Analgesic Effect of Intrathecal Morphine Combined With Low Dose Local Anesthetics on Postoperative Analgesia After Liver Resection

Analgesic Effect of Intrathecal Morphine Combined With Low Dose Local Anesthetics on Postoperative Analgesia After Liver Resection: A Randomized, Controlled Preliminary Study

Efficient postoperative pain control plays a vital part in the management of patients after surgery. In particular, major surgeries including hepatectomy cause intense postoperative pain that may result in cardiovascular or respiratory complications post-surgery. One of the current methods of postoperative pain control after hepatectomy involves a multimodal approach including intrathecal morphine injection immediately prior to surgery. Because morphine alone is inadequate for immediate postoperative pain control due to a late peak effect time of 6 hours, current literature advocates a combination injection including bupivacaine. However, higher doses of bupivacaine may inadvertently cause motor block or hemodynamic side effects. The aim of this study was to compare the effectiveness and side effects of intrathecal morphine combined with low dose bupivacaine against intrathecal morphine alone and no intrathecal injection.

Study Overview

• Status: Completed
• Conditions: Patients Receiving Hepatectomy Under General Anesthesia
• Intervention / Treatment: Drug: Percutaneous injection; Drug: Morphine; Drug: Morphine+Bupivacaine

Detailed Description

All patients enrolled in the current study will receive intrathecal injections immediately prior to general anesthesia. The patient will be on his or her side in the fetal position and after palpating the back to secure the space between the 3rd and 4th lumbar spine, the area will be properly disinfected and draped with a sterile towel. Using a 25G needle, a small volume of 1% lidocaine will be injected at the proposed puncture site. For the control group, 2ml of 1% lidocaine will be injected subcutaneously with the 25G needle used during local anesthetic injection. For the morphine group and the morphine + bupivacaine group, a 25G pencil point spinal needle will be used to advance into the intrathecal space. After confirming intrathecal position of the needle by CSF regurgitation, morphine 400mg or morphine 400mcg+ bupivacaine 5mg each to a total volume of 2ml will be injected. Afterwards, all patients will undergo general anesthesia by the same method.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Age 19 years to no upper limit
2. Patients receiving liver resection under general anesthesia (Including open surgery and laparoscopic surgery)
3. American Society of Anesthesiologists (ASA) physical status 1,2

Exclusion Criteria:

1. Patients presenting with coagulopathy prior to surgery
2. Patients with neurological deficits
3. Patients with spinal anomaly or disorders
4. Patients with allergies to opioids or local anesthetics
5. Patients with severe respiratory, cardiovascular, renal, or hepatic disorders
6. Severe systemic infection or infections involving proposed intrathecal injection site
7. Patients with severe psychological disorders severe that may interfere with pain evaluation
8. Patients with chronic diseases that require opioids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine	Drug: Morphine; Intrathecal injection of morphine 400mcg
Sham Comparator: Control; a sham procedure of 2 ml of 1% lidocaine injected percutaneously using the initial 25G needle	Drug: Percutaneous injection; A sham procedure of 2 ml of 1% lidocaine injected percutaneously using the initial 25G needle for local anesthetics
Experimental: Morphine+bupivicaine	Drug: Morphine+Bupivacaine; Intrathecal injection of 5mg of 0.5% bupivacaine chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first rescue analgesic	Time to first rescue analgesic during the first 72 hours after surgery (hr) was our primary outcome.	First 72 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score after surgery (visual analogue scale, VAS)	Visual analogue scale is a validated subjective measure for acute and chronic pain. Scores are measured on 10cm line where 0 represents no pain to 10cm representing the worst pain.	30 minutes, 1 hours upon arrival of the Postoperative anesthesia care unit(PACU), 5 hours post surgery, 1 day post-surgery
Total fentanyl dose administered via intravenous patient-controlled analgesia (PCA)	Further assessment of pain control was done by comparing total opioid dosage via PCA.	First 48 hour post surgery
Additional rescue analgesics given to the patient	Rescue analgesics were given only upon patients request. This was evaluated for further assessment of pain control.	until 3 days post-surgery.
Sensory and motor block	Sensory and motor block was assessed for prolonged effects of intrathecal injection.	30 minutes, 1 hours upon arrival of the Postoperative anesthesia care unit (PACU), 5 hours post surgery, 1 day post-surgery
Presence of complications (headache, nausea/vomiting, pruritus, respiratory depression, somnolence, low blood pressure, tingling, and shivering)	Common side effects to morphine or bupivacaine injections were assessed.	first 3 days post surgery

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Bon-Nye Koo, Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2018
• Primary Completion (Actual): April 18, 2020
• Study Completion (Actual): April 18, 2020

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: January 12, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 12, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bupivacaine; Morphine
• Other Study ID Numbers: 4-2018-0838

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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