RU2550968C1 - Integrated method of treating female patients suffering from chronic recurrent cystitis and refractory overactive bladder - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: treating female patients suffering from resistant overactive bladder and chronic cystitis is two-staged. The first stage involves a 10-day antibacterial therapy with an antibiotic preparation selected according to a microbial sensitivity as detected by urine examination in vitro and depending on whether the polymerase chain reaction diagnostics of urethral discharge shows a urinogenital infection to be stated. The second stage represents a therapeutic course involving 4 or 5 intra-bladder administrations of sodium hyaluronate 50 ml once a week. After unassisted bladder emptying and vulva treatment with 0.2% octenisept, the bladder is catheterised with a sterile urethral small catheter. After sodium hyaluronate administration, the patients are advised not to empty the bladder for 1 or 2 hours to prolong the preparation exposure.

EFFECT: method enables providing higher clinical effectiveness and prolonging the delaying time to recurrence.

2 ex

Description

The present invention relates to medicine, namely to the sections of gynecology and urology, and is intended for the treatment of patients with chronic recurrent cystitis and resistant overactive bladder in women.

In modern healthcare, the problem of violation of the act of urination is one of the most relevant and socially significant. With age, the prevalence of overactive bladder (GMF) increases and has a significant impact on the quality of life of patients [Milsom I., Stewart W., 2000; Apolikhina I.A., 2006]. In large population studies, the prevalence of GMF was found, which amounted to 15-20% among women [Milsom I., 2001; Temml S., 2005; Kupelian A.S., 2011] and about 6% among adult girls (15-20 years old) [Pakiz M., 2010]. In most cases, the cause of GMF remains undetermined (the so-called idiopathic GMF). Recently, the term resistant (refractory) overactive bladder has appeared in the medical literature, characterized by the persistence of symptoms after treatment by the patient with more than 2 M-anticholinergic drugs with bladder training for more than 1 year [Walsh S.A., 2011 ]. It is such a subtype of GMF that is most difficult to diagnose and treat due to the lack of data on its pathogenesis.

However, at present, the most relevant is the hypothesis of infectious damage to urothelium, lamina propria, and nerve endings, which can lead to hypertension or chronic recurrent cystitis. Urothelium is coated with a layer of glycosaminoglycan-chondroitin sulfates, sodium hyaluronate, glycoproteins and mucin to protect against damaging factors and prevent the adhesion of uropathogens to urothelium. Damage to urothelium is accompanied by hemorrhage and the production of cytokines, which triggers the proliferation and activation of mast cells [Lilly J.D., 1990; Hurst R.E., 1994; Graham E., 2006; Sivick K.E., 2010].

Chronic inflammation of the bladder is accompanied by numerous processes: infiltration of the bladder wall by mononuclear cells (macrophages, lymphocytes, mast and plasma cells), leading to irreversible changes in tissues - fibrosis, detrusor hyperactivity and hyperalgesia [Grover S., 2011].

In women with recurrent cystitis, a single dose and a short-term course of taking antibiotics are ineffective.

Drug treatment of GMF is aimed at reducing the contractile activity of the detrusor and increasing the bladder capacity by using drugs from the following groups - calcium antagonists, prostaglandin inhibitors, tricyclic antidepressants, as well as anticholinergics, which are currently the main treatment methods.

A known method of treating GMF in an experiment [Enzelsberger H. et al., 1995] using the anticholinergic drug oxybutynin hydrochloride, according to which the patient was injected within 10 days with a solution of oxybutynin (20 mg of oxybutynin was dissolved in 40 ml of sterile saline) , while statistical methods have been proven the effectiveness of intravesical use of oxybutynin, which increased the bladder capacity and increased its extensibility due to the effect on g bladder bladder muscles in the absence of local or general side effects.

The disadvantages of this method should be considered large doses of the drug administered, the difficulty of administering the drug during catheterization and the inability to retain patients even a small amount of fluid in the bladder, which significantly reduces the effectiveness of the treatment.

A known method of treating GMF by introducing into the body an anticholinergic drug in a physiologically acceptable dose and according to a predetermined scheme, according to which an anticholinergic drug containing oxybutynin in the form of an aqueous solution is introduced into the bladder through a catheter [Weese D.L. et al., 1993]. In accordance with the treatment regimen for catheterization, a 5 mg tablet of oxybutynin was dissolved in 30 ml of sterile water and the solution was injected intravesically 2-3 times a day. When implementing the known method, treatment according to the mentioned scheme was received by a group of 42 patients with a diagnosis of urgent urinary incontinence due to hyperreflexia or detrusor instability. All patients were previously unsuccessfully treated by oral administration of anticholinergics. After treatment in accordance with the known method, 55% of patients noted the disappearance or significant weakening of clinical signs (urinary incontinence).

However, despite the safety and effectiveness of the intravesical route of administration of the drug, confirmed by a number of other studies [Weil A. et al., 1986; Greenfield S.P., Fera M., 1991; Madersbacher H., Jilg G., 1991], the known method is not free from the drawback, which is the short duration of the effect of the drug on smooth muscles (walls), which is due to the low ability of patients to retain urine, and therefore the rapid withdrawal of the drug from the body, which as a whole, reduces the effectiveness of the treatment and increases its duration, and the repeated catheterization negatively affects the subjective sensations of patients and complicates the treatment procedure.

Nevertheless, no known closest analogues of the treatment of resistant GMF and chronic cystitis using intravesical instillations of hyaluronic acid have been found in medical sources.

The objective of the invention is to increase efficiency by increasing the duration of the effect of the treatment of chronic cystitis and resistant GMF women.

The problem is solved by the method consisting in the fact that they conduct a 10-day course of antibacterial therapy, taking into account the sensitivity of the selected microorganism in a culture study, followed by the appointment of 4-5 intravesical installations of 50 ml of sodium hyaluronate 1 time per week.

Improving the effectiveness of the proposed method, in our opinion, lies in the fact that when conducting replacement therapy with a solution containing glycosaminoglycans, the damaged layer of urothelium is restored.

The aim of the present invention is to develop and optimize a pathogenetically determined approach to the conservative treatment of resistant GMF and chronic cystitis in women.

In connection with the need to develop new approaches to the pathogenetic treatment of resistant GMF and chronic cystitis in women, a comprehensive therapeutic approach is proposed.

In practice, the method is as follows.

Stage I - a 10-day course of antibacterial therapy, the choice of antibiotic is carried out according to the sensitivity of the selected microorganism according to the culture of urine and the presence of urogenital infection in the study of discharge of the urethra by PCR, then

Stage II - a course of 4-5 intravesical injections of a solution of sodium hyaluronate in 50 ml once a week. After self-emptying the bladder and treating the external genitalia with a 0.2% octenisept solution, the bladder is catheterized with a small, sterile urethral catheter. After the introduction of sodium hyaluronate solution, patients are advised not to empty the bladder for 1-2 hours to increase the exposure of the drug.

The following examples illustrate the method of the invention.

Clinical example No. 1

Patient K., 40 years old. She complained of frequent urination (up to 17-20 times during the day, 3-4 times at night), urgent urges, a feeling of incomplete emptying of the bladder.

From the anamnesis: Considers herself a patient for 9 years. Asked for help from a urologist at the place of residence. Repeated courses of training the pelvic floor muscles in biological feedback mode in combination with the use of M-anticholinergics (trospium chloride 5 mg per day orally for 6 months, then solifenacin 5 mg per day orally for 4 months) with little effect.

Denies tuberculosis, viral hepatitis, diabetes mellitus and cancer. Married, does not smoke, works as a sales manager. Has 2 children, the first birth is a large fetus - 4100 g with an episiotomy.

Status presens: Weight 82 kg, height 168 cm; BMI 30 kg / m ² . The patient drinks a lot of coffee, lives a sexual life.

A gynecological examination attracted attention: moderate cicatricial deformity in the perineum, a slight prolapse of the posterior wall of the vagina, and a decrease in the tone of the mild pelvic floor muscles. From the uterus and appendages, pathological changes were not detected. The cough test and the Valsalva test are negative.

The urination diary: the number of urinations - 17 (in the daytime - 14, at night - 3), the number of urgent urges - 6.

Laboratory studies: general analysis of urine - without pathological changes, in urine culture - growth of Ent. faecalis 10 ³ CFU / ml. A smear on the flora, on a cytological examination - cervicitis.

With CUDI: Uroflowmetry - the maximum urine flow rate of 38 ml / sec with a urination volume of 178 ml - "rapid" urination. Signs of infravesical obstruction and residual urine were not detected. During cystometry, involuntary rises in detrusor pressure were detected in the filling phase, i.e. there were urodynamic signs of GMF in the presence of clinical. In samples (coughing and straining), the LPP was 65-80 cm H ₂ O. In the emptying phase, the contractility of the bladder is normal.

Was diagnosed with Resistant overactive bladder.

Treatment: At the first stage, a 10-day course of levofloxacin therapy was administered at 500 mg per day orally. Additionally, recommendations were given on the correction of diet and weight, given the presence of obesity.

After the end of antibiotic therapy, 5 intravesical injections of a solution of sodium hyaluronate, 50 ml once a week, were made.

Results of treatment: After treatment, the patient's condition improved significantly, which was confirmed both by the data on the diary of urination (a decrease in the number of urinations up to 8-9 times a day) and the results of the QUDI - in the filling phase, only a few involuntary rises in detrusor pressure were noted.

Clinical example No. 2

Patient O., 28 years old. She complained of burning and pain during urination, periodic frequent urination, a feeling of incomplete emptying of the bladder. She noted monthly exacerbations.

From the anamnesis: Considers herself a patient for 10 years, which connects with the onset of sexual activity. Asked for help from a urologist at the place of residence. Repeated courses of antibacterial and anti-inflammatory therapy were carried out with insignificant and short-term effects.

Denies tuberculosis, viral hepatitis, diabetes mellitus and cancer. Married, does not smoke, works as an accountant. There are no pregnancies.

Status presens: Weight 54 kg, height 168 cm; BMI 19 kg / m ² .

A gynecological examination attracted attention: the low location of the urethra, the presence of pathological discharge from the vagina. From the uterus and appendages, pathological changes were not detected. The cough test and the Valsalva test are negative.

The urination diary: the number of urinations - 9 (in the daytime - 8, at night - 1), The number of urgent urges - 1-2.

Laboratory studies: general analysis of urine - leukocyturia up to 15 p.p., nitrites - ++, in urine culture - growth of E. coli 10 ⁵ CFU / ml. A smear on the flora - vaginitis, on a cytological examination - cervicitis.

With uroflowmetry: "intermittent" urination. Signs of infravesical obstruction and residual urine were not detected.

Was diagnosed with Chronic cystitis. Vaginitis. Cervicitis.

Treatment: At the first stage, a 10-day course of therapy with cefixime 400 mg per day inside, antimycotic drugs in order to prevent candidiasis, was performed. Recommended treatment in conjunction with her spouse, the use of barrier methods of contraception to control healing, herbal remedies. After the end of antibiotic therapy, 4 intravesical injections of a solution of sodium hyaluronate, 50 ml once a week, were performed.

Results of treatment: After treatment, the patient's condition improved significantly, which was confirmed by laboratory examination data (general urine analysis is normal, the absence of bacteriuria in the culture of urine). A repeated course of intravesical instillations after 6-12 months is recommended.

This method can be used to treat resistant GMF and chronic cystitis in women.

The claimed method was used to increase efficiency by increasing the duration of the treatment effect in 47 women with chronic cystitis and 32 with resistant GMF. The results of the study showed improvement in 74% of patients.

Bibliography

1. Apolikhina I.A. Clinical epidemiology, differential diagnosis and conservative treatment of urinary incontinence in women: dis. ... Dr. med. Sciences: 14.00.01 / Apolikhina Inna Anatolevna. - M .: 2006. - 256 p.

2. Gill K., Kupelian A.S., Brackenridge L. et al. Symptoms most sensitive to urinary tract infection // International Journal of Urogynecology. - 2011. - No. 4 - P.1171-1177.

3. Graham E., Chai T.C. Dysfunction of bladder urothelium and bladder urothelial cells in inrestitial cystitis // Current urology reports. - 2006. - No. 7. - P.440-446.

4. Greenfield S.P., Fera M. Urodynamic evaluation of the patient with imperforate anus. J. Urol. - 1991. - No. 146. - P.539.

5. Grover S., Srivastava A., Lee R., Tewari A.K., Te A.E. Role of inflammation in bladder function and interstitial cystitis // Therapeutic Advances in Urology. - 2011 .-- Vol. 3. - No. 1. - P. 19-33.

6. Hurst R.E. Structure, function and pathology of proteoglycans and glycosaminoglycans in the urinary tract // World Journal of Urology. - 1994 .-- Vol. 12. - P.3-10.

7. Lilly J.D., Parsons C. L. Bladder surface glycosaminoglycans is a human epithelial permeability barrier // Surgery, Gynecology and Obstetrics. - 1990. - Vol. 171. - P.2543-2551.

8. Madersbacher H., Jilg G. Control of detrusor hyperreflexia by the intravesical administration of oxybutynin hydrochloride. Paraplegia. - 1991 .-- Vol.29. - P.84.

9. Milsom I., Abrams P., Cardoso L. et al. How widespread are the symptoms of an overactive bladder and how are they managed population - based prevalence study // International Brazilian Journal of Urology. - 2001. - Vol. 87. - P.760-1.

10. Milsom I., Stewart W., Thuroff J. The prevalence of overactive bladder // American journal of managed care. - 2000 .-- Vol.6 (11). - P.565-573.

11. Pakiz M., Blazevic S., But I. The prevalence and risk factors for OAB in adolescent girls // Abstract of Materials of ICS / IUGA Annual Meeting, Toronto. - 2010. - P.23.

12. Sivick K.E., Mobley H.L. Waging war against uropathogenic Escherichia coli: winning back the urinary tract [minireview] // Infection and Immunity. - 2010 .-- Vol. 78. - No. 2. - P.568-585.

13. Temml C., Heidler S., Ponholzer A., Madersbacher S. Prevalence of the overactive bladder syndrom by applying the International Continence Society Definition // European Urology. - 2005. - Vol. 48. - P.622.

14. Walsh C. A., Siddins A., Parkin K. et al. Overactive bladder in women: Does low-count bacteriuria matter? A review // Neurourology and Urodynamics. - 2011 .-- Vol.30 (1). - P.32-37.

15. Weese D.L. et al. Intravesical oxybutinin chloride: Experience with 42 patients. Urology. - 1993 .-- Vol.41 (6). - P.527-530.

16. Weil A. et al. Clinical significance of urethral instability. Obstet Gynecol. - 1986. - Vol. 68. - P.106.

Claims (1)

A method of treating patients with chronic recurrent cystitis and refractory overactive bladder is characterized in that at the first stage, a 10-day course of antibiotic therapy is carried out in accordance with the sensitivity of the isolated microorganism to antibiotics according to the culture of urine and the presence of urogenital infection in the study of discharge of the urethra by PCR, and at the 2nd stage, a course of 4-5 intravesical injections of 50 ml of the registered sodium hyaluronate solution is carried out 1 time per week after self-administration Yelnia emptying the bladder via catheterization sterile urethral catheter small.