What urologists need to know about ketamine‐induced uropathy: A systematic review

Abstract

Aims: Ketamine is a general anesthetic. Dissociative effects and low cost led ketamine becoming an illegal recreational drug in young adults. Ketamineinduced uropathy (KIU) is one of the complications observed in abusers. This study aimed to provide a systematic literature review on KIU clinical presentation, pathophysiology, and treatments. Methods: We performed the literature search in PubMed, Web of Science, Scopus, and Embase using the terms ketamine and bladder. English papers on human and animal studies were accepted. Results: A total of 75 papers were selected. Regular ketamine users complain about severe storage symptoms and pelvic pain. Hydronephrosis may develop in long-term abusers and is correlated to the contracted bladder, ureteral stenosis, or vesicoureteral reflux due to ureteral involvement and/or bladder fibrosis. Cystoscopy shows ulcerative cystitis. Ketamine in urine might exert direct toxicity to the urothelium, disrupting its barrier function and enhancing cell apoptosis. The presence of ketamine/ions in the bladder wall result in neurogenic/IgE-mediated inflammation, stimulation of the inducible nitric oxide synthase-cytokines-cyclooxygenase pathway with persistent inflammation and fibrosis. Abstinence is the first therapeutic step. Anti-inflammatory drugs, analgesics and anticholinergics, intravesical instillation of hyaluronic acid, hydrodistension and intravesical injection of botulin toxin-A were helpful in patients with early-stage KIU. In patients with end-stage disease, the control of intractable symptoms and the increase of bladder capacity were the main recommendations to perform augmentation enterocystoplasty.Conclusions: KIU is becoming a worldwide health concern, which should be taken into account in the differential diagnosis of ulcerative cystitis. K E Y W O R D S cystitis, inflammation, ketamine, lower urinary tract symptoms, substance-related disorders, urinary tract 1050 | CASTELLANI ET AL.

Is medicinal ketamine associated with urinary dysfunction issues? Assessment of both the European Medicines Agency (EMA) and the UK Yellow Card Scheme pharmacovigilance database‐related reports

“…A feature consistent with KIU diagnosis is indeed reduced functional bladder capacity, with values ranging between 10 and 150 mL 9 . Cystoscopic features are similar to those that are associated with interstitial cystitis/bladder pain syndrome (IC/BPS), thus including ulcers, submucosal ecchymosis and bleeding glomerulations 9 . The rate of upper urinary tract involvement, namely hydronephrosis and ureteral wall thickening, varies from 6% to 63% 9 .…”

“…Cystoscopic features are similar to those that are associated with interstitial cystitis/bladder pain syndrome (IC/BPS), thus including ulcers, submucosal ecchymosis and bleeding glomerulations 9 . The rate of upper urinary tract involvement, namely hydronephrosis and ureteral wall thickening, varies from 6% to 63% 9 . Hydronephrosis develops secondary to long‐term decreased compliance of the bladder or ureteral stenosis.…”

“…Patients with severe storage phase lower urinary tract symptoms (LUTS), a positive history of ketamine abuse and the absence of any other etiology should be considered to have KIU. The most typical LUTS in KIU patients include increased frequency, urgency, nocturia, urge urinary incontinence (UUI), pelvic discomfort/pain during voiding and hematuria 9 . A feature consistent with KIU diagnosis is indeed reduced functional bladder capacity, with values ranging between 10 and 150 mL 9 .…”

“…The most typical LUTS in KIU patients include increased frequency, urgency, nocturia, urge urinary incontinence (UUI), pelvic discomfort/pain during voiding and hematuria 9 . A feature consistent with KIU diagnosis is indeed reduced functional bladder capacity, with values ranging between 10 and 150 mL 9 . Cystoscopic features are similar to those that are associated with interstitial cystitis/bladder pain syndrome (IC/BPS), thus including ulcers, submucosal ecchymosis and bleeding glomerulations 9 .…”

“…Hydronephrosis develops secondary to long‐term decreased compliance of the bladder or ureteral stenosis. Both vesicoureteral reflux due to trigonal fibrosis and abnormal ureter peristalsis are further possible mechanisms of damage to the upper urinary tract 9 . Chronic kidney failure may develop as a final consequence.…”