KETAMINE CYSTITIS: A SYSTEMIC REVIEW AND METANALYSIS OF SURGICAL OUTCOMES OF RECONSTRUCTIVE SURGERY

Vizgan G1, Farooq M1, Prishtina L1, Blaivas J1

Research Type

Clinical

Abstract Category

Prevention and Public Health

Abstract 186
ePoster 3
Scientific Open Discussion ePoster Session 12
Thursday 19th November 2020
16:25 - 16:30 (ePoster Station 4)
Exhibition Hall
Painful Bladder Syndrome/Interstitial Cystitis (IC) Bladder Outlet Obstruction Surgery Underactive Bladder Overactive Bladder
1. Institute for Bladder and Prostate Research
Presenter
G

Gabriel Vizgan

Links

Abstract

Hypothesis / aims of study
Discovered in 1960, Ketamine hydrochloride is a glutamatergic N-methyl-D-aspartate antagonist and is used as a short-acting, but powerful, dissociative anesthetic employed in both human and veterinary medicine for the induction and maintenance of general anesthesia. However, its use as an anesthetic has been limited due to its hallucinogenic side effects, which have been described as a “near death” or “out of body” experience and generally occur during waking from the anesthetic [1]. Most recently, in March 2019 the FDA approved a ketamine based nasal spray as an antidepressant.

Amongst those involved in the UK’s “dance-scene,” the prevalence of ketamine use is 42% and has increased at approximately a 50% rate per year over a 5-year period from 1999 to 2003 [2]. A British Crime Survey [3] reported an increase in the rate ketamine abuse by 16–59 year olds by 0.1% between 2006 and 2007.  In 2006 ketamine was made a Class C substance via the Misuse of Drugs Act, and in 2007 0.8% of individuals aged 16—24 reported using ketamine in the last year. Ketamine is thought to be particularly popular in Asia, as the INCB reported in 2012 that 99% of all ketamine seizures worldwide took place in Asia. By the end of 2014 it was found that approximately 1% of the US population aged 16-24 had used ketamine recreationally.

Refractory ketamine cystitis (RKC) has devastating effects on the lower urinary tract (LUT) - disabling bladder pain, urinary frequency and small capacity bladder with low compliance leading to ureteral obstruction and even renal failure. The only effective treatment for RKC is major surgical reconstruction or urinary diversion (UD).  Nevertheless, there is a paucity of awareness about this destructive condition. The aim of this study is to analyze the outcomes of reconstructive lower urinary tract surgery (RLUTS) in patients with RKC.
Study design, materials and methods
This is an English language literature review of surgical outcomes in (KC) patients who underwent reconstructive lower urinary tract surgery (RLUTS) or urinary diversion (UD) through 9/15/19. Two independent researchers read each paper’s title and if both found the paper to be relevant its abstract was read and then, subsequently, the paper itself; all disagreements regarding reliance were settled by a third party. The following search terms were employed to search Pub Med and Scopus ketamine abuse, ketamine abuse and surgery, ketamine and interstitial cystitis, ketamine abuse and interstitial cystitis, ketamine abuse and complications, ketamine and cystitis, ketamine abuse and cystitis, ketamine and cystoplasty, ketamine abuse and cystoplasty, ketamine abuse and ileocecocystoplasty, ketamine and ileocecocystoplasty, ketamine and enterocystoplasty, ketamine abuse and enterocystoplasty, ketamine abuse and augmentation enterocystoplasty, ketamine and augmentation enterocystoplasty, ketamine and augmentation cystoplasty, ketamine abuse and augmentation cystoplasty, ketamine abuse and bladder, ketamine and bladder, ketamine cystitis, ketamine cystitis and surgery, ketamine and urinary diversion, ketamine abuse and urinary diversion, ketamine and cystectomy, and ketamine abuse and cystectomy. In vitro, animal studies, letters to the editor, and papers that did not evaluate surgical outcomes were excluded.  

We extracted the following data from each article: type of article (e.g. case report, case series, literature review), time period over which study was conducted, number of patients (male & female), age, symptoms, symptom scores, duration of ketamine abuse, , indications for surgery, type of surgery, surgical technique, alternative treatments, cryptoscopic findings, histological findings, pre and post-operative hydronephrosis, pre and post-operative serum creatinine, pre and post-operative maximum voided volume, pre and post-operative maximum flow rate, pre and post-operative post void residual, pre and post-operative compliance , pre and post-operative frequency, pre and post-operative nocturia, pre and post-operative cystometric bladder capacity, pre and post-operative urinary tract infection, pre and post-operative vesicoureteral reflux, pre and post-operative maximum bladder capacity, pre and post-operative pain, pre and post-operative strictures, length of follow up, reasons why complications, reoperations, and post-operative symptoms.  

Continuous variables were represented as mean ± standard deviation, and categorical data are represented by number and percentage (%). The statistical significance of our data was found by acquiring P values calculated using a paired one tail T test.  Statistical assessments were considered to be significant when P was <0.05.
Results
Of 49,077 identified articles, 525 were relevant based on title, 143 based on abstract, and 21 papers by content. The 21 studies yielded 822 ketamine cystitis patients of whom 140 underwent RLUTS (17%). Result are depicted in the Tables. The overall scientific quality of the studies was very poor; eg, only 77/140 studies (55%) even mention follow-up!
Interpretation of results
Ketamine abuse is becoming more prevalent in society, yet there is a dearth of information regarding its health consequences. Evident in our data – or lack-there-of – is the fact that that the scientific community has yet to establish a proper means for identifying and reporting cases of KC.

 In patients with severe KC there a host of empiric therapies that have been tried -antimuscarinics and non-steroid anti-inflammatory drugs, cystoscopic hydrodistension, and intravesical instillation therapy with hyaluronic acid or heparin - but there is little data about their efficacy. 

Surgical reconstruction is indicated for those with end stage bladder disease characterized by refractory overactive bladder symptoms, bladder pain, low bladder capacity, and low bladder compliance. The goals of surgery are to restore normal bladder capacity, reduce bladder pain, prevent or treat ureteral obstruction, to regain normal micturition and improve quality of life.

Of course, it is best accomplished before the onset of hydronephrosis and vesicoureteral reflux, but, over half the patients in this cohort already had hydronephrosis or vesicoureteral reflux at the time of their reconstruction. This data is disconcerting because of the apparent rapid progression from the beginning of KA to end stage bladder; there was only one year difference between the duration of ketamine abuse and those patients who underwent surgery (4.4 years) and those that did not (3.4 years). This suggests that the time interval from the beginning of ketamine cystitis until end-stage bladder and ureteral involvement may be measured in months or a year, confounding the decision-making about the optimal time to consider lower urinary tract reconstruction. This is especially relevant in so far as low bladder capacity, low compliance, vesicoureteral reflux and hydronephrosis are not likely to resolved after cessation of ketamine abuse.
Concluding message
Ketamine cystitis is a rapidly progressive, devastating condition that can lead to end-stage bladder within a few years after its onset. Once refractory symptoms and low bladder capacity and compliance occur, the only effective treatment is major reconstructive surgery ranging from augmentation enterocystoplasty to cysto-prostatectomy and urinary diversion. 

Our literature search found only 140 patients who underwent reconstructive surgery for KC and the overall quality of the outcomes research was poor. Nevertheless, a few conclusions seem warranted. All of the current reconstructive procedures appear to improve LUTS, relieve bladder pain (provided that the patient abstains from ketamine) and protect the kidneys, at least in the short term, unless ureteral obstruction occurs as a complication of the surgery itself.
Figure 1 Patient demographics & Types of Surgery. N = the number of patients for whom data was available. SD= standard deviation.
Figure 2 Surgical Results. N = the number of patients for whom data was available. SD= standard deviation.
References
  1. McCambridge J, Winstock A, Hunt N, Mitcheson L. 5-Year trends in use of hallucinogens and other adjunct drugs among UK dance drug users. Eur Addict Res 2007;13:57–64.
  2. Hoare, Jacqueline. “Drug Misuse Declared: Findings from the 2008/09: British Crime Survey: England and Wales.” PsycEXTRA Dataset, 2009, doi:10.1037/e586982012-001.
  3. McCambridge J, Winstock A, Hunt N, Mitcheson L. 5-Year trends in use of hallucinogens and other adjunct drugs among UK dance drug users. Eur Addict Res 2007;13(1):57—64.
Disclosures
Funding Institute for Bladder and Prostate Research Clinical Trial No Subjects None