Precision Analgesia for Cardiac Surgery

Precision Perioperative Methadone Use in Adult Cardiac Surgical Patients to Reduce Opioid Use Adverse Effects While Improving Analgesia and Outcomes

The proposed research is an important extension of an ongoing perioperative personalized analgesia and intravenous opioid pharmacogenetic research. This research focuses on two of the most commonly used oral opioid analgesics, oxycodone, and methadone in elderly adults undergoing cardiac surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Analgesia; Cardiac Surgery

Detailed Description

Cardiac surgery patients often experience significant acute postoperative pain, and untreated or undertreated pain has consequences. Each year, 900,000 painful cardiac surgeries occur in the US alone. Pain associated with cardiac surgery results from surgical incision, sternal retraction, internal mammary artery harvesting, saphenous vein removal, placement of mediastinal and chest drains, sternal wires, and release of pro-inflammatory mediators after tissue injury. One study reported that 49%, 62%, and 78% of patients reported severe pain at rest, movement, and coughing, respectively after coronary artery bypass surgery (CABG). Another study showed that 61.4% of patients undergoing cardiac surgery reported moderate to severe pain. Inadequate pain treatment is common in cardiac surgery due to health care providers' fears of causing cardiorespiratory compromise. Poor pain control can trigger sympathoadrenal responses leading to cardiac arrhythmias and myocardial ischemia, restrict mobility to cause venous thrombosis, impair clearance of secretions leading to pulmonary complications such as atelectasis and pneumonia, decrease patient satisfaction and predispose to the development of chronic, persistent surgical pain (CPSP).

Improving clinical practice by shifting paradigms: Our research is transformative and will evolve current reactive clinical practice towards proactive precision methods based on genetic risks for surgical pain and ORADE in elderly vulnerable population. This is the first effort to move in the direction of personalizing perioperative opioid use with precise dosing to improve safety and efficacy in cardiac surgery. Preoperative genotyping-based clinical decisions are expected to support clinical implementation in real-world settings. Importantly, investigators will be able to reach beyond the current best-in-class outcomes with precision multi-dose methadone analgesia based on proactive genetic risk identification to maximize safety and efficacy of opioids in all cardiac surgical patients and positively impact socio-economic outcomes in the future. By addressing these critical barriers, this research will help physicians identify patients at risk and improve the safety and efficacy of opioids and surgical pain management while preventing OD, misuse, overdose, and deaths.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Alisha Maslanka, BS, CCRC; Phone Number: 412-864-6779; Email: maslankaaa@upmc.edu
• Study Contact Backup: Name: Carly Riedmann, BS; Phone Number: 412-623-4147; Email: riedmannca@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
      • Contact: Amy Monroe, MPH, MBA; Phone Number: 412-623-6382; Email: monroeal@upmc.edu
      • Contact: Kathirvel Subramaniam, MD, MPH; Email: subramaniamk@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Elderly cardiac surgical patients over 60 years of age Both genders are included All races and ethnic groups undergoing elective open cardiac surgery through midline sternotomy

Description

Inclusion Criteria:

• Elderly cardiac surgical patients over 60 years of age

Exclusion Criteria:

• Methadone allergy
• Morbid obesity (BMI >40kg/cm2)
• Severe sleep apnea
• Severe pulmonary disease requiring oxygen therapy
• Preoperative mechanical circulatory support
• Emergency surgery
• Liver disease (liver enzymes more than two times normal)
• End-stage renal disease requiring dialysis
• Serum creatinine more than 2.0mg

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Genetic Factors - Opioid Related Adverse Events (RD)	Respiratory depression will be measured with binary yes/no responses obtained either via self-report from the patient or reported by the clinical care staff.	Immediately post-surgery during hospital stay
Determine Genetic Factors - Opioid Related Adverse Events (PONV)	Post-operative nausea and vomiting will be measured with binary yes/no responses obtained either via self-report from the patient or reported by the clinical care staff.	Immediately post-surgery during hospital stay
Determine Genetic Factors - Opioid Related Adverse Events (Excessive Sedation)	Excessive sedation will be measured with binary yes/no responses obtained either via self-report from the patient or reported by the clinical care staff.	Immediately post-surgery during hospital stay
Determine Genetic Factors - Uncontrolled severe pain	We postulate that specific CYP2B6, ABCB1, OPRM1, FAAH, and ORM1 genetic variants identify patients at risk for poor pain relief and ORADE with methadone in the immediate post-surgical period. Pain will be measured by the Numerical Rating Scale (NRS) in which 0 = no pain at all and 10 = worst pain imaginable. This will be self-reported responses by the patient.	Immediately post-surgery during hospital stay

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid use post-operatively	Opioid usage will be recorded via SOAPP-R, a 24-item validated opioid assessment. A score of 18 or higher is considered positive.	Post-operative Day 5 to 6-months post-operative
Patient-Reported Outcomes Measurement Information System	The PROMIS-29 v2.0 will be collected for this outcome measure. The PROMIS survey is scored by the following T-Score Cut Points: 20-55 = better health, 55-60 = mild, 61-69 = moderate, and 71+ = worse health. The general population mean = 50 (SD = 10).	Post-operative Day 5 to 6-months post-operative
Incidence of Chronic Persistent Surgical Pain (CPSP)	CPSP will be obtained via patient-self report as yes/no responses for follow-up assessments. This measure will be reported as mean(SD) for positive CPSP subjects.	Post-operative Day 5 to 6-months post-operative

Collaborators and Investigators

• Sponsor: Kathirvel Subramaniam
• Investigators: Principal Investigator: Kathirvel Subramaniam, MD, MPH, University of Pittsburgh; Study Director: Amy Monroe, MPH, MBA, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 3, 2022
• First Submitted That Met QC Criteria: November 3, 2022
• First Posted (Actual): November 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 11, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia
• Other Study ID Numbers: STUDY22060101

Drug and device information, study documents

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