Furosemide
symptomatic benefit from furosemide can be followed by
GENERAL INFORMATION
Furosemide is one of the so-called high-ceiling or loop
diuretics, which can achieve a much greater peak diuresis
than the thiazides. It is widely and frequently used both
orally and parenterally over a wider dosage range than the
thiazide diuretics, because its concentration–effect curve
is steeper and because it is effective in patients with mod-
erate renal insufficiency (creatinine clearance 5–25 ml/
minute), in whom the thiazide diuretics and most related
compounds are ineffective.
Furosemide is quickly and almost completely excreted
by kidney unmetabolized. The usual oral dose is 20–
120 mg. Much larger doses (for example 1000 mg) have
been used in renal insufficiency, but are not recom-
mended. It is very effective after intravenous injection,
and doses of 500 mg and more can be used in emergencies
(renal insufficiency, pulmonary edema). Most adverse
effects and reactions occur with the use of high doses [1].
General adverse effects and
adverse reactions
Disturbances of fluid and electrolyte balance, such as hypo-
natremia, hypokalemia, and dehydration with circulatory
disturbances (such as dizziness, postural hypotension, and
syncope), have been reported. Rarely gastrointestinal
symptoms are problems with high dosages and in the
elderly. Pancreatitis and jaundice seem to occur more
often than with the thiazide diuretics, but deterioration of
glucose tolerance seems to be less common. At serum
concentrations over 50 mg/ml, tinnitus, vertigo, and deaf-
ness, sometimes permanent, have been reported. Hemato-
logical disorders, particularly thrombocytopenia, and
serious skin disorders occur occasionally, as do hypersensi-
tivity reactions. Neither tumor-inducing effects nor second-
generation effects have been documented.
ORGANS AND SYSTEMS
Cardiovascular
Because furosemide, apart from its diuretic effect, has
transient but pronounced vasodilatory properties
(changes in both venous capacitance and peripheral arte-
riolar resistance have been described in anephric
patients), it can cause postural hypotension and syncope,
particularly if given together with other blood pressure-
lowering drugs [2,3]. Ischemic complications have been
reported in elderly patients. Reactions due to extracellular
volume depletion accounted for 9% of all adverse reac-
tions observed in 535 patients treated with furosemide [1].
Neuroendocrine activation and resultant increased
peripheral resistance (afterload) after furosemide reduce
cardiac output and stroke volume and increase cardiac
work, with the possibility of worsening myocardial and
tissue ischemia. Since many patients with heart failure
ã 2016 Elsevier B.V. All rights reserved.
have underlying myocardial ischemia or infarction, initial
detrimental effects on myocardial perfusion, with exten-
sion or completion of myocardial necrosis.
When it is used in cardiac failure, furosemide acts in two
ways: besides its diuretic effect it produces an immediate
fall in left ventricular filling pressure, which is indepen-
dent of and precedes diuresis. If furosemide is given intra-
venously in stable chronic heart failure (which it normally
is not), this can be an unwanted effect, causing deteriora-
tion [4], particularly in patients with pure left ventricular
failure.
Nervous system
Visual disturbances and drowsiness have been described,
but it is not clear whether these were caused by reduced
cerebral perfusion or by a direct effect of the drug itself.
Sensory systems
At high doses, and especially if serum concentrations are
over 50 mg/ml, furosemide can cause ototoxic reactions,
such as tinnitus, vertigo, and even deafness, sometimes
permanent [5]. Subclinical, audiometrically determined,
high-tone deafness has been reported to occur in 6.4% of
furosemide-treated patients [6]. It is generally consid-
ered advisable to use another diuretic in patients whose
hearing is already impaired, and to avoid using furose-
mide along with other ototoxic drugs, such as the
aminoglycosides.
Sensorineural hearing loss occurs in a small proportion
of very premature babies who are given furosemide. Var-
ious causative mechanisms have been suggested, including
bilirubin, drugs, infection, and/or hypoxic brainstem
injury. In a case–control study of 15 children and 30 con-
trols born before 33 weeks of gestation, renal insufficiency
and/or aminoglycoside use in conjunction with furosemide
was associated with sensorineural hearing loss [7].
A retrospective chart review (July 2000 to January
2002) of all survivors in a neonatal intensive care unit
was undertaken to evaluate the effect of furosemide on
hearing loss [8]. Of the 57 neonates who had received
furosemide nine had a subsequent abnormal hearing
screen, and of the 207 neonates who had not received
furosemide 33 also had an abnormal hearing screen. This
suggests that hearing loss in these neonates is not directly
related to the use of furosemide.
Endocrine
Furosemide rarely causes the syndrome of inappropriate
antidiuretic hormone secretion (SIADH) (although it has
been found useful in treating some patients with SIADH
who cannot tolerate water restriction [9]. In furosemide-
induced cases [10], serum ADH concentrations were
raised, total body sodium was normal, total body potas-
sium greatly reduced, and intracellular water raised at the
expense of extracellular fluid volume. However, such
cases are rare.