Pharmacogenomic variation and sedation outcomes during early intensive care unit admission: A pragmatic study

Abstract

Unpredicted responses to sedatives and analgesics are common in critically ill patients on mechanical ventilation (MV) and may be attributed to genetic variation. Our primary aim was to investigate the association between the pharmacogenomic (PGx) variation and sedation outcomes. The secondary aim was to capture intensive care unit (ICU) participants' perceptions of PGx. This was a prospective, observational PGx association study. Adult ICU patients receiving acute MV and sedatives/analgesics were enrolled. The number of altered PGx phenotypes in genes relevant to fentanyl, propofol, and midazolam (CYP2D6, CYP3A4/5, COMT, OPRM1, and CYP2B6) were tested with logistic regression for association with achieving ≥60% and ≥70% of time within Richmond Agitation-Sedation Scale (RASS) target range (0 to -2) in the first 24 and 48 h of MV. Participants' perceptions of PGx testing and satisfaction with the return of PGx results were collected. Participants (n = 78) had a median of 2 altered PGx phenotypes. Fentanyl and propofol combination was the most frequently administered regimen. There were non-significant associations of worse sedation outcomes with an increasing number of altered PGx phenotypes (i.e., adjusted odds ratio of achieving target RASS range = 0.46 to 0.96 for each altered phenotype increase at both 24 and 48 h). Individuals participating in the post-discharge survey had positive perceptions toward PGx. There were no associations between sedation outcomes and PGx variants in the studied 6 genes. Larger studies are needed to investigate the impact of these genes and to evaluate additional genes. ICU participants had positive attitudes and perceptions toward PGx.