Intrathecal Morphine Versus Epidural Analgesia for Open Colon Surgery

NCT ID: NCT06935708

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-08
• Study Completion Date: 2026-11-30

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 open colorectal cancer surgery.

The investigators expect intrathecal morphine to provide equal 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 open 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 open 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.

Conditions

Colorectal Carcinoma; Analgesia, Postoperative; Laparotomy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epidural group

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.

Group Type: ACTIVE_COMPARATOR

Epidural Analgesia

Intervention Type: PROCEDURE

Epidural analgesia with levobupivacaine and fentanyl mixture. For intraoperative intermittent analgesia, Epidural group will be given a loading dose of 5-10 milliliters of a mixture of 10 micrograms per milliliter (μg/mL) of fentanyl (Fentanyl Piramal Critical Care, 50 mcg/ml) and 0.25% levobupivacaine (Levobupivakain Kabi 5 mg/ml), followed by intermittent 4-5 mL boluses as needed throughout the surgery. Postoperative continuous epidural analgesia in the epidural 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.

Spinal group

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.

Group Type: EXPERIMENTAL

Intrathecal Morphine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Epidural Analgesia

Epidural analgesia with levobupivacaine and fentanyl mixture. For intraoperative intermittent analgesia, Epidural group will be given a loading dose of 5-10 milliliters of a mixture of 10 micrograms per milliliter (μg/mL) of fentanyl (Fentanyl Piramal Critical Care, 50 mcg/ml) and 0.25% levobupivacaine (Levobupivakain Kabi 5 mg/ml), followed by intermittent 4-5 mL boluses as needed throughout the surgery. Postoperative continuous epidural analgesia in the epidural 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.

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Meri Mirceta

OTHER

Sponsor Role: lead

Responsible Party

Meri Mirceta

Anesthesiologist, Doctor of Medicine (MD)

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

University hospital of Split

Split, , Croatia

Site Status: RECRUITING

Countries

Croatia

Central Contacts

Svjetlana Došenović, MD, PhD

Role: CONTACT

sdosenovic@yahoo.com

+38521556180

Meri Mirčeta, MD

Role: CONTACT

mircetameri@gmail.com

+38521556180

Other Identifiers

2181-147/01/06/LJ.Z.-25-02

Identifier Type: -

Identifier Source: org_study_id