DP47: WHEN PROPOFOL ISN'T ENOUGH: SEDATION RESISTANCE IN A CYP2C19 ULTRA-RAPID METABOLIZER
Michael Lafferty; Jaime Tellez; Amanda Frantz, MD; Peggy A White, MD
University of Florida College of Medicine
Introduction: Propofol is one of the most widely used intravenous anesthetics and is primarily metabolized through hepatic glucuronidation and hepatic hydroxylation, the latter of which utilizes cytochrome P450 enzymes. A rare CYP2C19 variant, CYP2C19 *17/*17, results in two copies of the increased-expression, *17, allele and classifies individuals as ultra-rapid metabolizers (URMs). CYP2C19 URMs have been found to have altered metabolization of proton-pump inhibitors, clopidogrel, and benzodiazepines; however, the metabolization of propofol in this subgroup has not been well studied.
Methods: A 40-year-old female with a two-year history of upper and lower gastrointestinal symptoms underwent pre-procedure CYP2C19 testing due to poor response to esomeprazole. She was identified as a CYP2C19 *17/*17 ultra-rapid metabolizer and scheduled for a combined colonoscopy and esophagogastroduodenoscopy. Standard bowel preparation was followed, and medical evaluation revealed no comorbidities, medication interactions, or CYP450-inducing agents. Under Monitored Anesthesia Care, propofol was selected as the sole sedative agent, initiated at 250 mcg/kg/min with standard ASA monitoring.
Results: Seven minutes after induction, the patient remained responsive to stimuli, requiring increased infusion rates and a 20-mg propofol bolus. Despite high-dose maintenance infusions and a second bolus, the patient remained intermittently responsive throughout the 37-minute procedure. Hemodynamics and ventilation remained stable with no adverse respiratory events.
Conclusion: Although CYP2C19 contributes to the metabolism of propofol, current evidence indicates its overall contribution is modest when compared with other cytochrome enzymes and hepatic glucuronidation. As a result, CYP2C19 *17/*17 status is not typically associated with increased propofol requirements, raising the possibility of additional unrecognized pharmacogenomic variants such as UGT1A9, CYP2B6, or GABA-receptor related genes. This case highlights the importance of individualized anesthetic plans and pharmacogenomic data should complement, not replace, clinical judgement. Our institution currently houses a database of CYP2C19 genotypes, providing an opportunity to further study the propofol and anesthetic requirements of this group of metabolically unique patients.