Ketamine-Associated Uropathy During Therapeutic and Nontherapeutic Use: Prevalence, Clinical Features, Mechanisms, and Strategies for Risk Reduction.

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.