The Ketamine Drive-Through

The drug is being prescribed via telehealth without in-person evaluation or monitoringFigure: ketamine, urinary tract injury, hydronephrosis, ulcerative cystitis, alkaline phosphatase, alanine aminotransferaseFigureA headline in the Washington Post brought me up short. It read: “This doctor prescribes ketamine to thousands online. It's all legal.” The article described a South Carolina family physician who over several years applied for and obtained a medical license in almost every state. This allowed him to prescribe ketamine lozenges to treat patients' depression after only a virtual telehealth visit. (Dec. 30, 2022; http://bit.ly/3IDn6Ji.) More than 10,000 patients have been treated at home, according to the article. Until recently, physicians were not permitted to write for controlled substances without interviewing and examining a patient in person. But the Drug Enforcement Administration changed the rules at the start of the COVID-19 pandemic, temporarily allowing physicians to prescribe medications such as ketamine after a telehealth appointment as long as the physician followed state rules. That rule change is still in place, and there is no indication of when or if it will be lifted. A number of startup companies have been formed to facilitate online prescription and home delivery of ketamine as a result. Many of these firms have attracted interest and investment from venture capitalists. This development is controversial and has been criticized by many psychiatrists and psychiatric organizations that point out home ketamine use has not been studied or proven to be safe. A position statement from the American Psychiatric Association—written before the pandemic but not yet revised or withdrawn—states that “we strongly advise against the prescription of at-home self-administration of ketamine.” (JAMA Psychiatry. 2017;74[4]:399.) We are now clearly in the middle of a mass social experiment in which ketamine is being prescribed on a large scale for home use without in-person evaluation or monitoring. This obviously increases the possibility that the drug will be misused or diverted, and many physicians are not familiar with the adverse effects that persistent exposure to ketamine can create. Ketamine Bladder Ketamine can cause devastating injury to the kidneys and bladder, a problem first identified in 2007. An important paper reported on 10 cases of bladder dysfunction in patients who abused ketamine for one to four years. (Hong Kong Med J. 2007;13[4]:311; https://bit.ly/3YJAD7W.) All of the patients had symptoms of lower urinary tract injury, such as urgency, frequency, dysuria, incontinence, and painful gross hematuria. Studies on seven of the patients revealed that they all had small noncompliant bladders with functional capacities between 30 mL and 100 mL. Eight of the patients also had bilateral hydronephrosis. A second paper from Toronto published the same year described nine daily users of ketamine who presented with similar symptoms. (Urology. 2007;69[5]:810.) CT scans in those patients revealed small bladders with thickened walls and findings consistent with severe inflammation. Cystoscopy showed that all had severe ulcerative cystitis. Subsequent papers demonstrated that some patients with so-called “ketamine bladder” also had significant kidney injury or papillary necrosis. The cause of ketamine-associated urinary tract damage has not been identified, but it may involve direct damage induced by ketamine or its metabolites, microvascular injury with ischemic changes, or an autoimmune process. Now, if all of the patients described in those two papers were users of street ketamine, was ketamine itself responsible for the pathology or was some adulterant the real culprit? Apparently, ketamine alone can cause these changes. One 16-year-old girl suffering chronic pain developed lower urinary tract symptoms after being treated with ketamine for nine days. Her symptoms resolved when ketamine was discontinued, but appeared again when the drug was restarted. (Urology. 2008;71[6]:1232.) Another case report described three patients in palliative care who experienced similar symptoms after being treated with ketamine for complex pain. (Palliat Med. 2009;23[7]:670.) Hepatic Damage Chronic ketamine use is also associated with liver injury. Interestingly, the majority of the 10 patients with bladder dysfunction described above also had evidence of liver injury with elevated alkaline phosphatase or alanine aminotransferase. (Hong Kong Med J. 2007;13[4]:311; https://bit.ly/3YJAD7W.) A later paper demonstrated that liver injury is relatively common among chronic abusers of ketamine. (Clin Gastroenterol Hepatol. 2014;12[10]:1759.) About 10 percent of the 297 patients who used ketamine had evidence of cholestatic liver injury with dilated common bile duct and fibrosis without apparent obstruction. All of the patients had abused ketamine by nasal insufflation. The authors suggested that damage to the biliary tree might be due to direct toxicity or ketamine-induced dysfunction of the sphincter of Oddi. It is still not clear if the current DEA rules allowing physicians to prescribe ketamine without a face-to-face encounter will lead to increased prevalence of urinary and liver damage. What is clear is that many cases will be missed unless clinicians are familiar with the association if this happens. The take-home lesson for emergency physicians is that patients who present with unexplained urinary tract symptoms or laboratory abnormalities on tests for liver injury should be asked about exposure to ketamine. Patients who chronically use ketamine should also be screened for renal and hepatic dysfunction and informed about the potential for kidney and liver damage. If a connection is not made in the emergency department, it will likely be missed by the inpatient service or primary care provider. It will be interesting to see how this all plays out. Dr. Gussowis a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago, an assistant professor of emergency medicine at Rush Medical College, a consultant to the Illinois Poison Center, and a lecturer in emergency medicine at the University of Illinois Medical Center in Chicago. Follow him on Twitter@poisonreview, and read his past columns athttp://bit.ly/EMN-ToxRounds.

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