Nalbuphine Dosing and Its Impact on Anxiety and Depression in Ectopic Pregnancy Surgery

Official title

Effects of Different Doses of Nalbuphine on Anxiety and Depression in Patients Undergoing Ectopic Pregnancy Surgery: A Prospective, Randomized, Controlled Study

Overview

This prospective, randomized, controlled study aims to evaluate the impact of different doses of nalbuphine on anxiety and depression in patients undergoing surgery for ectopic pregnancy. Ectopic pregnancy, which occurs in approximately 2% of all pregnancies, often requires surgical intervention, leading to potential psychological distress such as anxiety and depression in affected women. Effective postoperative pain management is essential to enhance recovery and reduce emotional disturbances. The study will involve 165 eligible patients diagnosed with ectopic pregnancy at Jinjiang District Maternal and Child Health Hospital. Participants will be randomly assigned to three groups, each receiving a different concentration of nalbuphine combined with metoclopramide for postoperative analgesia. The primary outcome will focus on changes in anxiety and depression scores measured on postoperative day three, while secondary outcomes will assess pain levels, the use of patient-controlled analgesia (PCA), the necessity for rescue analgesics, and the occurrence of adverse reactions. Sample size calculations suggest that at least 165 participants are required to achieve adequate statistical power. Data will be analyzed using SPSS 25.0 software, with results expected to provide insights into the effectiveness of nalbuphine in improving postoperative recovery and mental health in women experiencing ectopic pregnancy. The study has received ethical approval and is funded by the Chengdu Medical Research Projects (No. 2023465, 2022548, and 2023304).

Detailed description

Background:

Ectopic pregnancy occurs when a fertilized egg implants outside the uterine cavity, affecting approximately 2% of all pregnancies. Surgical intervention is the primary treatment, which can lead to significant psychological effects, including anxiety and depression. Studies indicate that patients may experience various emotional disturbances post-surgery, negatively impacting their social adaptability and interpersonal relationships. Effective postoperative pain management is crucial for recovery and may also help alleviate these emotional challenges. Nalbuphine, an opioid receptor agonist-antagonist that primarily acts on the kappa receptor, has been shown to provide pain relief with a lower incidence of respiratory depression and may have a positive impact on mental health compared to traditional opioids.

Objective:

The main objective is to investigate the effects of different concentrations of nalbuphine on anxiety and depression in patients with ectopic pregnancy post-surgery, focusing on changes in anxiety and depression scores on postoperative day three. The secondary objective is to compare the postoperative analgesic effects and the incidence of adverse reactions associated with different concentrations of nalbuphine.

Methods:

This study is designed as a single-center, prospective, randomized, controlled clinical trial conducted at Jinjiang District Maternal and Child Health Hospital. Ethical approval will be obtained, and all participants will provide informed consent.

Interventions:

165 eligible patients will be randomly assigned into three groups (N1, N2, N3), each receiving different doses of nalbuphine combined with metoclopramide for postoperative pain management, with a total volume of 150ml for each group. The groups are as follows:

* Group A: Nalbuphine 0.20 mg/ml (total 30 mg) * Group B: Nalbuphine 0.27 mg/ml (total 40 mg) * Group C: Nalbuphine 0.33 mg/ml (total 50 mg)

Patient-controlled analgesia (PCA) will be maintained for 48 hours.

Primary Outcome:

The primary outcome will be the assessment of anxiety and depression scores measured on postoperative day three.

Secondary Outcomes:

Secondary outcomes will include:

1. Visual Analog Scale (VAS) resting and activity pain scores at multiple time points (T1: 6 hours, T2: 12 hours, T3: 24 hours, T4: 48 hours). 2. Number of PCA button presses. 3. Use and frequency of rescue analgesics. 4. Incidence of adverse reactions such as drowsiness, dizziness, nausea, vomiting, and respiratory depression. 5. Time to mobilization and time to first flatus.

Ethics Approval:

This study has received approval from the ethics committee of Chengdu Jinjiang District Maternal and Child Health Hospital (Approval Number: 202312). All participants must sign an informed consent form to ensure the respect of participant rights and data confidentiality. The study will strictly adhere to relevant ethical standards and legal regulations to protect participant safety and privacy.

Funding:

The study is funded by the Chengdu Medical Research Projects (No. 2023465, 2022548, and 2023304).

Interventions

• Drug Nalbuphine 0.20mg/ml(total 30 mg)
  In this group, participants will receive an intravenous infusion of Nalbuphine at a concentration of 0.20 mg/ml, which delivers a total of 30 mg over the course of 48 hours. Additionally, 10 mg of Metoclopramide will be administered to manage potential postoperative nausea. This intervention aims to assess the analgesic efficacy and its subsequent effect on psychological outcomes, specifically anxiety and depression, in patients undergoing surgery for ectopic pregnancy.
• Drug Nalbuphine 0.27mg/ml(total 40 mg)
  Participants assigned to this group will be treated with an intravenous infusion of Nalbuphine at a concentration of 0.27 mg/ml, resulting in a total dosage of 40 mg administered during the 48-hour postoperative period. They will also receive 10 mg of Metoclopramide to mitigate nausea and vomiting. This intervention is designed to evaluate the effectiveness of this dose in pain management and its influence on anxiety and depression levels post-surgery.
• Drug Nalbuphine 0.33mg/ml(total 50 mg)
  In this group, subjects will receive Nalbuphine at a concentration of 0.33 mg/ml, totaling 50 mg, delivered through intravenous infusion for 48 hours. Along with this, 10 mg of Metoclopramide will be included to address potential postoperative discomfort. This intervention seeks to explore how this higher concentration impacts pain relief and subsequent psychological effects, specifically targeting anxiety and depression following ectopic pregnancy surgery.

Primary outcome measures

• Postoperative Anxiety and Depression Scores [Time frame: Day 3 post-surgery]

Secondary outcome measures (9)

• Visual Analog Scale (VAS) Pain Scores [Time frame: Postoperative 6 hours, 12 hours, 24 hours, and 48 hours]
• Effective Presses of the Pain Pump [Time frame: 48 hours post-surgery]
• Need for Rescue Analgesia [Time frame: 48 hours post-surgery]
• Number of participants experience feelings of drowsiness [Time frame: day 2 post-surgery]
• Time to Ambulate [Time frame: Perioperative]
• Time to Flatus [Time frame: Perioperative]
• Number of participants experience feelings of Dizziness [Time frame: day 2 post-surgery]
• Number of participants experience feelings of Nausea [Time frame: day 2 post-surgery]
• Number of participants experience feelings of Vomiting [Time frame: day 2 post-surgery]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of ectopic pregnancy, aged ≥18 years, and with normal psychological status.
• Patients planned to undergo single-port laparoscopic surgery under general anesthesia, followed by postoperative patient-controlled intravenous analgesia (PCIA).
• Patients classified as ASA I or II.
• Able to understand the study process and methods, voluntarily participate, and sign the informed consent form.

Exclusion criteria

• Patients using other analgesic methods or multiple analgesic approaches.
• Patients with a history of allergies or allergies to anesthetic drugs.
• Patients with a history of depression or mental illness.
• Patients with other severe organ dysfunction.
• Patients unable to operate the intravenous analgesia pump independently.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Bollig KJ, Friedlander H, Schust DJ. Ectopic Pregnancy and Lifesaving Care. JAMA. 2023 Jun 20;329(23):2086-2087. doi: 10.1001/jama.2023.7292. PMID 37261808
• Farren J, Jalmbrant M, Falconieri N, Mitchell-Jones N, Bobdiwala S, Al-Memar M, Tapp S, Van Calster B, Wynants L, Timmerman D, Bourne T. Posttraumatic stress, anxiety and depression following miscarriage and ectopic pregnancy: a multicenter, prospective, cohort study. Am J Obstet Gynecol. 2020 Apr;222(4):367.e1-367.e22. doi: 10.1016/j.ajog.2019.10.102. Epub 2019 Dec 13. PMID 31953115
• Farren J, Jalmbrant M, Falconieri N, Mitchell-Jones N, Bobdiwala S, Al-Memar M, Tapp S, Van Calster B, Wynants L, Timmerman D, Bourne T. Differences in post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy between women and their partners: multicenter prospective cohort study. Ultrasound Obstet Gynecol. 2021 Jan;57(1):141-148. doi: 10.1002/uog.23147. PMID 33032364
• Pan X, Wang J, Lin Z, Dai W, Shi Z. Depression and Anxiety Are Risk Factors for Postoperative Pain-Related Symptoms and Complications in Patients Undergoing Primary Total Knee Arthroplasty in the United States. J Arthroplasty. 2019 Oct;34(10):2337-2346. doi: 10.1016/j.arth.2019.05.035. Epub 2019 May 28. PMID 31229373
• Akshat S, Ramachandran R, Rewari V, Chandralekha, Trikha A, Sinha R. Morphine versus Nalbuphine for Open Gynaecological Surgery: A Randomized Controlled Double Blinded Trial. Pain Res Treat. 2014;2014:727952. doi: 10.1155/2014/727952. Epub 2014 Apr 14. PMID 24834352

Identifiers

NCT: NCT07009808 · 202427

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗