Skip to main content

Advertisement

SpringerLink
Log in

Ketamine-Associated Bladder Dysfunction—a Review of the Literature

  • Overactive Bladder and Lower Urinary Tract Symptoms (U Lee and S Adelstein, Section Editors)
  • Published:
Current Bladder Dysfunction Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The purpose of this review is to study the epidemiology, presentation, pathogenesis and management of ketamine cystitis and its complications.

Recent Findings

Recent data suggest that the toxicity of ketamine can be due to direct cytotoxicity, independent of a NMDA receptor-mediated mechanism. Bladder barrier dysfunction, neurogenic inflammation with abnormal neurotransmission and immunological mechanisms have also been proposed, based on data from animal models and in vitro studies. Effects on the bladder are dependent on the dose and duration of ketamine use. Clinical studies have showed that the model of outreach clinics with involvement of local urology services holds most promise, with a tiered approach to management based on stage of the disease.

Summary

Chronic ketamine use is associated with significant lower urinary tract symptoms including frequency, urgency, haematuria and bladder pain. This may progress to irreversible bladder dysfunction with poor capacity and compliance and upper tract dysfunction may also occur. The key to successful treatment is ketamine cessation. The role of medications is not well established but there may be benefit from drugs used for IC/BPS and bladder Botox. Patients with end stage disease will require surgery, but there is a high complication rate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Morgan CJ, Curran HV. Independent scientific committee on drugs. Ketamine use: a review. Addiction. 2012;107(1):27–38.

    Article  PubMed  Google Scholar 

  2. Dalgarno PJ, Shewan D. Illicit use of ketamine in Scotland. J Psychoactive Drugs. 1996;28(2):191–9.

    Article  PubMed  CAS  Google Scholar 

  3. Global drug survey [Online]. 2017 [accessed 2018 January2]; Available from URL: https://www.globaldrugsurvey.com/gds2017-launch/results-released/

  4. Yiu-Cheung C. Acute and chronic toxicity pattern in ketamine abusers in Hong Kong. J Med Toxicol. 2012 Sep;8(3):267–70.

    Article  PubMed  CAS  Google Scholar 

  5. Meng E, Wu ST, Cha TL, Sun GH, Yu DS, Chang SY. A murderer of young bladders: ketamine-associated cystitis. Urol Sci. 2013;24:113–6.

    Article  Google Scholar 

  6. Moore KA, Sklerov J, Levine B et al. Urine concentrations of ketamine and norketamine following illegal consumption. J Anal Toxicol 200;25(7):583–588.

  7. Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007;69:810–2.

    Article  PubMed  Google Scholar 

  8. Chu PS, Kwok SC, Lam KM, et al. ‘Street ketamine’-associated bladder dysfunction: a report of ten cases. Hong Kong Med J. 2007;13(4):311–3.

    PubMed  Google Scholar 

  9. Chu PS, Ma WK, Wong SC, et al. The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU Int. 2008;102:1616–22.

    Article  PubMed  Google Scholar 

  10. Cottrell AM, Gillatt DA. Ketamine-associated urinary tract pathology: the tip of the iceberg for urologists? Br J Med Surg Urol. 2008;1:136–8.

    Article  Google Scholar 

  11. Colebunders B, Van Erps P. Cystitis due to the use of ketamine as a recreational drug: a case report. J Med Case Rep. 2008;2:219.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Selby NM, Anderson J, Bungay P, Chesterton LJ, Kolhe NV. Obstructive nephropathy and kidney injury associated with ketamine abuse. NDT Plus. 2008;1(5):310–2.

    PubMed  PubMed Central  Google Scholar 

  13. Shahzad S, Antil S, Ferrie B, Ganta S. UP-3.073: dystrophic calcification of urinary bladder associated with ketamine use. Urology. 2009;74:S317.

    Article  Google Scholar 

  14. Chiew YW, Yang CS. Disabling frequent urination in a young adult. Ketamine-associated ulcerative cystitis. Kidney Int. 2009;76(1):123–4.

    Article  PubMed  Google Scholar 

  15. Tsai TH, Cha TL, Lin CM, Tsao CW, Tang SH, Chuang FP, et al. Ketamine-associated bladder dysfunction. Int J Urol. 2009;16:826–9.

    Article  PubMed  CAS  Google Scholar 

  16. Mason K, Cottrell AM, Corrigan AG, Gillatt DA, Mitchelmore AE. Ketamine-associated lower urinary tract destruction: a new radiological challenge. Clin Radiol. 2010;65:795–800.

    Article  PubMed  CAS  Google Scholar 

  17. Mak SK, Chan MT, Bower WF, et al. Lower urinary tract changes in young adults using ketamine. J Urol. 2011;186(2):610–4.

    Article  PubMed  CAS  Google Scholar 

  18. Wood D, Cottrell A, Baker SC, Southgate J, Harris M, Fulford S, et al. Recreational ketamine: from pleasure to pain. BJU Int. 2011;107:1881–4.

    Article  PubMed  Google Scholar 

  19. Misra S, Chetwood A, Coker C, Thomas P. Ketamine cystitis: practical considerations in management. Scand J Urol. 2014;48(5):482–8.

    Article  PubMed  Google Scholar 

  20. Huang LK, Wang JH, Shen SH, et al. Evaluation of the extent of ketamine-induced uropathy: the role of CT urography. Postgrad Med J. 2014;90(1062):185–90. In depth discussion of role of imaging in ketamine cystitis.

    Article  PubMed  Google Scholar 

  21. Tam YH, Ng CF, Pang KK, et al. One-stop clinic for ketamine-associated uropathy: report on service delivery model, patients' characteristics and non-invasive investigations at baseline by a cross-sectional study in a prospective cohort of 318 teenagers and young adults. BJU Int. 2014;114(5):754–60. Report on service delivery using a one stop clinic for assessment of ketamine cystitis.

    Article  PubMed  CAS  Google Scholar 

  22. Wu P, Wang Q, Huang Z, et al. Clinical staging of ketamine-associated urinary dysfunction: a strategy for assessment and treatment. World J Urol. 2016;34(9):1329–36. Report on treatment based on stage.

    Article  PubMed  CAS  Google Scholar 

  23. Jhang JF, Hsu YH, Kuo HC. Possible pathophysiology of ketamine-related cystitis and associated treatment strategies. Int J Urol. 2015;22(9):816–25. Review article focussing on pathophysiology.

    Article  PubMed  CAS  Google Scholar 

  24. Winstock AR, Mitcheson L, Gillatt DA, Cottrell AM. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int. 2012;110:1762–6.

    Article  PubMed  Google Scholar 

  25. Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJA, Curran HV. Journey through the K-hole: phenomenological aspects of ketamine use. Drug Alcohol Depend. 2008;95(3):219–29.

    Article  PubMed  CAS  Google Scholar 

  26. Gregoire MC, MacLellan DL, Finley GA. A paediatric case of ketamine-associated cystitis. Urology. 2008;71:1232–3.

    Article  PubMed  Google Scholar 

  27. Storr TM, Quibell R. Can ketamine prescribed for pain cause damage to the urinary tract? Palliat Med. 2009;23(7):670–2.

    Article  PubMed  CAS  Google Scholar 

  28. Shahzad K, Svec A, Al-Koussayer O, et al. Analgesic ketamine use leading to cystectomy: a case report. Br J Med Surg Urol. 2012;5:188–91.

    Article  Google Scholar 

  29. Andrade C. Ketamine for depression, 1: clinical summary of issues related to efficacy, adverse effects, and mechanism of action. J Clin Psychiatry. 2017;78(4):e415–9.

    Article  PubMed  Google Scholar 

  30. Lee CL, Jiang YH, Kuo HC. Increased apoptosis and suburothelial inflammation in patients with ketamine-related cystitis: a comparison with non-ulcerative interstitial cystitis and controls. BJU Int. 2013;112(8):1156–62.

    Article  PubMed  Google Scholar 

  31. Chung SD, Wang CC, Kuo HC. Augmentation enterocystoplasty is effective in relieving refractory ketamine-related bladder pain. Neurourol Urodyn. 2014;33(8):1207–11.

    Article  PubMed  CAS  Google Scholar 

  32. Sihra N, Ockrim J, Wood D. The effects of recreational ketamine cystitis on urinary tract reconstruction—a surgical challenge. BJU Int. 2017 Dec 12; https://doi.org/10.1111/bju.14094. One of the larger series describing reconstructive surgery for ketamine cystitis

  33. Kidger E, Stahlschmidt J, Garthwaite M, Fulford S, Southgate J, Baker SC. A rare urachal cyst in a case of ketamine-induced cystitis provides mechanistic insights. Urology. 2016;90:223.e1–7.

    Article  Google Scholar 

  34. Wai MS, Luan P, Jiang Y, Chan WM, Tsui TY, Tang HC, et al. Long term ketamine and ketamine plus alcohol toxicity—what can we learn from animal models? Mini Rev Med Chem. 2013;13(2):273–9.

    PubMed  CAS  Google Scholar 

  35. Baker SC, Shabir S, Georgopoulos NT, Southgate J. Ketamine-induced apoptosis in normal human urothelial cells: a direct, N-methyl-d-aspartate receptor-independent pathway characterized by mitochondrial stress. Am J Pathol. 2016;186(5):1267–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Shie JH, Kuo HC. Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome. BJU Int. 2011;108(2 Pt 2):E136–41.

    Article  PubMed  Google Scholar 

  37. Gu D, Huang J, Yin Y, Shan Z, Zheng S, Wu P. Long-term ketamine abuse induces cystitis in rats by impairing the bladder epithelial barrier. Mol Biol Rep. 2014;41(11):7313–22.

    Article  PubMed  CAS  Google Scholar 

  38. Baker SC, Stahlschmidt J, Oxley J, Hinley J, Eardley I, Marsh F, et al. Nerve hyperplasia: a unique feature of ketamine cystitis. Acta Neuropathol Commun. 2013;1:64.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Meng E, Chang HY, Chang SY, Sun GH, Yu DS, Cha TL. Involvement of purinergic neurotransmission in ketamine induced bladder dysfunction. J Urol. 2011;186(3):1134–41.

    Article  PubMed  CAS  Google Scholar 

  40. Wei YB, Yang JR, Yin Z, Guo Q, Liang BL, Zhou KQ. Genitourinary toxicity of ketamine. Hong Kong Med J. 2013;19(4):341–8.

    PubMed  CAS  Google Scholar 

  41. Jhang JF, Hsu YH, Jiang YH, Kuo HC. Elevated serum IgE may be associated with development of ketamine cystitis. J Urol. 2014;192(4):1249–56.

    Article  PubMed  CAS  Google Scholar 

  42. Chuang SM, Liu KM, Li YL, Jang MY, Lee HH, Wu WJ, et al. Dual involvements of cyclooxygenase and nitric oxide synthase expressions in ketamine-induced ulcerative cystitis in rat bladder. Neurourol Urodyn. 2013;32(8):1137–43.

    Article  PubMed  CAS  Google Scholar 

  43. Tan S, Chan WM, Wai MS, et al. Ketamine effects on the urogenital system—changes in the urinary bladder and sperm motility. Microsc Res Tech. 2011;74(12):1192–8.

    Article  PubMed  CAS  Google Scholar 

  44. Wang J, Chen Y, Gu D, Zhang G, Chen J, Zhao J, et al. Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-β1. Am J Physiol Renal Physiol. 2017;313(4):F961–72.

    Article  PubMed  Google Scholar 

  45. Yeung LY, Rudd JA, Lam WP, Mak YT, Yew DT. Mice are prone to kidney pathology after prolonged ketamine addiction. Toxicol Lett. 2009;191(2–3):275–8.

    Article  PubMed  CAS  Google Scholar 

  46. Wai MS, Chan WM, Zhang AQ, Wu Y, Yew DT. Long-term ketamine and ketamine plus alcohol treatments produced damages in liver and kidney. Hum Exp Toxicol. 2012;31(9):877–86.

    Article  PubMed  CAS  Google Scholar 

  47. Lo RS, Krishnamoorthy R, Freeman JG, Austin AS. Cholestasis and biliary dilatation associated with chronic ketamine abuse: a case series. Singap Med J. 2011;52(3):e52–5.

    CAS  Google Scholar 

  48. Yee CH, Lai PT, Lee WM, et al. Clinical outcome of a prospective case series of patients with ketamine cystitis who underwent standardized treatment protocol. Urology. 2015;86(2):236–43. Outcome of treatment from the largest prospective series of ketamine cystitis.

    Article  PubMed  Google Scholar 

  49. Lai Y, Wu S, Ni L, Chen Z, Li X, Yang S, et al. Ketamine-associated urinary tract dysfunction: an underrecognized clinical entity. Urol Int. 2012;89(1):93–6.

    Article  PubMed  CAS  Google Scholar 

  50. Middela S, Pearce I. Ketamine-induced vesicopathy: a literature review. Int J Clin Pract. 2011;65(1):27–30.

    Article  PubMed  CAS  Google Scholar 

  51. Raja H, Srirangam SJ, Pillai MK. Ketamine induced bladder dysfunction BJUI [Online] 2011 [accessed 2018 January 3]; Available from URL: http://www.bjui.org/ContentFullItem.aspx?id=629

  52. Oxley JD, Cottrell AM, Adams S, Gillatt D. Ketamine cystitis as a mimic of carcinoma in situ. Histopathology. 2009;55:705–8.

    Article  PubMed  Google Scholar 

  53. Ho CC, Pezhman H, Praveen S, Goh EH, Lee BC, Zulkifli MZ, et al. Ketamine-associated ulcerative cystitis: a case report and literature review. Malays J Med Sci. 2010;17(2):61–5.

    PubMed  PubMed Central  Google Scholar 

  54. Jalil R, Gupta S. Illicit ketamine and its bladder consequences: is it irreversible? BMJ Case Rep. 2012;2012:bcr2012007244.

    PubMed  PubMed Central  Google Scholar 

  55. Hopcroft SA, Cottrell AM, Mason K, Abrams P, Oxley JD. Ureteric intestinal metaplasia in association with chronic recreational ketamine abuse. J Clin Pathol. 2011;64(6):551–2.

    Article  PubMed  CAS  Google Scholar 

  56. Logan K, Gill P, Shaw C, et al. Users experience of ketamine bladder syndrome (KBS). Neurourol Urodyn. 2015;34(S3):47–8.

    Google Scholar 

  57. Cheung RYK, Chan SSC, Lee JHS, Pang AW, Choy KW, Chung TK. Urinary symptoms and impaired quality of life in female ketamine users: persistence after cessation of use. Hong Kong Med J. 2011;17:267–73.

    PubMed  CAS  Google Scholar 

  58. Chen R, Lee AM, Chan R et al. A study on the cognitive impairment and other harmful effects from ecstasy and ketamine abuse. Narcotics Division, Security Bureau. The Government of the Hong Kong Special Administrative Region. Narcotics Division 2004.

  59. Forster JA, Harrison SC. Ketamine uropathy: rising to the challenges of a new condition. BJU Int. 2012;109(9):1277–8.

    Article  PubMed  Google Scholar 

  60. Club drug clinic [Online]. 2018 [accessed 2018 January2 ]; Available from URL: http://clubdrugclinic.cnwl.nhs.uk/

  61. Smart C, Kabir M, Pati J. Treatment of ketamine-associated cystitis with chondroitin sulphate. Br J Nurs. 2013;22(18):S4. S6, S8-9

    Article  PubMed  Google Scholar 

  62. Zeng J, Lai H, Zheng D, Zhong L, Huang Z, Wang S, et al. Effective treatment of ketamine-associated cystitis with botulinum toxin type a injection combined with bladder hydrodistention. J Int Med Res. 2017;45(2):792–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Ng CF, Chiu PK, Li ML, et al. Clinical outcomes of augmentation cystoplasty in patients suffering from ketamine-related bladder contractures. Int Urol Nephrol. 2013;45(5):1245–51.

    Article  PubMed  CAS  Google Scholar 

  64. Jhang JF, Birder LA, Chancellor MB, Kuo HC. Patient characteristics for different therapeutic strategies in the management ketamine cystitis. Neurourol Urodyn. 2017;36(3):687–91.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Northern Devon Healthcare Trust, Raleigh Park, Barnstaple, EX31 4JB, UK

    Soumya Misra

Authors
  1. Soumya Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Soumya Misra.

Ethics declarations

Conflicts of Interest

The author declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards.

Additional information

This article is part of the Topical Collection on Overactive Bladder and Lower Urinary Tract Symptoms

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Misra, S. Ketamine-Associated Bladder Dysfunction—a Review of the Literature. Curr Bladder Dysfunct Rep 13, 145–152 (2018). https://doi.org/10.1007/s11884-018-0476-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11884-018-0476-1

Keywords

Search

Navigation