Intrathecal Morphine Versus Trocar-Site and Intraperitoneal Bupivacaine for Quality of Recovery After Laparoscopic Hysterectomy (ITM-LH-QoR)

December 2, 2025 updated by: Aysenur Dostbil, Ataturk University

Effects of Intrathecal Morphine Compared With Trocar-Site Infiltration and Intraperitoneal Bupivacaine on Postoperative Quality of Recovery and Inflammatory Markers After Laparoscopic Hysterectomy: A Prospective, Randomized, Double-Blind Controlled Trial

This study aims to compare the effects of intrathecal morphine with trocar-site infiltration and intraperitoneal bupivacaine on postoperative pain control, quality of recovery, and inflammatory response in patients undergoing elective laparoscopic hysterectomy. Laparoscopic hysterectomy is widely used for benign gynecologic conditions, but postoperative pain may result from trocar-site trauma, peritoneal irritation, and carbon dioxide insufflation. Effective postoperative analgesia can improve patient comfort, reduce opioid use, and enhance early recovery.

Intrathecal morphine is known to provide potent early postoperative analgesia but may cause side effects such as nausea, vomiting, pruritus, and respiratory depression. Local anesthetic techniques, including trocar-site infiltration and intraperitoneal bupivacaine, have also been shown to reduce postoperative pain after minimally invasive gynecologic surgery.

In this prospective, randomized, double-blind study, patients will be assigned to one of two groups:

Intrathecal morphine (ITM) administered before induction of anesthesia;

Local anesthesia group (LA) receiving trocar-site infiltration and intraperitoneal bupivacaine at the end of surgery.

The primary outcome is the Quality of Recovery-15 (QoR-15) score at 24 hours. Secondary outcomes include pain scores, opioid consumption, time to first rescue analgesia, postoperative nausea and vomiting, pruritus, respiratory depression, early mobilization, bowel function recovery, and perioperative inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII).

The results of this trial are expected to guide clinicians in selecting optimal analgesic strategies for laparoscopic hysterectomy and to contribute to improved patient recovery and postoperative satisfaction.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study Background and Rationale:

Despite its minimally invasive advantages, laparoscopic hysterectomy can cause significant postoperative pain due to trocar sites, visceral manipulation, and peritoneal irritation. This pain results in opioid consumption, associated side effects, and delayed recovery. Multimodal analgesia is the cornerstone of postoperative care. In this context, trocar site infiltration with intrathecal morphine (long-acting central analgesia) and intraperitoneal local anesthetic administration (peripheral techniques targeting somatic and visceral pain) are effective options. This study aims to compare the effects of these two different analgesic strategies on the quality of postoperative recovery through a patient-centered outcome measure, the QoR-15, and objective hematologic inflammatory markers.

Technical Details of Intervention Protocols:

General Anesthesia Standardization: All patients will receive standard general anesthesia. Induction will be achieved with propofol and fentanyl, rocuronium bromide will be used for neuromuscular blockade, and anesthesia will be maintained with sevoflurane.

Group ITM (Intrathecal Morphine) Intervention: Before induction of general anesthesia, patients will be in the sitting or lateral decubitus position and 200 µg (0.2 mg) of morphine will be injected into the subarachnoid space with a 25G (or 27G) pencil-point spinal needle at the L3-L4 intervertebral space. Hemodynamic and respiratory parameters will be closely monitored for 30 minutes after the injection.

Group LA (Local Anesthetic) Intervention: At the end of the surgical procedure, 5 mL of 0.25% bupivacaine will be infiltrated into each trocar incision. Additionally, 40 mL of 0.25% bupivacaine will be administered intraperitoneally, distributing to the subhepatic, diaphragmatic, and pelvic surfaces. The total bupivacaine dose will be calculated to avoid exceeding 2 mg/kg body weight to avoid the risk of toxicity.

Standard Perioperative Medication Regimen: All patients in both groups will receive the following medications intraoperatively as part of multimodal analgesia: 1 g Paracetamol, 800 mg Ibuprofen, 3 mg Granisetron, 40 mg Esomeprazole, and 8 mg Dexamethasone.

Methodological Details for Outcome Assessments:

QoR-15 Questionnaire: The validated and reliable Turkish version of the primary outcome measure, QoR-15, will be used. The questionnaire will be administered before surgery to obtain preoperative baseline values and at 24 hours postoperatively as the primary outcome.

Pain and Side Effect Monitoring: Postoperative pain will be assessed using a Visual Analog Scale (VAS: 0-10 cm) at rest and during coughing/activity. Assessments will be made at 2-hour intervals from the 2nd postoperative hour to the 24th hour. Nausea, vomiting, pruritus, and respiratory depression (SpO2 < 90% or respiratory rate < 8/minute) will be recorded using standard forms.

Hematological Inflammatory Markers: A complete blood count will be analyzed using an automated hematology analyzer from venous blood samples taken preoperatively (baseline, T0) and at the 24th postoperative hour (T13). Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR), Lymphocyte/Monocyte Ratio (LMR), and Systemic Immuno-Inflammation Index (SII = (Platelet count x Neutrophil count) / Lymphocyte count) will be calculated.

Blinding Protocol: Except for the anesthesiologist who performs the randomization and intervention, the patients, the surgical team, the investigators collecting postoperative data, and the statistical analyst will be blinded to group distinctions. Randomization will be stored using sequential, numbered, opaque envelopes.

Clinical Significance of the Study:

The findings of this study may provide evidence-based recommendations regarding the most effective multimodal analgesia regimen after laparoscopic hysterectomy. The demonstrated superiority of intrathecal morphine in reducing the systemic inflammatory response and patient-reported quality of recovery may result in less opioid use and faster recovery. Conversely, if local anesthetic techniques are adequate, the potential risks of central block may be avoided.

Study Type

Interventional

Enrollment (Estimated)

64

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Ayşenur Dostbil, Associate Professor
  • Phone Number: +90-533-367-66-96
  • Email: adostbil@hotmail.com

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female patients aged 18-65 years.
  • Elective laparoscopic hysterectomy planned for benign gynecological conditions.
  • American Society of Anesthesiologists (ASA) physical status I-III.
  • Ability to provide written informed consent.

Exclusion Criteria:

  • Coagulopathy or bleeding disorders.
  • Opioid dependence or chronic opioid use.
  • Allergy or contraindication to local anesthetics or morphine.
  • Contraindication to neuraxial (spinal) anesthesia.
  • History of chronic pain syndromes.
  • Severe renal or hepatic dysfunction.
  • Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intrathecal Morphine Group
Participants in this arm will receive 200 µg of preservative-free intrathecal morphine administered at the L3-L4 interspace prior to induction of general anesthesia. This intervention is intended to provide early postoperative analgesia following laparoscopic hysterectomy.
Drug: Intrathecal Morphine
A single dose of 200 µg preservative-free morphine will be administered intrathecally at the L3-L4 interspace prior to induction of general anesthesia. The injection is performed using a 25G spinal needle. This intervention aims to provide prolonged early postoperative analgesia in patients undergoing laparoscopic hysterectomy.
Active Comparator: Local Anesthesia Group
Participants in this arm will receive 0.25% bupivacaine infiltration (5 mL at each trocar site) and 40 mL of 0.25% bupivacaine administered intraperitoneally at the end of surgery. The total dose of bupivacaine will not exceed 2 mg/kg. This technique aims to reduce postoperative somatic and visceral pain after laparoscopic hysterectomy.
Drug: Trocar-Site Bupivacaine Infiltration
At the end of laparoscopic hysterectomy, 5 mL of 0.25% bupivacaine will be infiltrated into each trocar site. This intervention targets somatic pain originating from trocar entry points. It is administered only in the Local Anesthesia (LA) Group. The total dose of bupivacaine from all applications will remain within recommended safety limits.
Drug: Intraperitoneal Bupivacaine spray
A total of 40 mL of 0.25% bupivacaine will be instilled intraperitoneally after completion of the surgical procedure. This intervention is designed to reduce visceral and peritoneal irritation-related pain following laparoscopic hysterectomy. The combined bupivacaine dose from trocar-site infiltration and intraperitoneal instillation will not exceed 2 mg/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative quality of recovery at 24 hours measured by QoR-15
Time Frame: 24 hours postoperatively
The primary outcome is the overall postoperative recovery quality at 24 hours, assessed using the 15-item Quality of Recovery questionnaire (QoR-15). This scale evaluates physical comfort, emotional state, physical independence, psychological support, and pain to provide a comprehensive patient-centered measure of recovery.
24 hours postoperatively

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first rescue opioid requirement
Time Frame: From end of surgery until first rescue opioid administration (up to 24 hours)
Duration (in hours) from the end of surgery to the first administration of rescue opioid (oxycodone 5 mg) for postoperative pain relief.
From end of surgery until first rescue opioid administration (up to 24 hours)
Total opioid consumption within 24 hours
Time Frame: 0-24 hours postoperatively
Total amount of rescue opioid consumed by the patient within the first 24 hours after surgery, expressed in milligrams.
0-24 hours postoperatively
Time to first mobilization
Time Frame: 0-24 hours postoperatively
Time (in hours) from the end of surgery until the patient is able to ambulate independently for the first time postoperatively.
0-24 hours postoperatively
Time to first bowel movement
Time Frame: 0-24 hours postoperatively
Time (in hours) from the end of surgery until the patient reports the first postoperative bowel movement.
0-24 hours postoperatively
Postoperative complications
Time Frame: 0-24 hours postoperatively
Incidence of postoperative nausea, vomiting, pruritus, and respiratory depression within the first 24 hours after surgery.
0-24 hours postoperatively
Neutrophil-to-lymphocyte ratio (NLR)
Time Frame: Preoperative baseline and 24 hours postoperatively
NLR measured preoperatively and at 24 hours postoperatively to evaluate systemic inflammatory response.
Preoperative baseline and 24 hours postoperatively
Platelet-to-lymphocyte ratio (PLR)
Time Frame: Preoperative baseline and 24 hours postoperatively
PLR measured preoperatively and at 24 hours postoperatively to evaluate systemic inflammatory response.
Preoperative baseline and 24 hours postoperatively
Lymphocyte-to-monocyte ratio (LMR)
Time Frame: Preoperative baseline and 24 hours postoperatively
LMR measured preoperatively and at 24 hours postoperatively to evaluate systemic inflammatory response.
Preoperative baseline and 24 hours postoperatively
Systemic immune-inflammation index (SII)
Time Frame: Preoperative baseline and 24 hours postoperatively
SII measured preoperatively (T0) and at 24 hours postoperatively (T13) to evaluate systemic inflammatory response.
Preoperative baseline and 24 hours postoperatively
Postoperative pain scores (VAS)
Time Frame: 2-24 hours postoperatively
Pain intensity will be assessed using the Visual Analog Scale (VAS), a continuous scale ranging from 0 to 10. Scores are recorded by patients marking a line, where 0 represents "no pain" and 10 represents "the worst pain imaginable". Higher scores indicate a worse outcome (more severe pain). Assessments will be performed at rest and during movement (e.g., coughing) at 2-hour intervals from 2 to 24 hours postoperatively.
2-24 hours postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ataturk University

Investigators

  • Principal Investigator: Ayşenur Dostbil, Principal Investigator, Ataturk University Department of Anesthesiology and Reanimation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2025

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 2, 2026

Study Registration Dates

First Submitted

November 14, 2025

First Submitted That Met QC Criteria

November 14, 2025

First Posted (Estimated)

November 18, 2025

Study Record Updates

Last Update Posted (Actual)

December 8, 2025

Last Update Submitted That Met QC Criteria

December 2, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B.30.2.ATA.0.01.00/697
  • 2025/1 (Other Identifier: Atatürk University Clinical Research Ethics Committee)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) will not be shared because the study involves sensitive patient health information, and data confidentiality will be strictly maintained according to institutional ethical guidelines.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Postoperative Pain Management

Clinical Trials on Intrathecal Morphine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Sweden

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe