Clinical trial NCT05612399: Precision Analgesia for Cardiac Surgery
Official title: Precision Perioperative Methadone Use in Adult Cardiac Surgical Patients to Reduce Opioid Use Adverse Effects While Improving Analgesia and Outcomes
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Analgesia
Cardiac Surgery
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2022-11-10
Enrollment: 400
Sex: ALL
Minimum age (years): 60
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine Genetic Factors - Opioid Related Adverse Events (RD)
timeFrame: Immediately post-surgery during hospital stay
measure: Determine Genetic Factors - Opioid Related Adverse Events (PONV)
timeFrame: Immediately post-surgery during hospital stay
measure: Determine Genetic Factors - Opioid Related Adverse Events (Excessive Sedation)
timeFrame: Immediately post-surgery during hospital stay
measure: Determine Genetic Factors - Uncontrolled severe pain
timeFrame: Immediately post-surgery during hospital stay
Secondary outcomes:
measure: Opioid use post-operatively
timeFrame: Post-operative Day 5 to 6-months post-operative
measure: Patient-Reported Outcomes Measurement Information System
timeFrame: Post-operative Day 5 to 6-months post-operative
measure: Incidence of Chronic Persistent Surgical Pain (CPSP)
timeFrame: Post-operative Day 5 to 6-months post-operative
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Kathirvel Subramaniam, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Amy Monroe, MPH, MBA
role: STUDY_DIRECTOR
References: