Case Report #41: Ketamine Bladder Pain by Dr Matthew Cole and Dr Sunil Dasari

Ketamine is a synthetic anaesthetic agent first produced in 1962.  It acts as a non-competitive antagonist of the N-methyl-D-aspartate acid receptor complex.  It has a range of medical uses including anaesthesia, pain management and depression treatment ⁶. At higher doses it induces a state of dissociative anaesthesia, a trance-like state providing analgesia, sedation and amnesia.  Its properties of relative preservation of airway reflexes along with an increase in heart rate, blood pressure and cardiac output make it suited as an induction agent in trauma patients.  It is the dissociative effect of ketamine that makes it a popular recreational drug.  It gained significant popularity in the UK in the 1990s with the emergence of the rave and underground dance culture scene.  It has increased in popularity over the years with the Home Office estimating that there were 94 000 users in 2015/16 among 15–59 year olds ⁷.

In recent years the link between ketamine use and damage to the urinary tract has become apparent.  The exact pathogenesis of ketamine induced cystitis (KIC) is unknown, but studies suggest that it may stem from inflammatory pathways triggered by ketamine metabolism.  KIC involves chronic inflammation of the bladder with increased urinary frequency, dysuria and suprapubic pain.  Some common pathological findings are increased thickness of the bladder wall and bladder contraction.  The bladder is stripped of its urothelium and contains eosinophils and mast cells due to the inflammatory response.  There is a positive correlation with the dose of ketamine taken and the severity of the symptoms.

The severe pain experienced with ketamine uropathy is associated with nerve cell hyperplasia within the lamina propria as well as the occurrence of prominent nerve fascicle hyperplasia superficially, a finding not seen in other painful bladder conditions ⁸.

Timely treatment of KIC is crucial for managing LUTS, reducing pain and preventing upper urinary tract involvement.  Treatment is categorised into ketamine cessation, non-invasive interventions, intravesical instillations and surgery.

Classification

Patients can be classified into three stages of ketamine uropathy ⁹.  Stage 1 is the inflammatory phase, characterized by normal ureters, renal function and lack of bladder contracture.  This stage is where cessation of ketamine, bladder training and oral medications can resolve the situation. 

Stage 2 is where structural changes to the bladder occur. There is fibrosis and a thickened bladder wall with reduced capacity, occasionally the ureters are involved, renal function is preserved.  This stage can receive some benefit from bladder instillations  and intra-detrusor botulinum toxin A injections. 

Stage 3 represents patients with established fibrosis and bladder contracture, ureteric wall inflammation, hydronephrosis and decompensated renal function.  These patients are often managed with augmentation cystoplasty or urinary diversion with or without cystectomy.