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

Overview

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.

Interventions

• 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.
• 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 f

Primary outcome measures

• Pain intensity at rest 24 hours after surgery. [Time frame: 24 hours]

Secondary outcome measures (12)

• Pain scores at rest and during movement at 1, 3, 6, 48, and 72 hours, and during movement at 24 h after surgery [Time frame: 1, 3, 6, 24, 48, and 72 hours after surgery]
• Intraoperative use of fentanyl. [Time frame: For the duration of surgery.]
• Time to the first request for rescue analgesia. [Time frame: 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. [Time frame: Total amount of tramadol and metamizole within 72 hours after surgery.]
• Patient satisfaction [Time frame: 24, 48, and 72 hours after surgery]
• Quality of sleep. [Time frame: 24, 48, and 72 hours after surgery]
• Quality of Recovery [Time frame: 72 hours after surgery]
• Length of stay (LOS) in HDU (high dependency unit) [Time frame: From the time of the admission to HDU until ward discharge (up to 30 days)]
• Length of hospital stay [Time frame: Form the day of surgery until hospital discharge (up to 90 days)]
• Time to ambulation [Time frame: From the end of surgery until patient ambulation (up to 30 days)]
• Time to gastro-intestinal recovery [Time frame: From the end of surgery until the first documented stool, flatus or oral intake (up to 3 days)]
• Sedation score [Time frame: After extubation and 24 hours after surgery.]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Croatia · 1 center

• University hospital of Split — Split

Identifiers

NCT: NCT06935708 · 2181-147/01/06/LJ.Z.-25-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗