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Evaluation of Levels of Triamcinolone Acetonide in Human Perilymph and Plasma After Intratympanic Application in Patients Receiving Cochlear ImplantsA Randomized Clinical Trial

Educational Objective
To investigate and compare perilymph and plasma concentrations of triamcinolone acetonide after intratympanic application.
1 Credit CME
Key Points

Question  How much intratympanically injected triamcinolone acetonide diffuses to the perilymph and plasma?

Findings  In this randomized clinical trial of 40 patients undergoing cochlear implantation, there were similar levels of triamcinolone acetonide in the perilymph 1 hour and 24 hours after injection, and triamcinolone acetonide could be quantified in all analyzed patients at a median (range) level of 796.0 (46.4-7706.7) ng/mL. There was minimal dissemination to the plasma, especially in patients with unremarkable middle ear mucosa.

Meaning  Triamcinolone acetonide can be found in the perilymph after intratympanic application, even on the day after injection.

Abstract

Importance  The use of intratympanically applied steroids is of increasing interest. Consequently, research has focused on finding an ideal drug that diffuses through the round window membrane and can be retained in the perilymph.

Objective  To compare levels of triamcinolone acetonide (TAC) in perilymph and plasma after intratympanic injection.

Design, Setting, and Participants  This randomized clinical trial included 40 patients receiving cochlear implants at a single tertiary care center in Vienna, Austria. Patients were randomized to 1 of 4 treatment groups receiving 1 of 2 intratympanic doses of TAC (10 mg/mL or 40 mg/mL) at 1 of 2 approximate time points (24 hours or 1 hour) before sampling the perilymph. Inclusion was carried out between November 2017 and January 2020, and data were analyzed in December 2020.

Interventions  All patients underwent intratympanic injection of TAC. During cochlear implantation, perilymph and plasma were sampled for further analysis.

Main Outcomes and Measures  Levels of TAC measured in perilymph and plasma.

Results  Among the 37 patients (median [range] age, 57 [26-88] years; 18 [49%] men) included in the analysis, TAC was present at a median (range) level of 796.0 (46.4-7706.7) ng/mL. In the majority of patients (n = 29; 78%), no drug was detectable in the plasma after intratympanic injection. Levels above the limit of detection were less than 2.5 ng/mL. The 1-factorial analysis of variance model showed lower TAC levels in the group that received TAC, 10 mg/mL, 24 hours before surgery (median, 271 ng/mL) compared with the group that received TAC, 10 mg/mL, 1 hour before surgery (median, 2877 ng/mL), as well as in comparison with the groups receiving TAC, 40 mg/mL, 24 hours before surgery (median, 2150 ng/mL) and 1 hour before surgery (median, 939 ng/mL). The 2-factorial analysis of variance model showed lower TAC levels in the group receiving TAC, 10 mg/mL, 24 hours before surgery than the group receiving TAC, 10 mg/mL, 1 hour before surgery, and higher TAC levels in the group receiving TAC, 40 mg/mL, 24 hours before surgery compared with the group receiving TAC, 10 mg/mL, 24 hours before surgery. Patients with thickening of the middle ear had statistically significantly higher plasma levels (median, 1.4 ng/mL vs 0 ng/mL) and lower perilymph levels (median, 213.1 ng/mL vs 904 ng/mL) than individuals with unremarkable middle ear mucosa.

Conclusions and Relevance  In this randomized clinical trial, TAC was shown to be a promising drug for intratympanic therapies, with similar levels in perilymph 1 hour and 24 hours after injection (distinctly in the groups receiving the 40 mg/mL dose). There was also minimal dissemination to the plasma, especially in patients with unremarkable middle ear mucosa.

Trial Registration  ClinicalTrials.gov Identifier: NCT03248856

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: July 28, 2021.

Published Online: September 30, 2021. doi:10.1001/jamaoto.2021.2492

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Dahm V et al. JAMA Otolaryngology–Head & Neck Surgery.

Corresponding Author: Christoph Arnoldner, Department of Otorhinolaryngology–Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria (christoph.arnoldner@meduniwien.ac.at).

Author Contributions: Ms Dahm and Mr Arnoldner had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Dahm, Honeder, Gabor, Arnoldner.

Acquisition, analysis, or interpretation of data: Dahm, Gausterer, Auinger, Reznicek, Kaider, Riss.

Drafting of the manuscript: Dahm, Kaider, Arnoldner.

Critical revision of the manuscript for important intellectual content: Gausterer, Auinger, Honeder, Gabor, Reznicek, Riss, Arnoldner.

Statistical analysis: Reznicek, Kaider, Arnoldner.

Obtained funding: Dahm, Arnoldner.

Administrative, technical, or material support: Gausterer, Auinger, Riss.

Supervision: Honeder, Gabor, Arnoldner.

Conflict of Interest Disclosures: Dr Honeder reported receiving grants from MED-EL outside the submitted work. Dr Riss reported receiving grants from MED-EL paid to his institution outside the submitted work. No other disclosures were reported.

Funding/Support: This work was funded by the Medical Scientific Fund of the Mayor of the City of Vienna.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2.

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