Analgesic Potentials of Preoperative Pregabalin,Magnesium Sulphate and Their Combination in Acute Post-thoracotomy Pain

Analgesic Potentials of Preoperative Oral Pregabalin,Intravenous Magnesium Sulphate and Their Combination in Acute Post-thoracotomy Pain.(Randomized,Double-Blind Study)

This study evaluates the effect of giving preoperative adjuvant drug as pregabalin or magnesium sulphate or a combination of both drugs to decrease postoperative morphine consumption and pain intensity in the first 24 hours in postoperative period . quarter of patients receive single dose oral pregabalin 300mg 1 hour preoperatively ,other quarter receive single intravenous Magnesium sulphate 50mg per Kg over 200ml saline over 20 minutes preoperatively , other quarter receive combination of both drugs , the last quarter receive placebo drugs . All patients receive 0.1mg per Kg intravenous morphine sulphate intraoperatively

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Placebo; Drug: Pregabalin & Placebo; Drug: Magnesium sulphate & Placebo; Drug: Pregabalin & Magnesium sulphate

Detailed Description

Magnesium (Mg) acts on N-methyl-D-aspartate (NMDA) receptor as a non-competitive antagonist with antinociceptive effects.

Gabapentin is an alkylated analogue of gammaaminobutyric acid (GABA) developed primarily as an anticonvulsant drug. It was described as an analgesic drug for the treatment of neuropathic pain in the 1990s. Although it is named Gabapentin,it does not bind at the GABA A or GABA B receptor. It binds with high affinity for the α2δ subunit of the presynaptic voltage-gated calcium channels, which reduce calcium-dependent release of pro-nociceptive neurotransmitters in the pain pathways. Pregabalin is a structural analogue of GABA was introduced after Gabapentin. If we used these drugs in combination to opioids preoperatively as preventive analgesia may decrease postoperative opioid consumption and pain intensity.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11796
    • National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ASA status of1 or 2
2. Patients undergoing thoracotomy
3. Body mass index (BMI): Less than forty and more than twenty.

Exclusion Criteria:

- 1. Known sensitivity or contraindication to drugs used in the study. 2. History of psychological disorders and/or chronic pain. 3. Patients receiving medical therapies that are considered to result in tolerance to opioids.

4. Significant liver or kidney diseases that will affects the pharmacokinetics of study drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pregabalin & placebo; : will receive single dose oral Pregabalin 300 mg one hour preoperative and 200 ml of normal saline over 20 min.	Drug: Pregabalin & Placebo
Active Comparator: Magnesium sulphate & Placebo; will receive preoperative single dose IV Magnesium Sulphate 50mg /kg infused over 20 minutes diluted in 200 ml normal saline and a placebo capsule similar to pregabalin 300 mg.	Drug: Magnesium sulphate & Placebo
Active Comparator: Pregabalin & Magnesium sulphate; : will receive single dose oral pregabalin 300mg one hour preoperative and single dose IV Magnesium Sulphate 50mg /kg infused over 20 minutes diluted in 200 ml normal saline.	Drug: Pregabalin & Magnesium sulphate
Placebo Comparator: Placebo; will receive placebo medications at the same time and route of administration of other groups.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total morphine consumption	patients are given regular intravenous morphine through patient controlled analgesia (PCA) and morphine consumption calculated from the PCA device	First 24 hours in postoperative period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity using Visual Analogue Scale	Assessment of pain intensity every 4 hours in the first 24 hours in postoperative period	First 24 hours in postoperative period
Recovery Time	Time taken for recovery of the patient to be fully awake	Immediately after ending the surgery
Heart Rate	Assessment of Heart Rate every 4 hours	First 24 hours in postoperative period
Blood Pressure	Assessment of Blood Pressure every 4 hours	First 24 hours in postoperative period
Oxygen saturation	Assessment of Oxygen saturation every 4 hours	First 24 hours in postoperative period
Respiratory Rate	Assessment of Respiratory Rate every 4 hours	First 24 hours in postoperative period
Postoperative nausea and vomiting	Postoperative nausea and vomiting scale (none 0, mild 1, moderate 2 , sever 3)	First 24 hours in postoperative period
Side effects from the used drugs		First 24 hours in postoperative period
Sedation score	Using Ramsay Sedation score	First 24 hours in postoperative period

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt
• Investigators: Study Chair: Naglaa A Ahmed, MD, National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Sagit M, Yalcin S, Polat H, Korkmaz F, Cetinkaya S, Somdas MA. Efficacy of a single preoperative dose of pregabalin for postoperative pain after septoplasty. J Craniofac Surg. 2013 Mar;24(2):373-5. doi: 10.1097/SCS.0b013e31827fece5.
• Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011 Jan;55(1):31-5. doi: 10.4103/0019-5049.76605.
• Salah Abdelgalil A, Shoukry AA, Kamel MA, Heikal AMY, Ahmed NA. Analgesic Potentials of Preoperative Oral Pregabalin, Intravenous Magnesium Sulfate, and their Combination in Acute Postthoracotomy Pain. Clin J Pain. 2019 Mar;35(3):247-251. doi: 10.1097/AJP.0000000000000673.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: February 5, 2016
• First Submitted That Met QC Criteria: February 6, 2016
• First Posted (Estimate): February 9, 2016

Study Record Updates

• Last Update Posted (Actual): September 22, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Pregabalin; Magnesium Sulfate
• Other Study ID Numbers: NCI,IRB 2010014053.3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be available within 6 months of study completion