The Effects of Dexmedetomidine on Intestine and Other Organ Damages After Cardiac Surgeries

Cardiac surgery with cardiopulmonary bypass (CPB) provokes a systemic inflammatory response that can often lead to dysfunction of major organs. Activation of the contact system, endotoxemia, surgical trauma, and ischemic reperfusion injury are all possible triggers of inflammation. Previous studies demonstrated that pro-inflammatory cytokines play an important role during this process. However, very little is known about the susceptibility of the splanchnic organs to ischemic reperfusion injury. Although the incidence of intestinal complications reported to be low, the in-hospital mortality in these patients was high at 15% to 63%.

Dexmedetomidine, a highly selective α2-adrenergic agonist, can reduce the consumption of other sedative and antinociceptive drugs and provide sufficient sedative effects with minimal respiratory side effects. In addition, dexmedetomidine gradually has gained popularity in the field of critical care. Preemptive administration of dexmedetomidine has shown to be protective against inflammation, intestinal, renal, and myocardial injuries in animal and human studies. Dexmedetomidine is also used as an anesthetic adjuvant during surgery to offer good perioperative hemodynamic stability and an intraoperative anesthetic-sparing effect. Perioperative use of dexmedetomidine can reduce intestinal and hepatic injury after hepatectomy with inflow occlusion under general anesthesia. However, whether or not it can exert protective effects on the above-mentioned organs, especially intestine, after cardiac surgery remains unclear. The aim of this study is to evaluate the effects of dexmedetomidine on intestinal, hepatic, and other organ injury in patients receiving cardiac surgery with CPB.

In this double-blinded randomized controlled study, serum diamine oxidase activity, which is a sensitive and specific marker for the detection of intestinal injury, is taken as the primary endpoint. Other parameters reflecting the functions of liver (AST/ALT), lung (lung injury score and CC-16), kidney (BUN/Cre), and heart (CK-MB/Troponin T), the biomarker of endothelial injury (endocan) will also be determined. Besides, microcirculation parameters measured with Cytocam® and near-infrared spectroscopy (NIRS) will be used to estimate the protective effect of dexmedetomidine on microcirculation. The variables will be collected perioperatively and will be followed up for 3 days after the surgery. Clinical outcome parameters will be followed up for 3 months after the surgery.

Study Overview

• Status: Unknown
• Conditions: Cardiac Surgical Procedure
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Normal Saline

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Po-Yuan Shih, MD; Phone Number: 62158 886-2-23123456; Email: shih.poyuan@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Po-Yuan Shih, MD; Phone Number: 62158 886-2-23123456; Email: shih.poyuan@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Non-emergent cardiac surgery with cardiopulmonary bypass

Exclusion Criteria:

• left ventricle ejection fraction < 40%
• acute myocardial infarction within 3 months
• angina within 48 hours before surgery
• COPD
• previous history of inflammatory bowel disease
• diarrhea within 7 days before surgery
• previous cardiac surgery
• receiving non-pharmacological cardiac supportive management
• previous pulmonary embolism
• previous deep vein thrombosis
• allergic to dexmedetomidine
• refractory bradycardia (HR < 60/min )

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dexmedetomidine; Patients receiving intraoperative dexmedetomidine infusion. Infusion duration: from 10 minutes after anesthetic induction to the end of surgery.	Drug: Dexmedetomidine
Placebo Comparator: control; control group, receiving same volume of normal saline infusion.	Drug: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
diamine oxidase concentration	1 hours after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
diamine oxidase concentration	24 hours and 48 hours after surgery
endocam concentration	1 hours, 24 hours, and 48 hours after surgery
CC-16 concentration	1 hours, 24 hours, and 48 hours after surgery
cerebral tissue oxygen saturation (StO2) measured by NIRS	1 hours, 24 hours, and 48 hours after surgery
diamine oxidase concentration	10 minutes before anesthetic induction
endocam concentration	10 minutes before anesthetic induction
CC-16 concentration	10 minutes before anesthetic induction
diamine oxidase concentration	1 hour after start of cardiopulmonary bypass
endocam concentration	1 hour after start of cardiopulmonary bypass
CC-16 concentration	1 hour after start of cardiopulmonary bypass
cerebral tissue oxygen saturation (StO2) measured by NIRS	1 hour after start of cardiopulmonary bypass
diamine oxidase concentration	10 minutes after the end of cardiopulmonary bypass
Endocam concentration	10 minutes after the end of cardiopulmonary bypass
CC-16 concentration	10 minutes after the end of cardiopulmonary bypass
cerebral tissue oxygen saturation (StO2) measured by NIRS	10 minutes after the end of cardiopulmonary bypass
cerebral tissue oxygen saturation (StO2) measured by NIRS	10 minutes before anesthetic induction
perfused small vessel density	10 minutes before anesthetic induction
proportion of perfused small vessels	10 minutes before anesthetic induction
microvascular flow index	10 minutes before anesthetic induction
perfused small vessel density	1 hours after surgery
proportion of perfused small vessels	1 hours after surgery
microvascular flow index	1 hours after surgery
perfused small vessel density	24 hours after surgery
proportion of perfused small vessels	24 hours after surgery
microvascular flow index	24 hours after surgery
perfused small vessel density	48 hours after surgery
proportion of perfused small vessels	48 hours after surgery
microvascular flow index	48 hours after surgery

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Po-Yuan Shih, MD, Department of Anesthesiology, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 30, 2016

Study Record Updates

• Last Update Posted (Estimate): November 4, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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: 201512224MINB