Effects of Blocking Blue Light at Night on Patient Outcomes After Elective CABG Surgery

  • STATUS
    Recruiting
  • End date
    Jun 30, 2021
  • participants needed
    80
  • sponsor
    West Virginia University
Updated on 26 January 2021

Summary

Cardiovascular disease is the leading cause of death in the US. Each year, more than 500,000 coronary revascularization surgeries are performed. The in-hospital mortality rate among patients undergoing coronary artery bypass graft (CABG) surgery has declined to less than 6% in recent years, but potentially serious complications still occur and can prolong hospitalization, impair quality of life, and substantially increase medical costs. Excessive post-surgical inflammation can contribute to adverse outcomes, and the investigators hypothesize that exposure of patients to extraneous light at night during in-hospital recovery potentiates the inflammatory response to CABG, in turn, compromising several aspects of recovery. This hypothesis is based on the investigators' mouse models of brief global and focal cerebral ischemia; mice exposed to dim light at night (dLAN) during ischemic recovery have substantially more inflammation, neurological damage, and functional deficits than mice exposed to dark nights during ischemic recovery. The circadian system of mammals, including mice and humans, is most sensitive to light within the blue range of the spectrum (450-485 nm); substituting longer wavelength light for night time exposures of mice recovering from ischemia eliminates the detrimental effects of the exposure to light at night (LAN). Based on these data, the investigators hypothesized that filtering the light CABG patients are exposed to at night during in-hospital recovery will reduce inflammation, and in turn improve functional outcome.

Description

Background

Recent studies using rodent models have demonstrated that exposure to light at night, particularly short (i.e., blue) wavelengths, increases inflammatory response following cardiac arrest surgery, alters timing of food intake, elevates body mass, and promotes depression- and anxiety-like symptoms. However, filtering out the blue wavelengths in full spectrum light rescues this phenotype. Hence, the investigators aim to investigate if this effect is also observed in patients undergoing coronary artery bypass graft (CABG) surgery. Moreover, the investigators seek to determine the relationship between inflammatory response after surgery and the observed cognitive decline during this period.

Significance If manipulating nighttime light in hospital rooms improves patient outcomes, then it would be a relatively easy and inexpensive innovation that could reduce post-surgical complications and save millions of dollars per year in health care costs by shortening the length of hospital stays and reducing morbidity.

Purpose

The purpose of this study is to determine whether filtering out blue light at nighttime reduces post-surgical inflammation and/or moderates cognitive decline and mood and sleep alterations in patients undergoing elective CABG surgery. If manipulating nighttime light in hospital rooms improves patient outcomes, then it would be a relatively easy and inexpensive innovation that could reduce post-surgical complications and save millions of dollars per year in health care costs by shortening the length of hospital stays and reducing morbidity. The investigators aim to determine the relationship between inflammation and cognitive dysfunction after CABG surgery.

Primary Objective

The primary objective of this study is to determine whether filtering out blue light at nighttime improves outcomes for patients undergoing elective, on-pump, CABG surgery. The investigators will measure changes in outcome by assessing differences in inflammatory markers, cognition and mood pre- and post-surgery.

Study Design

Life on Earth evolved under 24-hour solar days. Circadian rhythms evolved as adaptations to respond to predictable daily cycles of light and dark for the synchronization of behavioral and biological processes to the external environment. For nonhuman animals, restricting activities to the appropriate temporal niche is crucial to fitness and survival. For humans, temporal organization of physiology is equally important for health and wellness. Over the past century, the boundaries of day and night have been obscured by the widespread adoption of electric lighting devices at night. Disruption of internal circadian rhythms has become common in developed countries. For humans, the health consequences of chronic circadian disruption by nighttime light exposure are becoming increasingly apparent.

The investigators have extensive experience with animal studies on the effects of LAN. For example, the investigators have established, in mice that have experienced an experimental cardiac arrest (CA) or stroke, display reduced survival after only 4-7 nights of exposure to dim light at night (dLAN, 5 lux-a child's nightlight 1 meter from the eyes). The investigators also detected depression-like behavioral responses, massive neuroinflammation, and increased neuronal cell death in the brain after this relatively brief exposure to dLAN. Exposure to dimly lit nights also elevated hippocampal cell death and microglia activation following CA. Dim light at night likely affects CA recovery by elevating neuroinflammation; selective inhibition of IL-1 or TNF ameliorated the effects of LAN on CA outcome. Furthermore, the circadian system likely mediates the effects of dLAN, as adjusting the wavelength of the nighttime light exposure to ~640 nm (red) eliminated the detrimental effects of LAN on CA outcome. Together, these data suggest that lighting in clinical settings may affect patient recovery.

In terms of the circadian system, not all lighting is treated equally. The intrinsically photosensitive retinal ganglion cells (ipRGCs) that project to the master circadian pacemaker in the suprachiasmatic nucleus (SCN) contain melanopsin and are most responsive to the blue region of the visible light spectrum, ranging from 450 to 485 nm. These wavelengths are present in broad spectrum white light such as natural sunlight and the majority of indoor lighting. In contrast, longer wavelengths of lighting, such as red light, do not activate ipRGCs and therefore minimally influence the circadian system. Thus, the investigators hypothesized that the circadian system is involved in dLAN-induced damage following CA with ipRGCs communicating the light information. To test this hypothesis in humans, the investigators propose that blocking blue light exposure at night, in patients who are undergoing an elective CABG surgery, should have reduced inflammation and thus, better outcomes. The investigators chose CABG patients because these patients are the most homogeneous. The investigators' mouse results indicate that adjusting environmental lighting could prove to be an inexpensive and effective way to improve patient outcome in cardiac intensive care units. Because of patient safety concerns and the need for monitoring, hospital ICU rooms are rarely completely dark and it is not uncommon for patients to be exposed to bright lights (100 lux) several times per night. Using the blue-light blocking goggles should prevent disruption of circadian rhythms and concomitant neuroinflammation and depressive/cognitive impairments post-surgery. Only minimal risk is involved for the participants.

Baseline and Post-Surgical Cognitive Testing

Testing will occur at baseline, during their preoperative visit, (typically 2-5 days prior to surgery) and on day 5 post-surgery, prior to discharge from the hospital. In accordance with the Consensus Statement on Assessment of Neurobehavioral Outcomes After Cardiac Surgery, the battery of instruments includes: Trail Making Test (part B), Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), Digit Symbol subtest of the WAIS-R, Randt Memory Test, Modified Visual Reproduction Test from Wechsler Memory Test. Each test also has received a high ranking for sensitivity to variation at the high end of cognitive spectrum (http://trans.nih.gov/CEHP/hbpcog-list.htm). Participants will also be administered an edited Hamilton Depression Scale questionnaire (http://www.assessmentpsychology.com/HAM-D.pdf; the investigators will not assess suicide or suicidal ideation) and the short version of the Pittsburgh Sleep Quality Index survey (https://doi.org/10.1155/2018/9643937). Total testing time is expected to be approximately 30 min per session (~20 min of actual test taking). The investigators will use a Reliable Change Index to identify cognitive deficits; it calculates the distribution of expected change from baseline performance and takes into account factors such as test-retest changes in performance. Post-operative cognitive deficit is a decline from baseline of at least 1 standard deviation for at least one of the instruments [2]. The Confusion Assessment Method (CAM) Diagnostic Algorithm also will be used by attending medical staff on post-surgical days 1-5 to identify whether the participant is experiencing delirium on a given day (sensitivity 94-100%, specificity 90-95%; [2]. If the participant is determined to have depressive symptoms, the participant will not be eligible for the study, and the investigators will provide them with an information pamphlet with psychological and psychiatric resources (pamphlet documents are attached to this document). If any participants develop depression symptoms during the study, the investigators will provide them with the same resources.

Baseline and Post-Surgical Assessment of Inflammation and Markers of Tissue Damage

Approximately 10 mL of blood sample are taken on a daily basis as part of the pre- and post-operative CABG surgery standard of care.The investigators will collect an aliquot (~1 mL) from these routine samples; thus, no additional blood draws will be required. The investigators will acquire samples from the pre-surgery, 5 day post-surgery, and 30d follow up samples, to assay for cortisol and inflammatory markers. Samples will be assayed for cortisol, TNF-, IL-1, IL-2, IL-6, IL-8, IL-10, C-reactive protein (CRP), brain natriuretic peptide (BNP), n-terminal of the prohormone of brain natriuretic peptide (NT-proBNP), highly sensitivity (hs) troponin I, and creatine kinase (CK-MB). Blood samples will be collected as close to 10:00 h and 22:00 h as possible to provide a morning and evening sample. CABG increases plasma concentrations of indicators of cardiac ischemia, including troponin T, hs troponin I, NT-proBNP, and CK-MB, and cerebral ischemia markers (S100) as well as the pro-inflammatory marker IL-6 [3]. The WVU General Clinical Research Center will perform the assays on a fee basis.

Controlling Night-time Light Exposure

As described, the intrinsically photosensitive retinal ganglion cells are most responsive to the blue region of the visible spectrum ranging from 450 to 485 nm, with longer wavelengths of lighting minimally impacting the circadian system [4]. Therefore, study participants will use goggles beginning the evening of surgery. The participants in the control group will be provided with goggles that allow the full spectrum of light to enter the retina (comparable to not using goggles), whereas the participants in the experimental group will have goggles that filter out the blue wave lengths (comparable to red light exposure in the mouse studies). Goggles will be provided two (2) nights prior to admission to allow participants to habituate to sleeping with them. The goggles are produced by Uvex (Honeywell, USA) and can be worn with or without prescription glasses; visual acuity is good with the goggles and similar glasses have been used in studies in which healthy participants engaged in their normal range of evening behaviors while wearing the goggles [5-7]. The participants in the investigators' study will be exposed to typical hospital room lighting from 07:00-21:00h, then will put on the goggles from 21:00-07:00h. The participants will use the goggles each night they remain in the hospital, even if the eyelids of sedated patients are taped shut (light can pass through closed lids to affect physiological responses [8]). HOBO light recorders (Onset Computer Corporation, MA) will be placed in each participant's room to record ambient light levels throughout the study.

Additional data that will be collected from medical charts and personal interviews and then compared between groups: age, race, body mass index, education level, previous myocardial infarction, hypertension, hypercholesterolemia, diabetes mellitus, carotid artery stenosis, history of stroke, history of smoking (no, yes but <0.5 pack per day, yes but greater than 0.5 pack per day), New York Heart Association functional class, pre-operative left ventricular function (%), duration of anesthesia (min), type of anesthesia, duration of surgery (min), aortic clamp time (min), trough nasopharyngeal temperature during surgery, use of intra-operational hypothermia, number of grafts, number of proximal anastomoses, number of distal anastomoses, prior/current statin, beta-blocker, and aspirin use, use of post-surgical ionotropes, blood loss (mL), blood transfusion on day of surgery (mL), use of vasopressors, amount of heparin (IU), duration of mechanical ventilation in ICU (h), post-operative atrial fibrillation, duration of stay in ICU (h), duration of post-operative stay in the hospital (days), evidence of post-surgical stroke, whether transferred to long-term care facility, pre-surgical and post-surgical use of antidepressants, wound infection, need for reoperation, and mortality.

Details
Condition Circadian Dysregulation
Treatment Blue light-blocking goggles, Clear goggles
Clinical Study IdentifierNCT04578249
SponsorWest Virginia University
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 45 yrs and 75 yrs?
Gender: Male or Female
Do you have Circadian Dysregulation?
Do you have any of these conditions: Do you have Circadian Dysregulation??
Both men and women undergoing elective (non-emergency) on-pump CABG surgery
Ages 45-75 years
No history of diagnosed psychiatric disorders or organ failure

Exclusion Criteria

Age outside of range from 45-75 years of age
Evidence or diagnosis of dementia or other cognitive deficit
Diagnosed psychiatric disorder (including depression and anxiety)
Organ failure [kidney (creatine > 1.5 mg/dL), liver, etc.]
Chronic obstructive pulmonary disease
Any immune disorder
Acute infection
Prior cardiac surgery
Combined cardiac operations
Left main stenosis greater than 70%
Left ventricular ejection fraction (LVEF) lower than 0.5
Any condition that increases likelihood of the need for a blood transfusion during or after the surgery
Clotting disorder
Suspected less than 8th grade English reading comprehension level
Clear my responses

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