Comparison of Intrathecal and Intravenous Analgesia in Patients Undergoing Liver Resection

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

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.

Study Overview

• Status: Unknown
• Conditions: Liver Diseases; Liver Metastases; Liver Cancer
• Intervention / Treatment: Procedure: Intrathecal morphine; Procedure: Intravenous morphine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 02-097
      • Recruiting
      • Department of General, Transplant and Liver Surgery, Medical University of Warsaw
      • Contact: Michał Grąt, M.D., Ph.D.; Phone Number: +48225992545; Email: hepaclin@wum.edu.pl
      • Sub-Investigator: Michał Grąt, M.D., Ph.D.
      • Principal Investigator: Wojciech Figiel, M.D.
    • Warsaw, Mazowieckie, Poland, 02-097
      • Recruiting
      • II Department of Anaesthesiology and Intensive Care, Medical University of Warsaw
      • Contact: Grzegorz Niewiński, MD, PhD; Phone Number: +48225992367; Email: grzegorzniewinski@wp.pl
      • Sub-Investigator: Marta Dec, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrathecal morphine; Intrathecal morphine (0,4 mg) immediately before operation	Procedure: Intrathecal morphine; 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
Active Comparator: Intravenous morphine; Intravenous morphine (0,15 mg/kg body mass) immediately after the operation	Procedure: Intravenous morphine; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Investigators: Principal Investigator: Grzegorz Niewiński, MD, PhD, Medical University of Warsaw

Publications and helpful links

General Publications

• Niewinski G, Figiel W, Grat M, Dec M, Morawski M, Patkowski W, Zieniewicz K. A Comparison of Intrathecal and Intravenous Morphine for Analgesia After Hepatectomy: A Randomized Controlled Trial. World J Surg. 2020 Jul;44(7):2340-2349. doi: 10.1007/s00268-020-05437-x.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2018
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: August 2, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2018
• Last Update Submitted That Met QC Criteria: October 3, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: pain; analgesia; liver resection; postoperative recovery
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 1WB1/2018/1

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
• product manufactured in and exported from the U.S.: No