RU2424821C1 - Method of treating exudative otitis media in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to otolaryngology, and can be used for treatment of exudative otitis media. Method includes shunting of tympanic cavity with hollow prosthesis, introduction to patients in post-operation period of antibacterial medication of wide spectrum of action, mucolytic medication, endaural introduction of proteolytic medication, vasoconstrictive drops into nose. Additionally simultaneously, perorally introduced is preparation "Reaferon-EC-Lipint" in dose: children of 3-15 years 125000 IU daily 2 times per day for 7 days, children from 16-18 years - 250000 IU daily 2 times per day for 7 days. From eighth to tenth day of treatment patients continue to obtain peroral introduction of Reaferon-EC-Lipint in the following dose: children of 3-15 years 250000 IU daily 2 times per day for 3 days, children from 16-18 years -500000 IU daily 2 times per day for 3 days.

EFFECT: method makes it possible to increase efficiency of treatment of exudative otitis media in children and reduce number of disease recurrences.

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Description

The invention relates to medicine, namely to otorhinolaryngology, and for the treatment of exudative otitis media in children.

Exudative otitis media (ESO) is one of the most actively studied diseases of the middle ear [1], however, today there remain urgent issues in the study of the etiology, pathogenesis and therapy of this disease. Despite the fact that most experts believe that the basis for the occurrence of exudative otitis media can be a combination of tubular dysfunction and sluggish inflammation of the mucous membrane of the middle ear [1, 2], immunological [1], allergic factors can also play a special role [3, 4] , genetic [5] and infectious factors [6]. Questions about the role of viral infection in the development of exudative otitis media are still relevant and are actively discussed by domestic and foreign otiatrists.

Acute respiratory viral infections are currently the most common viral infectious diseases in children [7] and may partly be a possible etiological factor for exudative otitis media, as evidenced by data from foreign literature on the role of adenoviruses [8, 9], respiratory syncytial virus [ 10, 11], rhinoviruses [8, 11, 12], coronoviruses [10], type A parainfluenza viruses, influenza viruses, herpes viral infections [13], there are also single published reports on the role of Epstein-Barr in iris infection in the development of exudative otitis media [14]. Damage to the middle ear by respiratory viruses seems extremely likely, since the cavities of the middle ear through the auditory tube communicate with the nasopharynx, in addition, the middle ear is lined with a cylindrical ciliary epithelium of the respiratory type, to which these viruses have a pronounced tropism [15]. Short-term exudation in the tympanic cavity is a common symptom of acute respiratory viral infections. Viruses also violate the protective mechanisms of the mucous membrane of the middle ear, in particular by sharp inhibition of mucociliary clearance, the induction of local immunodeficiency predisposing to the development of exudative otitis media.

A known method of treating exudative otitis media by oral administration of fenspiride (erespal). Patients, in addition to traditional therapy (vasoconstrictor drops in the nose, catheterization of the auditory tube with the introduction of steroid hormones and enzymes, pneumatic massage of the tympanic membrane), also received erespal. The drug was prescribed in the first 3 days, 1 tablet 3 times a day, then 1 tablet 2 times a day. After a meal, a course of 10 days [16].

The disadvantages of the method: Lack of effectiveness (duration of treatment, a high probability of relapse) due to the fact that the drug does not have immunomodulating and antiviral effects, which is not pathogenetically justified in cases of exudative otitis media occurring against a background of viral infections.

Also known is the treatment of exudative otitis media by oral administration of a suspension of Co-Amoxiclav (20 mg / kg of amoxicillin, 5 mg / kg of clavulonic acid). Patients were prescribed the drug orally 3 times a day for 14 days, while 0.25% Xylometazoline was used [17].

The disadvantages of the technique: lack of effectiveness (duration of treatment, high probability of relapse), due to the fact that the drug does not have immunomodulating and antiviral effects.

Closest to the claimed is a method of treating exudative otitis media by performing tympanostomy. A teflon shunt was installed in the posterior quadrant of the tympanum. The drum cavity was treated with a 0.5% solution of novocaine with chemotrypsin. Then, a solution of a suspension of hydrocortisone in an amount of 0.5 ml is introduced into the tympanic cavity. In the postoperative period, for 7 days, a 0.5% dioxin solution with a suspension of hydrocortisone 5: 1, 2 drops 2 times a day was instilled into the ears in children and a broad-spectrum antibiotic was orally administered [18].

The disadvantages of the method. Lack of effectiveness (duration of treatment, high probability of relapse) due to the fact that there is no drug in the treatment regimen with antiviral and immunomodulating effects.

A new technical task is to increase the effectiveness of the treatment of virus-induced exudative otitis media by accelerating the healing process.

To solve the problem in a method of treating exudative otitis media, including antiviral and immunomodulating therapy against the background of a surgical method of treatment, virus diagnosis, the introduction of antibacterial, mucolytic, vasoconstrictive and proteolytic agents, Reaferon-EU-Lipint is orally administered to children aged 3 -15 years for 125,000 IU daily 2 times a day for 7 days, for children from 16-18 years old - 250,000 IU daily 2 times a day for 7 days. At the end of the course, oral administration of Reaferon-EU-Lipint in the following dosage is continued for 8-10 days after surgical treatment: for children aged 3-15 years old, including 250,000 IU daily 2 times a day for 3 days, for children from 16-18 years old - 500,000 IU daily 2 times a day for 3 days.

Reaferon-EU-Lipint (CJSC Vector-Medica, Novosibirsk) is a domestic preparation of recombinant human interferon-α2b in liposome form (registration certificate of the Ministry of Health of the Russian Federation R No. 000821 / 01-2001 dated November 16, 2001). The drug has antiviral and immunomodulatory activity. Liposomes, unlike polymer drug delivery systems, are fully biodegradable and biocompatible, protect the protein from the acidic contents of the stomach, provide complete and rapid absorption through the intestines and prolonged circulation of interferons (IFN) in the blood with further induction of endogenous IFN. Reaferon-EU-Lipint is easily dosed, available in use, safe [19].

The use of Reaferon-EU-Lipinta is known in the treatment of patients with acute respiratory viral infections in young children (3-6 years). Children were prescribed Reaferon-EU-Lipint 250,000 units 2 times a day 30 minutes before meals for 3 days. The drug was used against the background of basic therapy, which included a preservative regimen, a diet by age, warm alkaline drink, and, according to indications, decongestants, antiseptic treatment of the pharynx, antitussive and antipyretic drugs [20].

The use of Reaferon-EC-Lipinta in the basic treatment of chronic Epstein-Barr virus infection in children is known. Children 2-3 years old take 250 thousand units, over 3 years old - 500 thousand units 2 times a day inside 10-20 days, followed by transition to maintenance therapy [21].

The use of Reaferon-EU-Lipint is known in the treatment of acute purulent-destructive pulmonary diseases. For this, the patient after sanitizing the purulent lesion in the lungs is orally administered Reaferon-EU-Lipint at a dose of 10,000-15,000 IU / kg, then blood sampling and extracorporeal treatment of leukocytes with immunofan are followed, followed by intravenous drip of leukocytes and Reaferon is administered orally -ES-Lipint at a dose of 10-15 thousand units / kg once a day for 5 days [22].

A known method for the prevention of pneumonia in patients with ischemic stroke. The method is as follows: a patient with ischemic stroke, upon admission after restoring breathing parameters, blood pressure is prescribed Mildronate 10% -10 ml and Reaferon-EU-Lipinta orally or through a probe at a dose of 10-15 thousand units / kg for 6 days [ 23].

A known method of treating purulent meningitis, including the relief of infectious toxic shock, after which the patient is additionally prescribed oral administration of Reaferon-EU-Lipint at a dose of 10-15 thousand units / kg. Then the patient’s blood is taken, his leukocytes are obtained and the patient is intravenously dripped. After this, oral administration of Reaferon-EC-Lipint is carried out in a dose of 10-15 thousand units / kg. Once a day for 5 days. The method allows to reduce the number of complications and mortality by reducing immunodeficiency [24].

A known method of treating chronic viral hepatitis C. For this, a drug from the group of alpha-interferons (Reaferon-EC-Lipint) is orally administered, taken orally 1 million ME 2 times a day for 10 days and then 1 time every 6 months every other day 1 time per day (at night) in combination with the drug roncoleukin 500 mg, which is taken orally for 3 months 2 times a week [25].

The use of Reaferon-EC-Lipint for the prevention of influenza and other acute respiratory infections is known. The use of this drug for the prevention of influenza and ARI at a dose of 250,000 ME 2 times a week for 4 weeks was effective in the group of children of primary school age (7-10 years) and resulted in a decrease in the incidence of influenza and ARI [20].

Based on the analysis of the known sources of information, no information was found on the use of Reaferon-EU-Lipint in the treatment of middle ear diseases

The method is as follows.

Patients after shunting of the tympanic cavity with a hollow prosthesis and oral administration in the postoperative period (7 days) of a broad-spectrum antibacterial drug, a mucolytic drug (for example, Ambroxol at an age-related dosage), endaural administration of proteolytic agents (for example, trypsin), endonasal administration of vasoconstrictor drops (oxymetazoline 0.025% and 0.05%), the Reaferon-EU-Lipint drug is additionally orally administered in a dosage: for children aged 3-15 years, 125,000 IU daily 2 times a day for 7 days, for children from 16-18 years old - 250,000 IU daily 2 times a day for 7 days. At the end of the course of this therapy, oral administration of Reaferon-EU-Lipint in the following dosage is continued for 8-10 days after surgical treatment: for children aged 3-15 years, 250,000 IU daily 2 times a day for 3 days, for children from 16-18 years - 500,000 IU daily 2 times a day for 3 days.

The oral route of administration of the drug is affordable, non-traumatic, which is very important in the treatment of children. Interferon is enclosed in liposomes, microscopic fatty capsule shells that protect it from destruction in the gastrointestinal tract and allow it to enter the bloodstream through the digestive system.

A new property of the drug - the use for the treatment of virus-induced exudative otitis media was discovered during clinical observations.

The effectiveness of the proposed new method of treatment was confirmed on the basis of the TF "Scientific and Clinical Center of Otorhinolaryngology FMBA of Russia" in the treatment of 46 children with acute exudative otitis media and exacerbation of chronic exudative otitis media.

Patients according to the principle of randomization were divided into two groups. In 22 patients of the first, control, group, the traditional treatment of the disease was performed: shunting of the tympanic cavity, broad-spectrum antibiotics, vasoconstrictor drops in the nose (oxymetazoline), mucolytics (ambroxol), proteolytic enzymes (trypsin) were endaurally introduced. Reaferon-EU-Lipint was orally administered to 24 patients of the second, main, group against the background of traditional antibacterial therapy in the following dosage: for children aged 3-15 years, 125,000 IU daily 2 times a day for 7 days, for children 16-18 years old - 250,000 IU daily 2 times a day for 7 days. Then, for 8-10 days, Reaferon-EU-Lipint continued to be taken in the following dosage: for children aged 3-15 years, 250,000 IU daily 2 times a day for 3 days, for children from 16-18 years old - 500,000 IU daily 2 times per day for 3 days.

Thresholds of auditory perception in patients were studied using an Orbiter 922-2 audiometer (GN Otometrics, Denmark).

Evaluation of the clinical recovery of patients in both groups was carried out according to the following criteria: absence of congestion in the ear, lack of lateralization in Weber's experiment, improvement of auditory perception thresholds by audiometry, normalization of the otomicroscopic picture and restoration of the ventilation function of the auditory tube, as an indicator of a decrease in the severity of inflammation in the tympanic cavity after shunting tympanic cavity, the number of relapses in 1 year, general indicators of inflammation.

Along with the traditional general clinical examination, patients were tested for viruses in the exudate of the tympanum and swabs from the nasopharynx, the method of polymerase chain reaction (PCR) to detect the DNA of adenoviruses, respiratory syncytial virus and Epstein-Barr viruses, ELISA to determine early and late AT viruses Epstein-Barr (ELISA VEB EVA Ig, ELISA VEB EVnA), MFA for respiratory viruses (for adenoviruses, PC virus).

The results of the study. The course of treatment lasted for 14 days. Patients in the control group during the traditional treatment noted the disappearance of congestion in the ear by 13 days, the absence of lateralization in the Weber experiment on the 14th day of observation, and normalization of the otomicroscopic picture by the 11th day. During the 14 days of therapy in the main group of patients who received, along with the traditional treatment, antiviral, immunomodulating therapy with Reaferon-EU-Lipint, a faster regression of signs of inflammation was noted: the disappearance of congestion in the ear was recorded on days 8-9, the lack of lateralization in Weber’s experiment was 10 days, and the normalization of the otomicroscopic picture on the 9th day.

Thus, upon completion of treatment in all patients (100%, 22 people) of the main group, an improvement was achieved. In the control group, the effectiveness of traditional therapy reached only 87.5% (21 people); in three patients, by the 14th day of treatment, complaints of congestion in the ear persisted. The terms of treatment of patients with the use of an antiviral drug decreased in all studied parameters, which is confirmed statistically.

Example 1. Patient M., aged 16, was admitted to an ENT clinic with a diagnosis of chronic bilateral exudative otitis media. Adenoids of the I-II degree. From the anamnesis: frequent SARS. Hearing loss was noted during the year, was treated by an otorhinolaryngologist in a clinic, and courses of treatment of exudative otitis media were conducted, consisting of blowing the auditory tube, transtimpanal administration of dexamethasone and adrenaline, antibiotic therapy. Drum cavity shunting was performed with a hollow shunt. However, within a week after the operation, the patient continued with otorrhea and symptoms of otitis media. After the examination - the diagnosis of viruses (adenoviruses, respiratory syncytial virus and Epstein-Barr virus), the traditional treatment was supplemented with the oral administration of Reaferon-EU-Lipint according to the standard scheme: 250,000 IU daily 2 times a day for 7 days. And then, on the eighth to tenth days of treatment, Reaferon-EU-Lipint was continued in a dosage of 500,000 ME 2 times a day for 3 days. The appointment of the drug led to a clear positive trend. The restoration of auditory perception thresholds occurred already on the 10th day of treatment, the bone-air interval was reduced from 30 to 3.7 dB. Changes in hearing thresholds according to tonal threshold audiometry are presented in Table 1. (Dynamics of indicators of auditory function of patient M. before and after treatment).

The patient noted the subjective improvement already on the 8-9th day of treatment, the otomicroscopic picture recovered after 12 days of treatment. In blood tests, the pathological manifestations of inflammation decreased, ESR decreased, and antibody titers to viruses were normalized. The patient was examined six months and a year after hospitalization, no exacerbation of the process was noted.

Example 2

Patient A., aged 8, was admitted to the children's ENT department with a diagnosis of acute exudative otitis media. The disease arose after hypothermia. Conservative treatment (anti-inflammatory drug - Erespal 30 ml 2 times a day, vasoconstrictor drops in the nose - Xylometazoline 0.1%, antihistamine drug Zirtec 10 mg 1 time per day) for 2 weeks was ineffective. In connection with this treatment: shunting of the tympanic cavity, antibiotic therapy was prescribed in the postoperative period (Flemoklav Solutab 250 / 62.5 mg 3 times a day), mucolytic drugs (Ambroxol 2 ml (50 drops) 2 times a day), vasoconstrictors drops (oxymetazoline 0.025% and 0.05%) in the nose, at the same time Reaferon-EU-Lipint was administered orally at a dosage of 125,000 IU daily 2 times a day for 7 days. On the eighth to tenth days of treatment, Reaferon-EU-Lipint was administered orally at a dosage of 250,000 IU. Improvement of well-being is registered after 4 days. Blood counts returned to normal: white blood cell count decreased from 13.9 to 8.8 × 10 ⁹ , ESR decreased from 45 to 21 mm / h. Lack of congestion in the ear was noted on the 7th day, lateralization of sound in Weber's experiment disappeared on the 8th day. There was no relapse of the disease during the observation period of up to a year.

Thus, the assessment of the clinical recovery parameters of the patients examined by us confirms that the use of the antiviral, immunomodulating drug Reaferon-EU-Lipint is an effective approach in the treatment of both acute and relapses of chronic exudative otitis media.

The advantages of the proposed method are as follows: the method is simple, safe, has high efficiency in the combined treatment of exudative otitis media. Using the method reduces the duration of treatment and the hospitalization of patients.

Table 1 Thresholds of perception by air, dB Thresholds for bone perception, dB 500 Hz 1000 Hz 2000 Hz 4000 Hz M 500 Hz 1000 Hz 2000 Hz 4000 Hz M to-in interval before treatment 40 40 45 45 42.5 10 fifteen fifteen 10 12.5 thirty after treatment fifteen fifteen fifteen fifteen fifteen fifteen 10 10 10 11.3 3,7

Sources of information used in compiling the description

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Claims (1)

A method of treating exudative otitis media, including shunting of the tympanic cavity with a hollow prosthesis and oral administration in the postoperative period for 7 days of a broad spectrum antibacterial drug, a mucolytic drug, endaural administration of a proteolytic agent, endonasal administration of vasoconstrictive drops, characterized in that it is additionally simultaneously orally administered Reaferon-EU-Lipint drug in dosage: for children aged 3-15 years, 125,000 ME daily 2 times a day for 7 days d, children from 16-18 years of age - 250,000 ME daily 2 times a day for 7 days, then from the eighth to tenth days of treatment, oral administration of Reaferon-EU-Lipint is continued in the following dosage: for children aged 3-15 years, 250,000 ME daily 2 times a day for 3 days, for children from 16-18 years old - 500,000 ME daily 2 times a day for 3 days.