Precision Medicine in Anesthesia: Genetic Component in Opioid-induced Respiratory Depression

Overview

The concept of precision medicine - taking individual variability into account when planning preventions and interventions - is not new but is quickly gaining attention in this age of powerful methodology of patient characterization and development of tools to analyze large sets of data. Oncology is the most obvious field in which this information has been readily applied. Increasing focus, nationally and internationally, on developing broad databases of patient genetic information and research efforts evaluating those data will, hopefully, lead to the development and application of evidence-based data enhancing the practice of all fields of medicine. It has yet to become obvious how this information can best be applied to the field of anesthesiology. Most genomics work in anesthesia has been focused in the area of pain medicine. There is a known genetic influence on the potency of opioid-induced analgesia, however; a genetic component of opioid-induced respiratory depression has yet to be thoroughly evaluated. Respiratory depression plays a role in clinical care - from procedures requiring sedation with monitored anesthesia care to treating post-opertative pain and chronic pain - but perhaps its largest current role in the public arena is the unfortunate deaths caused by side effects due to drug overdose. Personalized medicine remains on the horizon for the field of anesthesia, but, as genetic testing becomes more affordable and mainstream in clinical practice, the potential applications are broad. Most readily would be its incorporation into development of patient specific pain regimens. Respiratory depression is a potentially lethal side effect of opioid therapy. In light of the opioid epidemic and CDC-scrutiny of opioid use, determining genetic profiles susceptible to respiratory depression could prove useful in further tailoring the treatment of pain both in the perioperative setting and in the chronic pain management setting.

This would be a prospective study for which patients not prescribed chronic pain medication (defined as not using narcotic medications in 3 months prior to surgery) and presenting for surgery would be recruited. Preop administration of sedating medications (i.e. midazolam) would be avoided. On the day of surgery, once in OR and standard ASA monitors placed, a standardized dose of 2mcg/kg ideal body weight IV fentanyl is administered. The patient is then monitored for respiratory depression for 5 minutes prior to administration of additional induction agents. \[would include respiratory rate, with RR \< 10, or O2 Sat \< 90%\]. Would not provide supplemental oxygen during this time unless patient was already on supplemental oxygen. Patient would then be preoxygenated and general anesthesia induced. Once general anesthesia is induced, a blood sample is collected and stored. \[sample could also be collected in preop upon IV placement\]. Blood will be tested for Single Nucleotide Polymorphisms of genes related to opioid-induced analgesia. \[Potential target genes listed in 7.0-1\] This genomic data will be evaluated for any correlations of the presence of opioid-related SNPs and concomitant opioid-induced respiratory depression.