Pain Control and Quality of Recovery After Intravenous Methadone Versus Intravenous Remifentanil in Craniotomy Surgery

Обзор

Postoperative pain is prevalent after intracranial surgery. Patients undergoing craniotomy are typically managed with short acting opioids to enable early and reliable post-operative neurological exam as well as avoid the risk of respiratory depression. However, a plethora of studies have shown that a majority of these patients experience moderate to severe pain in first 48 hours after surgery. Suboptimal pain control can lead to complications such as arterial hypertension and post-operative intracranial hemorrhage, and hence, increased morbidity and mortality. 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 that underwent orthopedic, abdominal, complex spine, and cardiac surgery. Similar findings have been shown in obstetric patients that underwent caesarean delivery under general anesthesia as well as patients that underwent gynecologic surgery and received IV methadone intraoperatively. In a recently published retrospective study, a single intraoperative dose of IV methadone was well tolerated with lower pain scores as well as MME (oral morphine milligram equivalents) requirements for up to 72 hours after elective intracranial surgery. IV methadone has, however, never been compared with conventional management via IV remifentanil for functional recovery in patients undergoing elective intercranial surgery. The investigator's hypothesis is that intravenous (IV) methadone is non-inferior to IV remifentanil in patients who undergo elective intracranial surgery. It offers the advantage of being a single dose noninvasive analgesic modality that may contribute to decreasing MME consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving quality of recovery after surgery.

Подробное описание

Postoperative pain is prevalent after intracranial surgery. Patients undergoing craniotomy are typically managed with short acting opioids to enable early and reliable post-operative neurological exam as well as avoid the risk of respiratory depression. However, a plethora of studies have shown that a majority of these patients experience moderate to severe pain in first 48 hours after surgery. Suboptimal pain control can lead to complications such as arterial hypertension and post-operative intracranial hemorrhage, and hence, increased morbidity and mortality.

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 that underwent orthopedic, abdominal, complex spine, and cardiac surgery. Similar findings have been shown in obstetric patients that underwent caesarean delivery under general anesthesia as well as patients that underwent gynecologic surgery and received IV methadone intraoperatively.

In a recently published retrospective study, a single intraoperative dose of IV methadone was well tolerated with lower pain scores as well as MME (oral morphine milligram equivalents) requirements for up to 72 hours after elective intracranial surgery.

IV methadone has, however, never been compared with conventional management via IV remifentanil for functional recovery in patients undergoing elective intercranial surgery.

The investigator's hypothesis is that intravenous (IV) methadone is non-inferior to IV remifentanil in patients who undergo elective intracranial surgery. It offers the advantage of being a single dose noninvasive analgesic modality that may contribute to decreasing MME consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving quality of recovery after surgery.

Вмешательства

• Препарат Remifentanil
  Intravenous Remifentanil
• Препарат Methadone
  Intravenous Methadone

Первичные конечные точки

• Quality of recovery after surgery on postoperative day 1,2,3 using QoR-15 psychometrical questionnaire (range 0-150). [Срок оценки: 24 hours, 48 hours, 72 hours]

Вторичные конечные точки (6)

• Morphine Milligram Equivalent [Срок оценки: 24 hours, 48 hours, 72 hours]
• Numeric Rating scale (NRS) pain scores (0-10) as noted over post-operative day 0, 1, 2, and 3. [Срок оценки: 24 hours, 48 hours, 72 hours]
• Overall Benefits of Analgesic Score (OBAS) as noted over post-operative day 0, 1, 2, and 3. [Срок оценки: 24 hours, 48 hours, 72 hours]
• Complications and side effects as noted over post-operative day 0, 1, 2, and 3. [Срок оценки: 24 hours, 48 hours, 72 hours]
• Length of Stay in Post-Anesthesia Care Unit (PACU) [Срок оценки: 0 hours, 24 hours]
• Length of Stay in Hospital [Срок оценки: From day of surgery to hospital discharge, expected to range from 5 to 10 days]

Критерии участия

Критерии включения

• Adult Patients between ages 18 and 65 years old.
• Undergoing supratentorial intracranial surgery
• American Society of Anesthesiologists (ASA) physiological status I-III
• Body Mass Index (BMI) between 18.5 and 45
• Ability to understand and read English

Критерии исключения

• Being unable or unwilling to sign a consent
• Anticipated discharge within 24 hours after surgery
• Patients requiring Emergent Surgery
• Preoperative usage of Methadone, or allergy to it.
• Patients with chronic pain, requiring daily opioid use at the time of surgery, MME >60 as FDA defines opioid tolerant as 60 MME, long-acting forms of opioids such as fentanyl patch, oxycontin
• 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
• Preoperative chronic renal insufficiency or failure (defined as a serum creatinine more than 2 mg/dl),
• Pregnancy
• Significant liver disease (cirrhosis or hepatic failure)
• QTc >450 on preoperative electrocardiogram
• Pulmonary disease necessitating home oxygen therapy
• Inability to speak or read the English language

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

• Russell T, Mitchell C, Paech MJ, Pavy T. Efficacy and safety of intraoperative intravenous methadone during general anaesthesia for caesarean delivery: a retrospective case-control study. Int J Obstet Anesth. 2013 Jan;22(1):47-51. doi: 10.1016/j.ijoa.2012.10.007. Epub 2012 Dec 7. PMID 23219678
• Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633. PMID 25837528
• Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24. PMID 20418538
• Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available. PMID 6128949
• 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
• Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available. PMID 21173206
• Basali A, Mascha EJ, Kalfas I, Schubert A. Relation between perioperative hypertension and intracranial hemorrhage after craniotomy. Anesthesiology. 2000 Jul;93(1):48-54. doi: 10.1097/00000542-200007000-00012. PMID 10861145
• Molnar L, Simon E, Nemes R, Fulesdi B, Molnar C. Postcraniotomy headache. J Anesth. 2014 Feb;28(1):102-11. doi: 10.1007/s00540-013-1671-z. Epub 2013 Jul 12. PMID 23846599

Идентификаторы

NCT: NCT06810336 · HSR240122

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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