RecruitingPhase 2Phase 3NCT06996561

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


Sponsor

Dr. Asma Abdus Salam

Enrollment

263 participants

Start Date

Sep 1, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria4

  • 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

Exclusion Criteria8

  • 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

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Interventions

DRUGNalbuphine 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 assessed for 24 hours postoperatively using verbal rating scale (VRS) with 0 = no pain and 10 = worst pain. Sedation will be assessed as 0=no sedation, 1= mild sedation, (eye-opening on verbal commands), 2= moderate sedation (eye-opening on painful stimulus), 3= deep sedation (not waking up on pain). All patients will be prescribed paracetamol one gram IV six hourly and nalbuphine 1-2 mg IV infusion in the first 24 hours post operatively.

GENETICNext 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 NGS analysis. These samples will undergo whole exome sequencing via NGS, based on patient parameters and pain scores, after being categorized as responders or non-responders to nalbuphine

GENETICwhole 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


Locations(1)

Ziauddin University

Karachi, Sindh, Pakistan

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