Effect of Methylprednisolone on Orthostatic Intolerance and Heart Rate Variability in Hip-arthroplasty Patients

Study Overview
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Brief Summary
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The study evaluates the pathophysiological effects of a single dose Methylprednisolone administered prior to total hip-arthroplasty (THA) surgery. The investigators examine the effect on orthostatic intolerance, orthostatic hypotension and heart rate variability (HRV) to evaluate the efficacy of Methylprednisolone regarding blood pressure regulation and autonomic responses after THA. Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo. The investigators hypothesize that the group receiving Methylprednisolone will be less orthostatic intolerant, experience less orthostatic hypotension and have an improved autonomic response compared to the placebo-group, early after THA.

Detailed Description
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The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects in postoperative pain, postoperative nausea and vomiting are well-documented. Hip-arthroplasty surgery and the inflammatory stress response in general affect the potential of recovery. Early postoperative orthostatic intolerance is common in patients undergoing THA with an incidence of 40%. The mechanism is thought related to an impaired autonomic regulation caused by surgery-induced inflammation. The effect of glucocorticoids on orthostatic intolerance, orthostatic hypotension and HRV after hip-arthroplasty surgery is unknown and calls for further investigation. The study is to be considered as exploratory. The primary analysis of the primary outcome measure is a comparison of the incidence of orthostatic intolerance from baseline to 6 hours postoperatively between the two groups. For calculation of sample size the difference in incidence between groups (40% versus 10%) from baseline (before surgery) to 6 hours after THA-surgery, a risk of type I errors 5% and a risk of type II errors 20% (80% power) were used. The primary analysis is carried out on all included patients (intention-to-treat) with baseline values as covariate. Secondary exploratory per-protocol analysis might be performed. Missing outcomes will be analysed using multiple imputation due to expected strong time trends. The secondary outcomes measures; Non-invasive blood pressure, systemic vascular resistance, cardiac output, HRV, plasma-hemoglobin, C-reactive protein. For further details please also view the European Clinical Trials Database (EudraCT) registration: EudraCT nr.: 2015-000102-19

Official Title
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Effect of Preoperative Intravenous High Dose Methylprednisolone on Orthostatic Intolerance and Heart Rate Variability in Patients Scheduled for Total Hip-arthroplasty

Conditions
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Osteoarthrosis

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Isotonic Sodium Chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthrosis Undergoing total unilateral hip-arthroplasty surgery Speak and understand Danish Have given informed content Exclusion Criteria: Revision or bilateral hip-arthroplasty surgery General anaesthesia Allergy or intolerance towards Methylprednisolone Local or systemic infection Permanent systemic treatment with steroids within 30 days peroperatively Insulin-dependent diabetes Atrial fibrillation Neurological disease incl. Parkinsons Daily use of hypnotics or sedatives Alcohol abuse >35 units per week Active treatment of ulcer within 3 months preoperatively Cancer disease Autoimmune disease incl. rheumatoid arthritis Pregnant or breast feeding women Menopause <1 year

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylprednisolone<br>Preoperative single high dose of Solu-Medrol 125 mg iv. | Drug: Methylprednisolone<br>* Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo)<br>* Other names: Solu-Medrol;|
| Placebo Comparator: Isotonic Sodium Chloride<br>Preoperative single dose of isotonic Sodium Chloride | Drug: Isotonic Sodium Chloride<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in incidence of orthostatic intolerance from baseline to 6 hours after surgery |  | 6 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in incidence of orthostatic intolerance from baseline to 24 hours after surgery |  | 24 hours after surgery | 
| Change in non-invasive blood pressure from baseline to 24 hours after surgery |  | 24 hours after surgery | 
| Change in heart rate variability from baseline to 24 hours after surgery |  | 24 hours after surgery | 
| Change in stroke volume and cardiac output from baseline to 24 hours after surgery |  | 24 hours after surgery | 
| Change in systemic vascular resistance from baseline to 24 hours after surgery |  | 24 hours after surgery | 
| Change in pain intensity from baseline to 24 hours after surgery |  | 24 hours after surgery | 
| Change in concentration of plasma-hemoglobin from baseline to 48 hours after surgery |  | 48 hours after surgery | 
| Change in concentration of C-reactive protein from baseline to 48 hours after surgery |  | 48 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Orthostatic Intolerance, Heart Rate Variability, Hip arthroplasty, total, Glucocorticoid