title: Genetic risk signatures of opioid-induced respiratory depression following pediatric tonsillectomy.
abstract: Background: Respiratory depression is a clinically and economically important but preventable complication of opioids. Genetic factors can help identify patients with high risk for respiratory depression. Methods: In this prospective genotype blinded clinical study, we evaluated the effect of a panel of variants in candidate genes on opioid-related respiratory depression in 347 children following tonsillectomy. Results: Using unsupervised hierarchical clustering and a combination of candidate genotypes and clinical variables, we identified several distinct clusters of patients at high risk (36-38%) and low risk (10-17%) of respiratory depression; the relative risk of respiratory depression for high versus low risk clusters was 2.1-3.8 (p = 0.003). Conclusion: Genetic risk predictions (genetic signatures) along with clinical risk factors effectively identify children at higher and lower risks of opioid-induced respiratory depression. Genetic signatures of respiratory depression offer strategies for improved clinical decision support to guide clinicians to balance the risks of opioid adverse effects with analgesia. Original submitted 9 July 2014; Revision submitted 19 September 2014.
authors.affiliation: Division of Biomedical Informatics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Jacek
authors.initials: J
authors.lastname: Biesiada
authors.forename: Vidya
authors.initials: V
authors.lastname: Chidambaran
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Meller
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Sadhasivam
keywords: children; depression; genetic signature; morphine; opioid; pediatric tonsillectomy; pharmacogenetics; respiratory; surgical pain