Evaluation of Intraoperative Dexmedetomidine Use in Patients Undergoing Surgical Aortic Valve Replacement

Study Overview
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Brief Summary
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Aim of this randomized prospective study is to investigate the immunomodulatory effects of dexmedetomidine on outcomes in patients with isolated aortic stenosis after surgical aortic valve replacement.

Detailed Description
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Study will investigate effects of two different doses of dexmedetomidine on concentrations of tumor necrosis factor-α and interleukin-6, on inflammatory parameters (C reactive protein and procalcitonin) and inflammatory complications, renal function, postoperative delirium, anaesthetic and analgetic consumption and compare it to control group. It should provide a better understanding of dexmedetomidine effect on decrease of inflammatory response in patients undergoing cardiac surgery. Short-term infusion of dexmedetomidine could reduce inflammatory postoperative complications, contribute to improvement of perioperative renal function and occurrence of postoperative delirium, supporting recovery and shortening hospital stay.

Official Title
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Evaluation of Intraoperative Dexmedetomidine Use on Reducing Inflammatory Response Caused by Cardiopulmonary Bypass in Patients Undergoing Surgical Aortic Valve Replacement

Conditions
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Systemic Inflammatory Response, Aortic Valve Stenosis

Intervention / Treatment
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* Drug: Placebo
* Drug: Dexmedetomidine 0.5mcg/kg/h
* Drug: Dexmedetomidine 1 mcg/kg/h


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: isolated aortic stenosis adult patients with written consent Exclusion Criteria: BMI <30kg/m2 1st, 2nd and 3rd degree AV block bradycardia HR<50/min upon arrival to operating theatre neurological disorders (Parkinson's disease, Myasthenia gravis, multiple sclerosis, brain tumors in anamnesis) recent use of psychoactive drugs alcohol and illicit drug addiction diabetes type I with complications patients who develop hypotension after initiation of dexmedetomidine infusion requiring vasoconstriction therapy patients receiving corticosteroids in perioperative period patients with known allergy to dexmedetomidine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>Continuous infusion of saline starting after invasive monitoring placement and before initiation of cardiopulmonary bypass (CPB) until the end of surgery | Drug: Placebo<br>* Continuous infusion of saline starting after invasive monitoring placement before cardiopulmonary bypass (CPB) initiation up to surgery completion<br>* Other names: saline;|
| Experimental: Dexmedetomidine 0.5<br>Continuous infusion of dexmedetomidine in dose 0.5 mcg/kg/min starting after invasive monitoring placement and before initiation of cardiopulmonary bypass (CPB) until the end of surgery | Drug: Dexmedetomidine 0.5mcg/kg/h<br>* Continuous infusion of dexmedetomidine in 0.5mcg/kg/h dose starting after invasive monitoring placement before cardiopulmonary bypass (CPB) initiation up to surgery completion<br>* Other names: dexmedetomidine in 0.5mcg/kg/h dose;|
| Experimental: Dexmedetomidine 1<br>Continuous infusion of dexmedetomidine in dose 1 mcg/kg/min starting after invasive monitoring placement and before initiation of cardiopulmonary bypass (CPB) until the end of surgery | Drug: Dexmedetomidine 1 mcg/kg/h<br>* Continuous infusion of dexmedetomidine in 1mcg/kg/h dose starting after invasive monitoring placement before cardiopulmonary bypass (CPB) initiation up to surgery completion<br>* Other names: dexmedetomidine in 1 mcg/kg/h dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| interleukin 6 | Concentration of IL-6 24 hours preoperatively (T0), before CPB initiation (T1), 5 hours post CPB (T2) and 12 hours post CPB (T3) | 24 hours preoperatively up to 12 hours post CPB | 
| tumor necrosis factor alpha | Concentration of TNF-alpha 24 hours preoperatively (T0), before CPB initiation (T1), 5 hours post CPB (T2) and 12 hours post CPB (T3) | 24 hours preoperatively up to 12 hours post CPB | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory marker concentration during hospital stay | Determination of concentration of CRP and procalcitonin during hospital stay | From recruitment date up to 30 days postoperatively | 
| Infection rate | Determining incidence of wound infection, pneumonia, urinary infection and sepsis during hospital stay | From recruitment date up to 30 days postoperatively | 
| Renal function - diuresis | Determining parameters of renal function: Daily 24-hour urine output in ml | From recruitment date up to 10 days postoperatively | 
| Renal function - diuretic consumption | Determining parameters of renal function: diuretic consumption | From recruitment date up to 10 days postoperatively | 
| Renal function - GFR | Determining parameters of renal function: glomerular filtration rate | From recruitment date up to 10 days postoperatively | 
| Renal function - creatinine | Determining parameters of renal function: creatinine concentration | From recruitment date up to 10 days postoperatively | 
| Renal function - urea | Determining parameters of renal function: urea concentration | From recruitment date up to 10 days postoperatively | 
| Postoperative delirium | Determining incidence of postoperative delirium using Confusion Assessment Method questionaire | From recruitment date up to 30 days postoperatively | 
| Analgesic and anesthetic consumption | Determining intraoperative anesthetic consumption (midazolam, sufentanil, propofol and sevoflurane) and postoperative analgesic use | From recruitment date up to 10 days postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dexmedetomidine