Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management

Обзор

The goal of this study is to identify the genes as well as their association with Nalbuphine. This will help the investigator to identify opioid vulnerability in Pakistani population in the postoperative patients and will contribute to overcoming the opioid crisis, resulting in better and safer outcomes. Research question is: Is there any association between the underlying genetic variations and the analgesic efficacy of Nalbuphine in postoperative patients? The Research Objectives are 1. To identify the underlying genes in postoperative patients having pain. 2. To find an association between identified genes and nalbuphine clinical efficacy. Procedure: After the written informed consent adult men and women will be enrolled in the study. On the day of surgery in the preoperative area, a 5 ml blood sample will be drawn before surgery and will be sent to laboratory for analysis. After routine hemodynamic monitoring in the operative room, general anesthesia will be given including nalbuphine. Standard routine anesthesia monitoring will be done and maintained while monitoring heart rate, ECG, NIBP oxygen saturation, ETCO2 and temperature. Incremental analgesia will be provided whenever needed. After extubation and shifting to recovery room the 2nd sample of blood will be taken and will be sent for analysis. Pain score, nausea vomiting, sedation, requirement of analgesia will be assessed till 24 hours postoperatively.

Подробное описание

The available data suggests that nalbuphine, tramadol, and morphine exhibit comparable efficacy in treating moderate to severe postoperative pain. However, significant individual variations exist in the analgesic response, which can be attributed to genetic differences. These are the variations that are influenced by a combination of demographic, clinical, and environmental factors with a significant contribution from genetic factors that regulate receptor function and signal transduction. Due to the limited availability of morphine, nalbuphine is an extensively used alternative for managing intraoperative and postoperative pain in many LMICs, particularly in Pakistan. While nalbuphine is clinically effective, there is a gap in understanding the molecular factors that contribute to its efficacy in this genetically distinct population. This highlights the need to investigate the genetic variability and to establish the analgesic efficacy of nalbuphine within Pakistani population. There is no molecular data from the region where the investigator belongs, which highlights the importance of genetic testing to tailor opioid therapy to individual needs, optimizing pain management while minimizing risks such as overdose or inadequate pain relief. By implementing genetics into clinical practice, the investigator can offer more personalized, effective, and safer opioid use, addressing the challenges associated with opioid therapy in diverse patient populations.

Вмешательства

• Препарат Nalbuphine Injection
  Anaesthesia induction will be done with propofol (2 mg/kg) nalbuphine (0.1mg/kg) and atracurium (0.6mg/kg) intravenously. Maintenance of anaesthesia will be achieved with oxygen (O2), nitrous oxide (N2O) in 1:2 ratio and isoflurane (0.8-1%). Intermittent top up of the study drug 1-2 ml boluses will be administered if either the patient's HR or BP increased to 20 % above baseline and when other causes of tachycardia and hypertension are excluded. Timing of analgesia will be recorded. Pain will be
• Генная терапия Next Generation Sequencing
  5ml of blood samples by venipuncture will be obtained from the first 70 patients half an hour before extubation at the time of muscle closure. These blood samples will be processed for DNA analysis. Only the 15 samples where pain persisted despite nalbuphine administration, with a pain score remaining above 4, continuous use of rescue analgesia, or any documented opioid side effects (such as nausea, vomiting, or sedation), or the need for additional analgesia within 24 hours, will be sent for NG
• Генная терапия whole exome sequencing
  Only the 15 samples will be sent for NGS based on patient parameters and pain scores after being categorized as responders or non-responders to nalbuphine

Первичные конечные точки

• pain score [Срок оценки: 24 hours postoperatively]

Вторичные конечные точки (3)

• sedation score [Срок оценки: 24 hours]
• nausea vomiting score [Срок оценки: 24 hours postoperatively]
• rescue analgesia [Срок оценки: 24 hours postoperatively]

Критерии участия

Критерии включения

• All adult men or women
• Age 18 to 70 years
• ASA criteria 1,2 and 3
• Abdomino-pelvic surgeries (open hernia repair, appendicectomy, open cholecystectomy, laparotomy, hysterectomy, cystectomy) lasting 2-4 hours

Критерии исключения

• Surgical procedure duration lasting more than 4 hours
• Patients taking anti fungal fluconazole, anticoagulant (Warfarin or Clopidogrel) SNRI (Amitryptalline), Rifampicin or Buprenorphine,
• History of hypersensitivity or allergy to opioids,
• Pregnant or breastfeeding mothers,
• History of narcotic dependency, addiction, and withdrawal
• Patients experiencing any adverse side effects or complications during surgical procedure requiring intensive care admission
• Refusing to participate in the study
• Surgical procedures utilizing other modes of intraoperative analgesia e.g epidural analgesia or nerve blocks

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Пакистан · 1 центр

• Ziauddin University — Karachi

Публикации

• Agarwal D, Udoji MA, Trescot A. Genetic Testing for Opioid Pain Management: A Primer. Pain Ther. 2017 Jun;6(1):93-105. doi: 10.1007/s40122-017-0069-2. Epub 2017 Apr 13. PMID 28409480

Идентификаторы

NCT: NCT06996561 · Nal-Gene123

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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