1508 | Suspected Ketamine-Associated Lower Uri- nary Tract Symptoms Tzu-Rong Peng,1 Ming-Chia Lee,1 Ta-Wei Wu,1 Chou-Chin Lan2,3 Keywords: ketamine;‎urination‎disorders;‎lower‎urinary‎tract‎symptoms;‎etiology. INTRODUCTION An‎increasing‎number‎of‎case‎reports‎of‎ketamine‎involving‎in‎urinary‎system‎com-plications,‎such‎as‎lower‎urinary‎tract‎symptoms‎(LUTS)‎or‎ulcerative‎cystitis,‎have‎been‎cited‎from‎the‎chronic‎abuse‎of‎ketamine.(1-7)‎Many‎health‎care‎professionals,‎ however,‎are‎not‎aware‎of‎these‎under-diagnosed‎adverse‎effects.‎Thus,‎we‎report‎on‎a‎case‎of‎ suspected‎ketamine‎associated‎contracted‎bladder‎and‎hydronephrosis‎and‎conduct‎a‎review‎ of‎the‎related‎literature. CASE REPORT A‎45-year-old‎male‎was‎admitted‎to‎our‎emergency‎department‎due‎to‎changed‎consciousness‎ and‎renal‎function.‎He‎had‎a‎3-year‎history‎of‎intranasal‎ketamine‎use‎and‎increased‎urinary‎ frequency‎and‎urethral‎pain‎sine‎one‎year‎ago.‎The‎symptoms‎began‎only‎after‎the‎onset‎of‎ ketamine‎use‎and‎resolved‎with‎treatment‎of‎oral‎propiverine‎15‎mg‎twice‎daily‎and‎oral‎tam- sulosin‎0.2‎mg‎once‎daily‎and‎cessation‎of‎ketamine‎use.‎After‎two‎years‎then,‎however,‎the‎ symptoms‎recurred‎after‎inhaled‎ketamine‎reused.‎In‎this‎admission,‎urine‎analysis‎showed‎ hematuria‎and‎proteinuria.‎Urine‎cultures‎were‎sterile.‎The‎blood‎tests‎revealed‎white‎blood‎ Corresponding Author: Chou-Chin Lan, MD Division of Pulmonary Medicine, Bud- dhist Tzu-Chi General Hospital, Taipei Branch, Taiwan. Tel: +886 2 6628 9779 Fax: +886 2 6628 9009 E-mail: bluescopy@yahoo.com.tw Received November 2012 Accepted December 2012 1 Department of Pharmacy, Buddhist Tzu Chi General Hospi- tal, Taipei Branch, Taiwan. 2 Department of Internal Medi- cine, Buddhist Tzu Chi General Hospital, Taipei Branch, Taiwan. 3 School of Medicine, Tzu Chi University, Hualien, Taiwan. CASE REPORT Case Report 1509Vol. 11 | No. 02 | March- April 2014 |U R O LO G Y J O U R N A L Ketamine and LUTS | Peng et al cell‎20,200/µL,‎neutrophil‎bands‎3%,‎neutrophil‎segments‎ 88%,‎ C-reaction‎ protein‎ 21.25‎ mg/dL,‎ serum‎ creatinine‎ 11.8‎mg/dL,‎blood‎urea‎nitrogen‎106‎mg/dL,‎sodium‎104‎ mmol/L,‎potassium‎6.6‎mmol/L,‎alkaline‎phosphatase‎944‎ IU/L,‎gamma-glutamyltransferase‎1998‎IU/L,‎total‎bilirubin‎ 2.46‎mg/dL,‎direct‎bilirubin‎2.25‎mg/dL,‎lipase‎1,165‎IU/L,‎ and‎amylase‎212‎IU/L.‎The‎computed‎tomography‎imaging‎ of‎the‎abdomen‎showed‎bilateral‎hydronephrosis‎and‎small‎ bladder‎capacity‎and‎no‎sign‎of‎pancreatitis.‎Besides,‎ the‎ echo‎imaging‎of‎abdomen‎revealed‎gallbladder‎sludge.‎A‎full‎ screening‎confirmed‎the‎exclusion‎of‎other‎causes‎of‎liver‎ disease.‎Ketamine‎associated‎lower‎urinary‎tract‎syndrome‎ was‎diagnosed‎and‎ketamine‎associated‎gallbladder‎sludge‎ was‎suspected‎(Figure).‎The‎hemodialysis‎and‎ureteral‎dou- ble-J‎placement‎were‎performed‎for‎poor‎renal‎function‎and‎ bilateral‎hydronephrosis.‎Oral‎silymarin‎was‎given‎for‎poor‎ liver‎function.‎Intravenous‎levofloxacin‎750‎mg‎single‎dose‎ and‎500‎mg‎every‎other‎day‎was‎administrated‎for‎treating‎ infection.‎After‎seven‎days,‎his‎renal‎and‎liver‎function‎im- proved,‎serum‎creatinine‎1.7‎mg/dL,‎blood‎urea‎nitrogen‎38‎ mg/dL,‎total‎bilirubin‎0.54‎mg/dL,‎direct‎bilirubin‎0.52‎mg/ dL,‎ gamma-glutamyltransferase‎ 1,617‎ IU/L,‎ lipase‎ 1,405‎ IU/L,‎and‎amylase‎328‎IU/L,‎but‎no‎sign‎of‎pancreatitis,‎so‎ he‎was‎discharged‎home‎due‎to‎stable‎condition.‎He‎also‎ was‎referred‎to‎drug‎rehabilitation‎center‎for‎the‎problem‎of‎ ketamine‎abuse. DISCUSSION Ketamine,‎an‎N-methyl-D-aspartic‎acid‎(NMDA)‎receptor‎ antagonist,‎has‎been‎used‎in‎veterinary‎medicine‎and‎for‎an- esthesia‎purposes‎more‎than‎30‎years.‎It‎has‎been‎abused‎as‎ a‎recreational‎drug‎in‎nightclubs‎due‎to‎the‎effects‎of‎hal- lucination‎ and‎ “near-death‎ experiences”.(8)‎ However,‎ the‎ detrimental‎effects‎of‎ketamine‎are‎not‎understood‎by‎many‎ recreational‎users,‎in‎particular‎on‎the‎central‎nervous‎sys- tem,‎ respiratory‎ and‎ cardiovascular‎ systems.‎ Since‎ 2007,‎ several‎case‎reports‎of‎ketamine‎associated‎LUTS‎have‎been‎ described,(1-7)‎ all‎ patients‎ had‎ a‎ history‎ of‎ ketamine‎ use.‎ The‎ clinical‎ presentations‎ of‎ LUTS‎ include‎ dysuria,‎ fre- quent‎urination,‎small‎volume‎voids‎and‎painful‎hematuria. (1,8)‎In‎addition,‎some‎reports‎indicated‎that‎the‎computed‎ tomography‎imaging‎of‎the‎abdomen‎showed‎a‎small‎blad- der capacity and unilateral or bilateral hydronephrosis.(1,4,8)‎ Our‎patient’s‎LUTS,‎a‎small‎bladder‎capacity‎and‎bilateral‎ hydronephrosis‎are‎consistent‎with‎previous‎reports.‎Cystos- copy‎and‎biopsy‎were‎both‎refused‎by‎the‎patient.‎However‎ the‎LUTS‎of‎our‎patient‎resolved‎after‎cessation‎of‎ketamine‎ and‎ recurred‎ when‎ he‎ re-inhaled‎ ketamine.‎ The‎ Naranjo‎ probability‎scale‎ (7‎ points)‎ indicated‎a‎ probable‎ relation- ship‎between‎ketamine‎and‎LUTS‎in‎this‎patient.(10)‎Tsai‎and‎ colleagues‎demonstrated‎that‎the‎time‎of‎onset‎of‎LUTS‎af- ter‎ketamine‎abuse‎ranged‎from‎1‎month‎to‎a‎few‎years.(5)‎ In‎our‎patient,‎the‎onset‎of‎symptoms‎was‎about‎1-2‎years‎ and‎the‎doses‎of‎ketamine‎are‎unknown.‎The‎mechanism‎of‎ ketamine‎associated‎LUTS‎is‎still‎not‎clear.‎High‎concentra- tions‎of‎ketamine‎and‎its‎metabolites‎can‎be‎detected‎in‎the‎ urine‎of‎patients‎using‎ketamine.(11)‎The‎direct‎toxicity‎of‎ ketamine‎and‎its‎metabolites‎may‎cause‎significant‎bladder‎ irritation‎and‎kidney‎damage.(4,12)‎At‎the‎early‎stage‎of‎the‎ disease,‎ketamine‎cessation‎may‎resolve‎the‎LUTS.‎Cheung‎ and‎colleagues‎have‎indicated‎the‎subjects‎who‎had‎ceased‎ ketamine‎use‎for‎less‎than‎3‎months‎had‎significantly‎more‎ urinary‎symptoms‎than‎those‎who‎had‎stopped‎for‎3‎months‎ or‎more.‎However,‎those‎persons‎who‎abused‎ketamine‎for‎ 2‎years‎or‎more‎and‎ceased‎for‎less‎than‎3‎months,‎endured‎ significantly‎poorer‎quality‎of‎life.(13) In addition, pentosan polysulfate‎sodium,‎antihistamine,‎and‎corticosteroid‎may‎ help‎alleviate‎ the‎irritable‎voiding‎symptoms.‎As‎the‎dis- ease‎becomes‎more‎severe,‎such‎as‎painful‎hematuria,‎or‎ impaired‎renal‎function,‎enterocystoplasty‎may‎be‎required.‎ It‎is‎important‎to‎note‎that‎delayed‎diagnosis‎and‎interven- Figure . The computed tomography imaging of the abdomen showed bilateral hydronephrosis (A), small bladder capacity (B) and gallbladder sludge (C). 1510 | tion‎will‎eventually‎lead‎to‎irreversible‎renal‎damage.(4,12)‎ The‎biliary‎abnormality‎due‎to‎chronic‎ketamine‎use‎is‎fully‎ reversible,‎so‎Lo‎and‎colleagues‎suggest‎that‎biliary‎stent- ing‎should‎be‎avoided‎unless‎absolutely‎necessary.(13) Ac- cording‎to‎our‎patient,‎ketamine‎associated‎urinary‎tract‎and‎ biliary‎abnormality‎could‎appear‎simultaneously.‎Therefore,‎ ketamine‎abuse‎should‎be‎considered‎as‎a‎potential‎cause‎if‎ patients‎have‎unexplained‎cholestatic‎liver‎function‎tests‎and‎ urinary‎tract‎syndrome.‎Health‎care‎workers‎should‎be‎alert‎ to‎this‎disease‎and‎at‎risk‎patients‎should‎be‎informed‎about‎ these‎possible‎side‎effects. CONFLICT OF INTEREST None declared. REFERENCES 1. Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007;69:810-2. 2. 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