Page 279 - Feline Cardiology

286 Section G: Congestive Heart Failure

heart failure despite up titration and maximization of plasma blood volume, furosemide decreases diastolic
furosemide dose (typically 3–4 mg/kg PO q 8–12 h) and filling pressure and hydrostatic pressure to decrease
standard adjunctive therapy. edema formation. Hemodynamic effects of decreasing
preload include reduction in pulmonary capillary pres-
General Principles sure, pulmonary artery pressure, and central venous
A combination of furosemide and an ACE inhibitor is pressure. Because furosemide activates the renin-
the standard treatment of congestive heart failure, irre- angiotensin-aldosterone system, concurrent use of an
spective of the specific etiology. Chronic oral dosing of ACE inhibitor is recommended.
furosemide ranges from 1 mg/kg PO q 24 hr to a generally- Furosemide is efficacious by oral or parenteral admin-
accepted maximal dose of 4 mg/kg PO q 8 h. Since the istration; the route of administration chosen depends on
veterinary formulation of furosemide is available as the severity of the heart failure. Minimal effective dose
12.5 mg tablets, cats are typically given 6.25 mg PO q is typically 1 mg/kg, with a maximal ceiling dose of
12–24 h for mild congestive heart failure and 12.5 mg PO approximately 4 mg/kg orally and much higher paren-
q 12 h for moderate heart failure in cases not requiring terally (see the section “Treatment of Hospitalized Cats
hospitalization. In order to help clear pulmonary edema with Acute Congestive Heart Failure, later in this
rapidly, often an injection of furosemide is given before chapter). Oral dosing frequency can be as low as daily
and as high as every 8 hours, depending on the severity
the patient leaves the hospital, a higher initial dose is
Congestive Heart Failure dose is decreased to the lowest effective dose that main- mide that resolves the clinical signs and radiographic
of the heart failure. The lowest effective dose of furose-
used for the first several days to a week, and then the
evidence of heart failure with minimal side effects
tains the cat free from clinical symptoms or radiographic
should be selected. Often a higher initial dose of furose-
evidence of heart failure. Although there is no clinical
mide is used for a few days to a week to effectively clear
evidence that ACE inhibitors increase survival time in
cats with heart failure, their use in cats is supported by
tive dose is used to maintain the cat free of symptoms
anecdotal experience and extrapolations from people
from edema formation. As heart failure severity worsens,
and dogs with heart failure (Fox 2003). the edema or pleural effusion, and then the lowest effec-
A majority of cats with heart failure have diastolic increasing frequency of dosing rather than increasing
dysfunction and preserved systolic function. Diastolic the dose may more effectively increase diuresis, since the
heart failure is also more commonly recognized in duration of diuresis lasts only up to 6 hours after oral
human medicine, with the proportion of cases ranging administration.
from 40–71% (Kindermann et al. 2008). Even in human
medicine, there is “a paucity of evidence for the treat- Drug properties of furosemide
ment of heart failure associated with normal left ven- Furosemide is highly protein bound (86–91%), trapping
tricular ejection fraction” (i.e., diastolic heart failure) it within the vascular space to be delivered to the proxi-
(Kindermann et al. 2008). There is theoretical rationale mal renal tubule, where 55% is excreted in the urine. The
to inhibit the RAAS in patients with diastolic heart remainder of the drug is eliminated by the liver. Renal
failure, which would consequently reduce myocardial excretion of furosemide is dependent on adequate
hypertrophy and fibrosis. However, although there are blood flow to deliver the drug and adequate renal func-
large numbers of (human) patients enrolled in clinical tion to excrete the drug. Decreased cardiac output and
trials of ACE inhibitors and angiotensin receptor block- renal blood flow may be a consequence of congestive
ers, “the evidence from these trials are inconclusive, and heart failure. Furosemide has a short half-life of 1.5–2
add up to a positive trend for morbidity end points for hours. Once the diuretic effect has dissipated, the
ACE inhibitors and the angiotensin receptor blocker nephron avidly reabsorbs sodium in a process called
candesartan, without any conclusive effect on mortality” rebound sodium retention. This is thought to occur due
(Kindermann et al. 2008). to distal nephron hypertrophy and is likely an explana-
tion for the lessened diuretic effect seen over weeks to
Diuretic Therapy months in the cat and other species. Renal insufficiency
Furosemide, a potent diuretic, is the drug of choice for prolongs the plasma half-life of furosemide because the
treatment of congestive heart failure. As a loop diuretic, excretion is slower, and congestive heart failure prolongs
furosemide inhibits the sodium-potassium-chloride the half-life due to decreased renal perfusion. The
+
+
−
cotransporter (Na /K /2Cl ) in the thick ascending loop average bioavailability of furosemide is 50%, but there
of Henle of the renal tubule, which causes urinary loss is a marked individual variability ranging from 10–
of water and electrolytes including sodium, chloride, 100%, creating unpredictability in dose responses
potassium, calcium, and magnesium. By reducing (Brater 1998).