THERAPY
Fluid therapy
For any paraneoplastic syndrome, diagnosing and treating the underlying neoplastic disorder is mandatory to best manage the
patient. However, pending definitive diagnosis of the primary disease, initial intervention for hypercalcemia should ideally
consist of vigorous rehydration with isotonic saline solution (0.9% sodium chloride). Severe dehydration and hemoconcentration
associated with hypercalcemia are common because of the anorexia, vomiting, and calcium-associated polyuria, despite the compensatory
polydipsia. A decreased glomerular filtration rate leads to additional calcium retention as the kidneys attempt to conserve
sodium. To reverse the established vicious cycle and increase calciuresis through an improved glomerular filtration rate,
fluids devoid of calcium such as physiologic saline are usually recommended. In addition, the fluid of choice will have a
high sodium concentration, since the sodium will compete with calcium for tubular reabsorption, resulting in enhanced calciuresis.15 However, the aggressive fluid therapy per se is more important than the actual type of fluid given, and lactated Ringer's
solution can be used if saline solution is not available.
After adequate hydration, a patient's kidneys will first excrete sodium and then calcium, with clinical improvement usually
seen within 24 hours of fluid therapy. Take the patient's hydration, renal, and cardiovascular status into consideration when
determining the fluid rate. Potassium supplementation may be required in some cases to avoid hypokalemia, especially if prolonged
potassium-free intravenous fluid therapy is administered. Intravenous fluid therapy should aim to correct the dehydration
over four to six hours after diagnosis in patients with moderate to severe hypercalcemia.
Loop diuretics
A loop diuretic, most commonly furosemide, may be added to the therapeutic regimen once the patient is adequately rehydrated.
Furosemide inhibits the renal membrane sodium-potassium-dichloride cotransporter present in the thick ascending limb of Henle's
loop.45,46
The Handbook of Small Animal Therapeutics, edited by Lloyd E. Davis in 1985, is one of the first references recommending the use of furosemide for hypercalcemia treatment
in dogs. The original recommended dosage was an initial bolus of 5 mg/kg followed by a constant-rate infusion (CRI) of 5 mg/kg/hr
intravenously. This high dose of furosemide is based on human antihypercalcemic therapy and strictly requires a high rate
of intravenous fluid administration (> three times maintenance fluid requirement) to avoid iatrogenic dehydration. We prefer
using a lower dose of furosemide initially (2 to 4 mg/kg t.i.d. to q.i.d. intravenously, subcutaneously, or orally) to minimize
the need for a high fluid rate.
In a recent study of six normocalcemic greyhounds, a 0.66-mg/kg loading dose of furosemide followed by a CRI of 0.66 mg/kg/hr
(equivalent to 6 mg/kg over eight hours) was evaluated for its calciuretic efficacy compared with the same total dose of furosemide
administered via two intravenous boluses of 3 mg/kg given four hours apart.47 Urine sodium and calcium loss as well as urine production and water intake were significantly larger in the CRI group compared
with the intravenous bolus groups. The study concluded that the same total dose of furosemide over a given time frame resulted
in more diuresis, natriuresis, and calciuresis, as well as less kaliuresis, compared with repeated intravenous boluses.47 Similar to the results obtained in normal greyhounds, it is our experience that the low-dose bolus followed by a CRI effectively
reduces the degree of hypercalcemia.
Thiazide diuretics are absolutely contraindicated because of their hypercalcemic effect, as they cause tubular reabsorption
of calcium rather than calciuresis.15,22
Glucocorticoids
The use of glucocorticoids is controversial for treating hypercalcemia and is not a component of standard therapy in people
because of glucocorticoids' side effects and limited therapeutic value. The exact mechanisms of action of glucocorticoids
in hypercalcemia are unknown, though it has been suggested that they increase renal calcium excretion, reduce bone resorption,
and potentially decrease intestinal absorption.15,16,19 Glucocorticoids are most effective for hypercalcemia secondary to lymphoma, as they then also are part of the cytotoxic
therapy aimed at the underlying cause. Prednisone at a dosage of 1 to 2.2 mg/kg given twice a day intravenously, subcutaneously,
or orally or dexamethasone at a dosage of 0.1 to 0.22 mg/kg given twice a day intravenously, subcutaneously, or orally has
been recommended.19,22 These high dosages should not be maintained indefinitely, and appropriate tapering is advised.
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