Ketamine is popularly referred to as a ‘horse tranquilliser’ and commonly assumed to be used primarily in veterinary medicine. In fact, ketamine, which was first synthesised in 1964, is used in both human and veterinary medicine because of its anaesthetic and analgesic properties (Wood et al, 2011). It is the drug of choice on the battle field and was used extensively in the Vietnam War (Jhang et al, 2015) because it does not suppress respiration or lower heart rate while producing analgesia and amnesia (Morgan and Curran, 2011; Niesters et al, 2013).

 

‘... although the agitation, panic attacks, hallucinations and dissociative effects associated with the drug limit its clinical use, it is these psychedelic effects that make ketamine popular with recreational drug users.’


 It is still used in specialist anaesthesia such as paediatrics, in veterinary anaesthesia, field medicine, and in countries which have limited access to resuscitation equipment (Morgan and Curran, 2011). Its high level of safety makes it indispensable for surgery in low- and middle-income countries, disaster situations and conflict zones, where anaesthesiologists are scarce, and where running water, electricity and oxygen are unreliable (World Health Organization [WHO], 2016).

More recently, its use in pain management, heroin and alcohol addiction (Morgan and Curran, 2011), and as an antidepressant in patients who may have treatment–resistant depression has been explored (Cullen et al, 2018; Wilkinson et al, 2018). Furthermore, although the agitation, panic attacks, hallucinations and dissociative effects associated with the drug limit its clinical use, it is these psychedelic effects that make ketamine popular with recreational drug users (Niesters et al, 2013; Misra, 2018).

RECREATIONAL DRUG USE OF KETAMINE

Ketamine was first reported as being used recreationally in the 1960s, but gained significantly in popularity in the UK in the ‘90s with the emergence of the rave and underground dance culture scene (Winstock et al, 2012). It has increased in popularity year on year, with the Home Office estimating that there were 94,000 users in 2015/2016 among 15–59 year olds (DrugWise, 2018). Some users report taking it intermittently such as at weekends, while others take it daily and many may take extremely high doses (Wood et al, 2011). In many parts of the Far East, it is the number one drug of choice. Indeed, Li et al (2011) stated that at least 80% of drug abusers under 21 in Hong Kong were ketamine users. There are also reports of ketamine being widely used in China, Taiwan, Singapore, Malaysia and other parts of Europe (Li et al, 2011; Chung et al, 2014; Jhang et al, 2015; Zeng et al, 2017) and the United States (Li et al, 2011).

Special K, Vitamin K, Green, Donkey Dust and Super K or KitKat are just some of the many different street names for ketamine (Li et al, 2011; Morgan and Curran, 2011; DrugWise, 2018). It is often used in combination with other substances such as cocaine or alcohol (Winstock et al, 2012; Misra, 2018). Users report taking anything from 50–200mg usually four to five times a day (Misra, 2018). Until 2014, it was in the same C-class as drugs such as anabolic steroids, growth hormones and lorazepam. It is now a B-class drug, putting it in the same category as amphetamines, barbiturates, codeine and cannabis. It is illegal to possess and/or distribute the drug. Possession carries a maximum of five years imprisonment and/or a fine, while trafficking offences carry a maximum sentence of 14 years imprisonment and a fine (BBC, 2014; DrugWise, 2018).

Ketamine’s popularity stems from the fact that it is easy to get hold of and relatively cheap. The cost of a gram of ketamine is about £21 compared to £50 for cocaine and £45 for heroin (DrugScope, 2006). The fact that it is versatile and can be manufactured in either pill form or as a liquid or powder means it can be disguised as products such as rosewater or hair gel and imported illegally (Daly, 2016). Although illegal laboratories for making the drug have been found in countries such as China and India, diverting the drug which has been made for legitimate use is the main source of ketamine (Morgan and Curran, 2011; Daly, 2016).

Another reason for its popularity is the misconception that it is not an addictive drug and is a relatively safe one to use (Chu et al, 2008). However, while it may not be physically addictive, it is psychologically and therefore results in the same psychological problems (such as craving and increasing tolerance) as other drugs, such as heroin and cocaine, although there is no physical withdrawal state after stopping the drug, even with longterm use (Niesters et al, 2013).

Effects of ketamine

Ketamine can be ingested, snorted or injected. Users experience a dissociative effect, which has been described as an out of body experience, and at large doses, the effect is described as ‘entering the K-hole’ , where the user experiences complete detachment from reality and altered perception of time and space (Morgan and Curran, 2011). Some describe it as having a spiritual experience and a sense of calm and serenity. However, short-term effects also include confusion, disorientation, hallucinations, loss of motor coordination and cardiovascular effects, including hypertension and tachycardia to name but a few (Box 2). Even low doses can result in mild dissociation, vivid hallucinations and distortion of time and space, as well as memory loss (Niesters et al, 2013). Higher doses may result in agitation, aggressive behaviour and displaying paranoid behaviour. The dissociative effect of the drug happens almost immediately, with other effects ‘kicking in’ after 15 minutes if injected, up to 20 minutes if snorted, and 30 minutes if ingested (Jhang et al, 2015). The effect of the drug lasts for approximately two hours, even at high doses (Li et al, 2011; DrugWise, 2018).

Being unable to control oneself and being dissociated from the body puts the user at risk of injury and death, as when in the ‘K-hole’ users have no awareness of what is around them or what is happening to them, or if they are putting themselves in danger. They are also at higher risk of automutilation (Ng et al, 2010). Long-term abuse may result in memory defects and schizophreniclike symptoms persisting or reoccurring regularly, even when no longer taking the drug (Niesters et al, 2013). Ketamine is also used as a ‘date rape’ drug because even at low doses it results in a dissociative state with amnesia (Li et al, 2011). Long-term use of the drug may lead to more irreversible damage, such as neurological and hepatic damage, as well as damage to the urinary tract (Niesters et al, 2013) (Box 3).
Box 1
Box 2
Box 3
Box 3

KETAMINE AND THE URINARY TRACT

In recent years, the link between ketamine use and damage to the urinary tract has become apparent, with estimation that at least 26–30% of users experience at least one bladder symptom (Winstock et al, 2012; Misra, 2018). Using ketamine at least three times a week over a period of two years has been shown to result in altered bladder function, with some patients complaining of severe urological problems (Mak et al, 2011). This syndrome is often called ‘ketamine bladder’ or ‘ketamine cystitis’ in the literature (Jhang et al, 2015; Misra, 2018)

The severity of symptoms is linked to the dose and frequency of use (Jhang et al, 2015). Patients typically present with lower urinary tract symptoms (LUTs), including painful bladder, frequency, dysuria, haematuria and suprapubic pain or ‘K cramps’, as they are known (Winstock et al, 2012) (Box 4). Some users experience the onset of symptoms quickly within a few weeks or months of taking the drug, while others have a history of long-term use and increasing dosage before symptoms manifest themselves (Misra, 2018).
The cause may not be immediately apparent to healthcare professionals when these patients present, as these could also be symptoms of other problems such as severe urinary tract infections (UTIs), bladder stones or bladder cancer (Chu et al, 2008). Furthermore, the problem is often misdiagnosed, especially as this group of patients may not readily volunteer the information that they are taking recreational drugs (Winstock et al, 2012). The relatively young age of the person presenting with these symptoms should set off alarm bells for healthcare professionals, particularly if there is no obvious cause of the problem. In severe cases, damage to the bladder causes it to shrink, the walls to thicken and it is extremely painful. The problem may also involve the kidneys as a result of vesico-ureteric reflux, resulting in upper tract obstruction and papillary necrosis leading to renal failure (Misra, 2018). The exact mechanism as to why ketamine has this effect is not known, although it is thought that the toxic effects of the high amounts of ketamine metabolites found in the urine may cause the irritation and inflammation of the bladder (Zeng et al, 2017), and disrupt the bladder epithelial barrier, allowing leakage of irritative agents causing an inflammatory response and cystitis-like symptoms (Jhang et al, 2015).

Diagnosis

It is important to eliminate all other possible causes of lower urinary tract symptoms. Keeping a voiding diary would give an insight into the frequency of micturition, any episodes of incontinence and a clearer picture of fluid input and output. Urine should also be tested for any underlying infection. Blood tests for renal and liver function are key (Misra, 2018) and an ultrasound scan of the bladder and urodynamic tests may be indicated to determine bladder damage (Zeng et al, 2017).

Cystoscopy and bladder biopsy are also indicated, especially if the patient has acute symptoms (Chu et al, 2008; Misra, 2018). It is good practice to also undertake ultrasonography and imaging of the upper urinary tract to check renal involvement. If damage is suspected, renal function tests may also be indicated to determine how much function has been lost (Wood et al, 2011) and a computer tomography (CT) urogram should also be considered (Mason et al, 2010).

Treatment

Key to any treatment plan is to make sure that the patient comes off ketamine. However, this is not always easy even when the patient understands or experiences the benefits of coming off the drug (Chu et al, 2008; Wood et al 2011; Jhang et al, 2015). As symptoms are dose and length of addiction related, early diagnosis and timely intervention is key to stopping more damage and reversing the symptoms (Logan et al, (2015). Research has shown that in 51% of cases the symptoms will reverse and bladder function will improve or get back to normal (Winstock et al, 2012).

However, the longer the person is on ketamine, the more severe the symptoms and the less chance there is of reversal (Mak et al, 2011). Anticholinergic agents may improve symptoms of urgency in some cases, but as most symptoms are caused by inflammation and contracted bladder, these drugs will not be effective in all cases. Nevertheless, it is worth trying patients on these drugs, especially those with mild symptoms, as they may show some improvement (Jhang et al, 2015). There is some evidence that using intravesical instillations of urothelium protective agents, such as hyaluronic acid, to restore the urothelium barrier function (the glycosaminoglycan or GAG layer) may be helpful in some patients, although longer term studies are needed before this becomes standard treatment (Jhang et al, 2015; Misra, 2018).

The greatest problem experienced is bladder pain. This can be so extensive that the patient resorts to taking ketamine to alleviate the pain, but ultimately this will only make the symptoms worse (Wood et al, 2011; Logan et al, 2015). The cycle needs to be broken and therefore it is important to ensure that the patient is started on a pain relief regimen, which means ketamine is no longer needed to relieve it. Non-steroidal anti-inflammatory drugs (NSAIDs) are first-line treatment, although the more severe the bladder pain and the later the stage of ketamine cystitis, the less effective they are. Similarly, steroids may be effective to deal with inflammation, although they are not as helpful in severely damaged or painful bladders (Jhang et al, 2015). Wood et al (2011) describe a successful strategy developed by urologists in collaboration with the pain team in Bristol, which involves patients wearing buprenorphine patches and taking cocodamol and amitriptyline at night. More recently, researchers in China have found that injecting painful bladders with botulin toxin type A (BOTOX), together with hydro distention (i.e. stretching the bladder under anaesthetic), successfully reduced bladder and abdominal pain and LUT symptoms for some patients (Zeng et al, 2017).
RememberPatients who have reduced bladder capacity, thickened bladder walls and hydronephrosis (swelling of the pelvis of the kidney as a result of build up of urine) do not usually recover function, even if they stop taking the drug (Jhang et al, 2015). Patients may need ureteric stents or a nephrostomy tube inserting if there is obstruction or reflux to the kidney to allow urine to drain and relieve hydronephrosis, preserve renal function and stop further irreversible damage (Chu et al, 2008; Jhang et al, 2015).

A review of the literature by Misra (2018) found that up to 7% of patients present with impaired renal function caused by hydronephrosis. Chu et al (2008) found 51% of patients in their study had upper urinary tract involvement. If damage is extensive and irreversible, patients may eventually go onto renal dialysis because their kidneys fail (Li et al, 2011).

In some cases, conservative treatment does not alleviate the problem and the damage to the bladder and upper urinary tract is extensive and irreversible. If the bladder is very small and painful and symptoms are not compatible with the patient having any quality of life, the only resort is surgical augmentation (Chung et al, 2014) with or without ureteric reimplantation (Jhang et al, 2015), or complete removal of the bladder and formation of either a continent urinary diversion or an ileal conduit (Sihra et al, 2017a; Misra, 2018). There is research to support the fact that this group of patients seem to be at a higher than normal risk of complications post-surgery (up to 71%), which may be related to their ketamine abuse (Sihra et al, 2017a and b).

Unfortunately, once recovered and pain-free, some patients may go back onto ketamine and in many cases the drug will also affect the tissue of the augmented or neobladder and result in symptoms returning (Ng et al, 2013; Chung et al, 2014). It is vital that patients are aware of the danger and importance of staying off the drug. However, this group cannot always be relied on to adhere to follow-up protocols and many are lost to follow up, making it difficult to ascertain long-term outcomes, as well as how many are back on the drug and what, if any, problems they are experiencing (Wood et al, 2011). Misra (2018) reported that up to 59% of his patients did not return for appointments.
 

‘It is vital that patients are aware of the danger and importance of staying off the drug. However, this group cannot always be relied on to adhere to follow-up protocols and many are lost to follow up, making it difficult to ascertain long-term outcomes... .’

IMPLICATIONS FOR PRACTICE

Healthcare professionals need to be aware that this is a growing problem which they are likely to encounter at some point in their practice. If someone presents with lower urinary tract symptoms, especially if young and with no apparent explanation as to the cause of the problems, they should entertain the possibility that this may be a result of ketamine abuse (Mason et al, 2010).

Clinicians need to be asking the right questions about recreational drug use, even if it is uncomfortable to do so, to ensure that patients are diagnosed quickly and steps taken to reverse and treat symptoms (Logan, 2011). This should be done in a non-judgmental and supportive way to help patients concur with treatment and feel that they can trust those caring for them (Misra, 2018). Patients may benefit from referral for support to drug agencies to help with their addiction. In fact, many drug helplines and information websites such as Frank (2018) or DrugWise (2018) are aware of the problem and highlight this in their information. Patient counselling may also be indicated to help them come off and stay off the drug, as this is key to whatever treatment is needed. However, fear and embarrassment may delay patients seeking help, and, when they do, many report feeling judged and treated with contempt by healthcare professionals (Logan et al, 2015). Healthcare professionals need to be aware that care for these patients is multifaceted and should involve intra-agency and multidisciplinary working (Logan 2011; Logan et al, 2015; Misra, 2018).

Key Points

- Ketamine was first reported as being used recreationally in the 1960s, but gained significantly in popularity in the UK in the ‘90s with the emergence of the rave and underground dance culture scene.

- Using ketamine at least three times a week over a period of two years has been shown to result in altered bladder function, with some patients complaining of severe urological problems.

- The problem is often misdiagnosed, particularly as this patient group may not readily volunteer the information that they are taking recreational drugs.

- Key to any treatment plan is to make sure that the patient comes off ketamine. However, this is not always easy even when the patient understands or experiences the benefits of coming off the drug.

- Clinicians need to be asking the right questions about recreational drug use, even if it is uncomfortable to do so, to ensure that patients are diagnosed quickly and steps taken to reverse and treat symptoms.

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