Steroids in Bilateral Total Knee Replacement

Study Overview
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Brief Summary
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Inflammation related to cytokine release is known to occur with surgery. The cytokine IL6, a major marker of inflammation is known to increase during total joint replacement surgery. IL6 has been found to be elevated postoperatively in patients with hip fractures and has been linked to mental status changes and possibly other complications. It is known to lead to shock and participate in the inflammatory state seen in sepsis. High levels have further been linked to postoperative fever, confusion, symptoms of depression, acute respiratory distress syndrome (ARDS) and fat embolism syndrome (FES). Previously the investigators found that low dose steroids given in two doses in the initial perioperative period decreased the amount of IL6 released compared to placebo, but this was not sustained past 24 hours. Desmosine is a stable breakdown product of elastin from lung tissue that can be measured in urine samples. It is considered to be a marker of lung injury and is found to be elevated in patients with ARDS, congestive obstructive pulmonary disease and FES. Previously, the investigators have found that urine desmosine levels rise with bilateral total knee replacement compared to unilateral total knee replacement indicating possible lung injury. Therefore the investigators hypothesize: Continued low dose steroids given three times over a 24 hour period will: Significantly decrease peak IL6 cytokine release during bilateral total knee replacement and maintaining this reduction in IL6 beyond 24 hours. Decrease urinary desmosine levels, and hence be protective of lung injury.

Official Title
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Effect of Steroids Given Over 24 Hours on Cytokine Release and Urinary Desmosine Levels in Patients Undergoing Bilateral Total Knee Replacement

Conditions
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Postoperative Inflammatory Response

Intervention / Treatment
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* Drug: Hydrocortisone
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for bilateral total knee replacement Between 50-90 years of age Exclusion Criteria: Patients on steroid therapy Patients that require stress-dose steroid pre-operatively Patients that smoke Patients that are diabetic Patients younger than 50 or older than 90 years

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Steroid<br>Hydrocortisone 100 mg IV Q 8hrs x3 | Drug: Hydrocortisone<br>* Prepared by pharmacy, 100 mg, IV, every 8 hours, 3 times<br>|
| Placebo Comparator: Control<br>Saline IV Q8hr x3 | Drug: Saline<br>* Prepared by pharmacy same volume as study drug, IV, every 8 hours 3 times<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in IL6 Level |  | 24 hours postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Desmosine Level |  | 24 hours postoperative | 
| Blood Glucose |  | 24 hours postoperative | 
| Length of Hospital Stay |  | Length of hospital stay, an expected average of 5 days | 
| In Hospital Infection Rate |  | Length of hospital stay, an expected average of 5 days | 
| Mortality |  | Length of hospital stay, an expected average of 5 days | 
| Ability to Ambulate |  | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bilateral total knee replacement, cytokine, desmosine