Magnesium Sulfate and Neuroendocrine Hormone

Neuroendocrine Changes Associated With Magnesium Sulfate Administration in Surgical Patients

Total knee arthroplasty is a procedure that relieves pain in patients with severe symptomatic osteoarthritis, but it can be associated with postoperative pain, which hinders recovery. In the previous study, we reported evidence of increased pain in patients undergoing staged total knee arthroplasty, in whom the second operated knee had greater sensitivity (tertiary hyperalgesia) as a result of the surgical injury to the first operated knee.

Magnesium sulfate is an effective analgesic adjuvant for postoperative pain. Its analgesic property seems to be associated with the regulation of calcium influx into the cells, or antagonism of N-methyl-D-aspartate receptors in the central nervous system. Additionally, magnesium is known to have an anti-inflammatory effect. Inflammatory state may accompany with pain via peripheral or central sensitization.

Recently, we reported that magnesium sulfate effectively attenuates not only postoperative pain but also increased pain intensity without serious adverse effects in the bilateral staged total knee arthroplasty. However, the exact mechanism regarding these effects of magnesium sulfate remains unclear.

In the present study, we will investigate the analgesic mechanism of magnesium sulfate via analysis of endocrine neurosteroid levels in patients undergoing bilateral staged total knee arthroplasty.

Study Overview

• Status: Recruiting
• Conditions: Arthropathy of Knee; Magnesium Sulfate; Cortisol; Dehydroepiandrosterone
• Intervention / Treatment: Drug: Magnesium sulfate; Drug: Isotonic Saline

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hyun-Jung Shin, MD., PhD.; Phone Number: 0317877508; Email: hjshin.anesth@gmail.com

Study Locations

• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Hyun-Jung Shin, Ph.D., M.D.; Phone Number: 82317877499; Email: hjshin.anesth@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients who undergo staged bilateral total knee arthroplasty
• Spinal anesthesia
• American Society of Anesthesiologists physical status 1 and 2

Exclusion Criteria:

• Patients who undergo unilateral total knee arthroplasty
• General anesthesia
• Musculoskeletal disease
• Hypermagnesemia
• Atrioventricular block
• Previous history of administration of calcium channel blockers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group M; Patients in the magnesium sulfate group received magnesium sulfate 50 mg/kg for 15 minutes after spinal anesthesia and then 15 mg/kg/hour by continuous intravenous infusion until the end of surgery	Drug: Magnesium sulfate; Magnesium group receives magnesium sulfate (50 mg/kg) in 100 mL of isotonic saline over 15 minutes after spinal anesthesia, followed by a continuous magnesium sulfate infusion (15 mg/kg/hour) until the end of surgery.
Placebo Comparator: Group S; Patients in the saline group received the same volume of isotonic saline over the same period with magnesium infusion protocol	Drug: Isotonic Saline; Isotonic saline group receives the same volume of isotonic saline, administered according to the same methods as in the magnesium group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The profiles of cortisol in the saliva	The cortisol concentrations in the saliva, at the evening before the operation (21:00~22:00), just after wake-up in the morning of the operation day, and 30 and 60 minutes after wake-up	From the evening (21:00) before the operation day to the morning (60 minutes after wake-up) of the operation day, for each stage of the operation
The profiles of dehydroepiandrosterone (DHEA) in the saliva	The DHEA concentrations in the saliva, at the evening before the operation (21:00~22:00), just after wake-up in the morning of the operation day, and 30 and 60 minutes after wake-up	From the evening (21:00) before the operation day to the morning (60 minutes after wake-up) of the operation day, for each stage of the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain	Numerical rating scale pain score	Postoperative 24 hour
Postoperative pain	Numerical rating scale pain score	Postoperative 48 hour
Patient controlled analgesia (PCA)	Amounts of PCA consumption	Postoperative 24 hour
Patient controlled analgesia (PCA)	Amounts of PCA consumption	Postoperative 48 hour
Nausea	Incidence of nausea	Postoperative 24 hour
Nausea	Incidence of nausea	Postoperative 48 hour
Vomiting	Incidence of vomiting	Postoperative 24 hour
Vomiting	Incidence of vomiting	Postoperative 48 hour
Anti-emetics	Amounts of anti-emetics consumption	Postoperative 24 hour
Anti-emetics	Amounts of anti-emetics consumption	Postoperative 48 hour

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Seoul National University Bundang Hospital
• Investigators: Principal Investigator: Hyun-Jung Shin, MD., PhD., Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2021
• Primary Completion (Anticipated): December 15, 2021
• Study Completion (Anticipated): December 15, 2021

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): September 24, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; 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; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: B-2008/631-002

Drug and device information, study documents

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