The prevalence and natural history of urinary symptoms among recreational ketamine users

Authors


Angela M. Cottrell, Bristol Urological Institute, Southmead Hospital, Bristol BS10 5NB, UK. e-mail: angecottrell@hotmail.com

Abstract

Study Type – Symptom prevalence (prospective cohort)

Level of Evidence 1b

What's known on the subject? and What does the study add?

Case series have described lower urinary tract symptoms associated with ketamine use including severe pain, frequency, haematuria and dysuria. Little is known regarding the frequency of symptoms, relationship of symptoms with dose and frequency of use and natural history of symptoms once the ketamine user has stopped.

This study describes the prevalence of ketamine use in a population of recreational drug users in a dance music setting. It shows a dose–frequency relationship with ketamine use. It shows that urinary symptoms associated with recreational ketamine use may lead to a considerable demand on health resources in the primary-, secondary- and emergency-care settings. It shows that symptoms may improve once ketamine use is decreased.

OBJECTIVE

  • • To investigate the prevalence and natural history of urinary symptoms in a cohort of recreational ketamine users.

PATIENTS AND METHODS

  • • A purposeful sampling technique was used.
  • • Between November 2009 and January 2010 participants were invited to undertake an on-line questionnaire promoted by a national dance music magazine and website.
  • • Data regarding demographics and illicit drug-use were collected.
  • • Among respondents reporting recent ketamine use, additional information detailing their ketamine use, experience of urinary symptoms and use of related healthcare services was obtained.

RESULTS

  • • In all, 3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine use within the last year.
  • • Of the ketamine users, 17% were found to be dependent on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary symptoms.
  • • Urinary symptoms were significantly related to both dose of ketamine used and frequency of ketamine use.
  • • Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% reported improvement in urinary symptoms upon cessation of use with only eight (3.8%) reporting deterioration after stopping use.

CONCLUSIONS

  • • Urinary tract symptoms are reported in over a quarter of regular ketamine users.
  • • A dose and frequency response relationship has been shown between ketamine use and urinary symptoms.
  • • Both users and primary-care providers need to be educated about urinary symptoms that may arise in ketamine users. A multi-disciplinary approach promoting harm reduction, cessation and early referral is needed to manage individuals with ketamine-associated urinary tract symptoms to avoid progression to severe and irreversible urological pathologies.
Abbreviations
DSM-IV

Diagnostic and Statistical Manual of Mental Disorders, 4th edition.

INTRODUCTION

Ketamine is a dissociative anaesthetic commonly used as a paediatric analgesic and anaesthetic and in the fields of emergency and obstetric medicine [1]. Over the last decade it has become increasingly prevalent in the UK especially among those involved in the dance and underground music scenes [2]. The non-medical use of ketamine has been illegal in the UK since it was classified as a Class C drug in 2006. In Hong Kong, ketamine is now the most common illicit drug of abuse after heroin [3]. Ampoules of the liquid anaesthetic may be dried to produce a powder which is then typically snorted but may alternatively be taken intravenously. Ketamine's effects are strongly dose related and include feelings of arousal and euphoria, out of body and near death experiences [4,5]. Often used in combination with other substances to modulate the effect [6], the major acute risks related to ketamine use are accidental trauma [7]. Clinically the most common acute presentations are related to transient and self-limiting cardiovascular stimulation [8], acute adverse psychological experiences [9], abdominal pain (‘k cramps’) and lower urinary tract symptoms (including frequency, urgency, suprapubic pain, dysuria and haematuria) [10–12]. Chronic use can lead to complications such as persistent urinary symptoms, upper tract involvement (including hydronephrosis and renal impairment) and when conservative management fails, surgical intervention in the form of cystectomy and urinary diversion may be necessary [11].

An increasing number of patients are presenting to urological services with ketamine-associated urinary symptoms, presenting a new clinical challenge to specialists. This has been recognized by BAUS and a national meeting has been organized to review current knowledge and further our understanding about this new condition. Lack of awareness of ketamine-associated pathology by general practitioners and urologists may mean that patients present at a relatively late stage. Some patients may not actively disclose their drug use. Symptoms may be severe and investigation of more recognizable pathology such as urinary tract infection or painful bladder syndrome may prove inconclusive and symptoms may persist.

There are few data available on the prevalence of urinary symptoms among ketamine users and the factors associated with their development. Given the relatively low level of use of ketamine among the general population (the recent British Crime Survey estimated ‘ever use’ at about 2% [13]) assessing the epidemiology of ketamine-associated urinary symptoms is best conducted among a population with higher rates of use. Drug users associated with the dance music scene and clubbing scene are one such population [14]. Such populations may be difficult to engage through traditional epidemiological public health surveillance and are poorly represented among those seeking drug treatment. As such they can be considered to be a relatively hidden and difficult-to-access group of drug users. More novel and collaborative approaches are therefore required. Although findings may be limited in their generalizability to other drug users within the population, this group represents a vulnerable cohort who are valuable in defining harms and identifying risk factors.

Our group has successfully used anonymous on-line surveys as a way of rapidly accessing large numbers of drug users from this sentinel drug-using population since 2002, identifying new drug trends and harms associated with a range of different substances [14–18]. The use of ketamine is particularly common among this population and between1999 and 2003 our group identified an increase in use by 50% per annum over a 5-year period [2]. As such, this population represents an ideal population in which to explore the prevalence and risk factors for the development of urinary harms related to the use of ketamine.

The aims of this current study were to assess the prevalence and patterns of ketamine use among a large cohort of current ketamine users and to determine the prevalence and correlates of urinary symptoms among this group. The subjects were recruited as part of our larger annual drug survey study assessing patterns of drug use and harms among those associated with the dance music scene.

METHODS

The research tool was an on line cross-sectional survey based on previous work by the research group [14–18] Using a previously established collaboration with a dance music publication called MixMag, our research questionnaire was heavily promoted on their website http://www.dontstayin.com (the surveys are available to view at http://www.globaldrugsurvey.com/mixmag). Ethical approval was received from the Joint South London and Maudsley and Institute of Psychiatry NHS Research Ethics Committee.

Core data regarding basic demographics and prevalence of lifetime (ever-used) and recent use (last year and days in the last month) of a large number of substances including ketamine were collected. Evidence for ketamine dependence was assessed. Among respondents reporting ketamine use within the last 12 months additional information was sought on the prevalence of a range of urinary symptoms, whether symptoms had persisted on cessation of use and whether medical help had been sought for symptoms.

Data were analysed using SPSS 15.0 for Windows (SPSS Inc., Chicago, IL, USA). For univariate comparisons, Pearson's chi-squared tests were used for categorical variables, unpaired t tests for normally distributed continuous variables, and Mann–Whitney U tests for continuous variables with skewed distributions.

RESULTS

A total of 3806 completed surveys was completed between 17 November 2010 and 4 January 2010. Of these, a total of 1947 (51.1%) reported ‘ever use’ of ketamine and 1285 (33.8%) participants reported use of ketamine within the last 12 months. Those who reported use within the last 12 months were directed to a series of questions further exploring their use of ketamine and their experience of problems associated with its use.

The sample was 1285 people reporting use of ketamine within the last 12 months. Of these, 80.3% (1032) were from the UK, 11.8% (151) were from the USA and 7.9% (102) were from elsewhere. The mean age was 23.5 years (sd 5.8), with mean age of first use being 20.42 (sd 4.3) years; 70.3% (869) were male; 92.6% (1144) were white; and 73.2% (873) were working. In all, 86.7% (1065) were heterosexual, 8.5% (105) were bisexual and 4.6% (59) were homosexual.

All ‘last 12 months’ users were asked to report on the typical amounts they used in a session, the maximum amount used in a session and also maximum number of consecutive days of use. Users were asked to select the dose that best described their typical session use from a number of fixed dose amounts. Subsequently, based on the normal distribution of responses, ketamine users were divided into low-use, medium-use and high-use typical dose groups: 31% (373) reported using 0.125 g or less during a typical session (low), 35% reported using 0.25 or 0.5 g (medium), with 34% (404) reporting use of 1 g or more (high) during a typical session. Some users (4.9%; 63) could not remember or did not know how much they took and 5.2% (67) reporting regularly taking ≥3 g in a session. In term of maximum amounts ever used, 54.2% (674) reported having ever taken a gram or more in a session, 24.6% (307) reported ≥3 g in a session and 6.6% (74) reported ever use of ≥5 g in a session.

With regards to frequency of use, the mean number of maximum number of consecutive days of use was 3.5 (modal 2), with 11.6% (143) reporting ever using on 7 days or more consecutively. Last-month users (792) were asked to report how many days they had used ketamine in the last month with a mean of 4.2 days (sd 4.87) with a modal of 1 day/month. Users were divided into low (1–4 days/month, 70% of subjects) medium (5–8 days/month, 15.6% of subjects) and high (≥9 days/month, equating to more than twice weekly, 13.4%). Route of use was only assessed for the subgroup of users for whom ketamine was the most recent drug they had taken for the first time (n= 307). Among this group 95% reported intranasal use.

All last-year users were also assessed for dependence using the seven Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for dependence [19]. These DSM-IV criteria were operationalized so as to provide a proxy measure for dependence. Given the diversity of the sample, additional markers of problematic use were also sought (personal concern over use, concern over use expressed by family or friends, a persistent desire or strong urge to use, desire to use less and desire for help to cut down). Using this proxy marker for the presence of dependence, 17% (218) of the sample could be considered as being dependent on ketamine (i.e. they reported experiencing three or more DSM symptoms together at some time in the last 12 months). Of last-month users, 22.7% (180) indicated that they would like to use less ketamine, with 5.9% (47) indicating that they would like help with their ketamine use. Dependence was strongly associated with amount (higher typical amounts used per session) (%, χ2= 170.9, P < 0.001) and frequency (days per month used) (%, χ2= 122.3 P < 0.001) of ketamine use.

Ketamine users tended to be experienced poly-drug users; last-year use was reported as 95.5% for 3,4-methylenedioxymethamphetamine (MDMA), 91.7% for cannabis, 78.7% for cocaine, 77.5% for tobacco, 66.5% for mephedrone, 32% for amphetamine and 27.5% for isopropyl nitrate (‘poppers’). In all, 98% reported last-year use of alcohol and were subsequently assessed with the brief alcohol screening tool the three-item AUDIT-C [20] (scoring 0–12, threshold for safe drinking is 3 for women, 4 for men). This assessment showed that 87.7% (323) of women and 93.4% (812) of men scored above the threshold for safe drinking with 35.3% (118) of women and 53.25% (463) of men scoring ≥8, indicating that they should be assessed for alcohol dependence. Almost a third, 31.2% (313), reported always drinking alcohol when they took ketamine, 13.4% (135) drank 75% of the time, 16.3% (165) drank 50% of the time, 20.4% (205) drank 25% of the time, and 18.6% (187) reported never drinking when they used ketamine. Men were significantly more likely to drink alcohol always or 75% of the time compared with women (44.6% versu 31.6%; P < 0.001) whereas women were significantly more likely to never drink alcohol when they used ketamine (30.8% versus 21.0%).

Ketamine users were asked whether they had experienced any of the following urinary symptoms associated with ketamine use in the last 12 months: pain in the lower abdomen; burning or stinging when passing urine; needing to pass urine frequently; leakage of urine (incontinence); or blood in the urine. In total, 340 (26.6%) participants reported experiencing at least one urinary symptom. The results are shown in Table 1. Using chi-squared analyses, there was no significant difference in the prevalence of any symptom between male and female participants.

Table 1.  Prevalence of urinary symptoms in ‘last-year’ ketamine users (n = 1285)
Symptom% (n) reporting ever experiencing that problem associated with ketamine in the last 12 months
Pain in the lower abdomen11.3 (145)
Burning or stinging when passing urine8.1 (104)
Needing to pass urine frequently17.4 (224)
Leakage of urine (incontinence)3.3 (43)
Blood in the urine1.5 (19)

Higher typical doses were associated with significantly higher rates of experiencing burning or stinging when passing urine (χ2= 37.95, P < 0.001), frequency of urination (χ2= 78.29, P < 0.001), lower abdominal pain (χ2= 39.0, P < 0.001), blood in the urine (χ2= 6.52, P= 0.038), leakage of urine (χ2= 7.44, P= 0.024).

More frequent use was also associated with significantly higher rates of lower abdominal pain (χ2= 52.0, P < 0.001), frequency of urination (χ2= 39.56, P < 0.001), experiencing burning or stinging when passing urine (χ2= 9.8, P= 0.007) but not blood in the urine (χ2= 0.62, P= 0.74), nor leakage of urine (χ2= 5.66, P= 0.06).

Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% (128) reported improvement in urinary symptoms upon cessation of use, 43% (108) reported that their symptoms had stayed the same while they had continued to use, with only 3.8% (8) reporting deterioration on stopping use. Of note there was no significant difference in any of these outcomes variables between high-use and low-use groups.

Subjects who had experienced urinary symptoms were also asked if they had sought help for their urinary problems. Of these, 10% (35) had sought help from their general practitioner, 2.9% (10) had been referred to specialist services and 1.8% (6) had attended accident and emergency departments.

DISCUSSION

This is the largest study to date assessing the prevalence of urinary symptoms in a large cohort of non-treatment-seeking ketamine users. This study clearly highlights that the harms to the urinary tract associated with ketamine are dose related and are particularly common among dependent users. Urinary symptoms are associated with an increased frequency of use and increased amount used per session. The study also indicates that in most individuals, cessation of ketamine use is associated with a cessation or improvement in symptoms; however, while ketamine use continues, symptoms may persist. In a few, symptoms may progress despite stopping drug use. Although the absolute number of individuals experiencing persisting urinary symptoms in the current sample was small, the symptoms were often troublesome enough for the participant to seek emergency or specialist help and over 1 in 10 sought advice from general practitioners.

This study is important because of the very limited data regarding the prevalence of medical problems associated with ketamine use. One cohort of 90 ketamine users (subdivided into frequent users, infrequent users and ex-ketamine users) described a highly significant decline in physical health among frequent ketamine users in over 70% of regular users [21]. Such physical sequelae include cystitis-like symptoms reported in 20% of frequent users, compared with 6.7% of infrequent users. The rate of urinary symptoms reported in frequent users is similar to our findings and supports our data showing an increased prevalence of urinary symptoms as the frequency of ketamine use increases. The absence of any association with gender should be noted.

With regards to the outcome of ketamine users experiencing urinary symptoms, it has been reported that symptoms may resolve with abstinence [11]. One survey of UK urologists showed that approximately one-third of cases of ketamine-associated urinary tract symptoms resolve after cessation, one-third remain static and one-third may progress [22]. This is similar to the current study in which over half of all users report an improvement in symptoms after stopping. While ketamine use continues, symptoms persist in approximately half of respondents. One study reported urinary symptoms in 13.3% of ex-ketamine users; however, reassuringly, in this study only a small proportion of current users describe a continuation of symptoms after cessation of ketamine use [21].

Ketamine users may seek medical advice regarding their urinary symptoms. In this study 10% of ketamine users experiencing urinary symptoms seek help from their general practitioners and 2.9% have subsequently been referred to urological services for further investigation. Symptoms were severe enough to warrant emergency department presentation in 1.8%. One study examined the emergency presentations of patients with a history of recent ketamine use and found that 12% of ketamine users presented acutely with urinary symptoms [10].

The high level of dependent use here may be an overestimation of the prevalence given the limitation of self-reported assessment and the use of a proxy measure of dependence as opposed to more clinically robust approaches that would have been reliant upon a full face-to-face assessment with a trained interviewer. However, the figure is not too dissimilar to the 22% of participants who reported that they would like to use less ketamine. Taken in combination with the 5% of users who indicated they would like help, there appears to be a need for liaison services between specialist drug treatment providers and their local urology services.

When judged against traditional epidemiological criteria for a good public health surveillance system this method has significant limitations, not least because it recruits from a self-nominating population that is relatively poorly characterized. In addition it relies upon population self-reported experiences with a substance of which the true composition is uncertain. High levels of poly-drug use, confounding effects from other substances on physical symptoms, uncertainty about dose quantification, purity of ketamine use and, most significantly, no information on route of use by the majority are also important. It is not possible therefore to exclude the possibility that intravenous use would be associated with higher risks. Given the more reinforcing effect of drugs obtained through injecting use one would expect there to be higher rates of dependence and associated problems among injectors. The study is also unable to exclude symptom misattribution, causation due to other substance use or acute poly-drug and or alcohol consumption or symtoms may be a result of other pre-existing pathologies.

It is clear that at present our understanding of ketamine-associated urinary tract pathology is limited but increasing. Case studies have provided us with a further knowledge of the symptomatology and complications of ketamine use and this study provides an insight into the scale of the problem in a drug-using population. The characteristic radiological features of ketamine use have been described showing lower tract changes such as bladder wall thickening and peri-vesical stranding and upper tract abnormalities including hydronephrosis and ureteric thickening. The pathological changes associated with ketamine use are well recognized as mucosal irritation, reactive atypia and eosinophilic lamina propria inflammation. The pathological mechanism of ketamine on the urinary tract is unknown. A number of theories have been postulated including direct damage to the urothelium by ketamine or its metabolites, microvascular changes associated with urinary ketamine or an autoimmune mechanism. An in vitro study has shown a novel receptor-mediated mechanism leading to the cytotoxic effect of ketamine on the urothelium. It is hoped that the collaboration of urologists, research scientists and addiction professionals facilitated by the BAUS will provide further insight into ketamine and urinary pathology.

This study shows the link between ketamine and urinary symptoms. There has been little information in the literature to inform healthcare professionals regarding the scale of the problem and potential natural history. Although treatment options for ketamine-associated urinary tract pathology are either symptomatic (in the form of analgesia, urinary diversion) or treat complications (such as percutaneous nephrostomy insertion) strategies are limited when individuals continue to use ketamine [22]. This study illustrated the problem of ketamine dependence and urinary symptoms. Both users and primary-care providers need to be educated about urinary symptoms that may arise in ketamine users [12]. A multi-disciplinary approach promoting harm reduction, cessation and early referral is needed to manage individuals with ketamine-associated urinary tract symptoms to avoid progression to severe and irreversible urological pathologies.

CONFLICT OF INTEREST

None declared.

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