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

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.

Study Overview

• Status: Terminated
• Conditions: Respiratory Depression
• Intervention / Treatment: Drug: Fentanyl

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Participants will be selected from the OR schedule and recruit/consent patients in the preop clinic or preop holding area during preop evaluation.

Description

Inclusion Criteria:

• Age 18-80 years old,
• English-speaking,
• Not on current opioid therapy,
• ASA I-III,
• Scheduled for elective surgery at UAB main

Exclusion Criteria:

• Chronic opioid therapy [Consistent use of opioid meds 3 months prior to surgery]
• pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ASA Patients I; Age 18-80 years old, English-speaking, not on current Fentanyl/opioid therapy, no use of opioid medications in the 3 months prior to surgery, scheduled for elective surgery at UAB main. A normal healthy patient Healthy, non-smoking, no or minimal alcohol use	Drug: Fentanyl; After the patient is attached to an ASA non-invasive monitor, a dose (2mcg/kg) of Fentanyl will be administered. Groups compared would include patients experiencing respiratory depression vs those not experiencing respiratory depression after fentanyl administration. Their samples would be evaluated for any differences in genetic make-up concerning selected, known sequences affecting opioid-induced analgesia.; Other Names: Durogesic; Denpax
ASA Patients III; Age 18-80 years old, English-speaking, not on current Fentanyl/opioid therapy, no use of opioid medications in the 3 months prior to surgery, scheduled for elective surgery at UAB main. A patient with severe systemic disease Substantive functional limitations; One or more moderate to severe diseases. Examples include (but not limited to): poorly controlled DM or HTN, COPD, morbid obesity (BMI ≥40), active hepatitis, alcohol dependence or abuse, implanted pacemaker, moderate reduction of ejection fraction, ESRD undergoing regularly scheduled dialysis, premature infant PCA < 60 weeks, history (>3 months) of MI, CVA, TIA, or CAD/stents.	Drug: Fentanyl; After the patient is attached to an ASA non-invasive monitor, a dose (2mcg/kg) of Fentanyl will be administered. Groups compared would include patients experiencing respiratory depression vs those not experiencing respiratory depression after fentanyl administration. Their samples would be evaluated for any differences in genetic make-up concerning selected, known sequences affecting opioid-induced analgesia.; Other Names: Durogesic; Denpax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single Nucleotide Polymorphisms	Preop-Blood will be tested for Single Nucleotide Polymorphisms of genes related to opioid-induced analgesia	5 min Preop

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Study Chair: Tim Ness, MD, PhD, UAB Anesthesiology and Perioperative Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2018
• Primary Completion (Actual): May 21, 2025
• Study Completion (Actual): May 21, 2025

Study Registration Dates

• First Submitted: February 15, 2018
• First Submitted That Met QC Criteria: February 15, 2018
• First Posted (Actual): February 22, 2018

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Respiratory Tract Diseases; Respiration Disorders; Mood Disorders; Respiratory Insufficiency; Depression; Depressive Disorder; Physiological Effects of Drugs; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Anesthetics, Intravenous; Anesthetics, General; Fentanyl
• Other Study ID Numbers: F23456789; UAB (Other Identifier: UAB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No