Harold Schuknecht first reported injecting streptomycin intratympanically for Meniere’s disease in 1965. Intratympanic (IT) or “transtympanic” injection is a drug delivery approach that is commonly offered as an office procedure performed by an otolaryngologist. IT therapy can be performed with minimal discomfort in a cooperative patient with topical or even no anesthesia. The main advantage of IT therapy is localized delivery of therapeutic agents to the middle and inner ear, thereby achieving higher doses to the target tissue with minimal systemic side effects compared to oral medications.

Corticosteroids are commonly recommended to treat a range of otologic disorders, but are associated with a long list of side effects including dysregulation of blood glucose levels, blood pressure changes, weight gain, appetite, mood changes, sleep disturbances, gastrointestinal symptoms, glaucoma, and even in rare instances, osteonecrosis of the femoral head leading to long term morbidity. In contrast, local drug delivery to the middle and inner ear has a favorable side effect profile and is not inferior to systemic steroids for the treatment of idiopathic sudden sensorineural hearing loss. IT therapy is a safer alternative for patients who face an increased risk of systemic steroids because of medical comorbidities, such as diabetes or glaucoma, or have a history of mood disorders with steroids.

The downsides of IT therapy include increased cost compared to oral regimens, multiple clinic visits, procedural discomfort, and risk of persistent perforation (especially in those patients with a history of radiation therapy). Ongoing studies have focused on the development and study of slow-release drug delivery vehicles (e.g., poloxamer) to reduce the need for repeated injections.

Steroids (e.g., dexamethasone or methylprednisolone) are by far the most common off-label medication delivered via IT technique and are offered for several otologic conditions. IT steroids are often given for the management of idiopathic sudden sensorineural hearing loss, either concomitantly with oral steroids or following treatment failure, but other indications may include:

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  Meniere’s disease

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  Autoimmune hearing loss

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  Inflammatory disorders affecting the middle or inner ear

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  Impulse noise exposure

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  Tinnitus

Gentamicin can also be administered using an IT approach and is known as a chemical labyrinthectomy. This is most often offered in Ménière’s disease unresponsive to maximal medical therapy and IT steroid therapy. IT gentamicin is also offered to patients with unilateral vestibular dysfunction who are unable to compensate for the loss despite appropriate physical therapy and time. The theory is that in some patients, a disease may cause a fluctuating vestibular dysfunction that limits central adaptive processes that are important for compensatory rehabilitation.

IT gentamicin should not be offered to patients who have severe or complete vestibular loss in the contralateral ear due to the risk of chronic oscillopsia and imbalance.

Other local approaches to the ear that would fall within the category of IT drug delivery include placement of a tympanostomy tube with a Silverstein Microwick, round window Microcather ( μCat ), transtympanic placement of Gelfoam saturated with drugs, use of nanocarriers or other novel vehicles such as hyaluronate gel or poloxamer for sustained drug release. Ongoing translational and clinical studies will determine the advantages of sustained drug release to treat otologic disease.

IT therapy can be administered safely with minimal discomfort in awake patients with the appropriate counseling and routine otologic instrumentation. As with all awake procedures, appropriate patient selection and favorable anatomy will help ensure an uneventful procedure.

Safety timeout : confirm with the patient and the witness to the consent that (1) the selection of the drug and expiration date and (2) the side of IT therapy are correct and consistent with the medical record, audiogram, and any relevant vestibular testing.

A clinical history, physical exam, and audiometric assessment are necessary before the procedure. If the procedure is a chemical labyrinthectomy with aminoglycosides, caloric or vestibular evoked myogenic potential testing should be reviewed to confirm function in the contralateral ear. Following informed consent with a witness to confirm patient, drug, and side of therapy, the patient is placed in a supine position. A speculum-assisted binocular microscopic approach or a 0-degree Hopkins rod telescope without a speculum would both provide excellent visualization of the tympanic membrane for IT therapy.

If the binocular microscope is used, select the largest ear speculum that fits comfortably in the external auditory meatus to optimize illumination and visualization of the tympanic membrane.

Anesthesia for the procedure can be achieved with a drop of phenol applied topically to the inferior and posterior quadrant of the tympanic membrane. An area of no more than 2 millimeters in diameter is typically adequate. Prepackaged kits with Phenol and a sponge-tip applicator are available for this purpose, but a drop of phenol can also be introduced effectively using any instrument that will transfer a small droplet of phenol ( Fig. 52.1 ). It is helpful to warn the recipient of an expected stinging or burning sensation associated with phenol application to avoid a startle reflex. With adequate warning, most patients will tolerate the few seconds of brief discomfort associated with phenol anesthesia. It has been posited that for some patients, the burning from the phenol application is comparable to the injection itself without anesthesia, and therefore, it is better to avoid phenol anesthesia entirely. However, the majority of patients require multiple injections spread over a few weeks, and it is usually not necessary to repeat phenol application on subsequent injections because the area of anaesthetized tympanic membrane typically remains insensitive for several weeks even if the perforation closes with a monomeric layer. The area anesthetized with phenol usually blanches to demarcate the insensate region ( Fig. 52.2 ). This demarcation fades with time but is usually still visible 2–3 weeks after initial application, which helps with guiding subsequent injections.

Sponge-tipped and fork-tipped phenol applicators.

Right ear, patient in upright position. Otoscopic view highlights a white patch on the inferior aspect of the tympanic membrane demarcating an insensate area from phenol application 2 weeks prior and a myringotomy created by a 27-gauge needle.

Once anesthesia is satisfactory, the medication can be injected with a hypodermic needle. A 25-gauge 2-inch length hypodermic needle and 1.0 mL syringe (either Luer lock or Tb) is adequate. This needle is often bent at a 20-degree angle at the hub to provide an unobscured view of the needle tip during injection. It is critical to be mindful of the depth of needle insertion because contact with the middle ear is uncomfortable for the patient or may result in injury to middle ear structures. Some providers routinely create two myringotomies to allow air escape during injection to encourage saturation of the middle ear with medication. However, with the appropriate technique, a ventilation hole is not needed. Specifically, a slow, gentle injection (observations of single drops filling the middle ear are a good visual reference) followed by slow removal of the needle from the middle ear usually results in effective filling of the middle ear without significant blowback around the injection site (0.5–0.75 mL). Priming the needle before introduction into the middle ear will help limit the volume of air injected into the middle ear. If the tympanic membrane appears to be ballooning during injection, gentle pressure with this side of the needle against the tympanic membrane often stretches the tympanotomy sufficiently to release any positive pressure in the middle ear without undue discomfort to the patient.

Patients can become dizzy during the injection and are encouraged to close their eyes to reduce the perception of vertigo. This occurs due to an abrupt temperature change, resulting in a caloric stimulation, and can be minimized by prewarming the medication either by hand or by a chemical warmer. Fortunately, these symptoms typically abate within a few minutes. Again, sufficient forewarning as the injection is initiated is often all that is needed to reassure the patient. Once the injection is complete, patients are instructed to remain in a supine position for 20 or 30 minutes with the injected ear facing up. Patients are encouraged to minimize maneuvers that would open the Eustachian tube, such as swallowing or yawning, during this period.