Effect of Dexmedetomidine on Postoperative Renal Function in Infective Endocarditis Patients Undergoing Open Heart Surgery

Acute kidney injury is major complication after open heart surgery. The cause of acute kidney injury following open heart surgery is related to activation of sympathetic nervous system, decrease of renal blood flow, ischemia-reperfusion injury and systemic inflammatory response.

Infective endocarditis patients undergoing open heart surgery have systemic inflammatory response associated with infective endocarditis. And the inflammatory response can be aggravated by cardiopulmonary bypass. The incidence of acute kidney injury following open heart surgery due to infective endocarditis was 50% in a previous report. And this acute kidney injury was related to the poor outcome and high mortality. Thus, the preventive method to protect kidney function will be needed in the patients with infective endocarditis undergoing open heart surgery.

Dexmedetomidine is a selective α2-agonist and has sedative, analgesic, and CNS depressive effect. And several experimental study demonstrated the renal protective effect. Intraoperative dexmedetomidine administration can reduce the amount of anesthetics needed and suppress the sympathetic response resulted by surgical stimulation. And dexmedetomidine was reported to reduce the level of serum cortisol, epinephrine and norepinephrine during the operation. Thus, these effects of dexmedetomidine can be expected to reduce the incidence of acute kidney injury.

Therefore, the investigators hypothesized that dexmedetomidine has renal protective effect and this effect might be related to the suppression of inflammatory response. Thus, the investigators will evaluate the incidence of acute kidney injury and the incidence of major adverse kidney events (MAKE) after open heart surgery due to infective endocarditis and the level of inflammatory mediators.

The primary end point of this study is the incidence of acute kidney injury after open heart surgery due to infective endocarditis. And secondary end point is the incidence of MAKE, the level of cystatin C which is related to the renal function, the level of inflammatory mediator and the postoperative morbidities.

Study Overview

• Status: Unknown
• Conditions: Infective Endocarditis
• Intervention / Treatment: Drug: dexmedetomidine; Drug: Normal saline

• Study Type: Interventional
• Enrollment (Anticipated): 94
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Recruiting
    • Department of Anaesthesiology and Pain Medicine, Yonsei University College of Medicine
    • Contact: Jae-Kwang Shim, MD; Phone Number: 82-2-2228-8500; Email: ANESHIM@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with infective endocarditis
• patients who are scheduled to undergo open heart surgery

Exclusion Criteria:

• chronic kidney disease
• taking high dose steroid (>10mg/day prednisolone or equivalent)
• age under 20 years
• cognitive dysfunction
• disabling mental change disorder
• unable to communicate or speak Korean

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group	Drug: Normal saline; Group given intravenous 0.4mcg/kg/h of normal saline from the beginning of the anesthesia to postoperative 1 day.
Experimental: dexmedetomidine group	Drug: dexmedetomidine; Randomly selected patients of the dexmedetomidine group are given intravenous 0.4mcg/kg/h of dexmedetomidine from the beginning of the anesthesia to postoperative 1 day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of acute kidney injury	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cystatin C level	serum cystatin C level (mg/L)	postoperative day 1,2,3 and 5
inflammatory mediator(IL-6) level	serum inflammatory mediator (IL-6(pg/mL)	postoperative day 1,2,3 and 5
inflammatory mediator(CRP) level	serum inflammatory mediator (CRP(mg/L))	postoperative day 1,2,3 and 5
inflammatory mediator(WBC) level	Serum WBC(/microL) level	postoperative day 1,2,3 and 5
inflammatory mediator(neutrophil count) level	serum inflammatory mediator (neutrophil count(/microL)) level	postoperative day 1,2,3 and 5
serum norepinephrine/epinephrine level(ng/mL)		postoperative day 1,2,3 and 5
intraoperative hemodynamics measured by amount of used vasopressors(mL)		postoperative day 1,2,3 and 5
intraoperative fluid intake and output	intraoperative intake and output measured by the amount of fluid(crystalloid/colloid)(mL) and blood administered(mL)	postoperative day 1,2,3 and 5
postoperative complications	postoperative complications such as development of myocardial infarction, arrhythmia, cerebrovascular accident, wound infection, and mortality.	postoperative day 1,2,3 and 5
Major adverse kidney events (MAKE)		3month, 1 year

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Rosner MH, Portilla D, Okusa MD. Cardiac surgery as a cause of acute kidney injury: pathogenesis and potential therapies. J Intensive Care Med. 2008 Jan-Feb;23(1):3-18. doi: 10.1177/0885066607309998.
• Conlon PJ, Jefferies F, Krigman HR, Corey GR, Sexton DJ, Abramson MA. Predictors of prognosis and risk of acute renal failure in bacterial endocarditis. Clin Nephrol. 1998 Feb;49(2):96-101.
• Ren J, Zhang H, Huang L, Liu Y, Liu F, Dong Z. Protective effect of dexmedetomidine in coronary artery bypass grafting surgery. Exp Ther Med. 2013 Aug;6(2):497-502. doi: 10.3892/etm.2013.1183. Epub 2013 Jun 25.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: February 15, 2016
• First Submitted That Met QC Criteria: February 29, 2016
• First Posted (Estimate): March 4, 2016

Study Record Updates

• Last Update Posted (Actual): January 15, 2019
• Last Update Submitted That Met QC Criteria: January 14, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: acute kidney injury; dexmedetomidine; Infective endocarditis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cardiovascular Infections; Endocarditis, Bacterial; Endocarditis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 4-2015-0839

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO