KETAMINE ABUSE DISORDER SYNDROME: FROM ELECTROLYTE IMBALANCES TO UROLOGIC PATHOLOGY AND HEPATOBILIARY FAILURE

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Ketamine, a noncompetitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist initially developed in 1963 as an anesthetic, has been recently used for analgesia and treatment of asthma and depression. Its popularity, resulted in an increased incidence of addiction, especially in East Asia and in United States. Chronic use of ketamine affects neurologic, urologic, and gastrointestinal systems. We hereby describe a rare case of chronic recreational ketamine use that presented with severe hyponatremia, hyperkalemia, hemorrhagic cystitis and intrahepatic biliary ductal dilation and acute hepatic failure with cholestatic pattern CASE PRESENTATION: 26-year-old Asian woman presented with generalized weakness, lethargy, and hematuria. She endorsed using ketamine for 3 months but denied any other medications use. Found to have severe protein energy malnutrition with BMI of 14 kg/m2. Lab values showed severe hyponatremia (98 mmol/L); hyperkalemia (7.8 mmol/L), bicarbonate (11) and anion gap (21), associated peaked T waves on electrocardiogram and normal renal function. Total bilirubin (3.7mg/dL), direct bilirubin (2.2mg/dL), transaminases 5 times above upper normal and alkaline phosphatase (1426 IU/L) showing cholestasis pattern. Urine sodium was 32, urine toxicology was negative, HIV was non-reactive, Hepatitis B core and surface antibody was reactive, cortisol was 32. Computed tomography imaging and magnetic resonance cholangiopancreatography showed mild intrahepatic and extrahepatic biliary duct dilatation without visible etiology; gallbladder was unremarkable and a bifid right renal pelvis and bilateral moderate-severe hydronephrosis. Patient was admitted to intensive care unit. Received multiple hyperkalemic cocktails and was started on isotonic fluids for resuscitation. Hyperkalemia resolved; hyponatremia appropriately corrected not more than 8-10meq/ 24hrs. Acetylcysteine infusion was started for liver failure. Urology was consulted for hematuria and managed with foley catheter which improved with frequent irrigations. Patient had Escherichia coli bacteremia and treated with antibiotics. Patient clinically improved and safely discharged home. DISCUSSION: Ketamine causes smooth muscle relaxation directly through inhibiting the activation of NMDA receptors, resulting in biliary dilation and subsequent cholestasis in the absence of an obstructing lesion; due to accumulation of enantiomer in racemic ketamine (s-ketamine) as observed in vitro. Lower urinary tract symptoms, including cystitis have been described. Hydronephrosis has been very rarely reported CONCLUSIONS: This case has a very peculiar presentation given the findings of severe electrolyte abnormalities, upper-urinary tract and liver involvement. We highlight the importance of identifying this pathology for early intervention and appropriate management and prevent long term sequelae. REFERENCE #1: Zhu W, Ding Z, Zhang Y, Shi J, Hashimoto K, Lu L. Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant. Neurosci Bull. Dec 2016;32(6):557-564. doi:10.1007/s12264-016-0081-2 REFERENCE #2: Wang JW, Kivovich V, Gordon L. Ketamine Abuse Syndrome: Hepatobiliary and Urinary Pathology Among Adolescents in Flushing, NY. Pediatr Emerg Care. Aug 2017;33(8):e24-e26. doi:10.1097/PEC.0000000000000502 REFERENCE #3: Xu J, Lei H. Ketamine-an update on its clinical uses and abuses. CNS Neurosci Ther. Dec 2014;20(12):1015-20. doi:10.1111/cns.12363 DISCLOSURES: No relevant relationships by Christiana Atuaka, source=Web Response No relevant relationships by Claudia De Araujo Duarte, source=Web Response Speaker/Speaker's Bureau relationship with pfizer Please note: $1001 - $5000 by Yizhak Kupfer, source=Admin input, value=Consulting fee No relevant relationships by Sanwal Mehta, source=Web Response No relevant relationships by Ratnam Santoshi, source=Web Response