RU2295364C2 - Method for treating neurogenic urinary bladder dysfunction cases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves applying sacral neuromodulation treatment including search and puncture sacral orifices using injection needles. Right and left sacral apertures are punctured at S3 level with alloplant solution being introduced into them. The quantity of the alloplant solution injected is equal to 2 ml in each orifice. The total treatment course is 3 injections long with one injection introduced every 3 days.

EFFECT: wider gamma of sacral neuromodulation methods; avoided adverse side effects; accelerated 10 days long treatment course.

4 cl, 12 tbl

Description

The invention relates to medicine, in particular to urology, and can be used to treat neurogenic bladder dysfunction in adults, regardless of gender.

In the framework of the International Society for the Retention of Urine (2002), a term was proposed to refer to rapid and urgent urination - an overactive bladder (GMF).

An overactive bladder includes idiopathic detrusor hyperactivity and neurogenic detrusor hyperactivity.

Typical symptoms of GMF are:

- an increase in the number of urination (more than 8 times a day);

- the presence of a strong sudden urge to urinate (urgency), which often cannot be suppressed by the patient;

- imperative urinary incontinence (urgent incontinence), in which the amount of lost urine can be significant, since often the bladder is empty completely.

For a long time it was believed that frequent urination is always the result of various urological, less often gynecological and surgical diseases.

In recent years, reports began to appear that urodynamic disorders most often occur at the level of the lower urinary tract and are caused by detrusor-sphincter dysinergia (neurogenic bladder dysfunction - neurogenic bladder).

Deviations in the work of the lower urinary tract indicate the presence of neurological diseases, such as various injuries, injuries, disorders of the spinal cord, as well as congenital spinal changes, such as spinal hernia.

Neurogenic bladder dysfunction also occurs in multiple sclerosis, discogenic myelopathy, spinal cord, as well as myelitis of the lumbar and sacral localization, diabetes mellitus, amyloidosis or shingles.

The most severe injuries of the spinal cord occur in fractures of the spine, gunshot wounds. In these cases, the connection between the upper and lower parts of the spinal cord is often completely interrupted and, therefore, serious disturbances in the functioning of the pelvic organs occur.

If the spinal cord is damaged above the sacral region, then bladder hyperreflection develops, a condition characterized by frequent urination - neurogenic detrusor hyperactivity (neurogenic GMF) - neurogenic bladder dysfunction [Abrams P., Wein A., 1997, 2002]. In addition, the formation of neurogenic bladder dysfunction is significantly affected by hemodynamic disturbances, detrusor bioenergy, as well as many urological diseases (cystitis, urethritis, bladder stones, pyelonephritis, etc.).

Depending on the level of damage to various parts of the nervous system, neurogenic dysfunctions are divided into supraspinal, suprasacral and sacral neurological disorders.

Recently, many scientists and specialists have been dealing with problems associated with neurogenic dysfunction of the bladder, for example, a book published by the Publishing House "Medicine" edited by M. D. Javad-Zade, V. M. Derzhavina. Neurogenic bladder dysfunction, 1989

A large number of experimental and clinical studies are known aimed at treating neurogenic bladder dysfunction.

For example, K.V. Kosilov, V.R. Orekhov (1993) used intravesical laser irradiation in the form of monotherapy to treat the hyperreflex form of the neurogenic bladder in children.

V.A. Pirogov, N.A. Sevastyanova, I.A. Andreeva (1995) developed a method for the treatment of neurogenic disorders of urination with laser puncture.

E.A. Gatkin et al. (1997) used low-intensity laser radiation to treat children with myelodysplasia.

But, as all authors note, it is recommended that laser therapy be carried out while taking medication.

Currently, pharmacological preparations with various points of their application, electrical stimulation of reflexogenic zones, interventions on the nervous system in the form of blockade or intersection of sacral roots, hydraulic stretching of the bladder under anesthesia, multiple detrusor myotomy, autocystoblicature, etc. are used to treat neurogenic bladder dysfunction. [ Ed. M.D. Javad-Zade, V.M. Derzhavina. Neurogenic bladder dysfunction, M., 1989, p. 294-343].

There are many drugs that are used to treat GMF [D.Yu. Pushkar. Overactive bladder in women. M .: MEDpress-inform, 2003, p. 72-79].

As the author notes, the main disadvantages of drugs are their lack of activity, in addition, the possibility of side effects, such as:

- dry mouth;

- blurred vision;

- tachycardia,

- the appearance of a rash, allergic spots;

- drowsiness, etc.

A promising new drug is tolterodine (Detruzitol, brand name Pharmacia & Upjohn).

According to studies by L. Nilvebrant et al., Tolterodine has a more pronounced selectivity for bladder exposure than other drugs, such as oxybutynin [D. L. Weese et al. Intravesical oxybutinin chljride: Experience with 42 patients. Urology, 1993, v.41, No. 6, pp.527-530], but nevertheless also has side effects on the tolerance of the drug [breast cancer, volume 8, No. 3 (104), 2000, p.145].

A known method of treating GMF by introducing into the body an anticholinergic drug containing oxybutinite hydrochloride, dimexide and an aqueous solution of polyvinyl alcohol, consisting of the following components, wt.%:

oxybutin hydrochloride - 0,020-0,025 dimexide - 20.0-25.0 polyvinyl alcohol - 5.0-15.0 water rest up to 100

[Pat. RU No. 2193401, IPC A61K 31/10, 2001].

The disadvantages of the known method of treatment include the difficulty in preparing the drug and strict adherence to the ratio of the components of the drug, as well as side effects associated with the presence of oxybutin and polyvinyl alcohol in the drug.

There is also a method of treating neurogenic bladder dysfunction using alpha-adrenergic blocking agents, such as doxazosin (cardura, artesin, firearm) [Pat. RU No. 2192864, IPC A61K 31/496, 2001].

The disadvantages of this method include the poor perception of drugs and a long recovery period, but not complete.

A more complete list of the use of drugs for the treatment of GMF is presented in the book: E.B. Mazo and G.G. Krivoborodov Overactive Bladder, M., Veche, 2003, pp. 73-103.

Recently, new methods of treatment with neuromodulation have been used to treat GMF.

An increased interest in neuromodulation was noted after the successful results of stimulation of the sacral nerves in patients with GMF [Tanagho E.A., Schmidt R.A. // J. Urol / (Baltimore)) / - 1988 .-- vol. 140. - p.1331-1339].

A number of authors have proposed stimulation of the tibial nerve (the tibial nerve is formed from I, II, III sacral nerves). Some neurons of the tibial nerve are located in the immediate vicinity of the sacred center of urination and for this reason, as well as due to its anatomical position, this nerve is most convenient for neuromodulation in case of lower urinary tract dysfunction [Chartier-Kastler et al. // Ibid. - 2000. - Vol. 164. - P.1476-1480].

Stimulation of the tibial nerve in the treatment of symptoms of GMF was proposed by E.J. McGuire, Zhang S. Horwinski E.R., Lytton B. // J. Urol. (Baltimore)) / - 1983. - vol. 129. p. 78-79].

In the journal "Urology" No. 5 for 2002, p.37 - authors G. G. Krivoborodov, E. B. Maso, P. G. Schwartz - the technique of electro-stimulation of the tibial nerve, which is as follows.

A needle with a diameter of 0.3 mm and a length of 8 cm (active electrode) was inserted through the skin to a point located 5 cm cranially from the medial ankle of the ankle joint. Both electrodes were connected to the Neuroelectro stimulation device. For stimulation, monophase rectangular pulses of 210 μs duration with a frequency of 25 Hz and a voltage of 0.5 to 5.0 V were used.

As the authors note, this type of treatment of GMF is not effective enough - a satisfactory result was noted in no more than 75% of patients.

Neuromodulation of the sacred roots is in many ways an alternative treatment for patients with GMF.

It has been proven that stimulation with a weak electric current of the nerve root of the third sacral segment (S ₃ ) affects detusor activity.

Neuromodulation leads to the suppression of uninhibited bladder contractions due to electrical stimulation of afferent anorectal fibers of the pelvic nerve and afferent fibers of the pudendal nerve, which reach the spinal cord along the dorsal sacral roots. Afferent impulses entering the sacral spinal cord via interneurons suppress the activity of the pelvic nerve, which is accompanied by an increase in the adaptive capacity of the bladder [E.B. Mazo, G.G. Krivoborodov. Temporary sacral neuromodulation in patients with urgent urinary incontinence. The journal "Urology", No. 4, 2000, p. 42-45].

The closest way to treat neurogenic bladder dysfunction to the claimed is sacred electrical stimulation using an implantable electrode [E.B. Mazo, GG Krivoborodov. Overactive Bladder, M .: Veche, 2003, p. 121-132, Fig. 14-17].

The treatment method is as follows.

First, bone landmarks and retrieval punctures of sacred holes are determined. To do this, use needles No. 18 G with a special insulating coating. After punctures, a passive electrode is placed in the gluteal region from the side of the proposed electrical stimulation, and the active electrode is alternately connected to a neurostimulator. For electrical stimulation, single-phase rectangular pulses with a duration of 210 μs and a repetition rate of 25 Hz are used. After the acute sacral stimulation test and the selection of the sacred hole by the needle, an electrode is inserted into the sacred hole. After installation, the electrode is fixed to the skin and connected to a portable device for nervous electrical stimulation. Typically, temporary electrical stimulation is carried out for 5 days, after which the electrode is removed and urodynamic studies are performed.

As the authors themselves point out, their proposed method of treating neurogenic bladder dysfunction with sacred neuromodulation is long and rather complicated, as well as difficult for patients to tolerate.

The proposed invention aims to develop a new method for the treatment of neurogenic bladder dysfunction.

The proposed method of treatment is based on the method of sacral neuromodulation, including the search and puncture of the right and left S ₃ sacral holes using injection needles with the introduction of a drug into them.

An alloplant dissolved in 10 ml of an isotonic sodium chloride solution is administered as a drug. The amount of alloplant solution introduced is 2 ml in each hole. The course of treatment consists of 3 injections with a frequency of 1 time in 3 days.

Alloplant is a lyophilized powder prepared from dispersed cadaveric tissue without antigenic activity.

Alloplant is produced in accordance with TU 42-2-537-2002. There is a Certificate of Conformity No. 5501170. Certification body ROSS RU 0001.11IM02.

Currently, the use of alloplant in ophthalmic surgery for eyelid plastic surgery, conjunctiva, layered keratoplasty, to replace lamellar and volume defects, etc. is known.

[Registration certificate No. 29/10081201 / 3584-02 of 05.22.2002].

The technique of sacred neuromodulation is as follows.

The patient is placed on the operating table in a position on the stomach. After processing the lower parts of the back, buttocks and sacral region, the puncture of the left and right sacral holes is performed (S ₃ ). Then, through the needles inserted into the left and right sacral openings at an angle of 60 ° to a depth of 3 to 7 cm (the depth of administration depends on the severity of subcutaneous fat), an alloplant solution of 2 ml (for an adult) is introduced into each hole. Alloplant (in 1 bottle of 50 mg) is diluted in 10 ml of an isotonic sodium chloride solution - a 0.005% solution is obtained.

The course of treatment consists of 3 injections with a frequency of 1 time in 3 days. 10 days after the start of treatment, the clinical dynamics are recorded according to cystometric indices and urination diaries.

To confirm the essence of the invention, we examined a group of patients with different durations of neurogenic bladder dysfunction, who underwent treatment according to the proposed method claimed by the invention.

Clinical researches

Patient 1. Neurogenic bladder dysfunction hyperreflex type.

Floor - female Date of Birth - 1939 Age - 65 years old Place of work - pensioner Disease duration - 7 years Date of examination before treatment - 03/11/04 First session date - 03/15/04 2nd session date - 03/19/04 3rd session date - 03/22/04 Date of examination after treatment - 03/25/04

Dynamics of clinical symptoms before and 10 days after treatment

Clinical symptoms Before treatment B / w 10 days after treatment Urination count fifteen 8 The number of imperative urges 3 one

Dynamics of cystometric indicators before and 10 days after treatment

Indicators Before treatment B / w 10 days after treatment Cystometric capacity, ml 160 250 The volume of fluid causing involuntary contraction of the detrusor, ml one hundred 150

Patient 2. Neurogenic bladder dysfunction hyperreflex type.

Floor - female Date of Birth - 1959 Age - 45 years Place of work - works at the factory, engineering Disease duration - 3 years Date of examination before treatment - 03/05/04 First session date - 03/10/04 2nd session date - 03/14/04 3rd session date - 03/17/04 Date of examination after treatment - 03/20/04

Dynamics of clinical symptoms before and 10 days after treatment

Clinical symptoms Before treatment B / w 10 days after treatment Urination count 12 6 The number of imperative urges 2 0

Dynamics of cystometric indicators before and 10 days after treatment

Indicators Before treatment B / w 10 days after treatment Cystometric capacity, ml 160 250 The volume of fluid causing involuntary contraction of the detrusor, ml one hundred 150

Patient 3. Neurogenic bladder dysfunction hyperreflex type.

Floor - male Date of Birth - 1970 Age - 34 years Place of work - disabled person 2 groups Disease duration - 5 years old, spinal injury 1999, lower paraplegia Date of examination before treatment - 02.03.04 First session date - 03/11/04 2nd session date - 03/15/04 3rd session date - 03/19/04 Date of examination after treatment - March 24, 04

Dynamics of clinical symptoms before and 10 days after treatment

Clinical symptoms Before treatment B / w 10 days after treatment Urination count fourteen 7 The number of imperative urges 2 0

Dynamics of cystometric indicators before and 10 days after treatment

Indicators Before treatment B / w 10 days after treatment Cystometric capacity, ml 150 250 The volume of fluid causing involuntary contraction of the detrusor, ml 70 130

Patient 4. Neurogenic bladder dysfunction hyperreflex type.

Floor - male Date of Birth - 1954 Age - 50 years Place of work - disabled person 2 groups Disease duration - 6 years old, spinal injury 1998 Previous treatment - Driptpan Date of examination before treatment - 02.03.04 First session date - 03/11/04 2nd session date - 03/15/04 3rd session date - 03/19/04 Date of examination after treatment - March 24, 04

Dynamics of clinical symptoms before and 10 days after treatment

Clinical symptoms Before treatment B / w 10 days after treatment Urination count 12 6 The number of imperative urges one 0

Dynamics of cystometric indicators before and 10 days after treatment

Indicators Before treatment B / w 10 days after treatment Cystometric capacity, ml 150 230 The volume of fluid causing involuntary contraction of the detrusor, ml 90 150

Patient 5. Neurogenic bladder dysfunction hyperreflex type.

Floor - female Date of Birth - 1957 Age - 47 years old Place of work - employee of a state enterprise Disease duration - 4 years Date of examination before treatment - March 16, 04 First session date - 03/20/04 2nd session date - March 24, 04 3rd session date - 03/27/04 Date of examination after treatment - 03/30/04

Dynamics of clinical symptoms before and 10 days after treatment

Clinical symptoms Before treatment B / w 10 days after treatment Urination count 13 7 The number of imperative urges one 0

Dynamics of cystometric indicators before and 10 days after treatment

Indicators Before treatment B / w 10 days after treatment Cystometric capacity, ml 140 230 The volume of fluid causing involuntary contraction of the detrusor, ml 90 150

Patient 6. Neurogenic bladder dysfunction hyperreflex type.

Floor - female Date of Birth - 1949 Age - 55 years Place of work - works at the factory, engineering Disease duration - 2 years Date of examination before treatment - 03/01/04 First session date - 03/06/04 2nd session date - 03/10/04 3rd session date - 03/13/04 Date of examination after treatment - 03/17/04

Dynamics of clinical symptoms before and 10 days after treatment

Clinical symptoms Before treatment B / w 10 days after treatment Urination count eleven 5 The number of imperative urges one 0

Dynamics of cystometric indicators before and 10 days after treatment

Indicators Before treatment B / w 10 days after treatment Cystometric capacity, ml 140 230 The volume of fluid causing involuntary contraction of the detrusor, ml 90 140

Based on the presented data, it can be concluded that the proposed method for the treatment of neurogenic bladder dysfunction extends the methods of sacral neuromodulation, is easily tolerated by patients, and allows to obtain effective results already on the 10th day.

The authors hope that the proposed method will be widely used in urological clinics and save many patients from a long unpleasant disease.

Claims (4)

1. A method of treating neurogenic bladder dysfunction of a hyperreflex type by sacred neuromodulation, which includes searching and puncturing sacral holes using injection needles, characterized in that the right and left S ₃ sacral holes are punctured with an alloplant solution introduced into them. 2. The method according to claim 1, characterized in that the alloplant is a lyophilized powder prepared from dispersed cadaveric tissue that does not have antigenic activity. 3. The method according to claim 1, characterized in that the introduced alloplant is a 0.005% solution in an isotonic sodium chloride solution. 4. The method according to claim 1 or 2, characterized in that the alloplant solution is injected into the sacral openings of 2 ml once every three days three times.