Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

TREATMENT OF HYPERCALCEMIA
Table 20.3 Potential causes of hypocalcemia. The disorders
highlighted in bold are those that require specific therapy for
hypocalcemia. Those italicized may or may not require
treatment depending on the severity of the hypocalcemia
Hypoparathyroidism
Eclampsia
Pancreatitis
Phosphate enema toxicosis
Ethylene glycol toxicity
Systemic inflammatory response syndrome
Tumor lysis syndrome
Malabsorption
Renal failure
Medullary carcinoma of thyroid
cal hypocalcemia. Given the large number of hyperthyroid
cats in some countries that undergo bilateral
thyroidectomy, iatrogenic hypoparathyroidism is relatively
commonly encountered.
The clinical signs of hypocalcemia generally relate to
the neuromuscular system. These signs include focal
muscle spasms or fasciculations, tremors, twitching,
tetany and generalized seizures. The number and severity
of these signs relate to the magnitude of the hypocalcemia
and the rate of change of ionized calcium.
Once hypocalcemia induces neuromuscular signs,
particularly tetany or seizures, prompt treatment is
required.
TREATMENT OF HYPERCALCEMIA
Once persistent clinical hypercalcemia has been identified,
treatment is warranted while the underlying cause
is identified. Generally, short-term success is achieved
using simple measures such as intravenous fluid therapy
with or without diuretic administration. More prolonged
control will require more specific intervention
and currently bisphosphonates are the most appropriate
and potent drugs available.
General supportive therapy
Intravenous fluid therapy
Many hypercalcemic animals are dehydrated when presented
which exacerbates the hypercalcemia. Rehydration
with mild volume expansion eliminates the effects
of dehydration and promotes calciuresis.
Normal saline is the fluid of choice as it contains no
additional calcium and it promotes calciuresis as sodium
competes with calcium for tubular resorption. Potassium
supplementation may be required.
Approximately 2–3 times maintenance (120–180 mL/
kg/d) is required over the dehydration deficit (this can
be replaced in the first 4–6 h).
Care should be taken to avoid volume overload.
Diuretic therapy
The loop diuretic furosemide enhances the effect of
volume expansion by inhibiting calcium resorption in
the thick ascending limb of the loop of Henle. By contrast,
thiazide diuretics are unhelpful as they decrease
calcium excretion, thereby promoting hypercalcemia.
Furosemide may also protect against the risk of volume
overload associated with saline diuresis.
Furosemide is initially administered intravenously as
a 5 mg/kg bolus followed by a 5 mg/kg infusion or 2–
4 mg/kg q.8–12 h.
The use of furosemide should only be considered once
any dehydration deficits have been replaced and volume
expansion instituted.
Glucocorticoids
Glucocorticoids decrease circulating calcium concentration
potentially through a variety of mechanisms
although few have been specifically evaluated in dogs or
cats. Glucocorticoids counter the effect of 1,25(OH) 2 D
and enhance renal excretion of calcium. Glucocorticoids
are also cytotoxic to neoplastic lymphocytes and can
inhibit the growth of neoplastic tissue and consequently
may decrease circulating calcium concentration in
malignancy-associated hypercalcemia.
However, their use can interfere with diagnostic tests
and may adversely affect the response to the treatment
of some disorders producing hypercalcemia (e.g. various
malignancies, granulomatous disorders due to infectious
agents). As a result, the use of glucocorticoids in
managing hypercalcemia is usually limited to the hypercalcemia
associated with vitamin D intoxication (including
granulomatous disease) or in cats with idiopathic
hypercalcemia where glucocorticoids alone have
reportedly been effective.
Prednisolone is the most common agent used at a
dose of 1–2 mg/kg/12 h. Alternatively dexamethasone
at a dose of 0.1–0.2 mg/kg/12 h can be used. These
drugs are administered orally, subcutaneously or
intravenously.
Adverse effects of glucocorticoids are described elsewhere
(Chapter 11). However, it is worth noting here
that glucocorticoids potentially increase the risk of
calcium oxalate urolithiasis in hypercalcemia but this
is usually countered by a decrease in the filtered load
of calcium as the hypercalcemia itself is addressed.
Additionally dexamethasone’s long half-life markedly
increases the likelihood of adverse effects when it is used
for any significant period with dosing frequencies of less
than 48 hourly.
Bisphosphonates
The bisphosphonates are pyrophosphate analogs
that act as inhibitors of bone mineralization.
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