HSC Section 8_April 2017

Otolaryngology–Head and Neck Surgery 154(5)

Table 4. Hearing Results from Included Studies.

Table 6. Therapy Side Effects Reported from Included Studies.

Reported Hearing Result

n (%)

Therapy Side Effects

n (%)

Hearing improvement Mixed hearing results

8 (42.1) 6 (31.6) 2 (10.5) 2 (10.5) 1 (5.3)

None reported

10 (52.6) 3 (15.8)

Abdominal discomfort

No hearing improvement or worsened

Abdominal discomfort, nausea, diarrhea

1 (5.3) 1 (5.3) 1 (5.3) 1 (5.3) 1 (5.3) 1 (5.3)

No result reported

Dry mouth, thirst, hypokalemia, weight loss, fatigue

Inconclusive hearing result

Fatigue

Hypokalemia and hyperuricemia

Hypotension

Paraesthesias, headaches, chest tightness

Table 5. Vertigo Outcomes Results from Included Studies.

Reported Vertigo Symptoms

n (%)

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.

Improvement in vertigo Mixed vertigo results

15 (79.0) 2 (10.5) 2 (10.5)

No result reported

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

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