What Urologists Need to Know

The increasing misuse of ketamine for pleasure and medical purposes causes severe urinary complications. At the 118^th French Congress of Urology, experts presented the importance of a multidisciplinary approach in managing ketamine-induced uropathy, a condition marked by intense pain and frequent urination, reportedly as high as “30-50 times a day.”

“The treatment approach must be multidisciplinary, involving addiction specialists, pain management experts, and psychiatrists,” François Meyer, MD, from Saint-Louis Hospital in Paris, France, stated. According to the literature, these urinary disorders can be reversed in 50%-85% of cases with “complete and sustained” ketamine withdrawal. 

To guide the management of ketamine-induced uropathy, the French Association of Urology (AFU) recently recommended treatments, such as oral pentosan polysulfate (Elmiron) and intravesical injections of botulinum toxin A (Botox or Dysport), for managing ketamine-induced uropathy.

Ketamine’s Growing Misuse

Originally used as an anesthetic, ketamine is widely misused because of its euphoric and hallucinogenic effects. It is also used off-label for the treatment of resistant depression and chronic pain.

Ketamine in the liquid form evaporates into fine crystals or a white powder, which is then sold for approximately 30-40 euros per gram and is consumed in parties for pleasure at half the price of cocaine. It is mainly snorted but can also be injected intravenously or intramuscularly.

According to data from the French Observatory of Drugs and Addictive Trends, 1.0% of high school students in France reported having experimented with ketamine in 2022. A 2023 survey revealed that 2.6% of adults have already tried ketamine, which brings the consumption of this product “ahead of that of heroin,” noted Meyer. 

Several countries have warned of the increase in recreational use of the drug as well as its misuse as medicine. In England and Wales, 3.8% of young adults (age, 16-24 years) experimented with ketamine in 2022-2023. Its off-label use for depression is gaining attention amid the growing mental health crisis. 

Currently, ketamine is being evaluated as a treatment for resistant depression. However, its misuse with the risk for addiction can have serious consequences. In the United States, the death of Friends actor Matthew Perry, caused by “the acute effects” of taking ketamine to treat his depression and anxiety, has raised awareness of this issue. 

Risks of Prolonged Use

The French National Agency for the Safety of Medicines and Health Products (ANSM) has warned about the risks associated with the misuse of ketamine and the precautions to be taken, particularly when ketamine is used off-label to treat intractable pain in palliative care or even chronic pain.

Serious complications associated with the administration of ketamine in a medical setting are regularly reported, indicated the ANSM. These include liver and biliary tract disorders (hepatitis, cholestasis, or cholangitis) or urinary tract disorders (noninfectious interstitial cystitis) with possible repercussions to the kidneys (acute renal failure, hydronephrosis, etc.).

The ANSM noted that these complications most commonly result from prolonged or repeated use of ketamine, which can lead to ketamine dependence. Among its recommendations, the agency advises against long-term prescribing or administration of ketamine and urges healthcare providers to instruct patients to monitor for symptoms, particularly the appearance of blood in the urine.

Clinical Presentation and Evaluation

Patients with lower urinary tract symptoms due to ketamine misuse are generally young, with an average age of 25 years, and have been using ketamine chronically for at least a year before the onset of voiding problems.

The symptoms include severe suprapubic pain, intense pollakiuria, and urgency, “with the need to urinate 30-50 times a day,” Meyer specified. Upper urinary tract disorders such as ureteral stenosis and kidney dilation (hydronephrosis) are common and are observed in 30% of patients.

The pathophysiology of the effects of ketamine on the urinary system “quite complex.” The active metabolite of ketamine is excreted via the urine, damaging the entire urinary tract. This results in disorders that go beyond those commonly known as ketamine-induced cystitis.

The clinical assessment includes a cytological cytobacteriological examination of the urine, a creatinine measurement to assess renal function, and an ultrasound to measure the post-micturition residue and look for possible dilation of the upper urinary tract.

Cystoscopy is also essential for assessing the condition of the mucous membranes and performing biopsies to rule out carcinoma. However, the examination must be performed under general anesthesia because of the intense pain it can cause. The same applies to urodynamic assessment.

Management Strategies

Sustainable withdrawal is essential to reduce these disorders. In cases of relapse, symptoms can return rapidly. Regular urine tests are advised to ensure the patient is successfully weaned off ketamine. Ongoing follow-up should include routine renal function tests.

The AFU guidelines recommend analgesics, such as paracetamol and ibuprofen for pelvic pain, as they have shown good efficacy, said Meyer. Phenazopyridine can also be used to treat urinary pain. However, opioids and pregabalin are less often recommended because of the risk for dependence.

Other Treatments

For persistent symptoms, oral pentosan polysulfate (Elmiron), a standard treatment for interstitial cystitis, is recommended as a first-line drug for ketamine-induced cystitis. However, anticholinergics are not recommended for this indication.

As with the treatment of painful bladder syndrome, hydrodistension, which fills the bladder with saline, is a first-line intervention. For symptoms of overactive bladder, intravesical injections of botulinum toxin are also recommended.

Reconstructive surgery involving the intestinal mucosa should be considered as a last resort, according to the AFU. Given that ketamine can also damage the intestinal mucosa, the effectiveness of this technique is limited, not to mention the risk for complications. 

As treatments for this indication are currently limited, other approaches are being considered. The use of mesenchymal stem cells or platelet-rich plasma facilitates the restoration of the urothelium.

This story was translated fromMedscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.