Comparison of Intrathecal and Intravenous Analgesia in Patients Undergoing Liver Resection

Study Overview
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Brief Summary
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The aim of this prospective, interventional, randomized trial is to compare the effectiveness of postoperative analgesia using single-dose intrathecal morphine and intravenous morphine in patients undergoing liver resection. The study is to include a total 36 patients randomized in a 1:1 ratio into two groups. The study will be single-blinded with respect to outcome assessors. Patients in the experimental group (n=18) will receive a single dose (0,4 mg) intrathecal morphine immediately before operation and patient-controlled analgesia (PCA) with morphine over first 24 postoperative hours and subcutaneous morphine (5 mg in case of numerical rating scale>4) over next two days in the postoperative period. Patients in the control group (n=18) will receive a single dose of intravenous morphine (0,15 mg/kg body mass) immediately after the operation and PCA with morphine over first 24 postoperative hours and subcutaneous morphine (5 mg in case of numerical rating scale>4) over next two days. Both groups will receive antiemetic prophylaxis with dexamethasone (4 mg) and ondansetron (4 mg) and standard baseline analgesia with paracetamol (1,0 g every 6 hours) and dexketoprofen (50 mg every 8 hours). Severity of pain at rest evaluated with numerical rating scale twice daily over 3 first postoperative days will be the primary outcome measure. Secondary outcome measures will include: severity of pain at coughing evaluated with numerical rating scale twice daily over 3 first postoperative days, total dose of morphine administered with PCA, time to patient mobilization, grade of sedation, intestinal motility, solid food intake tolerance, duration of hospitalization, and postoperative complications.

Detailed Description
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Effective analgesia in patients undergoing liver resection is an important measure to enhance the process of postoperative recovery. The aim of this prospective, interventional, randomized trial is to compare the effectiveness of postoperative analgesia using single-dose intrathecal morphine and intravenous morphine in patients undergoing liver resection. The study is to include a total 36 patients randomized in a 1:1 ratio into two groups. The patients scheduled for liver resection in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw) will be screened for eligibility basing on inclusion and exclusion criteria. Eligible patients will be included in the study following provision of informed consent. Randomization will be performed immediately before the surgical procedure in the operating theatre. The study will be single-blinded with respect to outcome assessors. Patients in the experimental group (n=18) will receive a single dose (0,4 mg) intrathecal morphine immediately before operation and patient-controlled analgesia (PCA) with morphine over first 24 postoperative hours and subcutaneous morphine (5 mg in case of numerical rating scale>4) over next two days in the postoperative period. Patients in the control group (n=18) will receive a single dose of intravenous morphine (0,15 mg/kg body mass) immediately after the operation and PCA with morphine over first 24 postoperative hours and subcutaneous morphine (5 mg in case of numerical rating scale>4) over next two days. Both groups will receive antiemetic prophylaxis with dexamethasone (4 mg) and ondansetron (4 mg) and standard baseline analgesia with paracetamol (1,0 g every 6 hours) and dexketoprofen (50 mg every 8 hours). Severity of pain at rest evaluated with numerical rating scale twice daily over 3 first postoperative days will be the primary outcome measure. Secondary outcome measures will include: severity of pain at coughing evaluated with numerical rating scale twice daily over 3 first postoperative days, total dose of morphine administered with PCA, time to patient mobilization, grade of sedation, intestinal motility, solid food intake tolerance, duration of hospitalization, and postoperative complications. Side effects of intrathecal morphine injection and intravenous morphine administration will be monitored. The thresholds for type I and type II errors will be set at 0.05 and 0.20, respectively.

Official Title
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Comparison of the Efficacy of Postoperative Analgesia by a Single Dose of Intrathecal Morphine and Intravenous Morphine: a Randomized Trial

Conditions
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Liver Diseases, Liver Cancer, Liver Metastases

Intervention / Treatment
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* Procedure: Intravenous morphine
* Procedure: Intrathecal morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: liver resection liver malignancy Exclusion Criteria: >3 points in American Society of Anesthesiology (ASA) scale contra-indications for intrathecal morphine administration chronic preoperative intake of analgetics a history of opioid dependency body mass index >45 kg/m2 allergy to any analgetic drug administered in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized in a 1:1 ratio into experimental and control group
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intrathecal morphine<br>Intrathecal morphine (0,4 mg) immediately before operation | Procedure: Intrathecal morphine<br>* Single dose (0,4 mg) intrathecal morphine immediately before operation, patient-controlled analgesia with morphine (2 mg intravenously, a least 20 min interval) over first 24 postoperative hours and subcutaneous morphine (5 mg in case of numerical rating scale>4, at least 6 hour interval) over next two days in the postoperative period<br>|
| Active Comparator: Intravenous morphine<br>Intravenous morphine (0,15 mg/kg body mass) immediately after the operation | Procedure: Intravenous morphine<br>* Single dose of intravenous morphine (0,15 mg/kg body mass) immediately after the operation, patient controlled analgesia with morphine (2 mg intravenously, a least 20 min interval) over first 24 postoperative hours and subcutaneous morphine (5 mg in case of numerical rating scale>4, at least 6 hour interval) over next two days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of pain at rest | Severity of pain assessed in numerical rating scale twice daily | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of pain at coughing | Severity of pain assessed in numerical rating scale twice daily | 3 days | 
| Morphine usage | Total dose of morphine administered intravenously and subcutaneously | 3 days | 
| Time to mobilization | Time to self-standing after the operation | 90 days | 
| Grade of sedation | Richmond Agitation and Sedation Scale | 3 days | 
| Solid food tolerance | Time to solid food intake | 90 days | 
| Duration of hospitalization | Postoperative hospital stay | 90 days | 
| Postoperative complications | Postoperative complications according to Clavien-Dindo classification | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver resection, analgesia, pain, postoperative recovery