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 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.

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.

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.

This is a double-blind study. Participants and postoperative outcome assessors are blinded to group allocation. Randomization is generated by an independent researcher, and allocation is concealed in sequentially numbered opaque envelopes. The clinician performing the postoperative assessments is not involved in anesthesia administration and remains blinded throughout the study.