Intrathecal Morphine Versus Trocar-Site and Intraperitoneal Bupivacaine for Quality of Recovery After Laparoscopic Hysterectomy

NCT07232108 | Recruiting

• 2 other identifiers: B.30.2.ATA.0.01.00/6972025/1
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Pain Management; Laparoscopic Hysterectomy; Postoperative Recovery

Keywords

Intrathecal Morphine; Trocar-Site Infiltration; Intraperitoneal Bupivacaine; Laparoscopic Hysterectomy; Quality of Recovery (QoR-15); Postoperative Pain; Opioid Consumption; Inflammatory Markers; Neutrophil-to-Lymphocyte Ratio (NLR); Systemic Immune-Inflammation Index (SII)

Outcome Measures

Primary Outcomes (1)

• Postoperative quality of recovery at 24 hours measured by QoR-15

  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 Outcomes (10)

• Time to first rescue opioid requirement

  From end of surgery until first rescue opioid administration (up to 24 hours)

• Total opioid consumption within 24 hours

  0-24 hours postoperatively

• Time to first mobilization

  0-24 hours postoperatively

• Time to first bowel movement

  0-24 hours postoperatively

• Postoperative pain scores (VAS)

  2-24 hours postoperatively

Study Arms (2)

Intrathecal Morphine Group

EXPERIMENTAL

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

Local Anesthesia Group

ACTIVE COMPARATOR

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; Drug: Intraperitoneal Bupivacaine spray

Interventions

Intrathecal Morphine DRUG

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.

Intrathecal Morphine Group

Trocar-Site Bupivacaine Infiltration DRUG

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.

Local Anesthesia Group

Intraperitoneal Bupivacaine spray DRUG

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.

Local Anesthesia Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ataturk University: lead

Study Sites (1)

Ataturk University

Erzurum, 25000, Turkey (Türkiye)

RECRUITING

Related Publications (13)

• Yang Y, Lin W, Zhuo Y, Luo Y, Wu X, Li J, Yao Y. Intrathecal Morphine and Ropivacaine for Quality of Recovery After Laparoscopic Colorectal Surgery: A Randomized Controlled Trial. Drug Des Devel Ther. 2024 Dec 18;18:6133-6143. doi: 10.2147/DDDT.S500316. eCollection 2024.

  PMID: 39717198 BACKGROUND

• Xing H, Yuan D, Zhu Y, Jiang L. A nomogram model based on SII, AFR, and NLR to predict infectious complications of laparoscopic hysterectomy for cervical cancer. World J Surg Oncol. 2024 Jul 24;22(1):190. doi: 10.1186/s12957-024-03489-0.

  PMID: 39049119 BACKGROUND

• Canikli Adiguzel S, Akyurt D, Bahadir Altun H, Tulgar S, Ultan Ozgen G. Can Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, or Systemic Immune Inflammation Index Be an Indicator of Postoperative Pain in Patients Undergoing Laparoscopic Cholecystectomy? Cureus. 2023 Jan 19;15(1):e33955. doi: 10.7759/cureus.33955. eCollection 2023 Jan.

  PMID: 36820108 BACKGROUND

• Aslanlar E, Aslanlar DA, Doganay C, Onal O, Sargin M, Cicekci F, Kara F, Kara I. The validity and reliability of the Turkish version of the quality of recovery-15 (QoR-15) questionnaire. Medicine (Baltimore). 2024 Apr 19;103(16):e37867. doi: 10.1097/MD.0000000000037867.

  PMID: 38640327 BACKGROUND

• Myles PS, Shulman MA, Reilly J, Kasza J, Romero L. Measurement of quality of recovery after surgery using the 15-item quality of recovery scale: a systematic review and meta-analysis. Br J Anaesth. 2022 Jun;128(6):1029-1039. doi: 10.1016/j.bja.2022.03.009. Epub 2022 Apr 14.

  PMID: 35430086 BACKGROUND

• Kleif J, Waage J, Christensen KB, Gogenur I. Systematic review of the QoR-15 score, a patient- reported outcome measure measuring quality of recovery after surgery and anaesthesia. Br J Anaesth. 2018 Jan;120(1):28-36. doi: 10.1016/j.bja.2017.11.013. Epub 2017 Nov 22.

  PMID: 29397134 BACKGROUND

• Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013 Jun;118(6):1332-40. doi: 10.1097/ALN.0b013e318289b84b.

  PMID: 23411725 BACKGROUND

• Pirie K, Doane MA, Riedel B, Myles PS. Analgesia for major laparoscopic abdominal surgery: a randomised feasibility trial using intrathecal morphine. Anaesthesia. 2022 Apr;77(4):428-437. doi: 10.1111/anae.15651. Epub 2022 Jan 17.

  PMID: 35038165 BACKGROUND

• Kaya C, Dost B, Turunc E, Ustun YB, Kibar AN, Cebeci H, De Cassai A, Elsharkawy H. Unilateral subcostal anterior quadratus lumborum block versus intrathecal morphine for postoperative pain in laparoscopic nephrectomy: a randomized controlled trial. Reg Anesth Pain Med. 2025 Jul 10:rapm-2025-106844. doi: 10.1136/rapm-2025-106844. Online ahead of print.

  PMID: 40639953 BACKGROUND

• Gluck O, Barber E, Feldstein O, Tal O, Kerner R, Keidar R, Wolfson I, Ginath S, Bar J, Sagiv R. The effect of subcutaneous and intraperitoneal anesthesia on post laparoscopic pain: a randomized controlled trial. Sci Rep. 2021 Jan 8;11(1):81. doi: 10.1038/s41598-020-80130-6.

  PMID: 33420214 BACKGROUND

• Lirk P, Thiry J, Bonnet MP, Joshi GP, Bonnet F; PROSPECT Working Group. Pain management after laparoscopic hysterectomy: systematic review of literature and PROSPECT recommendations. Reg Anesth Pain Med. 2019 Apr;44(4):425-436. doi: 10.1136/rapm-2018-100024. Epub 2019 Feb 3.

  PMID: 30914471 BACKGROUND

• Elsaeed UA, Algyoushy EAFIH, Hatem DLM. Effect of port-site and intraperitoneal local anesthetic injection versus placebo on postoperative pain and recovery after gynecologic laparoscopic surgery: a randomized controlled trial. Sci Rep. 2025 Sep 12;15(1):32466. doi: 10.1038/s41598-025-18389-w.

  PMID: 40940430 BACKGROUND

• Antoun L, Smith P, Afifi Y, Cullis K, Clark TJ. Short stay laparoscopic hysterectomy: An evaluation of feasibility and patient satisfaction. Facts Views Vis Obgyn. 2021 Dec;13(4):377-385. doi: 10.52054/FVVO.13.4.039.

  PMID: 35026099 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Ayşenur Dostbil, Principal Investigator

  Ataturk University Department of Anesthesiology and Reanimation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ayşenur Dostbil, Associate Professor

CONTACT

+90-533-367-66-96; adostbil@hotmail.com

Mehmet Akif Yılmaz, assistant doctor

CONTACT

+90-534-653-35-39; mehmetakifyilmaz025@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator Ayşenur Dostbil

Model Details: This study uses a two-arm, parallel-group design in which participants are randomized in a 1:1 ratio to receive either intrathecal morphine or trocar-site plus intraperitoneal bupivacaine.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 18, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 2, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)