Active Temperature Management After Cardiac Surgery and Its Effect on Postoperative Cognitive Dysfunction

NCT ID: NCT03947671

Last Updated: 2024-04-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-22
• Study Completion Date: 2026-10-31

Brief Summary

This study will assess the effect of active postoperative temperature management and its effect on the cognitive function in patients following coronary artery bypass graft (CABG) surgery to determine if active postoperative temperature management to maintain normothermia reduces postoperative cognitive dysfunction (POCD) in this population. Additionally, the investigators will explore differences in temperature control variability by using temperature management wraps combined with acetaminophen vs. acetaminophen alone in a pilot arm.

Detailed Description

As one of the more common hospital-based major interventional procedures, 180,476 CABG surgeries were performed in the United States in 2016, according to the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS ACSD). Of these, 23,545 operations also involved aortic or mitral valve repair or replacement. The demographic characteristics of patients undergoing cardiac surgery have changed over time, with a higher proportion of elderly patients undergoing increasingly complex procedures. The number of patients with neurological disease prior to surgery has nearly doubled from 1.4% in 2001 to nearly 2.8% as of 2010, and is rising as surgical care improves and includes more such patients .

The recognition of neurological complications associated with cardiac surgery has been report-ed widely, and neurological dysfunction can be categorized as type 1 (brain death, non-fatal stroke, and new transient ischemic attack) or type 2 (delirium and postoperative cognitive dys-function) . The incidence postoperative neurological complications, defined as "permanent stroke" by the STS ACSD, was noted in 2016 to be 1.3% following isolated CABG operations, but was noted to be higher, between 2-3% in CABG patients also receiving aortic or mitral valve surgery as part of their operation. Notably, this statistic does not capture POCD, although steps are being taken to better capture this, perhaps as a patient-reported outcome (PRO) in the future.

As early as 1955, POCD was described by Bedford in the Lancet under the designation "adverse cerebral effects of anesthesia on old people" . It can affect any age group, but does seem to dis-proportionately affect patients age 60 or older, causing difficulty in daily life and their ability to return to work . Short-term POCD, up to 6 weeks postoperatively, occurs in 20-50% of patients undergoing cardiac surgery. Longer-term POCD, defined as a subtle deterioration in cognitive function 6 months following surgery, occurs in 10-30% of cardiac surgery patients . In a longitudinal study with 8.5 years of follow-up, Steinmetz et al. found POCD to be associated with higher mortality (Cox proportional hazard ratio 1.63, 95% confidence interval 1.11-2.38; p = 0.01), earlier retirement, and greater utilization of social financial assistance . Monk et al. found that the risk of death within one year was greater among patients who had POCD when they were discharged from the hospital .

CABG and valve surgery most commonly use the extracorporeal cardiopulmonary bypass machine to perfuse the body during cardiac surgery. The aorta is cross-clamped to allow work and suturing in a near bloodless field. The major blood branches to the brain come off the aorta. When the aorta is cross-clamped, the brain undergoes a period of ischemia. While the patient is on bypass, the body and brain are kept at low temperatures to quell the effects of ischemia. Temperature elevation has been proposed to have an all-or-none response with a defined threshold beyond which the increased temperature aggravates ischemic injury. Hyperthermia leads to physiological and structural changes in the brain which include alterations of enzyme activity and damage to cytoskeletal proteins found in the brain. In addition, hyperthermia causes a release of excitatory neurotransmitters, the production of free radicals, an increase in blood-brain barrier permeability, and increase in intracellular acidosis after ischemic reperfusion all of which have all been proposed as mechanisms through which hyperthermia leads to brain tissue injury and can exacerbate ischemic brain injury .

Intraoperative temperature during cardiac surgery has long been thought to have an association with postoperative neurological outcomes, and has been well studied. In mitigating neuroinflammation and subsequent brain injury, intraoperative hypothermia as compared with normothermia has been the subject of much debate, and outcomes have varied considerably in various studies. The process of rewarming patients as they gradually disengage from cardiopulmonary bypass has been noted as another important process in modulating neuroprotection, and has al-so been studied extensively. Nearly all studies have associated a slower rate of intraoperative rewarming with a decreased incidence of POCD.

Postoperative hyperthermia is a much less well-studied phenomenon. It occurs in approximately 30% of all CABG patients , and one study has associated it with POCD, noting that patients with supra-normal temperatures in the first 24-hour postoperative period following CABG have poorer cognitive outcomes when compared to those with normal temperatures in this setting .

At our institution and many others, the current standard of care pertaining to postoperative hyperthermia management in cardiac surgery patients involves treatment with acetaminophen and room temperature if it rises to greater than or equal to 38.3 degrees.

The Altrix Precision Temperature Management System, and specifically the Rapr Round® product, offers a means by which medical staff may be able to control temperature in cardiac surgery patients postoperatively, while preventing fever from occurring and in per our hypothesis, may be able to decrease short term POCD and its associated sequelae in this patient population. This temperature management system is intended for circulating temperature controlled warm or cold water via patient contact thermal transfer devices for the application of regulating human body temperature in situations where a physician or clinician with prescription privileges determines that temperature therapy is necessary or desirable.

For this study, the Rapr Round® vest and leg wraps are placed around the torso and legs of the patient and adjust body temperature by circulating water through channels in the wrap. In this case the wraps will be used to maintain patient temperature in the intervention group at 36.5 +/- 0.2 degrees Celsius, or normothermia.

Conditions

Cardiac Surgery; Post-operative Cognitive Dysfunction; Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Body wrap

This group will receive the body wraps post surgery to maintain normothermia.

Group Type: EXPERIMENTAL

Rapr Rounds Hyper/Hypothermia Wraps

Intervention Type: DEVICE

Rapr Round® vest and leg wraps will placed around the torso and legs of the participant and will be adjusted to maintain normal body temperature

Tylenol

This group will receive the standard of care of monitoring temperature and administering Tylenol if a fever develops.

Group Type: ACTIVE_COMPARATOR

Acetaminophen

Intervention Type: DRUG

Acetaminophen will be administered as it would be per standard of care

Tylenol with body wrap

This group will receive the standard of care of monitoring temperature but will be administered Tylenol and body wraps if a fever develops.

Group Type: EXPERIMENTAL

Rapr Rounds Hyper/Hypothermia Wraps

Intervention Type: DEVICE

Rapr Round® vest and leg wraps will placed around the torso and legs of the participant and will be adjusted to maintain normal body temperature

Acetaminophen

Intervention Type: DRUG

Acetaminophen will be administered as it would be per standard of care

Interventions

Rapr Rounds Hyper/Hypothermia Wraps

Rapr Round® vest and leg wraps will placed around the torso and legs of the participant and will be adjusted to maintain normal body temperature

Intervention Type: DEVICE

Acetaminophen

Acetaminophen will be administered as it would be per standard of care

Intervention Type: DRUG

Other Intervention Names

Tylenol

Eligibility Criteria

Inclusion Criteria

1. scheduled coronary artery bypass graft surgery patients, with or without valve surgery

2. patients able to give informed consent

Exclusion Criteria

1. age < 20 years or > 89 years

2. patients with unscheduled CABG +/- valve surgery (i.e. emergency surgery)

3. deformity or skin condition of chest or thighs that would interfere with the successful placement of Rapr Round® vest and leg wraps

4. patients presenting to the ICU postoperatively with a fever ≥ 38.3

5. patients with planned intraoperative circulatory arrest

6. prisoners

7. pregnant patients

8. patients with symptomatic cerebrovascular disease, specifically residual motor deficits, expressive or receptive aphasia from prior stroke or cerebrovascular accident

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stryker Medical

INDUSTRY

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vishal Yajnik, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Other Identifiers

HM20015426

Identifier Type: -

Identifier Source: org_study_id