BY STUART ETENGOFF, DO, & ABDULLAH BOKHARI, AB, DO
A 20-year-old Caucasian man presented via EMS with a chief complaint of withdrawal from ketamine and secondary complaints of abdominal pain, blood in his urine, and painful urination with urgency for two days.
He said he had been using ketamine intravenously daily for the past five days, up to 35 grams over the past week. His last use was 24 hours prior to presentation to the ED. He stated that he had been using ketamine regularly for four years and that he has used it intravenously, orally, and intranasally.
He reported a history of ADHD and a family history of bipolar disorder and substance abuse. His mother had died two years earlier from an opiate overdose. He said he used ketamine daily, and had also used marijuana, cocaine, opiates, nitrous oxide, heroin, mushroom, tobacco, and occasionally alcohol.
The patient described his abdominal pain as sharp and crampy, radiating from the bladder upward with associated nausea for two days. He denied flank pain, recent trauma, any history of previous abdominal pain or urinary tract infection, fever, chills, discharge, diarrhea, constipation, chest pain, shortness of breath, and blood in stool. He also had no previous history of hematuria, kidney stones, or sexually transmitted diseases.
He appeared to be in mild to moderate discomfort and anxious, and was alert and oriented to person, place, and time. His blood pressure was 143/95 mm Hg, pulse 111 bpm, respiratory rate 18 bpm, temperature 96.6°F, and oxygen saturation of 97% on room air. His pupils were equal, round, and reactive to light and accommodation, and no nystagmus was noted.
The patient had no focal neurological deficits or acute respiratory distress, but was tachycardic. His lower extremities were negative for calf tenderness or pain, and multiple injection sites of various age noted. He had no signs of infection or cellulitis. His abdomen was soft, with minimal tenderness; no guarding or rigidity noted.
The patient's labs were a sodium 137 of mmol/L, potassium of 3.6 mmol/L, chloride of 98 mmol/L, glucose of 122 mg/dL, BUN of 12 mg/dL, creatinine of 0.9 mg/dL, GFR of 108 mL/min, and total CPK of 1769 U/L. His troponin was negative, calcium was 8.8 mg/dL, albumin 3.2 g/dL, total bilirubin 0.3 U/L, WBC 7.9 K/UL, RBC 4.9 M/UL, hemoglobin 14.9 g/dL, HCT 42.1%, platelet 396 K/UL, neutrophil 76.6%, and lymphocytes 14.1%. A standard urine drug screen was negative.
His urine analysis was cloudy and yellow, with 100 mg/dL of protein, trace ketones, no glucose, trace leukocyte esterase, and large blood, which showed microscopic hematuria with 50-100 RBC/HPF, 5-10 WBC/HPF, and trace bacteria. A urine culture was negative after 48 hours.
Urinalysis of patient with ketamine withdrawal.
The patient was treated symptomatically with IV rehydration and antianxiolytics, and he was observed in the ED for approximately four hours. He was subsequently discharged with directions to follow up with urology, and given information about substance abuse and rehab facilities in the area.
Ketamine-induced cystitis is a rare but increasing phenomenon. First described in 2007, it is usually seen in chronic users, recreational and prescribed. (Urology 2007;69:810.) The number of case appears to be increasing because of ketamine's popularity recreationally as a club drug (especially in Asia) and increased off-label use for depression and chronic pain. Reports put its incidence in chronic ketamine users at up to 30 percent. (Urol Sci 2015;26:153.) The studies have been limited, however, and the true incidence is difficult to report. The exact mechanism is unknown but thought to be caused by ketamine and its metabolites being excreted in the urine (85%), leading to inflammation. It is available in liquid, powder, tablet, or capsule form.
Complications to the urinary tract can include small painful bladder, urinary incontinence, upper urinary tract obstruction, ureteral hydronephrosis, reflux nephropathy, and papillary necrosis. (J Pharmacol Clin Toxicol 2017;5:1094.)
Cystoscopy findings include inflammatory changes, neovascularization, ulceration, and a small, contracted bladder. Complications include renal impairment with raised serum urea and creatinine levels. Current treatment consists of cessation of ketamine. NSAIDs, acetaminophen, and local bladder anesthetics such as phenazopyridine can be used for symptomatic treatment. Pentosan polysulfate sodium, chondroitin sulfate, and hyaluronic acid have been reported as effective treatments. (Addict Res Ther 2017;1: 1002.)
It appears that the majority of symptoms will improve by stopping ketamine use. The higher the dose and the longer the duration of usage increase the risks of long-term urinary and bladder problems.
Dr. Etengoff is the director of emergency services at the McLaren Emergency Department in Clarkston, MI. Dr. Bokhari is the senior emergency medicine resident at the McLaren Oakland Emergency Department in Pontiac, MI.