EBM: Hypercalcemia: What to do with it in the Emergency Department?

A regular shift in the emergency department comes with a lot of noise. The patient in room 26 has a lactate of 2.5. The new patient in the hallway has a glucose of 280. Your septic patient’s MAP just hit 58. Do you want to bolus more fluids or should you start pressors? Learning to task-switch and prioritize is one of the key traits that makes emergency physicians who we are.

The next alert you get is that your patient in room 21 has a calcium of 14.2. What does this mean? Is this information you place on the back burner or is it something that should play a major role in your decision making during their care?

Physiology

Calcium is regulated through the parathyroid glands and the kidneys. The parathyroid glands detect the calcium level in the blood stream and will secrete PTH to stimulate the kidneys to produce calcitriol. Additionally, vitamin D plays a key factor in aiding this process. This ultimately causes the bones to release calcium and for increased calcium absorption, increasing the serum calcium. Counteractively, when calcium levels are high, the parathyroid stops secreting PTH, downregulating this process. Additionally, the thyroid will secrete calcitonin to promote bones to resorb calcium and promote calcium filtration. See Figure 1.

 

Figure 1. Effects of parathyroid hormone (Crowley 2013)

 
 

Pathophysiology of Hypercalcemia

Figure 2. Causes of hypercalcemia (Lindner 2013)

There are various processes that can cause hypercalcemia (see Figure 2 below). For the purposes of this article, we will review the two most common forms. First with hyperparathyroidism and then hypercalcemia of malignancy.

Hyperparathyroidism can be broken down into two forms. Primary hyperparathyroidism, which is hypercalcemia caused by the over secretion of PTH. This is most commonly caused by adenomas or hyperplasia.  These patients will often present with more mild-range calcium levels.

The more feared cause of hypercalcemia would be hypercalcemia of malignancy. This is one of the most common forms of hypercalcemia and can often present with severe ranges of calcium. Of note, these patients can have up to a 50% 30-day mortality rate! The way malignancy causes this is often from a paraneoplastic syndrome, such as a PTHrP secreting tumor, or from osseus destruction from bone metastasis. Some tumors can also hydroxylate vitamin D themselves which leads to the development of hypercalcemia.

Signs and Symptoms

The symptoms are often vague. They can include muscle weakness, confusion, bone pain, perioral numbness, muscle spasms, polyuria and confusion. Some patients may also develop frequent nephrolithiasis. There can be some EKG changes as well. QTc shortening is the most common abnormality noted, but in rare cases AV blocks and bradycardia/asystole can occur as well (see Figure 4).

Figure 3. Risk factors & common clinical findings associated with hypercalemia (Taylor 2020)

Figure 4. EKG changes with hypercalcemia

Interpreting the lab value

The first step to interpreting the lab value is to correct it. Calcium binds to albumin, so in patients who are hypoalbuminemic, the values can be falsely elevated. The formula is as follows:

 
 

One caveat to this is that it can often times overestimate calcium. Another option you could do is to order ionized calcium, which is independent of the patient’s albumin.

Once you have an accurate calcium, you can now grade the patient’s hypercalcemia.

Mild: Corrected Ca 10.5-12 mg/dL OR iCa 1.4-2 mmol/L

Moderate: Corrected Ca 12-14 mg/dL OR iCa 2-2.5 mmol/L

Severe: Corrected Ca >14 mg/dL OR iCa >2.5 mmol/L

Managing the hypercalcemia

The grade of the patient’s hypercalcemia has a major impact on how this should be managed. Patients with severe range hypercalcemia is often from a malignant cause, where as mild ranges can be from various other causes, see Figure 5. Hypercalcemia may be the only presenting sign of a patient’s malignancy, so it is key to be aware of this and to work it up appropriately.

Figure 5. Characteristics of hypercalemic patients based on calcium level (Lee 2006)

Mild range calcium levels often times do not immediate treatment. However, a thorough medical history and medication review should be performed on these patients. They should be aware of these results and be provided with appropriate outpatient follow up. Moderate ranges are based entirely on the patient’s presenting complaint. Again, these patients require a thorough history and medication review. However, if they have signs/symptoms of the hypercalcemia, they should be treated. Severe range hypercalcemia should always be treated.

 The treatment of hypercalcemia includes three parts. The first is with IV fluids. Normal saline is the preferred method, as it has no calcium in it, although lactated ringers is appropriate as well. This will promote diuresis of calcium. These patients want to have a goal urine output of 100-150 cc/hr. Lasix is only indicated if the patient is unable to tolerate fluids or achieve this urine output without it. Next is calcitonin. As we reviewed above, this will promote diuresis of calcium, decreased intestinal absorption, and increased bone deposition. Lastly, bisphosphonates can be used to prevent bone resorption and aid in decreasing calcium levels. However, this will take days-weeks to act. Calcitonin acts within about 1-2 days. Of course, these patients requiring treatment need at a bare minimum telemetry admission. Although, based on comorbidities, an ICU admission or dialysis may be indicated in some circumstances.

POST BY: DR. DAN SAADEH (PGY3)

FACULTY EDITING BY: DR. NIK SEKOULOPOULOS

References

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