Intrathecal Morphine Versus Epidural Analgesia for Open Colon Surgery

Intrathecal Morphine Versus Thoracic Epidural Analgesia for Open Colorectal Cancer Surgery: a Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Carcinoma; Laparotomy; Analgesia, Postoperative
• Intervention / Treatment: Procedure: Epidural Analgesia; Drug: Intrathecal Morphine

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.

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Svjetlana Došenović, MD, PhD; Phone Number: +38521556180; Email: sdosenovic@yahoo.com
• Study Contact Backup: Name: Meri Mirčeta, MD; Phone Number: +38521556180; Email: mircetameri@gmail.com

Study Locations

• Croatia
  • Split, Croatia, 21000
    • Recruiting
    • University Hospital of Split

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.
Active Comparator: 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.	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores at rest and during movement at 1, 3, 6, 48, and 72 hours, and during movement at 24 h after surgery	Numeric Rating Scale	1, 3, 6, 24, 48, and 72 hours after surgery
Intraoperative use of fentanyl.	Total amount of administered fentanyl in mg.	For the duration of surgery.
Time to the first request for rescue analgesia.	Measured in minutes.	From the time of the surgery until the time to the first request for rescue analgesia (up to 3 days after the surgery)
Consumption of tramadol and metamizole.	Measured in mg.	Total amount of tramadol and metamizole within 72 hours after surgery.
Patient satisfaction	Measured with a 5-point Likert scale.	24, 48, and 72 hours after surgery
Quality of sleep.	Measured with a 5-point Likert scale.	24, 48, and 72 hours after surgery
Quality of Recovery	Measured with a 15-item Quality of Recovery 15 (QoR-15) scale.	72 hours after surgery
Length of stay (LOS) in HDU (high dependency unit)	Time to ward discharge in hours.	From the time of the admission to HDU until ward discharge (up to 30 days)
Length of hospital stay	Time from surgery to hospital discharge in days.	Form the day of surgery until hospital discharge (up to 90 days)
Time to ambulation	Measured in hours, defined as the patient independently getting out of bed.	From the end of surgery until patient ambulation (up to 30 days)
Time to gastro-intestinal recovery	First stool or flatus after surgery measured in hours, time to oral intake	From the end of surgery until the first documented stool, flatus or oral intake (up to 3 days)
Sedation score	Measured with a Ramsay sedation scale (1-6)	After extubation and 24 hours after surgery.
Incidence of respiratory depression	Respiratory rate <8 /min or need for assisted ventilation.	Within 24 hours after surgery.
Incidence of nausea or vomiting		Within 24 hours after surgery.
Incidence of post-dural puncture headache		Within 72 hours after surgery.
Incidence of technique failure	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.	Perioperative
Readmission rate	Readmission is defined as patient admission related to surgical procedure within 30 days after initial discharge.	Within 30 days after surgery
Incidence of shivering, pruritus, hypotension, bradycardia.	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.	Within 24 hours after surgery
Postoperative complications	Postoperative complications will be classified according to the Clavien Dindo Classification (1, 2, 3 a, 3 b, 4 a, 4 b, 5).	Until hospital discharge (up to 90 days)

Collaborators and Investigators

• Sponsor: Meri Mirceta

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: April 13, 2025
• First Submitted That Met QC Criteria: April 18, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: laparotomy; analgesia; postoperative pain; epidural; intrathecal morphine
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 2181-147/01/06/LJ.Z.-25-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No