| Part I:Preliminary study on the therapeutic pathway of inner ear targeted dexamethasone administration via postauricular injectionObjectivePostauricular injection is a simple, effective and reliable method for treatment of inner ear diseases. Glucocorticoid administered by postauricular injection was reported to significantly improve the recovery of the idiopathic sudden sensorineural hearing bss(ISSNHL). Moreover, animal experiments have confirmed that postauricular injection results in higher drug concentration in the inner, and can maintain it for a longer time when compared with intramuscular injection. However, it is unclear that how the drug enter the inner ear. This study preliminarily investigated the pathway of dexamethasone by postauricular injectioaMethods1. Dexamethasone was labeled by Cy5.2. Guinea pigs were randomly divided into two groups:postauricular injection group and intramuscular injection group.3.0.5ml of Cy5-dex was injected into the right postauricular area and right gluteus maximus respectively. Dynamic changes of local drug metabolism were evaluated for 120h with optical in vivo imaging system.4.0.5ml of Cy5-dex was injected into the right postauricular area and right gluteus maximus respectively, the guinea pigs were euthanized at 8 hours injection. Drugs distribution in the head, temporal bone, internal organs was observed with optical in vivo imaging system.5.0.5ml of Cy5-dex was injected into the right postauricular area and right gluteus maximus respectively, once a day, for three consecutive days. The animals were euthanized at day 4. The exact drug distribution in the eardrum, tympanic mucosa, endolymphatic sac and cochlea were observed by confocal laser scanning microscope.Results1. Local drug metabolism:Drugs were concentrated in the local area, and then spread to the surrounding tissues after postauricular injection and intramuscular injection. The fluorescence intensity of intramuscular injection reached the peak at 8h post-injection, which was higher than that of postauricular injection (peak at 12h), and then both of them decreased gradually. However, the postauricular injection allowed a slower decrease of drug fluorescence than the intramuscular injection. At 96h post-injection, the drug fluorescence was still strong in the postauricular injection group, while undetectable in the intramuscular injection group. The area under the metabolism curve of postauricular group was significantly larger than intramuscular group (P<0.05).2. Drug distribution in the head and internal organs:Compared with intramuscular injection, postauricular injection resulted in a significantly higher fluorescence intensity in the scalp, parietal, temporal bone (P<0.01). Fluorescence intensity in the heart and bladder of the postauricular group were significantly lower than that ofthe intramuscular group (P<0.01).3. Drug distribution in the eardrum, tympanic mucosa, endolymphatic sac and cochlea:Compared with the intramuscular injection group, the postauricular injection group had a significantly higher fluorescence intensity in the eardrum, tympanic mucosa, endorymphatic sac, and cochlea (all P<0.05).ConclusionsPostauricular injection had obviously slow-release effect, which could concentrate the drug in the local area for a longer time and reduce the drug distribution in systemic organs. Compared with intramuscular injection, postauricular injection resulted in a significantly higher drug concentration in the inner ear. The possible pathway of drugs entering the inner ear might be endo lymphatic sac pathway, the local diffusion permeation pathway, the body circulation pathway and thestylomastoid artery pathway.Part Ⅱ:Postauricular injection and systemic administration of glucocorticoids in treatment of low frequency idiopathic sudden sensorineural hearing lossObjectiveTo analyze the clinical features of low frequency idiopathic sudden sensorineural hearing loss (ISSNHL); To evaluate the therapeutic effect of postauricular injection and systemic administration of corticosteroids on low frequency idiopathic sudden sensorineural hearing loss.Methods1. The clinical information of patients with low frequency idiopathic sudden sensorineural hearing loss was collected and statistically analyzed.2. A total of 102 patients with low frequency idiopathic sudden sensorineural hearing loss were randomly divided into two groups, the systemic administration group and the postauricular injection group. The systemic administration group received the intravenous injection of Dexamethasone (DEX) in a dose of 10mgx3d, followed by 5mg×4d, and the postauricular injection group,40mg of Methylprednisolone Sodium Succinate of 40mg was postauricular injected every 2 days, for 15days. The pure-tone threshold audiometry was performed to evaluate the therapeutic effect of the treatment of low frequency idiopathic sudden sensorineural hearing loss.3. SPSS 18.0 software was used to perform the statistical analysis. The total effective rate and cure rate were compared by Chi-square test, the statistical difference was defined as P<0.05.ResultsA total of 102 patients, consisting of 43 men and 59women(the male to female ratio wasl:1.37), were enrolled in this study. The average age of patients was 42± 21.38 years, and the course of disease was 9.23±6.05days. The major initial clinical symptoms were tinnitus (91.18%), ear fullness (87.25%) and hearing loss (75.49%).In the systemic administration group,39.6%(19/48)of patients were recovery, 23.0%(11/48)of patients were improved dramatically,14.6%(7/48)of patients were improved,13.0%(11/48)of patients did not show any improvement, and the total effective rate was 77.1%(37/48). In the postauricular injection group, the recovery rate was 61.1% (33/54),13.0% (7/54) of patients were improved dramatically,9.3% (5/54)of patients were improved, while only 16.7% (9/54) of patients showed no improvement. The total effective rate was 83.3% (45/54). The recovery rate of postauricular injection group was significantly higher than the systemic administration group (P<0.05).Administration of methylprednisolone by postauricular injection had slight effect on the blood pressure and blood glucose.Recurrence was observed in 13 patients, the recurrence rate was 12.74%(13/102).ConclusionsLow frequency idiopathic sudden sensorineural hearing loss shows obvious young female predominance, the major clinical features are tinnitus, ear fullness and hearing loss. Postauricular injection of methylprednisolone is an effective, safe and simple treatment for low frequency sudden hearing loss, especially suitable for patients complicated with hypertension and/or diabetes. |
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