emergency. If conservative treatment is ineffective, low calcium bath or zero calcium bath hemodialysis are good alternatives. We report 4 patients treated with.
IntensiveCare Medicine
Intensive Care Med (1989) 15:471-474
© Springer-Verlag 1989
Case report Calcium free hemodialysis: an effective therapy in hypercalcemic crisis - report of 4 cases W. Kaiser 1, G. Biesenbach 1, R. Kramar 2 and J. Zazgornik 1 1General Hospital Linz, Second Medical Department and 2Hospital Wels, Third Medical Department, Austria Received: 20 November 1988; accepted: 8 June 1989
Hypercalcemic crisis represents a medical emergency. If conservative treatment is ineffective, low calcium bath or zero calcium bath hemodialysis are good alternatives. We report 4 patients treated with calcium free acetate hemodialysis because of hypercalcemic crisis due to breast cancer, hepatocellular carcinoma, cirrhosis of the liver and immobilisation with hydrochlorothiazids' medication. Following 3 h of hemodialysis, serum calcium concentrations fell from a mean value of 3.96 (range 3.53-4.46) mmol/1 to 2.71 (2.28-3.12) mmol/l. In 2 patients rapid clinical improvement was achieved and in one oliguric patient diuresis started spontaneously during hemodialysis. One patient died from gram-negative sepsis. In 3 cases the subsequent conservative treatment was sufficient to maintain serum calcium levels within the normal range. Together with the previously reported cases (5 patients treated by hemodialysis with low dialysate calcium and 3 patients by hemodialysis with calcium free dialysate) our experience indicates that hemodialysis is an effective and safe therapy for hypercalcemic crisis.
Abstract.
Key words: H y p e r c a l c e m i a
-
Hemodialysis
-
We report 4 cases with hypercalcemic crisis treated by calcium free acetate hemodialysis. The use of either hemodialysis or peritoneal dialysis in the treatment of severe hypercalcemia in 16 previously reported patients is reviewed. Patients and methods Four patients were treated by calcium free hemodialysis. All had been in hypercalcemic coma at the beginning of hemodialysis and had received prior treatment with forced saline diuresis, glucocorticoids, calcitonin and mithramycin (cases 1 and 3) without success. At the start of hemodialysis the average serum calcium value was 3.96 (3.53-4.46) mmol/1. Case 1
A 54 year-old woman was admitted to the hospital because of vomiting and rapid weight-loss. Breast cancer with bone metastases had been diagnosed 2 years previously. Serum calcium concentrations was 3.77 mmol/1. After 3 days of conservative treatment with forced diuresis (240 mg dally of furosemide), glucocorticoids (2x 100 mg prednisone), calcitonin (300 U intravenously daily) and mithramycin (25 ~g/kg pulse intravenously) a progressive mental disorder was noted. The serum calcium concentration remained unchanged at 3.8 mmol/1. After cerebral metastases were excluded, calcium free hemodialysis was performed.
Calci-
um free dialysate
Disturbances in calcium metabolism may provoke neurological, cardiovascular, renal and gastrointestinal symptoms. The usual therapeutic measures in hypercalcemic crisis are based on an increase of renal calcium excretion (forced saline diuresis [1], glucocorticoids [2]) and on the reduction of calcium mobilisation from the bones (calcitonin [2], mithramycin [3], diphosphonates [4-6]). Low or zero calcium bath hemodialysis produces a significant reduction in levels of biologically active intravascular calcium and may bring about a rapid clinical improvement.
Case 2
A 82 year-old male patient was hospitalized because of hypercalcemia caused by immobilisation and hydrochlorthiazide medication. Additionally, bradycardia due to overdose of digoxin (digoxin level 6.4 ng/ml, RIA) was diagnosed. The serum calcium concentration could be reduced from 3.92 mmol/1 to 3.53 mmol/1 by volume infusion (up to a central venous pressure of 12cm H20), furosemide (240 mg daily), glucocorticoids (2x 100 mg prednisone per day) and calcitonin (300 U intravenously daily). In view of oligoanuria and an increase in the serum creatinine from 150 ~tmol/l to 354 pmol/1 calcium free hemodialysis was performed on the 4th day. Case 3
A 74 year-old male patient was admitted because of hypercalcemic coma (serum calcium concentration 4.72 mmol/l). Despite intact re-
472
W. Kaiser et al.: Calcium free hemodialysis
nal function, initial treatment (volume replacement, furosemide 10 m g / h , 2 × 100 m g prednisone, 300 U calcitonin intravenously daily) was not effective. As there was no improvement, calcium free hemodialysis was started after 3 days.
Ca (rumor/I)
Diuresis (mi/day)
~0-'
v
5000
3,5-
4000
Case 4
3.0-
3000
A 74 year-old male patient was transferred from another hospital with hypercalcemic crisis and hepatic insufficiency. Conservative treatment was not successful. Thereafter 2 calcium free hemodialyses were performed.
2.5-
2000
2.0
1000 Day I
2
3
5
6
7
8
9
10
11
12 13
Methods
t+.O
Hemodialysis was performed via subclavian, jugular or femoral venous catheters. We used cuprophan or cellulose acetate membranes with a surface area of 1.3 m 2 on two occasions each. The commercially available dialysate (Fresenius) contains 1 3 5 m m o l sodium. 3 m m o l potassium 35 mmol/1 acetate and 4 g/1 glucose; to prevent cardiac arrhythmias, the dialysate concentration of potassium was increased to 4mmol/1. Blood flow was 2 0 0 - 2 5 0 m l / m i n , and dialysate flow 5 0 0 m l / m i n . As machines without programmed ultrafiltration were used, the rate of ultrafiltration could not be measured and fluid had to be substituted by weight and central venous pressure monitoring. A m e a n of 1.5 1 of 0.9°7o physiological saline solution and 500 ml glucose 40% were given. Central venous pressure remained approximately 12 cm H 2 0 during the whole procedure and body weight was continuously controlled. Each hemodialysis session lasted 3 h. Continuous monitoring of E C G (Sirecust 302, Siemens) and blood pressure (Dinamap 845, Critik0n) was performed in all patients. Calcium concentrations were estimated each hour (ph0tometrically by auto-analyser, O-cresolphtalein-complexion, Boehringer Mannheim, Hitachi 737). Measured calcium values were corrected according to the albumin concentration [7].
3.5
4000
3.0
3000
2
5000
2.5
2000
2.0
1000
Day .~] 2 ~
4,0
3 ~
t,
M
5 V
6
8
PTX
1-
3.5 3.0 2.5
2000
2.0
1000 Day 1
2 '7
3
4
5
4
4.0 3.5
3000
3.0
Results and clinical course (Fig.
1)
Case 1. By 3 h of hemodialysis the serum calcium concentration fell from 3.77 mmol/1 to 2.28 mmol/1 and neurologic symptoms disappeared. Over the following days, conservative measures (prednisone orally 35-50mg/day, one more pulse of mithramycin 25 ~tg/kg intravenously) were sufficient to maintain the serum calcium concentration within the normal range. One year later, the patient died from her primary disease. Case 2. The calcium concentration was reduced from 3.53 mmol/1 to 2.37 mmol/1 by hemodialysis. During dialysis treatment diuresis started spontaneously. Calcitonin therapy was continued for another 2 days (200 U daily) and further therapy was not necessary. Case 3. Reduction of the serum calcium concentration from 4.46 mmol/l to 3.12 mmol/l was not associated with clinical improvement. Within a few hours, hypercalcemia recurred and further mithramycin therapy (25 ~tg/kg pulse intravenously) was of no benefit. A second hemodialysis treatment had to be stopped be-
2.5 20 Day 1
2
3
4
5
6
7
8
9
Fig. 1. Efficiency of calcium-free acetate hemodialysis and clinical course. V hemodialysis, C, calcitonin; M, mithramycin; PTX, parathyroidectomy; + , death of the patient; 1 - 4 , case number). Solid line, serum calcium level; vertical bars, urine volume)
cause of circulatory collapse due to gram-negative septicemia (Enterobacter cloacae) with disseminated intravascular coagulation. As hyperparathyroidism was suspected (parathyroid hormone 650pg/ml, RIA Henning, PTH 44-68; one adenoma in thyroid gland region diagnosed by sonography) an emergency exploration of parathyroid glands was performed. The patient died during surgery. We found hepatic cirrhosis with hepatomas and an hemorrhagic lymph node adjacent to the thyroid gland at autopsy.
Case 4. The calcium concentration was reduced from 4.19 mmol/1 to 3.08 mmol/1 by one hemodialysis and from 3.38 mmol/l to 2.60 mmol/1 by a second hemo-
W. Kaiser et al.: Calcium free hemodialysis
473
dialysis session. A diuresis of about 2.5 1 daily was sufficient to keep calcium concentration with the normal range. After 9 days of therapy the patient died of hepatic failure. At autopsy a hepatocellular carcinoma was found.
Discussion
When conservative treatment of hypercalcemic crisis fails, more aggressive therapy such as peritoneal dialysis or hemodialysis using low or calcium free dialysates represent good alternatives. Desperate strategies, such as phosphate infusion [8], should be avoided because of the risk of metastatic calcification in the lungs, kidneys and vascular system [9]. There are 9 reports of calcium free hemodialysis in severe hypercalcemia [10-18]. Duration of treatment ranged from 10 h [13] to 120h [18]. Serum calcium levels were decreased from 4.16 (range 3.00-5.55) mmol/1 to 2.78 (1.93-3.35) mmol/1. Two patients showed rebound hypercalcemia [14, 18]. One patient with hyperparathyroidism died because of cardiac arrhythmias [14] and another three patients died because of their primary disease [18], or because of withdrawal of therapy [12]. The calculated mean efficiency of low or zero calcium bath hemodialysis in removing calcium is twofold and three-fold higher than forced saline diuresis and peritoneal dialysis (1.5 mmol per hour) respectively, as reported by Cardella et al. [19]. The maximum calcium elimination capacity of hemodialysis reaches 17 mmol calcium per hour, an eight-fold higher rate than forced saline diuresis (2 mmol calcium per hour) and a five-fold higher rate than the maximum of peritoneal dialysis (3.1 mmol calcium per hour) [19]. There are three previous reports of patients treated
with calcium-free hemodialysis [14, 19, 23] (Table 1). In another 5 patients [18-22] dialysate calcium concentrations ranging from 0.25 mmol/l to 2.0 mmol/1 have been used (Table l). Using calcium dialysate concentrations of 2 mmol/1, the efficiency falls to a maximum of 4 mmol calcium per hour [18]. Most commercially available dialysates contain 1.75 to 2.00 mmol/1 calcium. We prefer using calcium free dialysates in hypercalcemia because of its greather effectiveness. Despite rapid reductions of serum calcium concentration we did not observe any severe cardiac arrhythmias (Lown IV) during treatment and there was no need for antiarrhythmic therapy. We attribute this to the increase (to 4 mmol/1) of potassium dialysate concentration. We used acetate zero calcium bath hemodialysis. Despite the well-known risks of vasodilatation induced by acetate, this treatment was tolerated without severe hypotension in all patients, except during the second hemodialysis in patient 3. In this patient, circulatory collapse was probably caused by the gram-negative septicemia. In contrast to acetate, bicarbonate dialysis is not associated with vasodilatation. Therefore bicarbonate dialysate might also be effective but calcium free bicarbonate dialysates are not available commercially. A therapy that would be better tolerated is calcium-free hemofiltration, since norepinephrine is secreted normally during such treatment. Adequate volume replacement during hemodialysis is of importance, because blood pressure falls in linear correlation with the rate of ultrafiltration. Another reason for the relative vascular stability might be the small fluctuations of osmolality in hypercalcemic crisis, in contrast to the use of hemodialysis in chronic replacement therapy. In other reports, dopamine infusion has been required to maintain adequate systolic blood pressure [19].
Table 1. Hemodialysis in the management of severe hypercalcemia (PTX = Parathyroidectomy) Reference
Raphael [181 Leow [22] Strauch [21] Cardella [19] Eisenberg [20] Leroy [14] Cardella [19] Chavez [23] Our patients (1) (2) (3) (4) (5)
Calcium (mmol/l) Predialysis
Postdialysis
3.70 4.90 5.35 4.88 3.30 4.18 6.70 4.10 4.10 3.77 3.53 4.46 4.19 3.38
2.70 4.90 3.55 3.93 2.58 2.98 4.50 2.33 1.75 2.28 2.37 3.12 3.08 2.60
Dialysate caIcium (mmol/1)
Diagnosis
2.00 Mutiple myeloma 1.50 Parathyroid adenoma 0.625 Parathyroid adenoma Second dialysis followed by PTX 0.50 Vitamin D intoxication 0.25 Parathyroid adenoma 0 Parathyroid adenoma 0 Multiple myeloma 0 Not reported 0 Breast cancer 0 Thiazides and immobility 0 Liver cirrhosis 0 Hepatocellular carcinoma Second dialysis
Outcome
Improved Death Rebound and PTX Improved Improved Death Improved Not reported Improved Improved Rebound and death Active management withdrawn
474
In cases 1, 2 and 4 the serum calcium concentration was effectively reduced and rapid clinical improvement was noted in 2 patients (cases 1 and 2), and in one patient with oligo-anuria renal function was restored. In all these 3 patients subsequent conservative methods were sufficient to prevent hypercalcemic crisis. Despite the important fluctuations of electrolytes we did not notice cardiac arrhythmias. Case 3 was the only patient with severe rebound hypercalcemia. He had high parathyroid hormone values, probably caused by production in his hepatomas [23]. Strauch et al. [21] reported a patient with rebound hypercalcemia due to parathyroid adenoma, who needed a second low calcium bath hemodialysis before surgical exploration. We consider hemodialysis as an effective and safe therapeutic modality for hypercalcemic crisis. Serum calcium and electrolyte changes should be monitored closely during hemodialysis. If hypocalcemia appears during dialysis treatment, calcium should be added to the bath and dialysis can be continued.
W. Kaiser et al.: Calcium free hemodialysis
9.
10. 11. 12.
13. 14.
15.
16.
17.
18.
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Dr. W. Kaiser General Hospital Linz Second Medical Department KrankenhausstraBe 9 A-4020 Linz Austria
