The Dark Side of Ketamine: Brain, Bladder, and Beyond: a Focused Clinical Review for Emergency Medicine Clinicians

Ketamine is an indispensable therapeutic in emergency medicine, yet its pharmacologic profile carries a unique constellation of adverse effects that emergency medicine clinicians must recognize and manage. This focused clinical review examines four categories of these ketamine-specific adverse effects encountered in the emergency department (ED): acute psycho-perceptual adverse effects (PPAEs) (during analgesic use), ketamine-induced cystitis (KIC) (a progressive uropathy), ketamine-associated cholangiopathy (a sclerosing cholangitis–like syndrome), and ketamine use disorder (KUD) (encompassing dependence and withdrawal). The review summarizes current evidence addressing epidemiology, pathophysiology, clinical presentation, ED management, and disposition of patients experiencing these adverse effects and provides a practical approach for their management. Recreational ketamine use has surged globally, with illicit seizures in the United States increasing over 1,100% between 2017 and 2022 and UK treatment admissions rising fivefold since 2015. Psycho-perceptual effects occur in up to 92% of patients receiving sub-dissociative ketamine by intravenous push but can be reduced by approximately 40% with slow infusion. Ketamine-induced cystitis affects 25–27% of chronic users and is progressive yet partially reversible with early cessation. Ketamine-induced cholangiopathy occurs in roughly 10% of chronic users and mimics primary sclerosing cholangitis. Across all chronic toxicity syndromes, ketamine cessation is the single most important intervention. Emergency physicians are uniquely positioned to identify these conditions, initiate treatment, and connect patients to specialized care.