A pharmacogenetic precision medicine approach to analgesia and sedation optimization in critically ill adults

Abstract

Precision medicine is a growing field in critical care. Research increasingly demonstrated pharmacogenomic variability to be an important determinant of analgesic and sedative drug response in the intensive care unit (ICU). Genome-wide association and candidate gene finding studies suggest analgesic and sedatives tailored to an individual's genetic makeup, environmental adaptations, in addition to several other patient- and drug-related factors, will maximize effectiveness and help mitigate harm. However, the number of pharmacogenetic studies in ICU patients remains small and no prospective studies have been published using pharmacogenomic data to optimize analgesic or sedative therapy in critically ill patients. Current recommendations for treating ICU pain and agitation are based on controlled studies having low external validity, including the failure to consider pharmacogenomic factors affecting response. Use of a precision medicine approach to individualize pharmacotherapy focused on optimizing ICU patient comfort and safety may improve the outcomes of critically ill adults. Additionally, benefits and risks of analgesic and/or sedative therapy in an individual may be informed with large, standardized datasets. The purpose of this review was to describe a precision medicine approach focused on optimizing analgesic and sedative therapy in individual ICU patients to optimize clinical outcomes and reduce safety concerns.

Keywords: analgesics; dexmedetomidine; drug dosing; fentanyl; intensive care; ketamine; opioids; pharmacogenomics; propofol; sedatives.