Clinical trial NCT06935708: Intrathecal Morphine Versus Epidural Analgesia for Open Colon Surgery
Official title: Intrathecal Morphine Versus Thoracic Epidural Analgesia for Open Colorectal Cancer Surgery: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Colorectal Carcinoma
Analgesia, Postoperative
Laparotomy
Keywords: postoperative pain
analgesia
epidural
intrathecal morphine
laparotomy
Lead sponsor: University Hospital of Split
Sponsor class: OTHER
First posted: 2025-04-20
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Pain intensity at rest 24 hours after surgery.
timeFrame: 24 hours
Secondary outcomes:
measure: Pain scores at rest and during movement at 1, 3, 6, 48, and 72 hours, and during movement at 24 h after surgery
timeFrame: 1, 3, 6, 24, 48, and 72 hours after surgery
measure: Intraoperative use of fentanyl.
timeFrame: For the duration of surgery.
measure: Time to the first request for rescue analgesia.
timeFrame: From the time of the surgery until the time to the first request for rescue analgesia (up to 3 days after the surgery)
measure: Consumption of tramadol and metamizole.
timeFrame: Total amount of tramadol and metamizole within 72 hours after surgery.
measure: Patient satisfaction
timeFrame: 24, 48, and 72 hours after surgery
measure: Quality of sleep.
timeFrame: 24, 48, and 72 hours after surgery
measure: Quality of Recovery
timeFrame: 72 hours after surgery
measure: Length of stay (LOS) in HDU (high dependency unit)
timeFrame: From the time of the admission to HDU until ward discharge (up to 30 days)
measure: Length of hospital stay
timeFrame: Form the day of surgery until hospital discharge (up to 90 days)
measure: Time to ambulation
timeFrame: From the end of surgery until patient ambulation (up to 30 days)
measure: Time to gastro-intestinal recovery
timeFrame: From the end of surgery until the first documented stool, flatus or oral intake (up to 3 days)
measure: Sedation score
timeFrame: After extubation and 24 hours after surgery.
measure: Incidence of respiratory depression
timeFrame: Within 24 hours after surgery.
measure: Incidence of nausea or vomiting
timeFrame: Within 24 hours after surgery.
measure: Incidence of shivering, pruritus, hypotension, bradycardia.
timeFrame: Within 24 hours after surgery
measure: Incidence of post-dural puncture headache
timeFrame: Within 72 hours after surgery.
measure: Incidence of technique failure
timeFrame: Perioperative
measure: Postoperative complications
timeFrame: Until hospital discharge (up to 90 days)
measure: Readmission rate
timeFrame: Within 30 days after surgery
Other outcomes:
Locations:
city: Split
country: Croatia
facility: University hospital of Split
Study officials:
References: