Page 171 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Calcium: Hypercalcemia and Hypocalcemia 161

and zoledronate is more than 10,000 times the potency of mild volume expansion after dehydration has been
etidronate. 410,412 Zoledronate is 100 to 850 times more corrected.
active than pamidronate. 59 IV pamidronate at 1.3 to 2.0 mg/kg was highly effec-
Inhibition of bone resorption by pamidronate occurs tive in lowering serum calcium in dogs with experimental
earlier and is maintained longer than that induced by cholecalciferol intoxication. 499,500 Dogs treated with
etidronate. Intravenous infusion of pamidronate has been pamidronate (1.3 mg/kg in 150 mL saline administered
the treatment of choice for severe hypercalcemia intravenously over 2 hours), starting 1 day following
associated with malignancy in humans, 60,123 controlling ingestion, lost less weight and had significantly lower
cancer-induced hypercalcemia in more than 70% 510 to serum concentrations of phosphorus, tCa, and iCa than
90% of human patients. 60 Intravenous administration of those treated with saline or calcitonin. Mean serum tCa
bisphosphonates is preferred over oral administration decreased to within the reference range, and values for
for treatment of severe hypercalcemia because some iCa decreased but not to the same degree as that for
patients will be vomiting and cannot tolerate oral medica- tCa following pamidronate treatment. 500 In a subsequent
tion. The use of intravenous zoledronate is the new study, three different doses of pamidronate were given to
treatment of choice because of its increased potency over dogs after a single dose of cholecalciferol. 499 Clinical
pamidronate, as well as the more convenient infusion signs were fewest in dogs given the two higher doses of
protocol of only 15 minutes.* Serum tCa decreases more pamidronate. All dogs given any dosage of pamidronate
rapidly, and maintenance of normocalcemia is nearly were alert and lost less weight compared with saline treat-
twice as long when treated with zoledronate compared ment. The decreases in serum tCa were dose dependent.
with pamidronate. 611 Pamidronate lessened the reduction in the GFR in a dose-
Acute renal injury and renal failure attributed to dependent manner, but the GFR was still reduced by 20%
precipitation of insoluble calcium-bisphosphonate salts to 25% on day 14 (end of study). Minimal histopathologic
in the renal tubules was reported in the early days of IV lesions were seen in dogs treated with the low and inter-
bisphosphonate treatment in humans, often after multiple mediate doses of pamidronate; no lesions were detected
doses and some with preexisting chronic kidney in dogs treated with the high dose of pamidronate. It
disease. 25,341,352,439 Renal toxicity in dogs may be more appears that doses of pamidronate at 2.0 mg/kg are most
likely when doses of 10 mg/kg or more of pamidronate effective in dogs with cholecalciferol toxicity. Alhough
are given. 499 The rate of infusion and the particular not specifically reported, we have used this dose range
bisphosphonate chosen influence the possibilities for to treat dogs with primary hyperparathyroidism before
nephrotoxicity. 4,384 Dehydration should be corrected surgical correction in an effort to reduce crisis-level
before bisphosphonates are administered to lessen the hypercalcemia and to reduce postoperative “hungry-
chances of renal injury. Depending on the bisphosphonate bone” syndrome.
used, several hours of 0.9% saline infusion may be required Clodronate was used clinically to treat hypercalcemia of
to attenuate potential adverse effects. Acute renal failure is malignancy in one dog and hypervitaminosis D in another
very uncommon today due to efforts to ensure hydration dog. 448 Serum iCa and tCa concentrations were normal at
before, during, and after bisphosphonate infusion. People 36 and 48 hours after a 4-hour infusion of clodronate (20
with relatively severe azotemia can be safely given IV to25 mg/kg),butlong-termresultswerenotreported.In
infusions of bisphosphonates when given slowly and a dog with severe hypercalcemia associated with adenocar-
adequate hydration is maintained. 39,341,585 Acute intrin- cinoma of the anal sac, a single 2-hour infusion of
sic renal failure can occur in dogs given greater than or pamidronate rapidly reduced serum tCa and iCa that
equal to a dose of 10 mg/kg, according to the package had not previously responded to intravenous fluids, calci-
insert for pamidronate. Hypocalcemia can occur follow- tonin, and furosemide. 283 In seven dogs with clinical
ing treatment with bisphosphonates but this is not usually calcipotriene toxicity, pamidronate (1.3 to 2.0 mg/kg
a clinical problem. intravenously) resulted in a decrease in tCa, phosphorus,
IV pamidronate infusions at 1.0 to 2.0 mg/kg have and creatinine. 230 In another clinical report, seven dogs
been safely and effectively used to treat hypercalcemia and two cats were given pamidronate (1.05 to 2.0 mg/
in dogs and cats with malignancy, calcipotriene toxicity, kg intravenously) for a variety of disease processes, and
granulomatous disease, and idiopathic hypercalcemia of treatment rapidly decreased serum calcium without evi-
cats. 262 Beneficial effects were seen in these animals dence of toxicosis. 262 In dogs with bone tumors, intrave-
despite the presence of initial azotemia in more than nous pamidronate (1 mg/kg given over 2 hours as a
40% of these cases. It is important to deliver the constant rate infusion) was administered every 28 days
pamidronate as an infusion over at least 2 hours during depending on progression of the bone tumor. 171 One
hundred thirty-three doses of intravenous pamidronate
were given to this group of 33 dogs. Only one dog devel-
oped renal toxicity 16 days following the second
*References 38, 83, 347, 348, 411, 439, 611. pamidronate treatment; this dog also had paraneoplastic