An Intervention to Reduce Delirium After Cardiac Surgery

Coronary Artery Disease Clinical Trial

Official title:

An Intervention to Reduce Delirium After Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02587039
• Other study ID #: IRB00030360
• Status: Completed
• Phase: N/A
• First received: July 9, 2014
• Last updated: August 10, 2016
• Start date: June 2014
• Est. completion date: December 2015

Study information

• Verified date: August 2016
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Patients that have cardiac surgery may suffer from unrecognized cerebral ischemia or loss of blood flow to the brain temporarily during surgery. This temporary loss of blood flow to the brain may result in a condition called delirium. Delirium is a type temporary confusion. There are some strategies that can help reduce cerebral ischemia during cardiac surgery which can help lead to a reduction in the incidence of delirium. The investigator believes that a strategy called remote ischemic preconditioning will help to reduce the incidence of delirium incidence after cardiac surgery.

Remote ischemic preconditioning is a brief exposure to ischemia. This brief exposure to ischemia occurs in an area of the body that is not undergoing a procedure. This brief exposure to ischemia is not long enough to cause any damage to the body and it has been demonstrated to help protect against more severe ischemic injury that may occur later during surgery. In this study the investigator will use remote ischemic preconditioning to see if it can reduce the incidence delirium after cardiac surgery.

Description:

Delirium is common after cardiac surgery, occurring in 45-55% of patients, and is independently associated with increased postoperative complications, reduced functional capacity, cognitive decline, and increased mortality. Although the pathophysiology of delirium is unclear, a leading hypothesis is that delirium results from unrecognized cerebral ischemia during surgery. In preliminary data from the investigators group, delirium was reduced in patients randomized to optimal blood pressure control during cardiopulmonary bypass, using novel technology that determines an individual patient's lower limit of cerebral autoregulation. Thus, patients undergoing cardiac surgery may suffer from unrecognized cerebral ischemia that contributes to delirium, and strategies to attenuate the effects of cerebral ischemia may reduce the incidence of delirium.

Ischemic preconditioning represents a novel strategy to attenuate the effects of cerebral ischemia during cardiac surgery. Exposure to a brief period of ischemia, below the threshold for tissue injury, has been demonstrated to protect against the harmful effects of a subsequent more severe ischemic insult, in both animal and human studies. The protection provided by ischemic preconditioning may also be effective when the preconditioning is applied to a location remote from the organ of interest (i.e. a limb). Recently, a large randomized trial in patients undergoing cardiac surgery demonstrated a survival benefit among patients randomized to remote ischemic preconditioning vs. placebo. Remote ischemic preconditioning was achieved by simple inflation of a blood pressure cuff to supra-systolic pressures for 5 minutes, repeated for 3 cycles. However, neurological outcomes were not assessed in this trial, although animal models support potential neurological protection following remote ischemic preconditioning.

In this study the investigator will examine whether remote ischemic preconditioning can reduce delirium, functional decline, and biomarkers of cerebral injury after cardiac surgery. The investigator will explore the mechanism of preconditioning by examining proteomic analyses in a subset of patients. These results will provide data to support an NIH trial to examine the protective effects of remote ischemic preconditioning in cardiac surgery, identify potential mechanisms of action and potential targets for therapeutic pharmacologic interventions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• =65 years old

• Undergoing coronary artery bypass and/or valve surgery

Exclusion Criteria:

• Mini mental state exam < 23

• Delirium at baseline

• Inability to speak and understand English

• Severe hearing impairment, resulting in inability to converse

• Planned use of intraoperative ketamine

• Inability to place or tolerate upper extremity tourniquet

• Hemoglobinopathy (e.g. sickle cell disease)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congenital Heart Disease
• Coronary Artery Disease
• Coronary Disease
• Delirium
• Heart Defects, Congenital
• Heart Diseases
• Heart Valve Disease
• Heart Valve Diseases
• Myocardial Ischemia

Intervention

Procedure:
• Remote ischemic pre-conditioning
Remote ischemic preconditioning is exposure to a brief period ischemia to an area or limb that is not involved in surgery. This intervention is believed to reduce the incidence of cerebral (brain) ischemia during cardiac surgery.

Behavioral:
• Delirium Assessment
The Delirium assessment consist of a validated psychiatric screening tool called the Confusion Assessment Method. We will use this tool to determine if patients have any confusion after surgery.

Locations

Country	Name	City	State
United States	The Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Instrumental Activities of Daily Living		1 month and 6 months after surgery	No
Primary	Incident Delirium	Delirium will be assessed using the Confusion Assessment Method (CAM) on three of the first four postoperative days. The primary outcome will be positive if delirium occurs by CAM criteria at any of these assessments	First four postoperative days	No
Secondary	Levels of novel cerebral injury biomarkers	Biomarkers include inflammatory proteins, and markers of neuronal damage or change in homeostasis, including glial fibrillary acidic protein and neurotrophic factors	Within 1 hour before the surgical incision, immediately after cardiopulmonary bypass, 2 hours after cardiopulmonary bypass, and 20 hours after skin closure	No