Intrathecal Morphine Versus Epidural Analgesia for Laparoscopic Colon Surgery

Phase 4

Not yet recruiting

• Conditions: Analgesia; Colorectal Cancer; Surgery; Postoperative Pain
• Interventions: Procedure: Epidural Analgesia; Drug: Intrathecal Morphine

• Registration Number: NCT06881563
• Lead Sponsor: Meri Mirceta

Brief Summary

Effective pain management after abdominal surgery is essential for recovery. This study compares two pain relief methods-intrathecal morphine (a single spinal injection) and continuous epidural analgesia-for patients undergoing minimally invasive colorectal cancer surgery.

The investigators expect intrathecal morphine to provide better pain relief at rest 24 hours after surgery, while epidural analgesia may be more effective during movement. By 48 to 72 hours, both methods should offer similar pain control. The epidural group may require fewer additional pain medications but could experience more side effects, including a higher risk of low blood pressure and technical difficulties. Additionally, these patients may have a slightly longer hospital stay. In contrast, the intrathecal morphine group may have fewer overall side effects. Despite these differences, patient satisfaction, sleep quality, and recovery are expected to be similar in both groups.

By evaluating these methods, this study aims to determine the most effective and safe approach to post-surgical pain management, improving comfort and recovery outcomes for patients.

Detailed Description

Participants of this study will be randomly selected adult patients with colorectal carcinoma undergoing laparoscopic colorectal resection who fulfill the inclusion criteria and sign the informed consent for participation.

This sample represents the population of adult patients with colorectal cancer undergoing laparoscopic surgery by ERAS protocol in a tertiary hospital of a high-developed country.

Patients will be randomly divided into Epidural group (E group) or Spinal group (S group) and will receive different intraoperative and postoperative analgesia plans.

E group will be treated as a control group. Patients in S group will receive intrathecal morphine as analgesia for colorectal resection and it will be treated as experimental group.

Anesthesia induction and maintenance will be the same in both groups. The primary outcome is pain intensity at rest measured with the Numeric Rating Scale (0 = no pain and 10 = worst pain) 24 hours after surgery. Secondary outcome measures are analgesic consumption, time to rescue analgesia, patient satisfaction, quality of sleep, length of hospital stay, time to return of bowel function, and adverse events (such as respiratory depression, nausea or vomiting, hypotension and bradycardia).

Postoperative continuous epidural analgesia in the E group will consist of 2 μg/mL fentanyl added to 0.1 % levobupivacaine at the rate 5-8 mL/h during the first 24 hours after surgery.

Additional epidural boluses will be allowed by the nursing staff for pain Numerical Rating Scale (NRS)≥4.

Both groups will receive standard multimodal analgesic protocol with the goal of postoperative pain NRS\<4: intravenous (iv) paracetamol 1 g up to 4 times per day and iv metamizole 2.5 g up to 2 times per day and tramadol 50-100 mg iv as needed. In the control group, epidural analgesia will be used for postoperative pain relief for up to 24 h. An algorithm of postoperative rescue analgesia is established for each group.

Rescue antiemetics will be given in case of postoperative nausea and vomiting (PONV): metoclopramide 10 mg iv up to 3 times per day and granisetron 1 mg iv up to 3 times per day.

Severe pruritus will be treated with antihistamines or naloxone 40 mcg iv.

Study Timeline

• Status Verified: 2025-03
• Study Start: 2025-03
• Study First Submitted: 2025-03-05
• Study First Submitted QC: 2025-03-17
• Last Update Submitted: 2025-03-17
• Study First Posted: 2025-03-18
• Last Update Posted: 2025-03-18
• Primary Completion: 2026-07
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

• Male or female patients with colorectal carcinoma undergoing laparoscopic abdominal surgery aged 18-80 years, ASA classification I-III, Body Mass Index (BMI) 15-35 kg/m2.

Exclusion Criteria

• abnormal coagulation function, defined as prothrombin time or activated partial prothrombin time above standard laboratory values or an international normalised ratio (INR) ≥1.4; or receiving ongoing therapeutic anticoagulation,
• thrombocytopenia, defined as a platelet count <80×10 9 L-1,
• pre-existing skin infection at the neuraxial anesthesia puncture site,
• pre-existing neurologic deficit, including peripheral neuropathy,
• patients with dementia or other medical condition that includes communication difficulties,
• patients with bradycardia (pulse <50/min) or with conduction block (2nd or 3rd degree)
• history of opioid abuse,
• allergies to any of the drugs used in the study.

Additionally, patients converted from laparoscopy to laparotomy due to technical surgical issues, patients with postoperative surgical complications (need for revision) or if epidural catheter placement/spinal anesthesia is unsuccessful even after an attempt by a senior anesthesiologist will also be excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epidural group	Epidural Analgesia	Epidural group will have an epidural catheter inserted in the T10/11 or T11/12 interspace using a midline approach. The epidural space will be identified by a loss of resistance to saline with a Tuohy 18G epidural needle. Subsequently, the epidural catheter will be inserted 4-6 cm into the epidural space and a test-dose of 2% lidocaine, 50 mg, to detect intrathecal misplacement will be given. Epidural group will subsequently receive intraoperative intermittent epidural analgesia followed by postoperative continuous infusion of a levobupivacaine and fentanyl mixture.
Spinal group	Intrathecal Morphine	In Spinal group, 25 G or 27 G pencil point needle, depending on the preference of the anesthesiologist, will be inserted at L2-L3 or L3-L4 intervertebral space and 300 μg of preservative-free morphine (Morphine Kalceks ®, Kalceks, AS, Riga, Latvija, 10mg/ml) diluted with sterile saline to a volume of 3 mL will be injected intrathecally.

Primary Outcome Measures

Name	Time	Method
Pain intensity at rest 24 hours after surgery.	24 hours	Level of pain intensity will be validated using Numeric Rating Scale ranging from 0-10.

Secondary Outcome Measures

Name	Time	Method
Pain scores at rest and during movement at 1, 3, 6, 48, and 72 hours, and during movement at 24 h after surgery	1, 3, 6, 24, 48, and 72 hours after surgery	Numeric Rating Scale
Intraoperative use of fentanyl.	For the duration of surgery.	Total amount of administered fentanyl in mg.
Consumption of tramadol and metamizole.	Total amount of tramadol and metamizole within 72 hours after surgery.	Measured in mg.
Time to the first request for rescue analgesia.	From the time of the surgery until the time to the first request for rescue analgesia (up to 3 days after the surgery)	Measured in minutes.
Patient satisfaction	24, 48, and 72 hours after surgery	Measured with a 5-point Likert scale.
Quality of sleep.	24, 48, and 72 hours after surgery	Measured with a 5-point Likert scale.
Incidence of post-dural puncture headache	Within 72 hours after surgery.
Incidence of technique failure	Perioperative	Need to convert to a second analgesic technique due to multiple reasons, e.g., inability to perform spinal puncture, inability to insert an epidural catheter, inadequate analgesia, epidural catheter malfunction, or dislodgement.
Quality of Recovery	72 hours after surgery	Measured with a 15-item Quality of Recovery 15 (QoR-15) scale.
Length of hospital stay	Form the day of surgery until hospital discharge (up to 90 days)	Time from surgery to hospital discharge in days.
Length of stay (LOS) in HDU (high dependency unit)	From the time of the admission to HDU until ward discharge (up to 30 days)	Time to ward discharge in hours.
Time to ambulation	From the end of surgery until patient ambulation (up to 30 days)	Measured in hours, defined as the patient independently getting out of bed.
Time to gastro-intestinal recovery	From the end of surgery until the first documented stool, flatus or oral intake (up to 3 days)	First stool or flatus after surgery measured in hours, time to oral intake
Sedation score	After extubation and 24 hours after surgery.	Measured with a Ramsay sedation scale (1-6)
Incidence of respiratory depression	Within 24 hours after surgery.	Respiratory rate \<8 /min or need for assisted ventilation.
Incidence of nausea or vomiting	Within 24 hours after surgery.
Incidence of shivering, pruritus, hypotension, bradycardia.	Within 24 hours after surgery.	Hypotension defined as systolic blood pressure less than 90 mmHg or diastolic less than 50 mmHg, mean arterial pressure \< 60 mmHg, or decline \>20% from baseline, and bradycardia defined as heart rate \<50/min.
Potoperative complications	Until hospital discharge (up to 90 days)	Postoperative complications will be classified according to the Clavien Dindo Classification (1, 2, 3 a, 3 b, 4 a, 4 b, 5).
Readmission rate	Within 30 days after surgery	Readmission is defined as patient admission related to surgical procedure within 30 days after initial discharge.

Trial Locations

Locations (1)

University Hospital Split; 🇭🇷 Split, Croatia