Vitamin E reduces cisplatin ototoxicity.

OBJECTIVES/HYPOTHESIS: Cisplatin ototoxicity is a major dose-limiting factor in the treatment of several neoplasms. Vitamin E, a slow-acting free radical scavenger, has been shown to ameliorate nephrotoxicity and endothelial cell damage in animals receiving cisplatin. The purpose of the study was to determine the effectiveness of vitamin E as an otoprotectant. STUDY DESIGN: Prospective, randomized controlled trial in the rat model. METHODS: Wistar rats (weight, 261-386 g) were sedated using 172.4 mg/kg intramuscular ketamine and 3.4 mg/kg xylazine. Baseline auditory brainstem response (ABR) testing was performed in response to clicks and 8-, 16-, and 32-kHz tone bursts. After auditory thresholds were determined, the animals received intraperitoneal drug administration according to one of three group classifications. Group 1 received 4 g/kg vitamin E followed after 30 minutes by 16 mg/kg cisplatin. Group 2 received 6 mL/kg soybean oil followed after 30 minutes by cisplatin. Group 3 received soybean oil followed after 30 minutes by 16 mL/kg saline. After 3 days' follow-up, ABR testing was performed and threshold changes were recorded. Cochleae were removed and processed for scanning electron microscopy after follow-up auditory testing was carried out. RESULTS: Group 2 animals showed marked hearing loss with average threshold shifts of 28.75 +/- 2.3 dB for clicks, 30.0 +/- 1.9 dB at 8 kHz, 21.25 +/- 4.0 dB at 16 kHz, and 45.0 +/- 4.2 dB at 32 kHz. No significant loss was observed in group 3 with shifts of 2 +/- 1.3 dB, 3 +/-3.0 dB, -2.2 +/- 3.1 dB, and -1.1 +/- 4.0 dB for clicks and tone bursts at 8, 16, and 32 kHz, respectively. Significant protection was seen in group 1 animals compared with group 2 animals. In the former group, threshold shifts of 12.5 +/- 3.1 dB for clicks, 7.5 +/- 2.5 dB at 8 kHz, 5.0 +/- 3.3 dB at 16 kHz, and 24.4 +/- 5.6 dB at 32 kHz were observed. These findings were supported by the scanning electron microscope observations that severe outer hair cell destruction occurred in group 2 rats, whereas outer hair cells were preserved to a much greater extent in the cochleae of rats in group 1 that were pretreated with vitamin E. CONCLUSION: Vitamin E appears to have a protective effect against cisplatin ototoxicity.

Self-inflicted vocal cord paralysis in patients with vagus nerve stimulators. Report of two cases.

Vagus nerve stimulation for treatment of epilepsy is considered safe; reports of severe complications are rare. The authors report on two developmentally disabled patients who experienced vocal cord paralysis weeks after placement of a vagus nerve stimulator. In both cases, traction injury to the vagus nerve resulting in vocal cord paralysis was caused by rotation of the pulse generator at the subclavicular pocket by the patient. Traumatic vagus nerve injury caused by patients tampering with their device has never been reported and may be analogous to a similar phenomenon reported for cardiac pacemakers in the literature. As the use of vagus nerve stimulation becomes widespread it is important to consider the potential for this adverse event.