The Urodynamic Detection Of Ketamine-associated Bladder Cystitis And The Experimental And Clinical Evaluation Of The Bladder Hydrodistention

BackgroundKetamine is a phencyclidine derivative, commonly known as k powder, smoked with addiction and euphoria,which can produce hallucinations, such as:hovering, weightless and floating feel.After1hour its hallucinogenic effects dies away. The metabolism of ketamine in body mainly through two ways:one is the liver microsomal CYP3A4enzyme metabolism, the other way is urinary system. The substantial part of ketamine and its metabolites can secret by the excretion of urine.The youth abuse situation is increasingly prominent.Domestic and foreign research ontoxic damage of ketamine is still mainly in the cardiovascular and neuropsychiatric systems, Recently reported urinary system damage caused by ketamine abuse gradually, but the reports,which contains treatment means and the damage-mechanism to urinary system,is so less, less their cause damage to the urinary tract of basic research.2007, Shanhani et al first reported the ketamine-abused in patients occur with varying degrees of lower urinary tract damage symptoms, and called it ketamine associated lower urinary tract symptoms. Domestic and foreign scholars found that:long-term abuse of ketamine crowd there will be varying degrees of overactive bladder (OAB) symptoms, such as urinary frequency, urgency, dysuria,hematuria and urge incontinence.Urodynamic testing shows overly sensitive bladder, instability Bladder, urinary flow rate is low;Cystoscopy find bladder wall can be seen extensive mucosal congestion and redness;Imaging studies revealed obvious bladder contracture and volume reduction (minimum of30～100ml);Pathological examination confirmes that a large number of inflammatory cells in the the bladder mucosal epithelial cells invade with granulation of tissue growth;Generally no abnormal of blood and urine routine and antibiotic treatment is often not significant.Some scholars have called the lower urinary tract damage of ketamine abuseketamine-associated cystitis.The pathogenesis of Ketamine-associated cystitis is not very clear.there is a lack of effective therapies.It is often misdiagnosed as cystitis, prostatitis "and confused with a simple" overactive bladder(OAB)"The incidence rate was gradually rising trend in the world in recent years, especially in the Pan-Pearl River Delta and other economically developed areas is very obvious.Many doctors are not yet fully understand the pain and huge burden of the disease to patients and their families.So it is necessary that study ketamine-associated cystitis from the experimental and clinical.Meng used anesthetic dose of ketamine hydrochloride injection (80-150mg/kg),intraperitoneal injection of C57BL/6mice.The urodynamic study found that the voiding interval and bladder capacity was significantly reduced. Shu-Mien build ketamine ulcerative cystitis rat model induced by intraperitoneal injection of ketamine (25mg/kg).Urodynamics was based primarily on the basic principles and methods of electrophysiology and hydrodynamics.It understand the function and mechanism of the urinary tract on transportation urine and pathophysiology of the voiding dysfunction disease by detection of urinary tract pressure, bioelectrical activity and urinary flow rate.The urodynamic a ideal method which can reflect urinary tract function intuitively quantitatively.Therefore,for the disease of voiding dysfunction,urodynamic testing has important practical value on clinical diagnosis and treatment. Some scholars believe that in the bladder mucosa surface existence a protective layer, such as the ingredients of glycosaminoglycan (GAG), the asymmetric unitmembrane, ion pump and a high-density proteoglycans.After the destruction of the protective layer, Ketamine or its metabolites destroy the epithelial permeability barrier and damage to the bladder wall deep tissue.If the toxic substances enter the submucosal and detrusor layer and damage muscles and nerves, nerve fibers of the bladder wall been abnormal stimulation,then causing irritation symptoms of urgency, frequency, etc.Bladder hydrodistention with drug perfusion is the primary means for the treatment of OAB symptoms of clinical treatment,after which under anesthesia may contribute to the growth of the bladder mucosa.The mechanism of treatment of the bladder hydrodistention is considered that hydrodistention led to the ischemic and necrosis of the sensory nerves in the bladder wall,and reduce the density of sensory nerves in the bladder wall.PurposeBased on the above reasons,author through the establishment of ketamine-associated cystitis rat model,evaluate the urodynamic indicators before and after the treatment of bladder hydrodistention with infusion of drug.Besides, through clinical retrospective study evaluated the clinical effect of the bladder hydrodistention. In order to provide a new and effective way for the treatment of ketamine-associated cystitis.Method1. Establish theketamine-associated cystitis rat modelSelected female Sprague-Dawley2-month-old young rats30.Based on urodynamic examination was normal, all30rats were included in the experiment study.All rats were divided into a control group (A,10) and model group (B,20), all rats of group B were injected ketamine (30mg/kg) by intraperitoneal a total of12weeks. At the end of the4th,8th and12th weeks,take4times urodynamic testing on model rats to evaluate the bladder function.3days after the withdrawal the model rats were detected to find whether ketamine and its metabolites exist in their body. After he model is confirmed induction success, take two groups of rats a small bladder tissue under anesthesia,which was applicated to the conventional HE staining,for observing the pathomorphological changes of bladder mucosa and detrusor.Discuss the pathological basis which caused thed structural and functional changes of bladder.of ketamine-associated cystitis rats.2. The method for urodynamic detection on ratUse urethane anesthetized rats by intraperitoneal injection. Inserted the homemade single3F cystometry cathet into the urethra of rat. Inserted the homemade anorectal manometry tube into the anus about4cm.Then connected the two pipes with urodynamic gauge pressure sensors and micro-infusion pump.The infusion rate of the pump is adjusted to0.1ml/min.The measurement indicators include voiding interval, the maximum bladder capacity(MBC), the maximum bladder voiding pressure (MVP)and detrusor instability contraction frequency.Then the significance of urodynamic indicators changing is analysised on ketamine associated cystitis rats.3. The method of bladder hydrodistention with drug perfusionAfter12weeks each group stop using ketamine.At the same time Group B were randomly divided into two groups (B1, B2)(10rats/group). After stopping useing ketamine1,3,5weeks, the group B2was dealed with "bladder hydrodistention with drug perfusion"contrast the B1group were treated with drugs perfusion only.1week after cessation of treatment, urodynamic was processed to detect the changes of rat voiding interval, MBC, MVP, detrusor instability contraction frequency.Compare the difference betweenB1and B2groups, and the difference between before and after application of the treatment.Disscuss the therapeutic effect of bladder hydrodistention to the ketamine-associated cystitis.4.The statistical analysisUse spss16.0software deal with data analyzed by t-test and analysis of variance. In the case of P<0.05data is considered statistically significant.Result1. Urodynamic results show:The maximum bladder capacity (MBC) in saline control group (A group)and ketamine-associated cystitis rats (B group) were (0.663±0.091) and(0.234±0.060)and the difference between two groups were statistical significance (t=15.527,P=0.000).The voiding interval in two groups were (6.680±0.884VS2.433±0.614),and the difference between two groups were statistical significance (t=15.404,P=0.000).The instability contraction frequency in two groups were(0.100±0.316VS3.500±0.827)and the difference between two groups were statistical significance (t=-16.170,P=0.000).The maximum bladder voiding pressure(MVP) in two groups were (35.400±6.096VS36.005±6.095),but the difference between two groups were not statistical significance (t=-0.256,P=0.800).After the begining of induction4weeks、8weeks、12weeks, The urodynamic study results of ketamine-associated cystitis model (B group) suggested that the maximum bladder capacity (MBC) in three Point-in-time were (0.456±0.089VS0.290±0.096VS0.234±0.060) and the difference among group internally were statistically significant (F=101.64,P=0.000).The voiding interval in three Point-in-time were (4.615±0.899VS3.102±0.735VS2.433±0.614) and the difference among group internally were statistically significant(F=110.441,P=0.000).The instability contraction frequency in three Point-in-time were(0.850±0.745VS2.200±0.696VS3.500±0.827)and the difference among group internally were statistically significant (F=41.704,P=0.000).The maximum bladder voiding pressure(MVP) in three Point-in-time were (35.445±5.864VS35.705±5.934VS36.005±6.095) but the difference among group internally were not statistically significant (F=0.029,P=0.993).It can be seen that epithelial cell degeneration, mucosal edema, inflammatory cell infiltration on bladder mucosal of ketamine-associated cystitis rat model and fibroplasia, lymphangiectasia,infiltration of lymphocytes and mast cells infiltrate on detrusor layer by routine HE staining.2. In the group of ketamine-associated cystitis rat model (B), urodynamic results show that the maximum bladder capacity (MBC) before and after bladder hydrodistention with drug infusion were (0.228±0.055VS0.609±0.090) and the difference were statistically significant (t=-21.265P=0.000).The voiding interval were (2.345±0.561VS6.110±0.923) and the difference were statistically significant (t=-21.421P=0.000).The detrusor instability contraction frequency were (3.500±0.850VS0.800±0.632)and the difference were statistically significant (t=9.000P=0.000). The maximum bladder capacity (MBC) before and after drug infusion only were (0.240±0.067VS0.242±0.069) and the difference were not statistically significant (t=-1.000P=0.343).The voiding interval were (2.520±0.681VS2.550±0.675) and the difference were not statistically significant (t=-1.964P=0.081).The detrusor instability contraction frequency were (3.500±0.850VS1.500±0.527) and the difference were not statistically significant (t=9.487P=0.000).3.11patients of ketamine-associated cystitis were treated by bladder hydrodistention with drug infusion.The O’Leary-SantICPI score of the before and after treatment were (9.363±2.378VS3.000±1.612) and the difference were statistically significant (t=20.553P=0.000).The O’Leary-SantICSI score of the before and after treatment were (13.727±3.523VS4.091±2.022) and the difference were statistically significant (t=19.616P=0.000).Urodynamic results show The maximum bladder capacity (MBC) before treatment and1month after treatment were (57.727±15.787VS181.272±21.261) and the difference were statistically significant (t=-29.894P=0.000).The voiding interval were (29.000±7.797VS75.27±10.02) and the difference were tatistically significant (t=-40.417P=0.000).The detrusor instability contraction frequency were (2.545±1.036VS0.455±0.522) and the difference were statistically significant (t=-9.898P=0.000).The maximum flow rate were (6.627±1.872VS15.118±1.884) and the difference were statistically significant (t=-122.429P=0.000).The frequency of urination at daytimewere (26.909±8.068VS10.091±1.640) and the difference were statistically significant((t-8.192P=0.000). The frequency of urination at night were (4.546±1.440VS1.364±0.924) and the difference were statistically significant(t=14.056P=0.000). The maximum bladder voiding pressure(MVP) were (44.000±4.313VS43.814±4.262) and the difference were not statistically significant (t=0.154P=0.881).Conclusionl.The bladder of ketamine-associated cystitis induced by intraperitoneal injection of ketamine in pathology and functional lesions are similar to that of humans.2.Bladder hydrodistention with infusion of drug treats the rat of ketamine-associated cystitis with good effect.3.Bladder hydrodistention with infusion of drug can significantly improve the bladder function of ketamine-associated cystitis patient.It may be a effective and reasonable way which is uesd to treat ketamine-associated cystitis.