Effect of Preoperative Oral Pregabalin Versus Intraoperative Fentanyl on Postoperative Analgesia

The Effect of Preoperative Oral Pregabalin and Intraoperative Fentanyl on Postoperative Analgesia in Diagnostic Laparoscopic Gynecologic Surgery: a Comparative Study

Pregabalin is a structural analogue of gamma amino butyric acid (GABA). It binds to presynaptic alpha-2-delta subunit of voltage gated calcium channels in the brain and the spinal cord. Thus, it modulates the release of excitatory neurotransmitters, such as glutamate, norepinephrine, substance-P, and calcitonin gene related peptide. Also, it causes inhibitory modulation of overexcited neurons and restores them to a normal state.

Pre-emptive analgesia aims to reduce postoperative opioid consumption especially in ambulatory surgeries. Pregabalin (PGB) is an emerging drug in this field. Different doses of preoperative oral pregabalin (75, 150 and 300 mg) are described in the literature with a dose-response analgesic relationship and reduction of opioid use; however increasing the dose results in increasing the incidence of side effects mainly sedation and dizziness.

Perioperative use of opioids for analgesia may result in side effects; like nausea, vomiting, excessive sedation, respiratory depression, pruritus, and urinary retention.The concomitant use of opioids with pregabalin may result in excess sedation and somnolence, so, the use of opioids with pregabalin should be limited to patients with inadequate alternative options.

Study Overview

• Status: Recruiting
• Conditions: Post Operative Pain, Acute
• Intervention / Treatment: Drug: Pregabalin 150mg; Drug: Fentanyl 100 micrograms ampoule

Detailed Description

Our study aims to compare the postoperative analgesic effect of pre-operative oral pregabalin (Study group), to the intraoperative intravenous fentanyl (Control group) in diagnostic laparoscopic gynecologic surgery.

Patienrs will be selected by simple randomization by computer generated system. Pregabalin 150 mg oral capsule and a placebo capsule will be available on the morning of operation.

Also, 2 syringes of 10 ml volumes will be prepared; the first contains normal saline and the second contains the fentanyl dose of 1 µg /kg calculated according to the patient's body weight and diluted to a 10 ml volume.

Patients will then be divided into 2 equal groups of 40 patients each:

Group P: Patients will receive oral pregabalin capsule (150 mg) 90 min before induction of anesthesia, and will receive a bolus injection of 10 ml saline at induction of anesthesia.

Group F: Patients will receive oral placebo capsule identical to the trial drug in size, shape and color, 90 min before induction of anesthesia and will receive a bolus injection of 10 ml of 1µg /kg fentanyl at induction of anesthesia.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Ghada Mohamed Samir, MD; Phone Number: 002 01005043691; Email: dr.ghada216@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Ain-Shams University
    • Contact: Ghada Mohamed Samir, MD; Phone Number: 002 01005043691; Email: dr.ghada216@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• ASA physical status I

Exclusion Criteria:

• Patients' refusal
• use of sedatives, hypnotics, anti-psychotic or antidepressant drugs
• history of drug/alcohol abuse
• history of chronic pain
• daily intake of analgesics
• history of epilepsy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group Pregabalin; Patients will receive oral pregabalin capsule (150 mg) 90 min before induction of anesthesia, and will receive a bolus injection of 10 ml saline at induction of anesthesia	Drug: Pregabalin 150mg; Compare the postoperative analgesic effect of pre-operative oral pregabalin (Study group), to the intraoperative intravenous fentanyl (Control group) in diagnostic laparoscopic gynecologic surgery.
Active Comparator: Group Fentanyl; Patients will receive oral placebo capsule identical to the trial drug in size, shape and color, 90 min before induction of anesthesia and will receive a bolus injection of 10 ml of 1µg /kg fentanyl at induction of anesthesia	Drug: Fentanyl 100 micrograms ampoule; Compare the postoperative analgesic effect of pre-operative oral pregabalin (Study group), to the intraoperative intravenous fentanyl (Control group) in diagnostic laparoscopic gynecologic surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in post-operative pain score at rest over time	Intensity of pain will be monitored at 15 and 30min after arrival to the PACU, then 1h before discharge from the PACU. For analysis, pain severity will be categorized as absent (VAS=0), mild (VAS=1-3), moderate (VAS=4-7), severe (VAS=7-9), and very severe (VAS=10).	1 hour
Changes in post-operative pain score on coughing over time	Intensity of pain will be monitored at 15 and 30min after arrival to the PACU, then 1h before discharge from the PACU. For analysis, pain severity will be categorized as absent (VAS=0), mild (VAS=1-3), moderate (VAS=4-7), severe (VAS=7-9), and very severe (VAS=10).	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-operative level of patient sedation assessed by the sedation score	assessed 1 hour after administering the oral capsules by the sedation score from 0 to 4. 0=Awake and agitated, 1= Awake and comfortable, 2= Asleep and arousable, 3= Asleep with sluggish response to verbal commands or touch, 4= No response to verbal command or touch.	1 hour
Duration of surgery	Measured in minutes	2 hours
Duration of anesthesia	Measured in minutes	3 hours
mean values of systolic blood pressure (SBP)	mean values of SBP at pre-operative baseline, before induction of anesthesia, 5min after endotracheal intubation, before pneumoperitoneum, during the first 30 minutes (at 10, 20 and 30 min) of pneumoperitoneum, after release of pneumoperitoneum and 10 min after extubation in the PACU	4 hours
Intra-operative additional doses of fentanyl given	Rescue analgesia needed in micrograms	3 hours
Postoperative level of patient sedation	assessed by the sedation score from 0 to 4. 0=Awake and agitated, 1= Awake and comfortable, 2= Asleep and arousable, 3= Asleep with sluggish response to verbal commands or touch, 4= No response to verbal command or touch.	1 hour
Post-operative pain score	at rest and on coughing using the Visual Analogue Score (VAS) score from 0 to 10 where 0= no pain and 10 is the worst pain felt. Pain severity will be categorized as absent (VAS=0), mild (VAS=1-3), moderate (VAS=4-7), severe (VAS=7-9), and very severe (VAS=10).	12 hours
Pethidine requirements	Number of patients requiring pethidine in the PACU	1 hour
sPO2	recorded in the induction room and in the PACU	4 hours
changes in mean values of diastolic blood pressure (DBP)	mean values of DBP at pre-operative baseline, before induction of anesthesia, 5min after endotracheal intubation, before pneumoperitoneum, during the first 30 minutes (at 10, 20 and 30 min) of pneumoperitoneum, after release of pneumoperitoneum and 10 min after extubation in the PACU	4 hours
changes in mean values of mean blood pressure (MBP)	mean values of MBP,at pre-operative baseline, before induction of anesthesia, 5min after endotracheal intubation, before pneumoperitoneum, during the first 30 minutes (at 10, 20 and 30 min) of pneumoperitoneum, after release of pneumoperitoneum and 10 min after extubation in the PACU	4 hours
mean values of heart rate (HR)	mean values of HR at pre-operative baseline, before induction of anesthesia, 5min after endotracheal intubation, before pneumoperitoneum, during the first 30 minutes (at 10, 20 and 30 min) of pneumoperitoneum, after release of pneumoperitoneum and 10 min after extubation in the PACU	4 hours
total dose of pethidine given to the patient	total dose of pethidine given in milligrams will be recorded	12 hours

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: pregabalin; analgesia
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain, Postoperative; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Adjuvants, Anesthesia; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anticonvulsants; Calcium Channel Blockers; Pregabalin; Fentanyl
• Other Study ID Numbers: R18/2020/2021

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