Precision Medicine in Anesthesia

Overview

This study is designed to look at how often a decrease in the rate of breathing occurs after being given a routinely used intravenous (IV) pain medication. This pain medication (Fentanyl) is given in the research procedure room by the anesthesiologist. In addition to relieving pain, in some patients it has been observed that this medication may decrease the rate of breathing. Different pieces of one's genetic makeup (also known as genes) can affect how well this medication relieves pain. The investigators do not know if these same genes influence how large the effect of the medication has on breathing rate. The purpose of this study is to determine if the presence or alteration of these same genes may be associated with a decrease in rate of breathing.

Opioids are key analgesic drugs. Unfortunately, they have a high potential for abuse with potentially lethal consequences, more specifically death due to respiratory suppression. In both Canada and the US, the number of deaths from opioid overdose continues to rise at an alarming rate, far exceeding fatalities from motor vehicle accidents in Canada and becoming the number one cause of unintentional injury-related death in the US. 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. The purpose of the proposed study is to evaluate for a genetic component of opioid-induced respiratory depression. Our overall study hypothesis is that genetic variation influences opioid-induced respiratory depression. The primary aim of the study is to correlate an intravenous opioid bolus and genetic variations of opioid-related target genes. Secondary aims or outcomes are the determination of general variation in respiratory responses in response to a single intravenous fentanyl bolus. Other observed effects are age and gender related differences, the effect of a single fentanyl bolus on alertness, the incidence of emesis and opioid effects on micturition as determined by the modified Aldrete discharge criteria. Based on existing work on genetic determinants of opioid receptor effects, we propose to correlate clinical parameters of respiratory depression (proportional reduction in respiratory minute ventilation) with the expression of single-nucleotide polymorphisms (SNPs) of genes related to opioid-induced analgesia. We propose to identify a subset of participants with the most significant respiratory depression and contrast those with participants that exhibit no respiratory effects. The blood samples from these two groups will be used to compare genetic variances of genes related to opioid-induced analgesia. This will be a collaborative project between the clinical physicians and basic scientists in an effort to better characterize opioid-induced respiratory depression. We believe this work will be valuable as a means to prevent and treat opioid toxicity and guide development of safer approaches to opioid therapy and drug development.

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