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Review

The clinical toxicology of ketamine

, , , &
Pages 415-428 | Received 20 Oct 2022, Accepted 04 May 2023, Published online: 02 Jun 2023

References

  • Wolff K, Winstock AR. Ketamine: from medicine to misuse. CNS Drugs. 2006;20(3):199–218.
  • WHO. WHO model list of essential medicines, 22nd list. Geneva: World Health Organization. 2021 [cited 2023 Apr 14]. Available from: https://apps.who.int/iris/rest/bitstreams/1374779/retrieve
  • McEvoy GK, editor. AHFS drug information on ketamine. Bethesda (MD): American Society of Hospital Pharmacists; 2022.
  • Corazza O, Assi S, Schifano F. From “special K” to “special M”: the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther. 2013;19(6):454–460.
  • Jansen KL. Non-medical use of ketamine. BMJ. 1993;306(6878):601–602.
  • Papich MG. Saunders handbook of veterinary drugs: small and large animal. 3rd ed. Philadelphia (PA): Elsevier/Saunders; 2011.
  • Hansch C, Leo A, Hoekman D. Exploring QSAR. Hydrophobic, electronic, and steric constants. Washington (DC): American Chemical Society; 1995.
  • O'Neil MJ, editor. The merck index – an encyclopedia of chemicals, drugs, and biologicals. 14th ed. Whitehouse Station (NJ): Merck Research Laboratories; 2013.
  • Domino EF. History and pharmacology of PCP and PCP-related analogs. J Psychedelic Drugs. 1980;12(3–4):223–227.
  • Greifenstein FE, Devault M, Yoshitake J, et al. A study of a 1-aryl cyclo hexyl amine for anesthesia. Anesth Analg. 1958;37(5):283–294.
  • Corssen G, Domino EF. Dissociative anesthesia: further pharmacologic studies and first clinical experience with the phencyclidine derivative CI-581. Anesth Analg. 1966;45(1):29–40.
  • Siegel RK. Phencyclidine and ketamine intoxication: a study of four populations of recreational users. NIDA Res Monogr. 1978;21:119–147.
  • Kidd LR, Lyons SC, Lloyd G. Paediatric procedural sedation using ketamine in a UK emergency department: a 7 year review of practice. Br J Anaesth. 2016;116(4):518–523.
  • Merelman AH, Perlmutter MC, Strayer RJ. Alternatives to rapid sequence intubation: contemporary airway management with ketamine. West J Emerg Med. 2019;20(3):466–471.
  • Morgan MM, Perina DG, Acquisto NM, et al. Ketamine use in prehospital and hospital treatment of the acute trauma patient: a joint position statement. Prehosp Emerg Care. 2021;25(4):588–592.
  • Fernandez AR, Bourn SS, Crowe RP, et al. Out-of-hospital ketamine: indications for use, patient outcomes, and associated mortality. Ann Emerg Med. 2021;78(1):123–131.
  • Isoardi KZ, Parker LE, Page CB, et al. Ketamine as a rescue treatment for severe acute behavioural disturbance: a prospective prehospital study. Emerg Med Australas. 2021;33(4):610–614.
  • Abbar M, Demattei C, El-Hage W, et al. Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. BMJ. 2022;376:e067194.
  • Mills IH, Park GR, Manara AR, et al. Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions. QJM. 1998;91(7):493–503.
  • Cvrcek P. Side effects of ketamine in the long-term treatment of neuropathic pain. Pain Med. 2008;9(2):253–257.
  • Sigtermans MJ, van Hilten JJ, Bauer MCR, et al. Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain. 2009;145(3):304–311.
  • Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014;77(2):357–367.
  • Fang Y, Wang X. Ketamine for the treatment of refractory status epilepticus. Seizure. 2015;30:14–20.
  • Jacobwitz M, Mulvihill C, Kaufman MC, et al. Ketamine for management of neonatal and pediatric refractory status epilepticus. Neurology. 2022;99(12):e1227–e1238.
  • Reier CE. Ketamine “dissociative agent” or hallucinogen? N Engl J Med. 1971;284(14):791–792.
  • Jansen KL. A review of the nonmedical use of ketamine: use, users and consequences. J Psychoactive Drugs. 2000;32(4):419–433.
  • Kalsi SS, Wood DM, Dargan PI. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use. Emerg Health Threats J. 2011;4:7107.
  • Barrett SP, Gross SR, Garand I, et al. Patterns of simultaneous polysubstance use in Canadian rave attendees. Subst Use Misuse. 2005;40(9–10):1525–1537.
  • Hong YL, Yee CH, Tam YH, et al. Management of complications of ketamine abuse: 10 years’ experience in Hong Kong. Hong Kong Med J. 2018;24(2):175–181.
  • Palamar JJ, Keyes KM. Trends in drug use among electronic dance music party attendees in New York city, 2016–2019. Drug Alcohol Depend. 2020;209:107889.
  • Yockey RA. Past-year ketamine use: evidence from a United States population, 2015–2019. J Psychoactive Drugs. 2022;29:1–7.
  • EMCDDA. European drug report 2019: trends and developments. Luxembourg: Publications Office of the European Union. 2019 [cited 2022 May 27]. Available from: https://www.emcdda.europa.eu/system/files/publications/11364/20191724_TDAT19001ENN_PDF.pdf
  • EMCDDA. European drug report 2021: trends and developments. Luxembourg: Publications Office of the European Union. 2021 [cited 2022 Dec 20]. Available from: https://www.emcdda.europa.eu/system/files/publications/14644/TDAT22001ENN.pdf
  • Anis NA, Berry SC, Burton NR, et al. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol. 1983;79(2):565–575.
  • Zanos P, Moaddel R, Morris PJ, et al. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol Rev. 2018;70(3):621–660.
  • Sleigh J, Harvey M, Voss L, et al. Ketamine – more mechanisms of action than just NMDA blockade. Trends Anaesth Crit Care. 2014;4(2–3):76–81.
  • Ebert B, Mikkelsen S, Thorkildsen C, et al. Norketamine, the main metabolite of ketamine, is a non-competitive NMDA receptor antagonist in the rat cortex and spinal cord. Eur J Pharmacol. 1997;333(1):99–104.
  • Sinner B, Graf BM. Ketamine. Handb Exp Pharmacol. 2008;182:313–333.
  • Stein C. Opioid receptors. Annu Rev Med. 2016;67:433–451.
  • Hirota K, Okawa H, Appadu BL, et al. Stereoselective interaction of ketamine with recombinant mu, kappa, and delta opioid receptors expressed in Chinese hamster ovary cells. Anesthesiology. 1999;90(1):174–182.
  • Mathisen LC, Skjelbred P, Skoglund LA, et al. Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain. 1995;61(2):215–220.
  • Mikkelsen S, Ilkjaer S, Brennum J, et al. The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side effects in humans. Anesthesiology. 1999;90(6):1539–1545.
  • Sohnen S, Dowling O, Shore-Lesserson L. Single dose perioperative intrathecal ketamine as an adjuvant to intrathecal bupivacaine: a systematic review and meta-analysis of adult human randomized controlled trials. J Clin Anesth. 2021;73:110331.
  • Chang X, Wang J, Jiang H, et al. Hyperpolarization-activated cyclic nucleotide-gated channels: an emerging role in neurodegenerative diseases. Front Mol Neurosci. 2019;12:141.
  • Schwenk ES, Pradhan B, Nalamasu R, et al. Ketamine in the past, present, and future: mechanisms, metabolites, and toxicity. Curr Pain Headache Rep. 2021;25(9):57.
  • Martin LL, Bouchal RL, Smith DJ. Ketamine inhibits serotonin uptake in vivo. Neuropharmacology. 1982;21(2):113–118.
  • Robson MJ, Elliott M, Seminerio MJ, et al. Evaluation of sigma (σ) receptors in the antidepressant-like effects of ketamine in vitro and in vivo. Eur Neuropsychopharmacol. 2012;22(4):308–317.
  • Grant IS, Nimmo WS, Clements JA. Pharmacokinetics and analgesic effects of i.m. and oral ketamine. Br J Anaesth. 1981;53(8):805–810.
  • Clements JA, Nimmo WS, Grant IS. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharm Sci. 1982;71(5):539–542.
  • Yanagihara Y, Ohtani M, Kariya S, et al. Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers. Biopharm Drug Dispos. 2003;24(1):37–43.
  • Malinovsky JM, Servin F, Cozian A, et al. Ketamine and norketamine plasma concentrations after i.v., nasal and rectal administration in children. Br J Anaesth. 1996;77(2):203–207.
  • Peltoniemi MA, Saari TI, Hagelberg NM, et al. S-ketamine concentrations are greatly increased by grapefruit juice. Eur J Clin Pharmacol. 2012;68(6):979–986.
  • Idvall J, Holasek J, Stenberg P. Rectal ketamine for induction of anaesthesia in children. Anaesthesia. 1983;38(1):60–64.
  • Pedraz JL, Calvo MB, Lanao JM, et al. Pharmacokinetics of rectal ketamine in children. Br J Anaesth. 1989;63(6):671–674.
  • Pedraz JL, Lanao JM, Calvo MB, et al. Pharmacokinetic and clinical evaluation of ketamine administered by i.v. and epidural routes. Int J Clin Pharmacol Ther Toxicol. 1987;25(2):77–80.
  • Dayton PG, Stiller RL, Cook DR, et al. The binding of ketamine to plasma proteins: emphasis on human plasma. Eur J Clin Pharmacol. 1983;24(6):825–831.
  • Tyler MW, Yourish HB, Ionescu DF, et al. Classics in chemical neuroscience: ketamine. ACS Chem Neurosci. 2017;8(6):1122–1134.
  • Clements JA, Nimmo WS. Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth. 1981;53(1):27–30.
  • Domino EF, Domino SE, Smith RE, et al. Ketamine kinetics in unmedicated and diazepam-premedicated subjects. Clin Pharmacol Ther. 1984;36(5):645–653.
  • Fanta S, Kinnunen M, Backman JT, et al. Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing. Eur J Clin Pharmacol. 2015;71(4):441–447.
  • Geisslinger G, Hering W, Thomann P, et al. Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method. Br J Anaesth. 1993;70(6):666–671.
  • Grant IS, Nimmo WS, McNicol LR, et al. Ketamine disposition in children and adults. Br J Anaesth. 1983;55(11):1107–1111.
  • Hijazi Y, Bodonian C, Bolon M, et al. Pharmacokinetics and haemodynamics of ketamine in intensive care patients with brain or spinal cord injury. Br J Anaesth. 2003;90(2):155–160.
  • White PF, Schüttler J, Shafer A, et al. Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth. 1985;57(2):197–203.
  • Huge V, Lauchart M, Magerl W, et al. Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain. Eur J Pain. 2010;14(4):387–394.
  • Peltoniemi MA, Hagelberg NM, Olkkola KT, et al. Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clin Pharmacokinet. 2016;55(9):1059–1077.
  • Wieber J, Gugler R, Hengstmann JH, et al. Pharmacokinetics of ketamine in man. Anaesthesist. 1975;24(6):260–263.
  • Ellingson A, Haram K, Sagen N, et al. Transplacental passage of ketamine after intravenous administration. Acta Anaesthesiol Scand. 1977;21(1):41–44.
  • Mitchell J, Jones W, Winkley E, et al. Guideline on anaesthesia and sedation in breastfeeding women 2020: guideline from the association of anaesthetists. Anaesthesia. 2020;75(11):1482–1493.
  • Hijazi Y, Boulieu R. Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab Dispos. 2002;30(7):853–858.
  • Yanagihara Y, Kariya S, Ohtani M, et al. Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. Drug Metab Dispos. 2001;29(6):887–890.
  • Leung LY, Baillie TA. Comparative pharmacology in the rat of ketamine and its two principal metabolites, norketamine and (Z)-6-hydroxynorketamine. J Med Chem. 1986;29(11):2396–2399.
  • Moaddel R, Abdrakhmanova G, Kozak J, et al. Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors. Eur J Pharmacol. 2013;698(1–3):228–234.
  • Köppel C, Arndt I, Ibe K. Effects of enzyme induction, renal and cardiac function on ketamine plasma kinetics in patients with ketamine long-term analgosedation. Eur J Drug Metab Pharmacokinet. 1990;15(3):259–263.
  • Peltoniemi MA, Saari TI, Hagelberg NM, et al. St John’s wort greatly decreases the plasma concentrations of oral S-ketamine. Fundam Clin Pharmacol. 2012;26(6):743–750.
  • Peltoniemi MA, Saari TI, Hagelberg NM, et al. Rifampicin has a profound effect on the pharmacokinetics of oral S-ketamine and less on intravenous S-ketamine. Basic Clin Pharmacol Toxicol. 2012;111(5):325–332.
  • Hagelberg NM, Peltoniemi MA, Saari TI, et al. Clarithromycin, a potent inhibitor of CYP3A, greatly increases exposure to oral S-ketamine. Eur J Pain. 2010;14(6):625–629.
  • Peltoniemi MA, Saari TI, Hagelberg NM, et al. Exposure to oral S-ketamine is unaffected by itraconazole but greatly increased by ticlopidine. Clin Pharmacol Ther. 2011;90(2):296–302.
  • Chan WH, Sun WZ, Ueng TH. Induction of rat hepatic cytochrome P-450 by ketamine and its toxicological implications. J Toxicol Environ Health A. 2005;68(17–18):1581–1597.
  • Dinis-Oliveira RJ. Metabolism and metabolomics of ketamine: a toxicological approach. Forensic Sci Res. 2017;2(1):2–10.
  • Parkin MC, Turfus SC, Smith NW, et al. Detection of ketamine and its metabolites in urine by ultra high pressure liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;876(1):137–142.
  • Wang J, Huang J, Yang S, et al. Pharmacokinetics and safety of esketamine in Chinese patients undergoing painless gastroscopy in comparison with ketamine: a randomized, open-label clinical study. Drug Des Devel Ther. 2019;13:4135–4144.
  • Ihmsen H, Geisslinger G, Schüttler J. Stereoselective pharmacokinetics of ketamine: r (−)-ketamine inhibits the elimination of S(+)-ketamine. Clin Pharmacol Ther. 2001;70(5):431–438.
  • Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994;51(3):199–214.
  • Melendez E, Bachur R. Serious adverse events during procedural sedation with ketamine. Pediatr Emerg Care. 2009;25(5):325–328.
  • Laskowski K, Stirling A, McKay WP, et al. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011;58(10):911–923.
  • Schwenk ES, Goldberg SF, Patel RD, et al. Adverse drug effects and preoperative medication factors related to perioperative low-dose ketamine infusions. Reg Anesth Pain Med. 2016;41(4):482–487.
  • Bell RF, Dahl JB, Moore RA, et al. Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (cochrane review). Acta Anaesthesiol Scand. 2005;49(10):1405–1428.
  • Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol. 2016;54(7):556–562.
  • Green SM, Roback MG, Krauss B. Laryngospasm during emergency department ketamine sedation: a case-control study. Pediatr Emerg Care. 2010;26(11):798–802.
  • Lim DK. Ketamine associated psychedelic effects and dependence. Singapore Med J. 2003;44(1):31–34.
  • Kamaya H, Krishna PR. Ketamine addiction. Anesthesiology. 1987;67(5):861–862.
  • Ahmed SN, Petchkovsky L. Abuse of ketamine. Br J Psychiatry. 1980;137:303.
  • Chang F, Xu K, Huang MC, et al. Alcohol triggers reemergence of ketamine-like experience in a ketamine ex-user. J Clin Psychopharmacol. 2017;37(1):110–112.
  • Jansen KL. Ketamine–can chronic use impair memory? Int J Addict. 1990;25(2):133–139.
  • Gaulier JM, Canal M, Pradeille JL, et al. Rave parties: ketamine and prolintane. Acta Clin Belg. 2002;57(Suppl 1):41–46.
  • Ng SH, Tse ML, Ng HW, et al. Emergency department presentation of ketamine abusers in Hong Kong: a review of 233 cases. Hong Kong Med J. 2010;16(1):6–11.
  • Weiner AL, Vieira L, McKay CA, et al. Ketamine abusers presenting to the emergency department: a case series. J Emerg Med. 2000;18(4):447–451.
  • Green SM, Clark R, Hostetler MA, et al. Inadvertent ketamine overdose in children: clinical manifestations and outcome. Ann Emerg Med. 1999;34(4 Pt 1):492–497.
  • Wood DM, Bishop CR, Green SL, et al. Ketamine related toxicology presentations to the ED [abstract]. Clin Toxicol. 2008;46(7):630.
  • Felser JM, Orban DJ. Dystonic reaction after ketamine abuse. Ann Emerg Med. 1982;11(12):673–675.
  • Unintentional ketamine overdose in the operating room – mixing up the ampules. Aorn J. 2022;115(5):498–499.
  • Schifano F, Corkery J, Oyefeso A, et al. Trapped in the “K-hole”: overview of deaths associated with ketamine misuse in the UK (1993–2006). J Clin Psychopharmacol. 2008;28(1):114–116.
  • Capapé S, Mora E, Mintegui S, et al. Prolonged sedation and airway complications after administration of an inadvertent ketamine overdose in emergency department. Eur J Emerg Med. 2008;15(2):92–94.
  • Zsigmond EK, Matsuki A, Kothary SP, et al. Arterial hypoxemia caused by intravenous ketamine. Anesth Analg. 1976;55(3):311–314.
  • Jonnavithula N, Kulkarni DK, Ramachandran G. Prolonged apnea with intramuscular ketamine: a case report. Paediatr Anaesth. 2008;18(4):330–331.
  • Smith JA, Santer LJ. Respiratory arrest following intramuscular ketamine injection in a 4-year-old child. Ann Emerg Med. 1993;22(3):613–615.
  • Pandey CK, Mathur N, Singh N, et al. Fulminant pulmonary edema after intramuscular ketamine. Can J Anaesth. 2000;47(9):894–896.
  • Gill JR, Stajíc M. Ketamine in non-hospital and hospital deaths in New York city. J Forensic Sci. 2000;45(3):655–658.
  • Lee CW, Chao YY, Shiea J, et al. Ambient mass spectrometry for rapid diagnosis of psychoactive drugs overdose in an unstable patient. Am J Emerg Med. 2018;36(3):530.e1–530.e5.
  • Darke S, Duflou J, Farrell M, et al. Characteristics and circumstances of death related to the self-administration of ketamine. Addiction. 2021;116(2):339–345.
  • Dillon P, Copeland J, Jansen K. Patterns of use and harms associated with non-medical ketamine use. Drug Alcohol Depend. 2003;69(1):23–28.
  • Licata M, Pierini G, Popoli G. A fatal ketamine poisoning. J Forensic Sci. 1994;39(5):1314–1320.
  • Tao Y, Chen XP, Qin ZH. A fatal chronic ketamine poisoning. J Forensic Sci. 2005;50(1):173–176.
  • Lalonde BR, Wallage HR. Postmortem blood ketamine distribution in two fatalities. J Anal Toxicol. 2004;28(1):71–74.
  • Li CC, Wu ST, Cha TL, et al. A survey for ketamine abuse and its relation to the lower urinary tract symptoms in Taiwan. Sci Rep. 2019;9(1):7240.
  • Humphries Y, Melson M, Gore D. Superiority of oral ketamine as an analgesic and sedative for wound care procedures in the pediatric patient with burns. J Burn Care Rehabil. 1997;18(1 Pt 1):34–36.
  • Hansen G, Jensen SB, Chandresh L, et al. The psychotropic effect of ketamine. J Psychoactive Drugs. 1988;20(4):419–425.
  • Davis J, Bates L. Rapid sequence induction via an intraosseous needle. J Intensive Care Soc. 2016;17(2):178–179.
  • Drapkin J, Masoudi A, Butt M, et al. Administration of nebulized ketamine for managing acute pain in the emergency department: a case series. Clin Pract Cases Emerg Med. 2020;4(1):16–20.
  • Chan KW, Lee TM, Siu AM, et al. Effects of chronic ketamine use on frontal and medial temporal cognition. Addict Behav. 2013;38(5):2128–2132.
  • Tang WK, Liang HJ, Lau CG, et al. Relationship between cognitive impairment and depressive symptoms in current ketamine users. J Stud Alcohol Drugs. 2013;74(3):460–468.
  • Zhang C, Xu Y, Zhang B, et al. Cognitive impairment in chronic ketamine abusers. Psychiatry Res. 2020;291:113206.
  • Ke X, Ding Y, Xu K, et al. The profile of cognitive impairments in chronic ketamine users. Psychiatry Res. 2018;266:124–131.
  • Morgan CJ, Muetzelfeldt L, Curran HV. Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls. Addiction. 2009;104(1):77–87.
  • Morgan CJ, Dodds CM, Furby H, et al. Long-Term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation. Front Psychiatry. 2014;5:149.
  • Wang C, Zheng D, Xu J, et al. Brain damages in ketamine addicts as revealed by magnetic resonance imaging. Front Neuroanat. 2013;7:23.
  • Tang WK, Lau CG, Ungvari GS, et al. Recovery of cognitive functioning following abstinence from ketamine. Addict Behav. 2019;99:106081.
  • Grégoire MC, MacLellan DL, Finley GA. A pediatric case of ketamine-associated cystitis (letter-to-the-Editor RE: shahani R, streutker C, dickson B, et al: ketamine-associated ulcerative cystitis: a new clinical entity. Urology 69: 810-812, 2007). Urology. 2008;71(6):1232–1233.
  • Storr TM, Quibell R. Can ketamine prescribed for pain cause damage to the urinary tract? Palliat Med. 2009;23(7):670–672.
  • 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):311–313.
  • 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(11):1616–1622.
  • Ho CC, Pezhman H, Praveen S, et al. Ketamine-associated ulcerative cystitis: a case report and literature review. Malays J Med Sci. 2010;17(2):61–65.
  • Hopcroft SA, Cottrell AM, Mason K, et al. Ureteric intestinal metaplasia in association with chronic recreational ketamine abuse. J Clin Pathol. 2011;64(6):551–552.
  • Robles-Martinez M, Abad AC, Perez-Rodriguez V, et al. Delayed urinary symptoms induced by ketamine. J Psychoactive Drugs. 2018;50(2):129–132.
  • Srirangam S, Mercer J. Ketamine bladder syndrome: an important differential diagnosis when assessing a patient with persistent lower urinary tract symptoms. BMJ Case Rep. 2012;2012:bcr2012006447.
  • Tsai JH, Tsai KB, Jang MY. Ulcerative cystitis associated with ketamine. Am J Addict. 2008;17(5):453.
  • Chen CH, Lee MH, Chen YC, et al. Ketamine-snorting associated cystitis. J Formos Med Assoc. 2011;110(12):787–791.
  • 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.
  • Winstock AR, Mitcheson L, Gillatt DA, et al. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int. 2012;110(11):1762–1766.
  • Clemens JQ, Erickson DR, Varela NP, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022;208(1):34–42.
  • Chiew YW, Yang CS. Disabling frequent urination in a young adult. Ketamine-associated ulcerative cystitis. Kidney Int. 2009;76(1):123–124.
  • Misra S, Chetwood A, Coker C, et al. Ketamine cystitis: practical considerations in management. Scand J Urol. 2014;48(5):482–488.
  • 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):185–190.
  • Lai Y, Wu S, Ni L, et al. Ketamine-associated urinary tract dysfunction: an underrecognized clinical entity. Urol Int. 2012;89(1):93–96.
  • Mason K, Cottrell AM, Corrigan AG, et al. Ketamine-associated lower urinary tract destruction: a new radiological challenge. Clin Radiol. 2010;65(10):795–800.
  • Noorzurani R, Vicknasingam B, Narayanan S. Illicit ketamine induced frequency of micturition in a young malay woman. Drug Alcohol Rev. 2010;29(3):334–336.
  • Jalil R, Gupta S. Illicit ketamine and its bladder consequences: is it irreversible? BMJ Case Rep. 2012;2012:bcr2012007244.
  • Oxley JD, Cottrell AM, Adams S, et al. Ketamine cystitis as a mimic of carcinoma in situ. Histopathology. 2009;55(6):705–708.
  • Shahani R, Streutker C, Dickson B, et al. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007;69(5):810–812.
  • Jhang J-F, Hsu Y-H, Jiang Y-H, et al. Histopathological characteristics of ketamine-associated uropathy and their clinical association. Neurourol Urodyn. 2018;37(5):1764–1772.
  • Lo RS, Krishnamoorthy R, Freeman JG, et al. Cholestasis and biliary dilatation associated with chronic ketamine abuse: a case series. Singapore Med J. 2011;52(3):e52–e55.
  • Vu DM, Freyre K, Opsha O, et al. Recreational ketamine-induced cholangiopathy and ulcerative cystitis. Am J Emerg Med. 2021;45:682.e7–682.e9.
  • Wong GL, Tam YH, Ng CF, et al. Liver injury is common among chronic abusers of ketamine. Clin Gastroenterol Hepatol. 2014;12(10):1759–1762.
  • Ng SH, Lee HK, Chan YC, et al. Dilated common bile ducts in ketamine abusers. Hong Kong Med J. 2009;15(2):157.
  • Wong SW, Lee KF, Wong J, et al. Dilated common bile ducts mimicking choledochal cysts in ketamine abusers. Hong Kong Med J. 2009;15(1):53–56.
  • Selby NM, Anderson J, Bungay P, et al. Obstructive nephropathy and kidney injury associated with ketamine abuse. NDT Plus. 2008;1(5):310–312.
  • Bevan R, Burke D. Ketamine as a possible cause of cirrhosis in a patient with chronic pain. Frontline Gastroenterol. 2014;5(3):208–210.
  • Yu WL, Cho CC, Lung PF, et al. Ketamine-related cholangiopathy: a retrospective study on clinical and imaging findings. Abdom Imaging. 2014;39(6):1241–1246.
  • Seto WK, Ng M, Chan P, et al. Ketamine-induced cholangiopathy: a case report. Am J Gastroenterol. 2011;106(5):1004–1005.
  • Lui KL, Lee WK, Li MK. Ketamine-induced cholangiopathy. Hong Kong Med J. 2014;20(1):78.e1–78.e2.
  • Keta-Cov Research Group. Intravenous ketamine and progressive cholangiopathy in COVID-19 patients. J Hepatol. 2021;74(5):1243–1244.
  • Wendel-Garcia PD, Erlebach R, Hofmaenner DA, et al. Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome. Crit Care. 2022;26(1):148.
  • Noppers IM, Niesters M, Aarts L, et al. Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: a report of 3 cases. Pain. 2011;152(9):2173–2178.
  • Pavarin RM, Marani S, Turino E. Ketamine abusers referring to emergency departments in Northern Italy: a cross- sectional study. Ann Ist Super Sanita. 2019;55(4):338–344.
  • Poon TL, Wong KF, Chan MY, et al. Upper gastrointestinal problems in inhalational ketamine abusers. J Dig Dis. 2010;11(2):106–110.
  • Moreton JE, Meisch RA, Stark L, et al. Ketamine self-administration by the rhesus monkey. J Pharmacol Exp Ther. 1977;203(2):303–309.
  • Bonnet U. Long-term ketamine self-injections in major depressive disorder: focus on tolerance in ketamine’s antidepressant response and the development of ketamine addiction. J Psychoactive Drugs. 2015;47(4):276–285.
  • Morgan CJ, Curran HV. Ketamine use: a review. Addiction. 2012;107(1):27–38.
  • Cumming JF. The development of an acute tolerance to ketamine. Anesth Analg. 1976;55(6):788–791.
  • Roxas N, Ahuja C, Isom J, et al. A potential case of acute ketamine withdrawal: clinical implications for the treatment of refractory depression. Am J Psychiatry. 2021;178(7):588–591.
  • Connors NJ, Grino A, Tunik MG, et al. Chronic hematuria and abdominal pain. Clin Toxicol. 2014;52(3):231–232.
  • Zhou J, Shaw SG, Gilleece Y. Dilated common bile duct and deranged liver function tests associated with ketamine use in two HIV-positive MSM. Int J STD AIDS. 2013;24(8):667–669.
  • Bénichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990;11(2):272–276.
  • Kim JY, In MK, Kim JH. Determination of ketamine and norketamine in hair by gas chromatography/mass spectrometry using two-step derivatization. Rapid Commun Mass Spectrom. 2006;20(20):3159–3162.
  • Xiang P, Shen M, Zhuo X. Hair analysis for ketamine and its metabolites. Forensic Sci Int. 2006;162(1–3):131–134.
  • Wang X, Johansen SS, Nielsen MKK, et al. Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period. Forensic Sci Int. 2018;285:e1–e12.
  • Cooper GA, Kronstrand R, Kintz P. Society of hair testing guidelines for drug testing in hair. Forensic Sci Int. 2012;218(1–3):20–24.
  • Chen KT, Foo NP, Lin HJ. Frequent visits with urinary symptoms: subtle signs of ketamine abuse. Am J Emerg Med. 2008;26(9):1061–1062.
  • Corkery JM, Hung WC, Claridge H, et al. Recreational ketamine-related deaths notified to the national programme on substance abuse deaths, England, 1997–2019. J Psychopharmacol. 2021;35(11):1324–1348.
  • Grunwell JR, Travers C, McCracken CE, et al. Procedural sedation outside of the operating room using ketamine in 22,645 children: a report from the pediatric sedation research consortium. Pediatr Crit Care Med. 2016;17(12):1109–1116.
  • Green SM, Roback MG, Krauss B, et al. Predictors of airway and respiratory adverse events with ketamine sedation in the emergency department: an individual-patient data meta-analysis of 8,282 children. Ann Emerg Med. 2009;54(2):158–168.
  • Hampson-Evans D, Morgan P, Farrar M. Pediatric laryngospasm. Paediatr Anaesth. 2008;18(4):303–307.
  • Liu HT, Kuo HC. Intravesical botulinum toxin a injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007;70(3):463–468.
  • EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–267.

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