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Comparison of Three Different Doses of Intrathecal Morphine for Analgesia After Cesarean Section

Primary Purpose

Cesarean Section, Spinal Anesthesia, Postoperative Analgesia

Status
Completed
Phase
Not Applicable
Locations
Turkey
Study Type
Interventional
Intervention
80 mcg intrathecal morphine
120 mcg intrathecal morphine
160 mcg intrathecal morphine
Sponsored by
Ondokuz Mayıs University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cesarean Section focused on measuring Postoperative pain, Intrathecal morphine

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Patient undergoing cesarean section
  • Between the ages of 18-40,
  • ASA II,
  • Pregnant women with gestational week > 36

Exclusion Criteria:

  • Not accepting regional anesthesia,
  • İnfection at the injection site,
  • Coagulopathy, bleeding diathesis,
  • Severe hypovolemia,
  • İncrease in intracranial pressure,
  • Pregnant women with problems such as severe aortic stenosis, severe mitral stenosis for which spinal anesthesia is contraindicated,
  • Patients with a history of allergy to any drug included in the study protocol

Sites / Locations

  • Ondokuz Mayıs University Faculty of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Group 1

Group 2

Group 3

Arm Description

Group 1: Spinal Anesthesia (10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 80 mcg intrathecal morphine) + iv Fentanyl-PCA

Group 2: Spinal Anesthesia (10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 120 mcg intrathecal morphine) + iv Fentanyl-PCA

Group 3: Spinal Anesthesia (10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 160 mcg intrathecal morphine) + iv Fentanyl-PCA

Outcomes

Primary Outcome Measures

Fentanyl consumption in the first 24 hours after surgery
Fentanyl consumption in the first 24 hours was measured. Patients were able to request opioids via a PCA device when their VAS score is above 4 at rest and during activity (coughing and walking).

Secondary Outcome Measures

Post-operative acute pain
Pain status at rest and while activity (coughing and walking) was assessed by VAS scores at 0, 8, 24, 30, and 48 hours after surgery. The VAS is an 11-point numeric scale which ranges from 0 to 10 at rest and during activity.
The incidences of post-operative nausea and vomiting (PONV)
The severity of postoperative nausea and vomiting (PONV) was assessed using a Numeric rating scale(NRS) at 0, 8, 24, 30, and 48 hours after surgery. If a score of 3 or more is recorded, ondansetron 0,1 mg/kg iv was administered.
The incidence of side effects related to opioid use
Complications related to opioid use such as pruritus, fatigue, sedation or respiratory depression was recorded
Bromage Score Comparison
After spinal anesthesia was administered, motor block was evaluated according to the Bromage scale. Bromage score and motor block removal times were noted at the intraoperative 5th, 30th minutes, at the end of the operation, at the postoperative 30th minute and at the 2nd hour.
APGAR score
The 5th minute APGAR score was recorded.

Full Information

First Posted
March 4, 2022
Last Updated
April 8, 2022
Sponsor
Ondokuz Mayıs University
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1. Study Identification

Unique Protocol Identification Number
NCT05317572
Brief Title
Comparison of Three Different Doses of Intrathecal Morphine for Analgesia After Cesarean Section
Official Title
Comparison of Three Different Doses of Intrathecal Morphine for Analgesia After Cesarean Section
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
October 1, 2017 (Actual)
Primary Completion Date
January 1, 2019 (Actual)
Study Completion Date
September 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ondokuz Mayıs University

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
In our study, It was aimed to determine the dose of morphine that provides the most effective analgesia with the least incidence of side effects in the postoperative period.
Detailed Description
Spinal anesthesia is a widely used method in cesarean section operations. It has become a popular practice to add opioids to local anesthetic agents to improve the quality and prolong the duration of intraoperative and postoperative analgesia. Morphine and fentanyl are commonly used opioids for this purpose. In cesarean sections, intrathecal morphine (ITM) is preferred for postoperative analgesia due to its slow onset and long-term analgesia, and intrathecal fentanyl is preferred for intraoperative analgesia due to its faster onset of action. ITM can cause side effects such as nausea, vomiting, itching, sedation and respiratory depression. The quality of analgesia and the incidence of side effects may vary depending on the ITM dose used. There are studies indicating that reducing the dose of ITM results in good quality, long-term analgesia with a low incidence of side effects. However, the ideal dose of ITM providing optimal postoperative analgesia with the lowest incidence of side effects for cesarean section has not been determined yet in the literature. For this purpose, in this study it was compared the postoperative analgesia efficiency and incidence of side effects of three different ITM doses in order to contribute to the literature. Patients were divided into three groups: Group 1: 10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 80 mcg intrathecal morphine was administered. Group 2: 10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 120 mcg intrathecal morphine was administered. Group 3: 10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 160 mcg intrathecal morphine was administered. All patients received iv Patient Controlled Analgesia (PCA) prepared with fentanyl postoperatively.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cesarean Section, Spinal Anesthesia, Postoperative Analgesia
Keywords
Postoperative pain, Intrathecal morphine

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The patients were randomly divided into three groups of 50patients each. In the system where computer generated random numbers (SPSS v23.0, IBM,- Page 2 of 6 [DRAFT] -NewYork, USA) were used,
Masking
ParticipantOutcomes Assessor
Masking Description
The patients were randomly divided into three groups of 50patients each. In the system where computer generated random numbers (SPSS v23.0, IBM,- Page 2 of 6 [DRAFT] -NewYork, USA) were used, groups were determined at a ratio of 1:1:1 . Sealed and sequentially numbered envelopes were created. One hour before the operation, an experienced anesthesiologist, who was not involved in the intraoperative and postoperative follow-up of the patient and would only perform the spinal anesthesia procedure, opened a sealed opaque sealed envelope to learn the group that the patient would be included in. There were two different physicians who performed intraoperative and postoperative follow-up. Both of the follow-up physicians were blind to the patient group
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Active Comparator
Arm Description
Group 1: Spinal Anesthesia (10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 80 mcg intrathecal morphine) + iv Fentanyl-PCA
Arm Title
Group 2
Arm Type
Active Comparator
Arm Description
Group 2: Spinal Anesthesia (10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 120 mcg intrathecal morphine) + iv Fentanyl-PCA
Arm Title
Group 3
Arm Type
Active Comparator
Arm Description
Group 3: Spinal Anesthesia (10 mg hyperbaric bupivacaine + 20 mcg fentanyl+ 160 mcg intrathecal morphine) + iv Fentanyl-PCA
Intervention Type
Drug
Intervention Name(s)
80 mcg intrathecal morphine
Intervention Description
İntraoperative Management: Spinal anesthesia was administered to each patient in a sitting position, after aseptic conditions were achieved with a midline approach. A 25 gauge pencil point spinal needle was placed in the L3-4 or L4-5 space. Upon aspiration of clear cerebrospinal fluid (CSF), 10 mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 80 micrograms of morphine were injected into the intrathecal space together with the determined morphine doses. Postoperative analgesia management: Diclofenac sodium 2 × 75 mg was administered intramuscularly to all patients. All patients received iv Patient Controlled Analgesia (PCA) prepared with fentanyl postoperatively. For patients with pain VAS score of 5 or more, meperidine was administered at a rate of 25 mg each time and with a total daily dose of 200 mg.
Intervention Type
Drug
Intervention Name(s)
120 mcg intrathecal morphine
Intervention Description
İntraoperative Management: Spinal anesthesia was administered to each patient in a sitting position, after aseptic conditions were achieved with a midline approach. A 25 gauge pencil point spinal needle was placed in the L3-4 or L4-5 space. Upon aspiration of clear cerebrospinal fluid (CSF), 10 mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 120 micrograms of morphine were injected into the intrathecal space together with the determined morphine doses. Postoperative analgesia management: Diclofenac sodium 2 × 75 mg was administered intramuscularly to all patients. All patients received iv Patient Controlled Analgesia (PCA) prepared with fentanyl postoperatively. For patients with pain VAS score of 5 or more, meperidine was administered at a rate of 25 mg each time and with a total daily dose of 200 mg.
Intervention Type
Drug
Intervention Name(s)
160 mcg intrathecal morphine
Intervention Description
İntraoperative Management: Spinal anesthesia was administered to each patient in a sitting position, after aseptic conditions were achieved with a midline approach. A 25 gauge pencil point spinal needle was placed in the L3-4 or L4-5 space. Upon aspiration of clear cerebrospinal fluid (CSF), 10 mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 160 mcg of morphine were injected into the intrathecal space together with the determined morphine doses. Postoperative analgesia management: Diclofenac sodium 2 × 75 mg was administered intramuscularly to all patients. All patients received iv Patient Controlled Analgesia (PCA) prepared with fentanyl postoperatively. For patients with pain VAS score of 5 or more, meperidine was administered at a rate of 25 mg each time and with a total daily dose of 200 mg.
Primary Outcome Measure Information:
Title
Fentanyl consumption in the first 24 hours after surgery
Description
Fentanyl consumption in the first 24 hours was measured. Patients were able to request opioids via a PCA device when their VAS score is above 4 at rest and during activity (coughing and walking).
Time Frame
Postoperative Day 2
Secondary Outcome Measure Information:
Title
Post-operative acute pain
Description
Pain status at rest and while activity (coughing and walking) was assessed by VAS scores at 0, 8, 24, 30, and 48 hours after surgery. The VAS is an 11-point numeric scale which ranges from 0 to 10 at rest and during activity.
Time Frame
Postoperative Day 2
Title
The incidences of post-operative nausea and vomiting (PONV)
Description
The severity of postoperative nausea and vomiting (PONV) was assessed using a Numeric rating scale(NRS) at 0, 8, 24, 30, and 48 hours after surgery. If a score of 3 or more is recorded, ondansetron 0,1 mg/kg iv was administered.
Time Frame
Postoperative Day 2
Title
The incidence of side effects related to opioid use
Description
Complications related to opioid use such as pruritus, fatigue, sedation or respiratory depression was recorded
Time Frame
Postoperative Day 2
Title
Bromage Score Comparison
Description
After spinal anesthesia was administered, motor block was evaluated according to the Bromage scale. Bromage score and motor block removal times were noted at the intraoperative 5th, 30th minutes, at the end of the operation, at the postoperative 30th minute and at the 2nd hour.
Time Frame
Postoperative 2nd hour.
Title
APGAR score
Description
The 5th minute APGAR score was recorded.
Time Frame
The 5th minute APGAR score was recorded.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Patient undergoing cesarean section Between the ages of 18-40, ASA II, Pregnant women with gestational week > 36 Exclusion Criteria: Not accepting regional anesthesia, İnfection at the injection site, Coagulopathy, bleeding diathesis, Severe hypovolemia, İncrease in intracranial pressure, Pregnant women with problems such as severe aortic stenosis, severe mitral stenosis for which spinal anesthesia is contraindicated, Patients with a history of allergy to any drug included in the study protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ilke tamdoğan
Organizational Affiliation
Ondokuz Mayıs University Faculty of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ondokuz Mayıs University Faculty of Medicine
City
Samsun
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
9952150
Citation
Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999 Feb;90(2):437-44. doi: 10.1097/00000542-199902000-00018. Erratum In: Anesthesiology 1999 Apr;90(4):1241.
Results Reference
result
PubMed Identifier
7008655
Citation
Baraka A, Noueihid R, Hajj S. Intrathecal injection of morphine for obstetric analgesia. Anesthesiology. 1981 Feb;54(2):136-40. doi: 10.1097/00000542-198102000-00007.
Results Reference
result
PubMed Identifier
29310376
Citation
Weigl W, Bierylo A, Wielgus M, Krzemien-Wiczynska S, Kolacz M, Dabrowski MJ. Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study. Medicine (Baltimore). 2017 Dec;96(48):e8892. doi: 10.1097/MD.0000000000008892.
Results Reference
result
PubMed Identifier
12145067
Citation
Sarvela J, Halonen P, Soikkeli A, Korttila K. A double-blinded, randomized comparison of intrathecal and epidural morphine for elective cesarean delivery. Anesth Analg. 2002 Aug;95(2):436-40, table of contents. doi: 10.1097/00000539-200208000-00037.
Results Reference
result

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Comparison of Three Different Doses of Intrathecal Morphine for Analgesia After Cesarean Section

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