**4. Clinical presentation**

The irritative effects of ketamine on the urinary system, especially the bladder, produce myriad symptoms. These include:


The typical complaint from the affected patients is 'painful, small voids', closely mimicking that of interstitial cystitis. These symptoms typically develop after 2 years of ketamine abuse. A study in Hong Kong by Ng et al. has demonstrated the relative prevalence of symptoms as follows: urgency (92%), frequency (84%), nocturia (88%), dysuria (86%), and haematuria (68%) [18]. The most bothersome symptoms reported by users are typically urinary frequency, nocturia, and urgency. This is because of the need of frequency visits to the bathroom, which interferes significantly with their daily activities [7].

The clinician may evaluate symptoms using standardised methods such as frequency-voiding charts (also known as a 'bladder diary') and questionnaires such as the Pelvic Pain and Urgency/Frequency (PUF). A frequency-voiding chart involves the patient recording the volume of every fluid intake and void and also instances and degrees of urge incontinence, if any. Reviewing a frequency-voiding chart allows the patient to communicate effectively with the clinician the frequency and nocturia experienced. Ketamine cystitis typically produces a low-compliance bladder, manifesting as frequency, low-volume voids. Urge incontinence is the sudden and compelling desire to pass urine that is difficult to defer and is accompanied by involuntary leakage.

The Pelvic Pain and Urgency/Frequency questionnaire is a symptom score questionnaire developed and validated for the diagnosis of interstitial cystitis [19]. As mentioned, interstitial cystitis produces symptoms and histological changes in the bladder akin to those found in ketamine cystitis, and studies have validated the use of this questionnaire to score patients experiencing symptoms of ketamine cystitis [18]. The questionnaire includes eight questions evaluating daytime frequency, nocturia, pelvic pain, urinary urgency, the degree to which these symptoms bother the patient, and sexual function. PUF generates a symptom score and bother score, which total at 35. In a patient with history of significant ketamine abuse, a score of ≥15 indicates the presence of significant cystitis symptoms, thus leading to the diagnosis of ketamine cystitis. The PUF is a useful tool not only for the diagnosis of ketamine cystitis but also for symptom quantification so that its severity and response to treatment could be monitored over time.

#### **5. Clinical investigation findings**

Cystoscopy, computed tomography (CT), ultrasonography, and pyelography are examples of investigations that may demonstrate the structural damage implicated in ketamine cystitis [20]. Cystoscopy reveals inflammatory changes such as telangiectasia (indicative of neovascularisation), ulceration, or even petechial haemorrhage in severe cases. Biopsies of the affected bladder urothelium will reveal histological changes mentioned earlier in the chapter, including denuded epithelium and infiltration by eosinophils and lymphocytes. Computed tomography may show bladder wall thickening and peri-vesical stranding, both of which are indicative of chronic inflammation of the bladder wall (**Figure 1**). Upper tract damage usually manifests itself as unilateral or bilateral hydronephrosis, with ureteric wall thickening, or luminal narrowing and strictures. CT, pyelography, and ultrasound are all suitable modalities to demonstrate hydronephrosis (**Figures 2**–**4**). CT and pyelography have the additional benefit of evaluating the exact level of ureteric stricturing.

*Urological Effects of Ketamine Abuse DOI: http://dx.doi.org/10.5772/intechopen.91283*

#### **Figure 1.**

*Contrast CT scan image showing a thickened and contracted bladder in a patient with a 7-year history of ketamine abuse.*

#### **Figure 2.**

*Reconstructed contrast CT urogram showing bilateral hydronephrosis and hydroureter down to the level of the vesicoureteric junctions. The bladder also appears small with generalised wall thickening. This patient has an 8-year history of ketamine abuse.*

#### **Figure 3.**

*This is an antegrade pyelogram of a patient suffering from ketamine cystitis. Contrast is injected through the percutaneous nephrostomy. There is hydronephrosis and a contrast upholding at the level of the L3 vertebra. This is suggestive of a ureteric stricture at that level causing hydronephrosis.*

#### **Figure 4.**

*Ultrasound image of the left kidney of a patient with ketamine cystitis complicated by acute left pyelonephritis. This patient had a background of ketamine cystitis with bilateral hydronephrosis. She presented acutely with left loin pain and fever. The ultrasound image shows debris in the chronically dilated renal pelvis. This is compatible with acute pyelonephritis complicating ketamine cystitis. A combination of chronic obstruction and vesicoureteral reflux has likely contributed to the development of upper tract infection.*

Apart from assessing the degree of structural damage, the functional capacity of the urinary system should also be assessed. Urodynamic studies, such as video cystometrogram, reveal reduced bladder capacities, reduced bladder compliance, and sometimes detrusor overactivity even at low bladder volumes. Bladder capacities of

#### *Urological Effects of Ketamine Abuse DOI: http://dx.doi.org/10.5772/intechopen.91283*

ketamine cystitis patients are typically <150 ml, and detrusor overactivity has been shown to be evident at bladder volumes as low as 14 ml [21]. This means that such patients will not only complain of very frequent but small voids, they are also likely to experience urge incontinence. One can see how disabling such symptoms are from these investigation findings (**Figures 5**–**7**).

Renal impairment can be reflected from raised serum creatinine or impaired creatinine clearance and estimated glomerular filtration rate. Renal impairment may stem from vesicoureteral reflux (VUR) due to chronic reduction in bladder

#### **Figure 5.**

*Cystometrogram (filling phase) of a patient with a 10-year history of ketamine abuse. First desire to void was recorded at 14 ml of bladder filling. Also note the multiple spikes at the lowermost tracing indicative of detrusor overactivity. (Pves, intravesical pressure; Pabd, intra-abdominal pressure; Pdet, subtracted detrusor pressure of Pves–Pabd).*

#### **Figure 6.**

*Cystometrogram (filling phase) of the same patient after 3 years of abstinence. First desire to void at 51 ml. Note the difference in the scale of the x-axis denoting volume. The detrusor overactivity has also dampened, as shown by the smoother Pdet tracing.*

#### **Figure 7.**

*Cystometrogram (filling phase) of the same patient after 8 years of abstinence. First desire to void at 75 ml. Much improved bladder compliance as shown by the relatively smooth Pdet tracing.*

#### **Figure 8.**

*Contrast CT scan image of a patient with more than 3 years of ketamine abuse, showing bilateral atrophic kidneys and hydronephrosis. This patient required bilateral percutaneous nephrostomies (also seen on this image) for upper tract urinary diversion.*

compliance. VUR can be demonstrated on video cystometrogram as a reflux of contrast material from the bladder up to the ureters. VUR predisposes the upper tract from urinary tract infections, increasing the risk of recurrent pyelonephritis and resultant renal scarring (**Figure 2**). Hydronephrosis as a result of ureteric narrowing is also a cause of renal impairment in these patients. Ureteric narrowing is likely secondary to urinary ketamine and its metabolites causing transmural inflammation and swelling or even fibrosis and strictures (**Figure 8**).

Papillary necrosis may be seen on renal ultrasound or on contrast studies such as an intravenous urogram or computed tomography [11]. The contrast material fills necrotic cavities located in the renal papillae. Sometimes, sloughed necrotic material may pass into the ureter, causing obstruction, and appear as a filling defect.
