Methadone Pharmacokinetics in Cardiac Surgery

Официальное название

Evaluating Pharmacokinetics of Three Methadone Dosing Strategies During Cardiac Surgery With Cardiopulmonary Bypass

Обзор

Cardiac surgery frequently leads to significant postoperative pain, with multiple different drug regimens being utilized (both opioid and non-opioid) in an attempt to alleviate this surgical pain. Methadone is currently one of the drugs that is being utilized to help control the pain. It can be given during and/or after surgery. This study hopes to identify the optimal dose of methadone to use to treat this surgical pain.

Подробное описание

The uncertainty regarding optimal methadone dosing and the necessity of post-cardiopulmonary bypass (CPB) supplementation provides a compelling rationale for this study. Specifically, it remains unknown whether a single higher initial dose of methadone can adequately maintain analgesic plasma concentrations throughout cardiac surgery and recovery, or if a split-dosing strategy administering a lower initial dose followed by an additional dose post-CPB might offer similar or improved analgesic outcomes with fewer side effects. This study will evaluate pharmacokinetics of methadone using three different dosing strategies in patients undergoing cardiac surgery with CPB.

Вмешательства

• Препарат Single dose of methadone
  Single dose of methadone 0.3 mg/kg actual body weight (max 30 mg) administered at induction of anesthesia
• Препарат Split dose of methadone
  Split dose of methadone 0.2 mg/kg actual body weight at induction and 0.1 mg/kg actual body weight post cardiopulmonary bypass
• Препарат Balanced split dose of methadone
  Balanced split dose of methadone 0.15 mg/kg actual body weight at induction and 0.15 mg/kg actual body weight post cardiopulmonary bypass

Первичные конечные точки

• Plasma methadone concentration (ng/mL) 10 min post initial dose [Срок оценки: 10 minutes]
• Plasma methadone concentration (ng/mL) 30 min post initial dose [Срок оценки: 30 minutes]
• Plasma methadone concentration (ng/mL) 60 min post initial dose [Срок оценки: 60 minutes]
• Plasma methadone concentration (ng/mL) 10 min post start of cardiopulmonary bypass [Срок оценки: 10 minutes]
• Plasma methadone concentration (ng/mL) 30 min post start of cardiopulmonary bypass [Срок оценки: 30 minutes]
• Plasma methadone concentration (ng/mL) 60 min post start of cardiopulmonary bypass [Срок оценки: 60 minutes]
• Plasma methadone concentration (ng/mL) 10 min post cardiopulmonary bypass completion [Срок оценки: 10 minutes]
• Plasma methadone concentration (ng/mL) 120 min post start of cardiopulmonary bypass [Срок оценки: 120 minutes]
• Plasma methadone concentration (ng/mL) before first analgesic request [Срок оценки: up to 72 hours]
• Plasma methadone concentration (ng/mL) 3 hours post Intensive Care Unit arrival [Срок оценки: 3 hours]

Вторичные конечные точки (7)

• pain intensity score [Срок оценки: 2, 4, 8, 12, 24, 48, and 72 hours postoperatively and month 3]
• patient global impression of change [Срок оценки: 24, 48, and 72 hours after removal of the breathing tube]
• postoperative opioid consumption [Срок оценки: up 72 hours postop]
• duration of postoperative mechanical ventilation [Срок оценки: up to 72 hours postop]
• time of ambulation [Срок оценки: up to 48 hours postop]
• length of Intensive Care Unit stay [Срок оценки: up to 3 days postop]
• length of hospital length stay [Срок оценки: up to 7 days postop]

Критерии участия

Критерии включения

• Elective cardiac surgery requiring median sternotomy and cardiopulmonary bypass (CABG, valve, combined CABG/valve surgeries)
• Anticipated extubation within 12 hours postoperatively
• No prior opioid use within 30 days of surgery
• Ability to provide informed consent

Критерии исключения

• Severe liver or kidney dysfunction (Child-Pugh class B/C, eGFR <30 mL/min/1.73m², creatinine >2 mg/dL, dialysis)
• Allergy to methadone or fentanyl
• Use of CYP3A4 inducers (rifampin, phenytoin, carbamazepine), CYP3A4 inhibitors (ketoconazole, erythromycin, clarithromycin, itraconazole), SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine)
• Body mass index >40 kg/m²
• Corrected QT interval interval >500 milliseconds
• Intubation anticipated >12 hours
• History of illicit drug use or alcohol or opioid abuse use disorder within last 12 months
• Mechanical circulatory support, heart transplant, deep hypothermic circulatory arrest procedures
• Left Ventricular Ejection Fraction <30%
• Pulmonary disease requiring oxygen therapy
• Preoperative inotropic support or intra-aortic balloon pump
• Emergency surgery
• Postoperative regional anesthesia
• Hemofiltration during cardiopulmonary bypass

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Wake Forest University Health Sciences — Winston-Salem

Идентификаторы

NCT: NCT07226245 · IRB00136746

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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