RU2585727C1 - Method of treating children with overactive bladder - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to treating overactive bladder in children. Method involves introduction of preparations, increasing bladder volume, and introduction of desmopressine (minirine) for 3 months. Additionally deficient antidiuretic hormone level night osmotic concentration of urine. If the osmotic concentration 202±44.9 mosm/l desmopressine (minirine) is introduced, starting with minimum dose of 60 mcg within month with reception of not later than 19 hours. Further, dose is increased through one and two months if night diuresis is more than 40 % of daily one.

EFFECT: method provides higher clinical effectiveness of the disease in children, including due to selected conditions and minirine administration.

1 cl, 1 ex

Description

An overactive bladder (OAB) is a clinical symptom complex, which includes the presence of an urgent, irresistible urge to urinate, increased urination, combined with daytime urinary incontinence (International Standard of Terminology (ICS), 2002). This pathology is observed in 17% of children 5-12 years old [1]. The main pathogenetic factor in urinary incontinence in patients with OAB was always considered high intravesical pressure and a decrease in the functional capacity of the bladder [2]. It is the correction of this pathogenetic link that is aimed at treating patients with the indicated nosology and involves the use of drugs that increase the bladder volume, such as oxybutynin, tolterodine, trospium chloride, etc. [3].

At the same time, the results of treatment of children with OAB cannot be considered quite satisfactory, as often uncontrolled urination at night remains. From the level of knowledge on this issue, the following is noteworthy. For example, examination of patients at the center of urology-andrology and pathology of the pelvic organs with OAB syndrome in 2007-11. (16578 people) revealed in 40% (6458 people) the presence of rapid urination and night urinary incontinence of 2 or more per night [4]. Given the immaturity of the autonomic regulation of lower urinary tract function in children due to the uneven development of organs and structures during growth, we suggested that repeated emptying is uncontrolled due to an increase in nightly urine output in children. The combination of nocturnal polyuria and small volume create a stable "conflict situation" [5]. Its essence lies in the imbalance between the intensity of urine production and the ability of the bladder to accumulate at night. In these cases, diuresis at night exceeds the functional capacity of the bladder due to a deficiency of antidiuretic hormone (ADH), which fundamentally changes the usual course of urine excretion at the level of the lower urinary tract, and provokes frequent urination at night. At the same time, previously used drugs for the treatment of OAB at night are ineffective.

The problem solved by this invention is to increase the effectiveness of treatment of children with OAB. This problem is solved by taking into account the newly identified pathogenesis factor.

3

In all children with OAB, a study of day and night urine osmolarity was conducted and its relationship with the level of nocturnal polyuria was assessed. The group included 37 boys - 81% and 23 girls - 29%, age 9.78 ± 3.1. All children had nocturnal polyuria, which amounted to 57.7 ± 8.4% of daily diuresis, while night diuresis was significantly higher than daytime (P = 0.01; P <0.05) and averaged 433 ± 225 ml with daily 359 ± 188 ml. When assessing urine density in the Zimnitsky analysis, nighttime urine density was significantly lower than daytime - 1008 ± 0.5 (P = 0.0004; P <0.05), which indicates an insufficient osmotic concentration of urine (No. 1010), except In addition, in children, daytime and nighttime osmolarity of urine was determined. Daytime osmolarity was 359 ± 31.2 mosm / l, and night osmolarity was 202 ± 44.9 mosm / l, which is significantly lower than daily urine osmolarity (No. 300 mosm / l) (P = 0.0004; P <0.05) , a decrease in nighttime osmolarity of urine indicates a deficiency of ADH.

Thus, the indication for the appointment of minirin was the concentration of ADH by osmolarity of 202 ± 44.9 mosm / l. The start of treatment with a minimum dose of 60 mcg is due to the lack of experience with the use of this medication in patients with OAB. But the duration of treatment - 3 months is dictated by the official recommendation for the appointment of the drug in children.

40 patients received oxybutynin 5 mg 2 times a day and minirin in a monthly increasing dose of 60-120-180 mcg no later than 19 hours (taking into account the trend of an increase in urine concentration in the daytime, and so as not to combine two medicines at once), and 20 patients received only oxybutynin 5 mg 2 times a day. Side effects, in the form of dry mucous membranes when taking oxybutynin, were observed in only one patient. Reception minirina carried out without side effects.

Of the 60 children in 20, only oxybutynin was treated for 3 months. During therapy, episodes of daytime urinary incontinence stopped, nightly episodes of urinary incontinence remained unchanged. As expected, the bladder volume increased from 40.3 ± 16.2 ml to 97.3 ± 14.7 ml. The volume of nocturnal urine output was 45-51% unchanged, day and night osmolarity remained in the same ratio, indicating a continuing deficiency of ADH.

The initial dose of 60 μg minirin was increased after 1 month of taking the drug to 120 μg in all 40 people due to the continued prevalence of nighttime urine output to 51% of the daily. A dose increase from 120 to 180 mcg was carried out for 25 patients aged 14-17 years, after 1 month of administration due to the fact that their night diuresis was 42-47% of the daily. In 15 patients, minirin remained at the previous dose of 120 mcg due to a decrease in the proportion of nocturnal urine output to 36-40%. After 3 months of treatment in all 40 patients, the number of episodes of nocturnal incontinence was reduced to 0-1 times a week.

Disclosure of invention

The proposed method for the treatment of overactive bladder in children includes a medicamentous increase in the bladder using the known use of M-anticholinergic. But the method is characterized by an additional study of the concentration of antidiuretic hormone. When determining the deficit of antidiuretic hormone by the level of nocturnal osmolarity, 202 mosm / l ± 44.9 mosm / l is supplemented with desmopressin (minirin). The duration of treatment is 3 months. But the treatment of children with OAB is different in that minirin treatment is started with a minimum dose of 60 μg sublingually for a month, taken no later than 19 hours, followed by a dose increase after one and two months, with nighttime urine output exceeding 40% of the daily dose.

The effectiveness of the proposed method of treatment was higher in 40 children using oxybutynin and minirin than only oxybutynin. This was expressed in an increase in life periods without episodes of night and day urinary incontinence and an increase in bladder volume during treatment after 4-6 weeks compared with the group without minirin - only by the 10-12th week of treatment. As a result of treatment, the level of nocturnal polyuria decreased in all children, and stabilization of the level of nocturnal osmolarity of urine was noted.

Clinical example

Child B., 7 years old. A boy from a family with a heredity in urinary incontinence and urolithiasis on the part of the mother, as well as arterial hypertension, bronchial asthma and allergies from the father. From the 5th pregnancy, proceeding against the background of gestosis in the second half (dropsy of pregnant women). Second birth, on time, with stimulation and obstetric benefits. Born full-term (weight - 3300 g, height - 52 cm). Physical and neuropsychic development was delayed. It was observed by a neurologist about a delay in psychomotor development, hyperactivity disorder, sleep disturbances, and urinary incontinence (he received glycine, cohitum, physiotherapy, pantogam, semax, cortexin - without a pronounced effect). It is observed at the allergist's place of residence with a diagnosis of allergic conjunctivitis, allergic rhinitis, atopic dermatitis. An orthopedist with a diagnosis of hallux valgus deformity, poor posture, flat-valgus feet. Urinary incontinence from birth, without "bright" intervals, up to 4 years, urinary incontinence was observed during daytime sleep. Currently, urinary incontinence 1-2 times during the day at the height of the urge and 2-3 times at night without urge. Suffers from evening polydipsia (parents restrict fluid intake at night) and nightly polyuria (incontinence 3 times per night). During the examination: clinical and biochemical blood tests without features. Clinical analysis of urine unchanged, no urinary syndrome. Ultrasound of the kidneys and bladder revealed no pathology. Zimnitsky's test: daily diuresis = 130 ml, (specific weight 1012-1016), night diuresis = 200 ml (specific weight 1007). Urinary osmolarity in the daytime and at night is 342 and 202 mosmol / l, respectively, i.e. urine does not concentrate at night, which probably indicates a deficiency in the synthesis of antidiuretic hormone.

Urination rhythm: urinates 9 times a day with a volume of 50 to 100 ml. The average effective bladder volume is 85 ml. Uroflowmetry: (volume - 116 ml, average rate of urination - 23.8 ml / sec - rapid type of urination).

The child received the following therapy: oxybutynin 5 mg 2 times a day for 3 months and minirin 60 mcg at 18-30 once every day. After 1 month of administration, the volume of the bladder increased to 95-100 ml on average per serving, the volume of daily diuresis increased to 250 ml, and night diuresis remained 200 ml. The dose of minirin was increased to 120 mcg (sublingual tablets) once. When assessing the condition 3 months after therapy, the child has a clinical improvement. Day urinary incontinence is not observed, enuresis persists 1 time in 2 weeks. Urinary osmolarity in the daytime and at night - 442 and 220 mosmol / l. Daytime diuresis = 330 ml (specific gravity - 1024-1026), nocturnal diuresis = 170 ml (specific gravity - 1018-1024). Urinates 7-8 times a day with a volume of 80 to 150 ml with an active stream, at the urging. Urination rate of 20.9 ml / s with a volume of 180 ml, without residual urine. The average effective bladder volume is 165 ml. Thus, combination therapy showed a positive clinical result, which was not achieved in this child earlier on standard therapy with oxybutynin. The child has a decrease in nocturnal polyuria, stabilization of nocturnal osmolarity of urine, an increase in the average effective volume of the bladder, and a significant decrease in symptoms of OAB.

Literature.

1. Neveus, T. Oxybutinin, desmopressin and enuresis. j. urology 2001. dec; 166 (6): 2459-62.

2. Abrams P., Cordozo L., at al. The standardization of terminology of lower urinary tract function. Neurourology, Urodyn. 2002, 21: 167-78.

3. Anderson K.E. The overactive: Pharmacological basis of drag treatments. Urology 1997; 50 (suppl. 6A): 74-84.

4. The basic principles of diagnosis and treatment of urinary disorders in children and adolescents. Met. recommendations ДЗМ №10. Moscow, 2013, pp. 18-22.

5. Perales Cabanas L., Jimenez Cidre M. Hyperactive bladder. Arch. Esp. Urol. 2002. Nov; 55 (9): 1001-14.

Claims (1)

A method for the treatment of overactive bladder in children, including the introduction of drugs that increase the volume of the bladder, as well as the introduction of desmopressin (minirin) for 3 months, characterized in that it additionally determines the deficiency of antidiuretic hormone by the level of nighttime osmolarity of urine, at which 202 ± 44.9 mosm / l desmopressin (minirin) is administered starting with a minimum dose of 60 mcg for a month, taken no later than 19 hours, followed by a dose increase after one and two months with overnight diuresis e 40% of the daily.
.