This week’s Guest Post is by David Gillatt, Professor of Urology and Medical Director of the Bristol Urological Institute in the UK. David has considerable experience in the management of pelvic cancer, including prostate and bladder cancer, and is a world expert in the relatively recently discovered effects of ketamine on the urinary tract. In this article, Prof. Gillatt outlines current understanding of this increasing problem.
Although ketamine has been in use as a pharmaceutical agent for 50 years and a recreational drug since the early 1990s, it has only relatively recently been recognised as a cause of potential physical harm, damaging the urinary tract, hepatobiliary system and gut. Isolated case reports documenting bladder symptoms and a form of cystitis associated with prolonged recreational usage of ketamine began to appear in around 2007 mainly from Hong Kong, Canada and the United Kingdom.
The effects of ketamine
Bladder symptoms tend to occur in recreational ketamine users, usually those snorting the drug. The severity of the symptoms and the degree of bladder damage is in proportion to the amount taken, how often and for how long. Those taking five grams or more for a period of months or longer invariably develop bladder problems. However, some taking lower doses or even for medical reasons can develop symptoms with small numbers of cases being reported in those being treated with ketamine as part of a chronic pain programme or as palliation.
Symptoms typically include pain with passing urine, frequency and urgency of voiding, blood and matter in the urine, usually the bladder lining, and incontinence. The urine is usually clear of infection.
The changes that occur in the bladder are a direct result of ketamine and its metabolites being excreted via the kidneys into the urine, and coming into direct and prolonged contact with the bladder lining.
This initially results in inflammation and ulceration of the bladder lining. Prolonged exposure can result in damage to nerve endings and result in persistent pain, often a deep-seated pain requiring strong analgesics. Ultimately the bladder can become scarred and will shrink and at this stage the damage may be irreversible.
Managing ketamine side effects
Removing the insult to the bladder by stopping the ketamine gives the best chance of relief. In many cases the bladder will heal and although some symptoms may persist, these will become manageable. One major problem is control of the bladder pain during healing.
If cessation of ketamine is not possible, a variety of methods of symptom control may be used including anticholinergic drugs to reduce frequency and urgency, amitriptyline as an anticholinergic and sedative, and analgesics. Bladder protective agents such as hyaluronic acid may help in some cases. Bladder distension under anaesthetic may play a role in giving temporary relief of symptoms.
A small proportion a users will have persistent symptoms, despite stopping the drug. Reduced bladder capacity with severe frequency/urgency, persistent bladder pain and incontinence may all be indications for surgical intervention. This would usually involve removal of all or part of the bladder and replacement with an intestinal segment. As those affected are usually in their twenties this is a drastic step with potential long term sequelae including renal problems, continence issues and cancer.
Damage to the upper urinary tract
The upper urinary tract is also exposed to the same potential damage by being bathed in urine containing ketamine and its metabolites. Transit of urine through the upper tracts is more rapid than the bladder, therefore damage in the upper tract is less frequently seen. However scarring and narrowing of the ureters is well documented and can be seen at its early stages radiologically in a large percentage of users with bladder damage.
Upper urinary tract symptoms seem commoner in Asian countries, including hydronephrosis, possibly reflecting obstruction of the ureters causing toxic effects or scarring in the ureters. In one sample 51% had hydronephrosis, which was bilateral in 44% and unilateral in 7%, and 13% had papillary necrosis. Hydronephrosis may be the result of smooth muscle relaxation.
Ultimately if obstruction is prolonged and not relieved the end result may be renal failure.
Ketamine users with bladder symptoms should have imaging of their upper urinary tract and measurement of renal function. Those with obstruction, with or without symptoms, require surgical or radiological intervention to drain the kidneys and later correction of the blockage if it does not resolve.
David Gillatt is a Consultant Urologist with an interest in surgery for prostate and bladder cancer. He has one of the largest experiences in Europe of complex pelvic cancer surgery with more than 2000 major resections in a 20-year career. He was pivotal to the centralisation of complex Urological cancer surgery within the region. During this time, he introduced many innovations in service delivery including an Enhanced Recovery Programme for cystectomy, and a robotic pelvic surgery programme. Under his direction, the Centre has become the highest volume Urological cancer centre in t he UK and one of the busiest robotic centres in Europe.
Nationally he has served two five-year periods on the council of the British Association of Urological surgeons and is past Chair of the Section of Uro-Oncology. He sat on the NCRI trials groups for both bladder and prostate cancer and is on the Urology group for the NCIN as well as the Department of Health Prostate Cancer Action group. He was also a member of the NICE Guidelines development group for prostate cancer.
His research interests include recovery from surgery and aspects of prostate and bladder cancer. David founded the Bristol Prostate Cancer Research Network. He has visiting Chairs at the Universities of Exeter, West of England and Malaya. He has been visiting specialist or Professor at over 20 overseas institutions or groups. Active research projects include: 1) The evaluation of anti-angiogenic factors in prostate cancer, 2) Insulin derived growth factors in prostate and bladder cancer, 3) Enhanced recovery after surgery, 4) the influence of lifestyle intervention on recovery from cancer and surgery, 5) Circulating tumour cells and prognosis in prostate cancer.
He has a major interest in clinical trials being a chief investigator for the ProtectT trial in Bristol (total grants >£32m) and for RADICALS and BOXIT. He is on both trial management groups and trial steering committees.
You can follow this link to the Bristol Urological Institute website BUI