Case Report

Hypercalcemic crisis successfully treated with prompt calcium-free hemodialysis

Abstract

Hypercalcemic crisis, a life-threatening emergency, is defined as decompensated hypercalcemia presented with characteristic symptoms such as oliguria, cardiac arrhyth- mia, or coma. We report the case of a 63-year-old man diagnosed with mucosa-associated lymphoid tissue lym- phoma and multiple bony metastases, who presented to the emergency department (ED) with coma and severe hypercalcemia (4.15 mmol/L). Prompt hydration with normal saline and intravenous pamidronate failed to correct his hypercalcemic coma. Calcium-free hemodialysis ra- pidly decreased the level of serum total calcium to 2.15 mmol/L after a 2-hour session, and the patient dramatically regained consciousness shortly after hemodialysis. Cal- cium-free hemodialysis has proved favorable for rapidly correcting hypercalcemia in the presence of severe hypercalcemic symptoms, congestive heart failure, renal failure, or other conditions that contraindicate adequate hydration. This case highlights the fact that for all patients with comas of questionable cause in the ED, hypercalce- mia-induced coma must be considered, especially in patients with malignancies. Early diagnosis and prompt treatment with calcium-free hemodialysis not only rapidly improve patient consciousness but also prevent the fatal complication of hypercalcemia.

A 63-year-old man was brought to the emergency department (ED) because of delirium that progressed to coma in 2 weeks. He has chronic Peptic ulcer disease for decades. He had been diagnosed with mucosa-associated lymphoid tissue lymphoma and treated with chemotherapy (cyclophosphamide, adriamycin, vincristine, and predni- solone) for 8 months before admission. After 6 months, multiple bony metastases were confirmed by magnetic resonance imaging and whole-body positron emission tomography scans. He had not used Thiazide diuretics, vitamin D₃, or any calcium-containing drugs in recent months. On admission, physical examination revealed blood pressure of 106/50 mm Hg, pulse rate of 108 beats

per minute, respiratory rate of 20 breaths per minute, and body temperature of 36.5?C. This patient was comatose with decreased deep tendon reflexes and an absent Babinski sign. Impaired ability of expectoration and coarse crackle over trachea with mild respiratory distress were also noted. The patient had decreased bowel sounds upon auscultation. Dry mucosal membranes, flat jugular veins, and reduced skin turgor were also present, indicative of volume depletion.

A complete blood cell count showed that hemoglobin was

11.9 g/dL, white blood cell count was 7700/uL, and platelet count was 173 000/uL. Blood biochemistry findings included total calcium, 4.15 mmol/L; sodium, 140 mmol/L; potassium,

3.4 mmol/L; phosphate, 3.4 mg/dL; blood urea nitrogen, 26 mg/dL; creatinine, 0.9 mg/dL; albumin, 3.0 g/dL; and intact parathyroid hormone (iPTH), less than 1.0 pg/mL. brain computed tomography revealed no intracranial hemor- rhage, infarction, or mass lesion. Because of suspected hypercalcemia-induced coma, the patient was treated imme- diately with vigorous hydration with normal saline (1000 mL in 4 hours), 90 mg of palmidronate, and 20 mg of furosemide administrated intravenously. Four hours later, he remained comatose, and his rechecked serum calcium level was

4.13 mmol/L. Calcium-free hemodialysis (CFHD) was begun for treatment of hypercalcemia via a temporary noncuffed catheter. Dynamic change in serum total calcium, dialysate calcium, consciousness level, and blood pressure are shown in Table 1 and Fig. 1. Hemodialysis lasted for 2 hours and was stopped when the serum calcium level was sufficiently reduced (2.15 mmol/L). Shortly after hemodia- lysis, the patient’s consciousness dramatically improved. Furthermore, he was successfully rescued from potential airway compromise. Rebound hypercalcemia (2.65 mmol/L) was noted 12 hours after dialysis. Subsequently, the serum calcium was well controlled by hydration, bisphosphonate, and Furosemide administration.

Consciousness disturbance is a common problem in the ED [1], and it has various etiologies. Hypercalcemia is one of the treatable causes, but it is frequently ignored. Mild to moderate hypercalcemia can result in nonspecific manifesta- tions, such as nausea, vomiting, dehydration, progressive azotemia, cranial nerve palsies, emotional lability, depression [2], confusion, and lethargy. Coma and cardiac arrhythmia

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suggested that a 3- to 4-hour session with calcium-free dialysate was effective for treatment of hypercalcemic crisis. Major adverse events were hypotensive episodes, which occurred in 35% of hemodialysis sessions. Hypotensive episodes were transient and could be corrected by moderate Fluid loading. No severe cardiac arrhythmias were noted during CFHD, and all such incidents had uncomplicated resolutions. Hypotension during CFHD was probably related to (1) a rapid decline in calcium level resulting in the elimination of the vasoconstrictor effect of calcium, (2) underestimation of dehydration and insufficient treatment for it, and (3) exposure of patients to the risk of vasodilatation caused by acetate-containing dialysate [8].

Current facility of hemodialysis has changed greatly over the last decade. High efficiency as well as high-flux dialyzers are prevalent now, and these may explain a more rapid decline in serum calcium level in this patient than in previous reports [6,8]. Further investigation is necessary to confirm the exact efficacy of CFHD with current facility and guide the clinical practice. Although acetate has been largely replaced by bicarbonate as dialysate buffer, transient hypotension still occurred in this patient. More rapid removal of serum calcium and insufficient hydration may contribute to the hypotension the patient experienced. This

Table 1 Hypercalcemic crisis treated with calcium-free hemodialysis (CFHD) ^a

Hour after hemodialysis

0 1 2

eventually develop in cases of severe hypercalcemia, and such a condition is defined as a hypercalcemic crisis [3,4]. The most common underlying causes of hypercalcemic crisis are malignancy and hyperparathyroidism. Up to 20% to 30% of patients with malignancies present with hypercalcemia at some time during the course of their disease [5]. First-line treatment of hypercalcemia associated with cancer includes hydration, administration of furose- mide after rehydration, and intravenous bisphosphonates [3,5]. Hydration must be aggressive, with 200-500 mL of saline per hour, depending on the cardiovascular and renal status of the patient. With such treatment, the level of serum calcium will decline gradually in most cases. However, a patient with hypercalcemic coma may be further harmed by airway compromise with Aspiration pneumonia or respira- tory failure. In addition, cardiac arrhythmia may progress into complete heart block and cardiac arrest in extreme hypercalcemia [4]. For these reasons, rapidly and markedly decreasing the serum calcium level is crucial in the treatment of hypercalcemic crisis.

Calcium-free hemodialysis decreases the serum calcium levels more markedly and rapidly compared with hydration or the use of furosemide, bisphosphonates, glucocorticoids, calcitonins, and mithramycin [6]. Moreover, renal function impairment is very common in patients with hypercalcemia [1,7] and complicates the hydration procedure. Therefore, CFHD is beneficial for the treatment of hypercalcemia in the event of severe hypercalcemic symptoms, congestive heart failure, renal failure, or other conditions contraindicate adequate hydration [3,5,6,8]. The last report was a 33- patient study conducted in 1996 by Camus et al who

Fig. 1 Serum total calcium concentration, blood pressure, and consciousness level before and after calcium-free hemodialysis. GCS indicates Glasgow Coma Scale; MAP, mean arterial pressure; Total Ca, serum total calcium.

Case Report 1174.e3

case emphasizes that hydration must be administered aggressively before, during, and after administering CFHD not only to correct hypercalcemia but also to attenuate the severity of hypotensive episodes. On the other hand, CFHD facilitates the treatment of hypercalcemia and also serves as a safeguard against development of pulmonary edema during vigorous hydration in patients with renal failure or heart failure.

In conclusion, hypercalcemia should be considered as a cause of coma in the ED, especially in patients with malignancies. Hypercalcemic crisis is a life-threatening condition and required rapid decline in serum calcium to prevent fatal complication. Calcium-free hemodialysis is an effective tool for rapidly and markedly correcting hypercal- cemia without serious adverse events. Early diagnosis and prompt treatment are the key factors in successful treatment and a better outcome for patients.

Chih-Chiang Wang MD Division of Nephrology Department of Internal Medicine

Kaohsiung Armed Forces General Hospital Kaohsiung 802, Taiwan, R.O.C. Division of Nephrology Department of Internal Medicine Tri-Service General Hospital Taipei 114, Taiwan, R.O.C.

Yeu-Chin Chen MD Division of Hematology/Oncology Department of Internal Medicine Tri-Service General Hospital Taipei 114, Taiwan, R.O.C.

Jeng-Chuan Shiang MD Department of Internal Medicine Kaohsiung Armed Forces General Hospital Kaohsiung 802, Taiwan, R.O.C.

Shih-Hua Lin MD Pauling Chu MD, PhD Chia-Chao Wu MD, PhD Division of Nephrology

Department of Internal Medicine Tri-Service General Hospital Taipei 114, Taiwan, R.O.C.

E-mail address: [email protected] doi:10.1016/j.ajem.2009.01.026

References

1. Lee CT, Yang CC, Lam KK, et al. Hypercalcemia in the emergency department. Am J Med Sci 2006;331:119-23.
2. Papa A, Bononi F, Sciubba S, et al. Primary hyperparathyroidism: acute paranoid psychosis. Am J Emerg Med 2003;21:250-1.
3. Ziegler R. Hypercalcemic crisis. J Am Soc Nephrol 2001;12:S3-S9.
4. DeCristofaro J, Tsang R. Calcium. Emerg Clin North Am 1986;4: 207-21.
5. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med 2005;352:373-9.
6. Kaiser W, Biesenbach G, Kramar R, et al. Calcium free hemodialysis: an effective therapy in hypercalcemic crisis-report of 4 cases. Intensive Care Med 1989;15:471-4.
7. Triner WR, Birdwell MD. Severe hypercalcemia presenting with multisystem organ failure. Am J Emerg Med 1995;3:673-6.
8. Camus C, Charasse C, Jouannic-Montier I, et al. Calcium free hemodialysis: experience in the treatment of 33 patients with severe hypercalcemia. Intensive Care Med 1996;22:116-21.