Analgesic Ketamine Use Leading to Cystectomy: A Case Report

Shahzad, Khurram; Švec, Alexandr; Alkoussayer, Omar; Harris, Maya; Fulford, Simon

doi:10.1016/j.bjmsu.2011.06.005

Cited by 10 publications

(3 citation statements)

References 19 publications

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“…Ketamine’s illicit status makes this a difficult patient group to study, and so the full extent and incidence of the problem within the population is unknown, and poor documentation of ketamine usage with respect to the development of functional/structural bladder changes has hindered the causal and staged mapping of the pathogenic pathway. Reports of urological symptoms in a minority of patients prescribed ketamine for chronic pain suggests that some individuals may be highly susceptible [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Nerve hyperplasia: a unique feature of ketamine cystitis

Baker

Stahlschmidt

Oxley

et al. 2013

acta neuropathol commun

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BackgroundThere is an emerging association between ketamine abuse and the development of urological symptoms including dysuria, frequency and urgency, which have a neurological component. In addition, extreme cases are associated with severe unresolving bladder pain in conjunction with a thickened, contracted bladder and an ulcerated/absent urothelium. Here we report on unusual neuropathological features seen by immunohistology in ketamine cystitis.ResultsIn all cases, the lamina propria was replete with fine neurofilament protein (NFP+) nerve fibres and in most patients (20/21), there was prominent peripheral nerve fascicle hyperplasia that showed particular resemblance to Morton’s neuroma. The nerve fascicles, which were positive for NFP, S100 and the p75 low-affinity nerve growth factor receptor (NGFR), were generally associated with a well-developed and in places, prominent, epithelial membrane antigen+/NGFR+ perineurium. This peripheral nerve fascicle hyperplasia is likely to account for the extreme pain experienced by ketamine cystitis patients. Urothelial damage was a notable feature of all ketamine cystitis specimens and where urothelium remained, increased NGFR expression was observed, with expansion from a basal-restricted normal pattern of expression into the suprabasal urothelium.ConclusionsThe histological findings were distinguishing features of ketamine cystitis and were not present in other painful bladder conditions. Ketamine cystitis afflicts predominantly young patients, with unknown long-term consequences, and requires a strategy to control severe bladder pain in order to remove a dependency on the causative agent. Our study indicates that the development of pain in ketamine cystitis is mediated through a specific neurogenic mechanism that may also implicate the urothelium.

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Section: Introductionmentioning

confidence: 99%

Nerve hyperplasia: a unique feature of ketamine cystitis

Baker

Stahlschmidt

Oxley

et al. 2013

acta neuropathol commun

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“…The prophylactic concurrent administration of a ketamine PO 240mg/24h for chronic back pain. 95 However, urinary symptoms developed after only 9 days in a 16 year-old receiving ketamine PO 8mg/kg/24h. 96 Urinary symptoms have been reported in abusers of 'street' ketamine, generally taken as powdered ketamine via nasal insufflation.…”

Section: Dose and Usementioning

confidence: 99%

Ketamine*

Quibell

Fallon

Mihalyo

et al. 2015

Journal of Pain and Symptom Management

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The use of ketamine is associated with neuropsychiatric, urinary tract and hepatobiliary toxicity. Although most reports involve long-term recreational abusers, it has also arisen after only 1e2 weeks of therapeutic use (Box A). Accordingly, the use of ketamine should be restricted to specialists in pain or palliative care for patients who have failed to obtain relief from standard drug and non-drug treatments.Class: General anesthetic.Indications: Induction and maintenance of anesthesia; yneuropathic, inflammatory, ischemic limb and procedure-related pain unresponsive to standard treatments. 1,2 Contra-indications: Any situation in which an increase in blood pressure would constitute a hazard. PharmacologyKetamine, a derivative of phencyclidine (PCP), is a dissociative anesthetic which has analgesic properties in subanaesthetic doses. 2,3 Ketamine is the most potent NMDA-receptor-channel blocker available for clinical use, binding to the PCP site when the channels are in the open activated state (Fig. 1). 3 It also binds to a second membrane-associated site which decreases the frequency of channel opening. 3 The NMDA receptor-channel complex is closely involved in the development of central sensitization of dorsal horn neurons which transmit pain signals. 4 At normal resting membrane potentials, the channel is blocked by magnesium and is inactive. 3 When the resting membrane potential is changed as a result of prolonged excitation, the channel unblocks and calcium moves into the cell. This leads to neuronal hyperexcitability and results in hyperalgesia and allodynia, and a reduction in opioid-responsiveness. These effects are probably mediated by the intracellular formation of nitric oxide and cyclic guanosine monophosphate. 3 The reduction in opioid-responsiveness arises from cross-talk between opioid receptors and the NMDA receptor-channel. Opioid receptor activation results in phosphorylation and opening of the NMDA receptorchannel leading to a cascade of events which ultimately down-regulates the opioid receptor and its effects, thereby contributing towards tolerance and hyperalgesia. 3

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“…In the context of rising recreational ketamine use, severe side effects affecting the human urinary tract have been reported, such as frequent and painful urination, haematuria, suprapubic pain and ulcerative cystitis (Shahani et al 2007;Ho et al 2010;Kalsi et al 2011;Middela and Pearce 2011;Morgan and Curran 2012). Both emergency cystectomy and an association with urothelial carcinoma (Oxley et al 2009; Morgan and Curran 2012) have been reported in both recreational (Chu et al 2008;Middela and Pearce 2011;Reinhardt and Fode 2014) and therapeutic use (Shahzad et al 2012) of ketamine. In addition, studies on the side effects of ketamine treatment for chronic pain confirmed that urinary symptoms can emerge after repeated administration in high doses (Storr & Quibell, 2009;Persson 2010).…”

Section: Introductionmentioning

confidence: 99%

Urothelial toxicity of esketamine in the treatment of depression

et al. 2020

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Rationale Ketamine is the first widely used substance with rapid-onset antidepressant action. However, there are uncertainties regarding its potential urothelial toxicity, particularly after repeated application. In the context of rising recreational ketamine use, severe side effects affecting the human urinary tract have been reported. It is assumed that ketamine interacts with bladder urothelial cells and induces apoptosis. Objectives This study aimed to assess whether single or repeated doses of esketamine used in an antidepressant indication are associated with urinary toxicity. Methods We included male and female inpatients with a current episode of depression and a diagnosis of recurrent depressive disorder, bipolar disorder or schizoaffective disorder according to ICD-10 criteria (n = 25). The esketamine treatment schedule involved a maximum of 3× weekly dosing at 0.25–0.5 mg/kg i.v. or s.c. The primary outcome was the change in urine toxicity markers (leukocytes, erythrocytes, protein and free haemoglobin). Description of demographic, clinical and laboratory data was conducted using means, standard deviations, frequencies and percentages. Changes in urinary toxicity markers over time were evaluated using linear mixed models with gender as a covariate. Results The participants received an average of 11.4 (SD 8) esketamine treatments, and an average number of 11.2 (SD 8) urine samples were analysed over the course of treatment. Neither urinary leukocyte concentration (F(20; 3.0) = 3.1; p = 0.2) nor erythrocyte concentration (F(20;2.2) = 4.1; p = 0.2) showed a significant trend towards increase during the course of esketamine treatment. Similarly, free haemoglobin and protein concentrations, which were analysed descriptively, did not display a rise during treatment. There was a significant improvement in depression ratings after esketamine treatment (p < 0.001). Conclusions This study is, to the best of our knowledge, the first to focus on urothelial toxicity of esketamine used in antidepressant indication and dose. The results indicate that the use of single or repeated doses of esketamine is unlikely to cause urothelial toxicity. The results are in need of confirmation as sample size was small.

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Analgesic Ketamine Use Leading to Cystectomy: A Case Report

Cited by 10 publications

References 19 publications

Nerve hyperplasia: a unique feature of ketamine cystitis

Nerve hyperplasia: a unique feature of ketamine cystitis

Ketamine*

Urothelial toxicity of esketamine in the treatment of depression

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