Pain Control and Quality of Recovery After Intravenous Methadone Versus Intrathecal Morphine in Major Abdominal Surgery

Обзор

Moderate to severe postoperative pain is relatively common after major abdominal surgery. It is associated with less than optimal surgical experience, poor quality of recovery, and the development of persistent postsurgical pain. Opioids remain a significant component of postoperative pain management. Side effects of opioids used for the treatment of postoperative pain include constipation, pruritus, nausea, and vomiting. Enhanced recovery after surgery (ERAS) protocols involve the utilization of multimodal analgesia. Analgesic techniques used include epidural analgesia, nerve blocks, and Intrathecal (IT) administration of morph ne. IT morphine reduces the postoperative opioid requirement for 18-24 hours after major abdominal surgery and reduces hospital length of stay (LOS) compared with epidural analgesia. A significant number of patients who receive IT morphine still experience moderate to severe postoperative p in. Additionally, many patients refuse the invasive procedure or cannot receive IT morphine due to procedure contraindications, thrombocytopenia, and/or coagulopathy. Intravenous (IV) methadone has a long analgesic half-life and has N-methyl-D-aspartate (NMDA) receptor antagonist and serotonin and norepinephrine reuptake inhibitor (SNRI) properties. It has previously been shown to reduce postoperative opioid requirements, postoperative nausea and vomiting (PONV), and postoperative pain scores in patients who underwent orthopedic, abdominal, complex spine, and cardiac surg ry. Similar findings have been shown in obstetric patients who underwent cesarean delivery under general anesthesia as well as patients who underwent gynecologic surgery. IV methadone has, however, never been compared with IT morphine as a postoperative analgesic. The hypothesis is that intravenous (IV) methadone is non-inferior to IT morphine in patients who undergo major abdominal surg ry. It offers the advantage of being a noninvasive analgesic modality that may contribute to decreasing opioid consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving the quality of recovery after surgery.

Подробное описание

Moderate to severe postoperative pain is relatively common after major abdominal surgery. It is associated with less than optimal surgical experience, poor quality of recovery, and the development of persistent postsurgical pain. Opioids remain a significant component of postoperative pain management. Side effects of opioids used for the treatment of postoperative pain include constipation, pruritus, nausea, and vomiting. Enhanced recovery after surgery (ERAS) protocols involve the utilization of multimodal analgesia. Analgesic techniques used include epidural analgesia, nerve blocks, and Intrathecal (IT) administration of morph ne. IT morphine reduces the postoperative opioid requirement for 18-24 hours after major abdominal surgery and reduces hospital length of stay (LOS) compared with epidural analgesia. A significant number of patients who receive IT morphine still experience moderate to severe postoperative p in. Additionally, many patients refuse the invasive procedure or cannot receive IT morphine due to procedure contraindications, thrombocytopenia, and/or coagulopathy.

Intravenous (IV) methadone has a long analgesic half-life and has N-methyl-D-aspartate (NMDA) receptor antagonist and serotonin and norepinephrine reuptake inhibitor (SNRI) properties. It has previously been shown to reduce postoperative opioid requirements, postoperative nausea and vomiting (PONV), and postoperative pain scores in patients who underwent orthopedic, abdominal, complex spine, and cardiac surg ry. Similar findings have been shown in obstetric patients who underwent cesarean delivery under general anesthesia as well as patients who underwent gynecologic surgery. IV methadone has, however, never been compared with IT morphine as a postoperative analgesic.

The hypothesis is that intravenous (IV) methadone is non-inferior to IT morphine in patients who undergo major abdominal surg ry. It offers the advantage of being a noninvasive analgesic modality that may contribute to decreasing opioid consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving the quality of recovery after surgery.

Вмешательства

• Препарат Methadone
  Intravenous Methadone
• Препарат Morphine
  Intrathecal Morphine

Первичные конечные точки

• Quality of Recovery 15 score [Срок оценки: 24 hours, 48 hours, 72 hours, 42 days, 92 days]
• Overall Benefits of Analgesic Score [Срок оценки: 24 hours, 48 hours, 72 hours, 42 days, 92 days]
• morphine milligram equivalent [Срок оценки: 24 hours, 48 hours, 72 hours]
• Numeric Rating Scale pain scores (NRS) [Срок оценки: 24 hours, 48 hours, 72 hours]

Вторичные конечные точки (2)

• McGill Pain questionnaire score [Срок оценки: 42 days, 92 days]
• Numeric Rating Pain Score (NRS) [Срок оценки: 42 days, 92 days]

Критерии участия

Критерии включения

• Adult patients with an American Society of Anesthesiologists (ASA) physiological status I-III
• Undergoing laparotomy with midline incision
• Body mass index (BMI) between 18.5 and 45
• Ability to understand and read English
• Willingness and ability to comply with scheduled visits and study procedures

Критерии исключения

• Not able or unwilling to sign consent
• Patients undergoing ambulatory surgery or anticipated to be discharged sooner than 24 hours after surgery
• Patients with chronic pain, requiring daily opioid use at the time of surgery, MME >60 as the FDA defines opioid tolerant as 60 MME, long-acting forms of opioids such as fentanyl patch, oxycontin.
• Pregnant Women
• Patients requiring emergent surgery
• Contraindications to neuraxial anesthesia including:

• Coagulopathy
• localized infection at the site of injection
• pre-existing spinal pathology, specifically defined as active radiculopathy, severe central canal stenosis in the lumbar region, or an acute fracture in the lumbar region
• length of the QT interval (QTc) >450 on the most recent preoperative electrocardiogram (EKG)
• Prior spinal fusion
• Active or Prior Substance Use Disorder, undergoing active treatment with Medication of Opioid Use Disorder including methadone (once daily dosing), Buprenorphine (any formulation) and Naltrexone

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

Простое слепое

Основная цель

Организация здравоохранения

Центры проведения

США · 1 центр

• University of Virginia — Charlottesville

Публикации

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• Bauchat JR, Habib AS. Evidence-based anesthesia for major gynecologic surgery. Anesthesiol Clin. 2015 Mar;33(1):173-207. doi: 10.1016/j.anclin.2014.11.011. Epub 2014 Dec 31. PMID 25701935
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• Modesitt SC, Sarosiek BM, Trowbridge ER, Redick DL, Shah PM, Thiele RH, Tiouririne M, Hedrick TL. Enhanced Recovery Implementation in Major Gynecologic Surgeries: Effect of Care Standardization. Obstet Gynecol. 2016 Sep;128(3):457-66. doi: 10.1097/AOG.0000000000001555. PMID 27500337
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• Mancini I, Lossignol DA, Body JJ. Opioid switch to oral methadone in cancer pain. Curr Opin Oncol. 2000 Jul;12(4):308-13. doi: 10.1097/00001622-200007000-00006. PMID 10888415
• Slotkin TA, Seidler FJ, Whitmore WL. Methadone inhibits serotonin and norephinephrine uptake into rat brain synaptosomes and synaptic vesicles in vitro but not in vivo. Eur J Pharmacol. 1978 Jun 15;49(4):357-62. doi: 10.1016/0014-2999(78)90309-6. PMID 668807

Идентификаторы

NCT: NCT06387303 · HSR230492

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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