Continuing Education Activity

Magnesium toxicity is commonly caused by the overuse of magnesium-containing medication or under-excretion of magnesium by the kidneys. Early recognition, as well as a high index of suspicion, is critical when diagnosing magnesium toxicity before the onset of fatal complications such as hypotension, respiratory paralysis, and cardiac arrest. This activity reviews the evaluation and management of magnesium toxicity and highlights the interprofessional healthcare team's role in evaluating and treating patients with this condition.

Objectives:

• Identify the risk factors for developing magnesium toxicity.
• Outline the typical presentation of a patient with magnesium toxicity.
• Review the management options available for magnesium toxicity.
• Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients with magnesium toxicity.

Introduction

Magnesium is a mineral that is naturally found in your body and in the food you consume daily. It is responsible for many processes within the body that include, but are not limited to, protein synthesis, bone formation, blood pressure regulation, nerve function, and electrical conduction in the heart. However, whether due to over-consumption or under-excretion, too much magnesium can result in serious health issues for the patient. This activity will cover the causes, as well as the early symptomatic presentation of magnesium toxicity. Additionally, it will highlight the importance of diagnosing and treating magnesium toxicity early on and how a strong interprofessional effort is important to prevent fatal complications.[1]

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, and 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 that 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, regulation of blood pressure and glucose, 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 its free or ionized active form in blood vessels. Magnesium is also involved in sodium, potassium, and calcium channels. The homeostasis of magnesium depends on kidney and small bowel function and storage in bone and cells. When these processes are affected, whether it is 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. Starting at 5 to 10 mEq/L, patients will begin to develop ECG changes (prolonged PR interval, widened QRS). At 10 mEq/L, there will be a loss of deep tendon reflexes and muscle weakness. 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 obtaining a measurement of the concentration of magnesium in the blood. Levels that are greater than 2.2 mEq/L (or greater than 1.1 mmol/L) are diagnostic for hypermagnesemia. When suspicion for magnesium toxicity is high, workup including 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 also order a complete metabolic panel, including magnesium and phosphorus, to rule out additional electrolyte abnormalities as well as evaluate the patient's renal function as magnesium is excreted by the kidneys.[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 be used to 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]

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 within the list. Therefore, a provider’s workup should include other electrolytes such as potassium, calcium, and phosphorus, in addition to 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 subsequently lowered using diuretics or dialysis. However, if left untreated, magnesium toxicity has a high mortality rate due to respiratory paralysis and cardiac arrest.

Complications

Complications of magnesium toxicity can be both systemic and organ-specific, depending on the levels of magnesium concentration in the blood. Minor side effects seen early on 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]

Deterrence and Patient Education

Patient education on the effects of elevated magnesium is particularly important in the prevention of magnesium toxicity. Magnesium, a lesser-known electrolyte to the public compared to potassium, sodium, and calcium, should be committed to memory. This is especially true for patients with chronic kidney disease, being treated for preeclampsia, and those on dialysis.

Enhancing Healthcare Team Outcomes

An interprofessional team that provides a holistic and integrated approach to care can help achieve the best possible outcomes. If magnesium toxicity occurs, the role of prompt treatment cannot be undermined. The patient is to be stabilized as early as possible and subsequently monitored closely. Major complications associated with magnesium toxicity can be avoided if the interprofessional team can promptly diagnose and treat this disease.

Collaboration, shared decision-making, and communication are key elements for a positive outcome. The interprofessional care provided to the patient must use an integrated care pathway combined with an evidence-based approach to planning and evaluation of all joint activities.[17] The earlier signs and symptoms of a complication are identified, the better is the prognosis and outcome.[18] [Level 3] Nurses monitor patients, administer treatment, provide patient education, and report status changes to the rest of the team. Pharmacists should counsel patients with renal disease to avoid magnesium-containing over the counter products. [Level 5]