title: Interpatient variability in dexmedetomidine response: a survey of the literature.
abstract: Fifty-five thousand patients are cared for in the intensive care unit (ICU) daily with sedation utilized to reduce anxiety and agitation while optimizing comfort. The Society of Critical Care Medicine (SCCM) released updated guidelines for management of pain, agitation, and delirium in the ICU and recommended nonbenzodiazepines, such as dexmedetomidine and propofol, as first line sedation agents. Dexmedetomidine, an alpha-2 agonist, offers many benefits yet its use is mired by the inability to consistently achieve sedation goals. Three hypotheses including patient traits/characteristics, pharmacokinetics in critically ill patients, and clinically relevant genetic polymorphisms that could affect dexmedetomidine response are presented. Studies in patient traits have yielded conflicting results regarding the role of race yet suggest that dexmedetomidine may produce more consistent results in less critically ill patients and with home antidepressant use. Pharmacokinetics of critically ill patients are reported as similar to healthy individuals yet wide, unexplained interpatient variability in dexmedetomidine serum levels exist. Genetic polymorphisms in both metabolism and receptor response have been evaluated in few studies, and the results remain inconclusive. To fully understand the role of dexmedetomidine, it is vital to further evaluate what prompts such marked interpatient variability in critically ill patients.
authors.affiliation: University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Samantha F
authors.initials: SF
authors.lastname: Holliday
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Kane-Gill
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Empey
authors.affiliation: Banner Good Samaritan Medical Center, Department of Pharmacy, 1111 E. McDowell Road, Phoenix, AZ 85006, USA.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Buckley
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Smithburger
mesh_terms: D003422:Critical Care / Q000379:methods* / Q000592:standards; D016638:Critical Illness / Q000628:therapy*; D020927:Dexmedetomidine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D057285:Precision Medicine / Q000379:methods* / Q000592:standards
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine