Page 79 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Sodium and Water: Hypernatremia and Hyponatremia 69

Similarlesionshave beenreportedin experimentaldogs (e.g., furosemide) to effect more rapid correction of
with hyponatremia with correction rates of 15 mEq/L/ hyponatremia in overhydrated symptomatic patients.
day even without overcorrection to hypernatremia. 94 In The occurrence of chronic hyponatremia in patients with
veterinary medicine, myelinolysis first was reported in congestive heart failure is often a sign of advanced disease
two dogs after correction of hyponatremia associated with and responds poorly to treatment. Administration
trichuriasis. 122 In one dog, a serum sodium concentration of furosemide and an angiotensin-converting enzyme
of 101 mEq/L had been corrected to 136 mEq/L in less inhibitor (e.g., enalapril) may improve stroke volume
than 38 hours (correction rate, >22 mEq/L/day), and in and cardiac output by reducing preload and afterload
the other, a serum sodium concentration of 108 mEq/L and may decrease vasopressin secretion and enhance
had been corrected to 134 mEq/L in less than 38 hours water excretion, which in turn may facilitate resolution
(correction rate, >16 mEq/L/day). Clinical signs devel- of hyponatremia.
oped 3 to 4 days after correction of hyponatremia and Arginine vasopressin (AVP) receptor antagonists
consisted of lethargy, weakness, and ataxia progressing (vaptans) block either V 2 receptors (lixivaptan, tolvaptan,
to hypermetria and quadriparesis. Lesions were detected satavaptan) or both V 2 and V 1A receptors (conivaptan).*
by magnetic resonance imaging and were located in the Based on their mechanism of action, these drugs increase
thalamus as compared with the more typical pontine free water excretion by the kidneys and effectively nor-
location in affected human patients. From this experience, malize serum sodium concentration in patients with
it was recommended that dogswith asymptomatic chronic non-osmotic release of AVP causing euvolemic (e.g.,
hyponatremia be treated by mild water restriction and SIADH) or hypervolemic (e.g., congestive heart failure,
monitoringofserumsodiumconcentration.Symptomatic liver failure) hyponatremia. 111,117 Patients with
dogs with chronic hyponatremia should be treated conser- hypovolemic hyponatremia should be treated with an
vatively at correction rates of less than 10 to 12 mEq/L/ infusion of 0.9% NaCl or other isotonic fluid to replace
day (0.5 mEq/L/hr). Serial monitoring of serum sodium their volume deficits. The AVP receptor antagonists
concentration is necessary because the actual rate of cor- increase water but not solute excretion via the kidneys,
rection may not correspond to the calculated rate of cor- and likely will have major impact on the clinical manage-
rection. Correction should be carried out with ment of euvolemic and hypervolemic hyponatremia in the
conventional crystalloid solutions (e.g., lactated Ringer’s near future. 60
solutionand0.9% NaCl) inavolume calculated specifically Conivaptan is administered as an intravenous bolus in
to replace the patient’s volume deficit. The clinician must 5% dextrose followed by a constant rate infusion, whereas
remember that volume repletion in hypovolemic patients tolvaptan, lixivaptan, and satavaptan are administered
abolishes the nonosmotic stimulus for vasopressin release orally. In humans, adverse effects of the vaptans generally
and allows the animal to excrete solute-free water via the are limited to thirst and dry mouth. To minimize the risk
kidneys. This in itself tends to correct the hyponatremia. of osmotic demyelination, correction of serum sodium
Thus, caution should be exercised even when using concentration should be limited to <8 mEq/L per 24
conventional crystalloid fluid therapy. hours, especially when hyponatremia is chronic or of
Three additional cases of suspected myelinolysis in unknown duration. The pH of the conivaptan solution
dogs with chronic hyponatremia caused by hypoadreno- is low (3.0) and infusion site reactions are common.
corticism or trichuriasis have been reported. 11,24,105 The Because they antagonize only the V 2 receptor,
rates of correction of hyponatremia in these dogs were 22 lixivaptan and tolvaptan do not cause changes in blood
mEq/L on day 1 and 17 mEq/L on day 2, 32 mEq/L pressure. Vasopressin receptor antagonists promote
over 2 days, and 17 mEq/L in 9 hours. 11,24,105 The neu- aquaresis and correct hyponatremia in heart failure
rologic signs that developed (e.g., spastic tetraparesis, loss patients, but long-term beneficial effects on patient sur-
21,40
of postural and proprioceptive responses, dysphagia, tris- vival have not yet been documented. Conivaptan
mus, and decreased menace response) were similar to may be especially helpful in heart failure patients as a
those originally described by O’Brien. 122 The dogs of result of its effects of the V 1A receptor and potential to
these reports gradually recovered over several weeks. decrease total peripheral resistance. 54 Although the com-
Water intake should be carefully restricted to a volume bined V 2 /V 1A receptor antagonist conivaptan might be
less than urine output in normovolemic patients with expected to lower blood pressure, it only causes hypoten-
hyponatremia (e.g., psychogenic polydipsia), or drugs sion in 2.5% of treated patients, although orthostatic
causing an antidiuretic effect should be discontinued if hypotension may be seen in 5% of treated patients. 124
possible. Demeclocycline and lithium inhibit vasopressin Conivaptan is both a substrate for and inhibitor of
release and have been used to treat SIADH in humans, CYP3A4 (the 3A4 isoform of the cytochrome P-450
but water restriction is probably the safest approach. 48 enzyme). Administration of conivaptan with other
In edematous patients, dietary sodium restriction and CYP3A4 inhibitors (e.g., ketoconazole, itraconazole,
diuretic therapy should be considered. A 0.9% NaCl solu-
tion can be administered concurrently with loop diuretics *References 49, 55, 124, 126, 146, 165.