Magnesium Sulfate and Neuroendocrine Hormone

Study Overview
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Brief Summary
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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.

Official Title
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Neuroendocrine Changes Associated With Magnesium Sulfate Administration in Surgical Patients

Conditions
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Magnesium Sulfate, Arthropathy of Knee, Cortisol, Dehydroepiandrosterone

Intervention / Treatment
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* Drug: Magnesium sulfate
* Drug: Isotonic Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group M<br>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<br>* 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.<br>|
| Placebo Comparator: Group S<br>Patients in the saline group received the same volume of isotonic saline over the same period with magnesium infusion protocol | Drug: Isotonic Saline<br>* Isotonic saline group receives the same volume of isotonic saline, administered according to the same methods as in the magnesium group.<br>|

What is the study measuring?
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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 |