of deep tendon reflexes) as well as laboratory testing. Deep tendon reflexes are reduced well before either respiratory depression or cardiac arrest occurs. They are easy to perform, non-invasive, and provide immediate information.
  • Toxic serum concentration levels differ in preeclamptics:
    • Loss of patellar reflexes: 7–10 mEq/L
    • Respiratory depression: 10–13 mEq/L
    • Complete heart block: 15–25 mEq/L
    • Cardiac arrest >25 mEq/L
• Treatment of magnesium toxicity involves administering IV calcium gluconate. Calcium antagonizes the actions of magnesium in neuromuscular and cardiac functions. Additionally, in patients with normal renal function, IV diuretics may be used. In patients with abnormal renal function or renal failure, hemodialysis may be utilized.
• Other therapeutic uses for magnesium include the management of patients with subarachnoid hemorrhage or asthma.
• Plasma Mg²⁺ levels rise as renal function declines, because urinary excretion is its only regulatory system.

• Hypokalemia
• Preeclampsia
• Asthma
• Ventricular Tachycardia
• Tachycardia
• Ventricular Fibrillation

Matthew C. Gertsch , MD

Nina Singh-Radcliff , MD