Ketamine-Associated Uropathy During Therapeutic and Nontherapeutic Use

Summary & key facts

Researchers looked at the risk that ketamine can harm the urinary system when it is used either as a medicine or taken as a drug for fun. Studies of people who used ketamine recreationally found many had bladder or kidney symptoms. But studies of ketamine given for mental health (mainly for depression) did not show clear evidence that medical use causes the same urological problems. The review points to higher dose, more frequent use, longer treatment, and taking ketamine by mouth as possible risks. It also suggests simple steps that might lower risk, like drinking more fluids, urinating often on treatment days, and checking urine every few weeks.

Key facts:

• Among studies of people using ketamine for fun, about 40% to 80% had lower urinary tract symptoms such as bladder pain or needing to pee a lot.
• Those same recreational-study reviews found about 10% to 30% had problems higher up in the urinary system, like kidney or ureter damage.
• More recent studies that used different ways to find cases reported much lower risks, from a few percent up to about 25%.
• In a review of ketamine used to treat psychiatric problems (mainly depression), reported urinary symptoms ranged from 0% to about 25% of patients.
• In 14 trials that directly compared ketamine to other treatments, urinary symptom rates were similar between the ketamine groups and the comparison groups, so those trials did not show clear harm from medical use.
• The authors say the common idea that medical ketamine causes the same bladder disease seen in people who abuse ketamine is not convincingly supported by the evidence.
• Researchers explain how ketamine and its breakdown products in urine (not just in the blood) could irritate or damage the bladder; this helps explain why dose, how often it is taken, length of treatment, and taking it by mouth might change risk.
• To reduce possible urinary risk during long-term medical ketamine, the paper suggests measures such as high fluid intake, urinating frequently on treatment days, and checking urine every two to four weeks.

Abstract

Ketamine, introduced as an anesthetic drug, is now used for many indications beyond anesthesia; it is also increasingly a drug of abuse. Long-term recreational use and abuse of ketamine are associated with urological risks. This article discusses ketamine-associated uropathy from the perspective of prevalence, clinical features, mechanisms, and strategies for risk reduction in patients who require long term maintenance therapy with the drug for psychiatric indications. A systematic review and meta-analysis of 37 studies of uropathy in recreational (ab)users obtained prevalences of 44% to 77% for lower urinary tract symptoms and 8% to 30% for upper urinary tract disease; for reasons explained, these findings are potentially misleading and cannot be extrapolated to therapeutic contexts. More recent studies, using different methods of case ascertainment, present lower risks (2% to 27%). A systematic review of 27 studies of ketamine used to treat psychiatric disorders, mainly depression, found urological symptoms in 0% to 24% of patients; however, in 14 randomized controlled trials, urological symptom prevalences differed little between ketamine and comparison arms. The review presented no convincing evidence of ketamine-associated uropathy arising in therapeutic contexts. The literature on ketamine-associated uropathy is critically examined; reasons for false positive uropathy findings are considered. Ketamine pharmacokinetics are described to assist the understanding of how ketamine and its metabolites may predispose to uropathy. Mechanisms of uropathy, arising from exposure to ketamine and its metabolites in urine (rather than in circulation), are summarized. A reasonable conclusion is that higher doses of ketamine, more frequent dosing with ketamine, longer duration of treatment with ketamine, and oral administration of ketamine are all potential risk factors for ketamine-associated uropathy during maintenance therapy. High hydration and frequent voiding of urine on treatment days can reduce exposure of the bladder to ketamine and its metabolites, reducing urological risks. Fortnightly or monthly urine testing is also advisable.

Topics

Alcoholism and Thiamine Deficiency Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Anesthesia Anesthetic Clinical trial Dosing Drug Epidemiology Intensive care medicine Ketamine Medicine MEDLINE Obstructive uropathy Pharmacotherapy Randomized controlled trial Recreational Drug Substance abuse Urinary system Urine Urologic disease Urology

Substances

Ketamine

Conditions & symptoms

Depression Substance abuse disorder Addiction or harmful habbits