An Intervention to Reduce Delirium After Cardiac Surgery

Sponsor

Johns Hopkins University (Other)

Overall Status

Completed

CT.gov ID

NCT02587039

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Delirium Congenital Heart Disease Coronary Artery Disease Heart Valve Disease	Procedure: Remote ischemic pre-conditioning Behavioral: Delirium Assessment	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

An Intervention to Reduce Delirium After Cardiac Surgery

Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control: Usual care This group will receive usual care and delirium assessments.	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.
Experimental: Treatment: Ischemic Pre-conditioning Remote Ischemic pre-conditioning before cardiac surgery and delirium assessments.	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.

Arm

Intervention/Treatment

Placebo Comparator: Control: Usual care

This group will receive usual care and delirium assessments.

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.

Experimental: Treatment: Ischemic Pre-conditioning

Remote Ischemic pre-conditioning before cardiac surgery and delirium assessments.

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.

Outcome Measures

Primary Outcome Measures

Incident Delirium [First four postoperative days]
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

Secondary Outcome Measures

Levels of novel cerebral injury biomarkers [Within 1 hour before the surgical incision, immediately after cardiopulmonary bypass, 2 hours after cardiopulmonary bypass, and 20 hours after skin closure]
Biomarkers include inflammatory proteins, and markers of neuronal damage or change in homeostasis, including glial fibrillary acidic protein and neurotrophic factors