Evaluation of Levels of Triamcinolone Acetonide in Human Perilymph and Plasma After Intratympanic Application in Patients Receiving Cochlear Implants

Valerie Dahm,Clemens Honeder,Dominik Riss,Christoph Arnoldner,Franz Gabor,Alice Barbara Auinger,Julia Clara Gausterer,Alexandra Kaider,Gottfried Reznicek

doi:10.1001/jamaoto.2021.2492

Valerie Dahm, Clemens Honeder + Show 7 more

Open Access

https://doi.org/10.1001/jamaoto.2021.2492

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Abstract

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. To compare levels of triamcinolone acetonide (TAC) in perilymph and plasma after intratympanic injection. 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. All patients underwent intratympanic injection of TAC. During cochlear implantation, perilymph and plasma were sampled for further analysis. Levels of TAC measured in perilymph and plasma. 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. 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. ClinicalTrials.gov Identifier: NCT03248856.

Highlights

MethodsStudy Population Each patient provided written informed consent to participate in this prospective study, which was approved by the ethics committee of the Medical University of Vienna
Triamcinolone Acetonide Levels in Plasma Triamcinolone acetonide concentrations in the plasma were lower than the lower limit of detection in 29 of 37 patients
Serial sampling could not be performed, overall, the present results show that triamcinolone acetonide (TAC) levels were similar 1 hour and 24 hours after IT application, which means that either the elimination is much slower than calculated previously[10] or the remaining solution continuously diffuses through the round window membrane

Summary

Methods

Study Population Each patient provided written informed consent to participate in this prospective study, which was approved by the ethics committee of the Medical University of Vienna. Inclusion criteria were that patients were between 18 and 90 years old, undergoing cochlear implantation, and willing to participate in the study. Exclusion criteria were that patients were younger than 18 years, were receiving steroids on a regular basis or had received steroids intravenously or orally preoperatively, had contraindications against the administration of TAC, or had contraindications against IT injections (Supplement 1). Groups 1 and 2 received IT TAC approximately 24 hours before surgery, whereas groups 3 and 4 received the injection approximately 1 hour before surgery (Table 1). Groups 1 and 3 were treated with TAC, 10 mg/mL, and groups 2 and 4 with TAC, 40 mg/mL (Figure 1).

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Discussion

Conclusion