Magnesium Toxicity

Etiology

While magnesium toxicity is rare in the general population, there is a subset of patients at risk of developing this pathology. Magnesium is excreted in the kidneys, so those with chronic kidney disease are particularly at risk. However, magnesium excretion is only impaired when the creatinine clearance falls below 30 ml/minute. Patients on dialysis can also experience a quick rise in magnesium levels if their treatments are missed. Additionally, the magnesium concentration in cells is much higher than in plasma. Therefore, patients undergoing cancer treatment who have high rates of cellular hemolysis are also at risk. Lastly, women receiving preeclampsia treatment are also at risk for magnesium toxicity due to the high dosage needed to prevent seizures. Identifying the causes of magnesium toxicity, whether through over-absorption or under-secretion, is vital to identify patients at risk for magnesium toxicity and prevent future toxicities.[2]

Epidemiology

Magnesium toxicity occurs in both sexes as this condition is indirectly developed due to underlying pathology or excessive exogenous intake. However, women are more likely to develop magnesium toxicity as magnesium is universally used to treat pre-eclampsia, which complicates about 3% of pregnancies nationwide. Additionally, magnesium toxicity occurs at a higher rate in the U.S. versus worldwide, likely due to the wider availability of magnesium-containing over-the-counter supplements. The prevalence of hypermagnesemia among hospitalized patients in the U.S. was also found to be 9.3%.[3][4]

Pathophysiology

Magnesium serves as a co-factor for over 300 biochemical reactions within the body. Magnesium's importance is in protein synthesis, nerve and muscle functioning, bone growth, blood pressure and glucose regulation, and normal cardiac rhythm. An average adult has approximately 22 to 26 grams of magnesium. Approximately 60% of the total is stored in bone, 39% is stored intracellularly, and only 1% is found in blood vessels' free or ionized active form. Magnesium is also involved in sodium, potassium, and calcium channels. Magnesium homeostasis depends on kidney and small bowel function and storage in bone and cells. When these processes are affected, whether due to under-excretion by the kidneys, over-absorbance by the small bowel, or displacement of stored magnesium into the serum, hypermagnesemia occurs and leads to magnesium toxicity. The most common findings of early-onset toxicity are diarrhea, nausea and vomiting, muscle weakness, and low blood pressure. However, as levels continue to rise, patients experience loss of deep tendon reflexes, sinoatrial (SA) or atrioventricular (AV) node blocks, respiratory paralysis, and, eventually, cardiac arrest.[5][6]

Toxicokinetics

The toxic effects of magnesium are inherently linked to the levels (mEq/liters) found in the serum. As magnesium levels rise, different symptoms start to manifest, and the fatality of those symptoms is proportional to the levels of magnesium found. Patients develop ECG changes starting at 5 to 10 mEq/L (prolonged PR interval, widened QRS). At 10 mEq/L, deep tendon reflexes and muscle weakness are lost. At 15 mEq/L, signs of abnormal conductivity surface as SA/AV node block. Additionally, patients begin to experience respiratory paralysis. At 20 mEq/L or higher, the patient is likely to experience cardiac arrest.[7][8][9][10]

History and Physical

Obtaining a thorough history is paramount when diagnosing magnesium toxicity, as magnesium levels are not checked in a routine workup, and the symptoms that patients can present with tend to be nonspecific. As previously discussed, magnesium toxicity results from under-excretion, over-consumption, and storage displacement. The history should be focused on their etiology, such as a history of chronic kidney disease, the use of magnesium-containing medications such as antacids and laxatives, and recent chemotherapy treatment. Patients on dialysis who may have missed their treatments are also especially at risk. A physical exam is difficult as patients may present with nonspecific findings such as visual changes, flushing, muscle paralysis, and somnolence. However, loss of patellar reflexes should raise suspicion for magnesium toxicity. Patients receiving a magnesium infusion, such as those with preeclampsia, require a continuous reassessment of patellar reflexes.[11]

Evaluation

Hypermagnesemia can be diagnosed relatively quickly if there is a high index of suspicion. This can be done by measuring the magnesium concentration in the blood. Levels greater than 2.2 mEq/L (or greater than 1.1 mmol/L) are diagnostic for hypermagnesemia. When suspicion of magnesium toxicity is high, a workup includes an initial ECG, as this can be readily done and can identify lethal dysrhythmias that may require emergent treatments. In addition to an ECG, a clinician should order a complete metabolic panel, including magnesium and phosphorus, to rule out additional electrolyte abnormalities and evaluate the patient's renal function as the kidneys excrete magnesium.[12]

Treatment / Management

The treatment of magnesium toxicity begins with the discontinuation of all magnesium-containing supplements and medication. In severe cases, intravenous calcium gluconate can displace and neutralize the effects of magnesium. However, definitive treatment requires a reduction of magnesium levels within the body. In patients with normal kidney function, this is achievable through intravenous diuretics. For patients with impaired kidney function, dialysis treatment is necessary.[13](A1)

Differential Diagnosis

Due to the indistinct symptomatic presentation of magnesium toxicity, the differential diagnosis is wide. However, electrolyte imbalances, such as hypokalemia and hypercalcemia, should always be included in the list. Therefore, a provider’s workup should include other electrolytes such as potassium, calcium, phosphorus, and magnesium levels.

• Lithium 
• Depression
• Hypothyroidism
• Addison disease
• Familial hypocalciuric hypercalcemia
• Milk alkali syndrome

Prognosis

The prognosis of magnesium toxicity can include a complete resolution of symptoms without residual effects if diagnosed and treated early. Quality of life, long-term complications, and life expectancy are unaffected if toxic magnesium levels are stabilized early on using calcium gluconate and lowered using diuretics or dialysis. However, if left untreated, magnesium toxicity has a high mortality rate due to respiratory paralysis and cardiac arrest.

Complications

Magnesium toxicity can be systemic and organ-specific, depending on the levels of magnesium concentration in the blood. Minor side effects seen early in hypermagnesemia include flushed skin, nausea or vomiting, and generalized muscle weakness. However, as magnesium levels increase, the muscle weakness progresses to loss of deep tendon reflexes and, eventually, flaccid paralysis that can cause respiratory compromise. Further complications include those in the cardiovascular system, beginning with hypotension and bradycardia. If magnesium levels remain uncorrected, this can lead to a complete heart block and, subsequently, cardiac arrest.[14][15][16]