Chelation-induced ototoxicity in thalassemic patients: Role of distortion-product otoacoustic emissions and various management parameters

Abstract

Context and Aims: A limited number of studies have been conducted for the assessment of hearing loss in thalassemic patients on regular chelation therapy and even fewer studies were conducted using otoacoustic emissions (OAEs). The present study was conducted to assess the prevalence of ototoxicity in multiple transfused thalassemic patients on regular iron chelation therapy (with desferrioxamine [DFO] and deferasirox), to compare the efficacy of OAEs (distortion-product OAEs [DPOAEs]) with that of pure tone audiometry (PTA) for hearing assessment and to correlate ototoxicity with age, mean hemoglobin (Hb), serum ferritin levels, dose and duration of chelation therapy, and therapeutic index Settings and Design: This was a prospective, observational study conducted in a tertiary care hospital. Subjects and Methods: Thirty thalassemic patients undergoing regular iron chelation therapy with DFO and deferasirox were included in this prospective study. Hearing assessment was done using otoscopy, tympanometry, PTA, and DPOAEs between January 1, 2010, and June 30, 2010. Follow-up studies were conducted after 12 months of chelation therapy using the same tests. Patients with and without ototoxicity were compared with respect to age, mean Hb, serum ferritin levels, dose and duration of chelation therapy, and therapeutic index. Statistical Analysis Used: Statistical analysis was carried out using the Student's t-test for normally distributed data and Pearson Chi-square test for categorical data. For nonparametric variables, Mann–Whitney and Wilcoxon tests were applied. Results: Using DPOAEs, 36% of patients were detected having a hearing deficit at the start of the study which increased to 46% at the end of study, whereas using PTA, the detection of hearing loss was 10% and 23%, respectively. DPOAE analysis showed a statistically significant decrease in the signal to noise ratio after 1 year of therapy at 4000 Hz, 5714 Hz, and 8000 Hz with maximum number of patients showing abnormality at 5714 Hz. The analysis revealed no significant difference between the affected and unaffected groups with respect to age, sex, height, weight, serum ferritin level, mean Hb, cumulative dose, mean daily dose and duration of chelation, or therapeutic index. Conclusions: Despite DFO doses usually felt to be low risk for ototoxicity (<40 mg/kg/day), we found a high rate of ototoxicity in our patients using DPOAEs (46%). No variables were identified that reliably predict ototoxicity. We impress on the need for regular audiological screening using DPOAEs for early detection of ototoxicity.