The Effect of Dexmedetomidine on Prevention of Postoperative Acute Kidney Injury in Patients Undergoing Aortic Surgery

Study Overview
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Brief Summary
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Acute kidney injury(AKI) is a common and severe complication after the cardiac surgery. Postoperative AKI increases the in-hospital stay, intensive care unit(ICU) stay and postoperative mortality. Aortic surgery is the most risky surgery that causes the postoperative AKI, and the incidence of AKI after aortic surgery is about 50%. The α1- and α2-adrenergic receptors in the kidney modulate vasoconstrictor and vasodilatory effects, respectively. Agents that attenuate renal vasoconstriction may have potential as renoprotective drugs because vasoconstriction most likely contributes to the pathophysiology of AKI. Clonidine, an α2-agonist, has been shown experimentally to inhibit renin release and cause a diuresis, and it has been evaluated in an experimental AKI model, confirming its potential as a renoprotective agent. Furthermore, it has been already reported that dexmedetomidine, α2-agonist, reduce the impairment of renal function after cardiac operation. The aim of this study is to examine the association between preoperative dexmedetomidine infusion and the incidence of postoperative acute kidney injury(AKI) in patients undergoing aortic surgery.

Conditions
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Acute Kidney Injury(Postoperative Acute Kidney Injury in Patients Undergoing Aortic Surgery)

Intervention / Treatment
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* Drug: dexmedetomidine
* Drug: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the patients undergoing ascending, arch and/or proximal descending aorta surgery with cardiopulmonary bypass 20 - 100 yrs old Exclusion Criteria: having preoperative severe renal dysfunction (eGFR < 15 ml/min per 1.73m2) Left ventricular-ejection fraction < 30% Preexisting congestive heart failure Severe coronary artery disease Hemodynamically unstable arrhythmia Cardiogenic shock during perioperative period Ventricular assist device use cannot communication because of a language barrier or illiteracy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 100 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: dexmedetomidine<br>dexmedetomidine, 0.4 mcg/kg/h, IV, The infusion of study drug is started after anesthesia induction and continued until 24 hours after surgery. | Drug: dexmedetomidine<br>* Immediately after the induction of anesthesia, patients in the dexmedetomidine group received dexmedetomidine continuous intravenous (IV) infusion of 0.4 mcg/kg/h until 24 hours after surgery.<br>|
| Placebo Comparator: control<br>saline, same infusion rate (received equal volume of normal saline), IV, The infusion of study drug is started after anesthesia induction and continued until 24 hours after surgery. | Drug: saline<br>* same infusion rate (received equal volume of normal saline), IV, The infusion of study drug is started after anesthesia induction and continued until 24 hours after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute kidney injury (AKI) after aortic surgery (AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria) | 0.3 mg/dl increase in serum creatinine concentration within 48 hours OR, a 50% increase within 7 days postoperatively OR, urine volume < 0.5 ml/kg/h for 6 hours | up to 7 days after the aortic surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute kidney injury (AKI) after aortic surgery (AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria) | KDIGO stage 2: Serum creatinine increase to 2-3-fold from baseline OR urine output < 0.5 ml/kg/h for 12h | up to 7 days after the surgery | 
| Acute kidney injury (AKI) after aortic surgery (AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria) | KDIGO stage 3: Serum creatinine increase to 3.0-fold from baseline OR Increase in serum creatinine to ≥ 4 mg/dl OR Initiation of renal replacement therapy OR In patients <18 years, decrease in eGFR to < 35 ml/min per 1.73 m2 OR Anuria for ≥ 12h. | up to 7 days after the surgery | 
| major morbidity endpoint | acute kidney injury (same as the primary endpoint), permanent stroke, prolonged ventilator care >24h, deep wound infection, and mortality. | acute kidney injury - up to 7 days after the surgery; Other - during the hospitalization for surgery | 
| postoperative delirium | delirium - assessed with The American Psychiatric Association's fifth edition of the Diagnostic and Statistical Manual of Mental Disorders or Confusion Assessment Method for the ICU | up to 7 days after the surgery | 
| drug-related adverse events | hypotension (mean arterial pressure <60 mmHg) or bradycardia (<50 beats/min) OR the use of vasopressor, inotropes or temporary pacing, OR postoperative arrhythmia | hypotension or bradycardia: during surgery; Other - during surgery and 24 hours after surgery |