xRead - Olfactory Disorders (September 2023)

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380

INTERNATIONAL CONSENSUS ON OLFACTION

TABLE VII.7b (Continued) Study

Year LOE Study design Study groups

Clinical end point

Conclusions

1% tetracaine was capable of inducing transient hyposmia but only 4% lidocaine applied directly to the OC could cause transient anosmia Intranasal zinc gluconate is associated with severe hyposmia with parosmia or anosmia

Self-assessment SS-TDI Olfactory ERPs

Welge

2004 4

Prospective case series

Healthy patients (n =

Lüssen et al 370

20) given 1% tetracaine at 3 different locations and then 4% lidocaine in theOC

Jafek

2004 4

Case series

Patients with intranasal zinc gluconate–associated olfactory disturbance (n = 10) Propofol as sole anesthetic 6 case reports, dysosmia with varying anesthetics

Clinical history

et al 376

Clinical history Negative CT/MRI findings

Propofol (and other

Du

2018

4

Case report,

et al 366

anesthetics) may cause dysosmia; however, the mechanism is unknown

literature review

Yoshida

2017

4

Case report

Duloxetine 20 mg (n = 1) Initial T&T olfactometer Threshold and identification and then 7 days after cessation of duloxetine

Duloxetine may cause worsened threshold and identification levels that improve on cessation of medication Self-reported dysosmia that improved on

et al 367

Horger

2016

5

Case report

Midodrine 5 mg 3 times daily (n = 1)

Clinical history

et al 368

cessation of medication

Che

2018

5

Case report

Metoprolol (n = 1)

Clinical history

Self-reported dysosmia that improved on

et al 369

cessation of medication

CT = computed tomography; ERP = event-related potential; LOE = level of evidence; MRI = magnetic resonance imaging; OC = olfactory cleft; OF = olfactory function; RCT = randomized controlled trial; SS-TDI = Sniffin’ Sticks threshold, discrimination, identification combination; TDI = threshold, discrimination, identification; T&T = Toyoda and Takagi; UPSIT R = University of Pennsylvania Smell Identification Test.

The body of literature dedicated to medication-related changes in olfaction is of low quality and summarized in Table VII.8. Although many reports of olfactory loss following administration of medications are anecdotally described in large pharmaceutical databases, 361 there is increasing use of psychophysical olfactory testing used to describe the perturbations in olfaction. The drugs with the strongest data supporting the associations of decreased olfaction include zinc, tetrahydrocannabinol, remifentanil, and sildenafil. 362–364 Furthermore, it has long been recognized that chemotherapeutic agents may also impair the regenerative ability of the olfactory sys tem, leading to transient or more lasting effects. 358,365 Numerous other drugs are associated with reports of OD and include commonplace medications such as propo fol, duloxetine, midodrine, metoprolol, local anesthet ics, and oral antibiotics. 359,366–372 Meanwhile, there is some evidence that thyroid hormone modulation and α 1A

adrenoceptor antagonism may lead to olfactory improve ments, although the clinical significance and mechanism of these findings are unknown. 373 Although several studies have investigated the use of oral zinc supplementation to treat olfactory loss with out overall convincing evidence that it can, 374 it has been widely recognized that topical administration of zinc ions is associated with olfactory loss. Initially, during the 1930s, it was demonstrated that topical administration of zinc sulfate could result in OD, and ≈ 70 years later the topical administration of zinc gluconate was found to have similar effects. 375–379 In vitro animal studies sug gest that topical administration of zinc contributes to cell death of olfactory neurons and direct loss of the olfactory neuroepithelium. 380,381 Although the quality of evidence for each individual medication is of low quality and pathophysiologic mecha nisms are poorly understood, there is substantial evidence