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hotly debated, but the contribution of endolymphatic hydrops
to MD symptomatology remains a prevailing theory. If the
symptoms of MD are related to endolymphatic hydrops, then
plausible mechanisms of symptom relief with diuretic agents
could include reduction of the hydrops and/or reversal of ion
gradient aberrations that result in disruption of vestibular and
auditory physiology. Investigation of calcium homeostasis of
the endolymph in guinea pigs has shown that calcium is
transported into the endolymph of cochlea and out of endo-
lymph in the saccule and utricle.
27
The authors purport the
possibility that endolymphatic hydrops may arise from distur-
bance in calcium flow rather than changes in endolymph
volume.
27
One of the main regulators of the electrochemical
gradient within the cochlea is the stria vascularis. This struc-
ture is also central to the production of endolymph. In tem-
poral bone studies, relative ischemia of the stria vascularis
has been demonstrated in patients with a history of MD.
28,29
Whether this observation is the result or cause of hydrops
remains to be determined, but these findings serve as addi-
tional evidence that dysregulation of the electrochemical gra-
dient may be a pathophysiologic mechanism. To further
characterize if diuretic therapy has any direct benefit in treat-
ing MD, demonstration of attenuation of endolymphatic
hydrops or the modulation of electrochemical mediators is
needed.
The dosing and duration of therapy varied widely in this
review. Static dosing, tapering, and up-titration methods were
all used. The rationale for these dosing strategies was not
made clear. The outcomes reporting was heterogeneous with
either internal or arbitrary measures or the use of consensus
guidelines, including the Japan Society for Equilibrium
Research for MD,
30
the 1972 American Academy of
Ophthalmology and Otolaryngology Committee on Hearing
and Equilibrium guidelines,
31
and the 1985 or 1995 American
Academy of Otolaryngology—Head and Neck Surgery
Committee on Hearing and Equilibrium guidelines.
32,33
Diuretic therapy for MD appears to be well tolerated. Ten
(52.6%) studies reported no side effects, and 4 studies (21.1%)
reported abdominal discomfort. No significant morbidity or
mortality was reported in any study.
As with other conditions faced by otolaryngologists,
diuretic therapies for MD are often initiated as first-line
therapy, despite only low-level evidence to justify their use.
To compound the uncertainty created by the lack of existing
evidence, there is likely little impetus for institutions and
pharmaceutical companies to pursue elaborate and well-
funded multicenter RCTs to evaluate the use of generic
diuretics to treat patients with MD. Clinicians are then con-
fronted with a challenge to appraise the existing literature
and tailor therapy to suit the individual patient. If clinicians
observe strict adherence to the strength of evidence as the
basis for which clinical decisions are made, the efficacy of
diuretics in the treatment of MD could be described as spec-
ulative at best. However, in situations where a large body of
low-level evidence exists with a lack of affirmative high-
level evidence, we should not preclude the use of such
therapies. If we do, little will be left in our armamentarium.
Our systematic review has limitations to note. Inherent to
the design of our review, we purposefully included literature
of ‘‘lesser’’ quality than RCTs. In doing so, we have exposed
our conclusions to potential bias and error inherent to study
designs of less rigor. RCTs are the gold standard in prospec-
tive study design, owing to their ability to limit bias and
account for confounding variables. The downsides of RCTs
are the resources and expenses associated with their proper
execution. In an era of intense competition for research fund-
ing, it is not practical to develop, fund, and execute RCTs to
evaluate every therapeutic for every condition. This reality
leaves investigators few options other than to sort and com-
pile clinical observations with imperfect data from disparate
sources to arrive at conclusions on therapy efficacy. Another
limitation to our conclusions is the lack of standardization of
diuretic type, dosing, and duration of therapy. Our review
identified 8 medications with diuretic properties with varying
treatment regimens. The lack of therapy standardization pre-
vents us from making an inference on the efficacy of specific
pharmacologic mechanisms of action.
Table 6.
Therapy Side Effects Reported from Included Studies.
Therapy Side Effects
n (%)
None reported
10 (52.6)
Abdominal discomfort
3 (15.8)
Abdominal discomfort, nausea, diarrhea
1 (5.3)
Dry mouth, thirst, hypokalemia, weight loss, fatigue
1 (5.3)
Fatigue
1 (5.3)
Hypokalemia and hyperuricemia
1 (5.3)
Hypotension
1 (5.3)
Paraesthesias, headaches, chest tightness
1 (5.3)
Table 4.
Hearing Results from Included Studies.
Reported Hearing Result
n (%)
Hearing improvement
8 (42.1)
Mixed hearing results
6 (31.6)
No hearing improvement or worsened
2 (10.5)
No result reported
2 (10.5)
Inconclusive hearing result
1 (5.3)
Table 5.
Vertigo Outcomes Results from Included Studies.
Reported Vertigo Symptoms
n (%)
Improvement in vertigo
15 (79.0)
Mixed vertigo results
2 (10.5)
No result reported
2 (10.5)
Otolaryngology–Head and Neck Surgery 154(5)
31