Research

Reestablishing Sleep and Circadian Alignment in Medically Critically Ill Patients via a Mechanistic Randomized Controlled Trial of an ICU Sleep Chronobundle (ReAlign-ICU). ReAlign-ICU evaluates a bundled sleep and circadian intervention, including daytime bright light, time-restricted daytime feeding, increased daytime exercise and mobility, and overnight sleep promotion, to determine its effects on sleep and circadian disruption during critical illness. (R01 HL163659)

• Light exposure and circadian alignment in critical illness. Our work has characterized the ICU light environment and evaluated daytime bright light as a potential circadian intervention. ICU light exposure is highly variable. Daytime light is strongly influenced by time, season, and room characteristics, while nighttime light is more strongly influenced by patient-level factors. Pilot studies demonstrate that daytime bright light is feasible and well tolerated in critically ill patients, with preliminary urinary 6-sulfatoxymelatonin analysis suggesting potential effects on circadian timing. (Funding K23 HL138229; AASM Strategic Research Award; selected publications DOI: 10.3389/fneur.2026.1821697, PMID 34368424, PMID 30143362)
• Sleep measurement and neurophysiology in critical illness. We demonstrated that unattended portable polysomnography can provide interpretable sleep data in the MICU and documented short, highly fragmented sleep in critically ill patients. Subsequent EEG work showed that loss of normal stage N2 features, including K-complexes and sleep spindles, was associated with more severe encephalopathy and increased mortality. (Funding R21 NR011066; P30 AG021342; selected publications PMID 25023504, PMID 30179762)
• ICU sleep promotion (“Naptime”). We developed and tested a nocturnal clustered-care intervention designed to create a protected period for sleep. Naptime reduced overnight room entries and bedside activity, increased uninterrupted rest periods, and reduced sound levels, demonstrating that modification of routine ICU care can create a better opportunity for sleep. (Funding P20 NR014126; selected publications PMID 31258916, PMID 30214923)
• Circadian physiology in critical illness. We evaluated continuous heart rate monitoring as a scalable approach to detecting circadian rhythmicity in critically ill patients. Diurnal heart-rate variation was detectable in most patients with complete data, but circadian timing was frequently misaligned. Exploratory findings also suggested a potential relationship between circadian misalignment and mortality. (KL2 TR000140; selected publications PMID: 32760341)
• Nutrition timing and enteral feeding in critical illness. Our work has examined intermittent enteral feeding as a feasible, more physiological approach to nutrition in mechanically ventilated patients. Preliminary findings from our intermittent-feeding studies have shown the feasibility of this approach. Complementary work demonstrated that early achievement of goal enteral nutrition was associated with lower in-hospital mortality and greater likelihood of successful extubation and discharge. This work helped inform the time-restricted daytime feeding component of ReAlign-ICU. (Selected publications AJRCCM Abstract 2021, PMID: 38749534)
• Obstructive sleep apnea in critically ill patients. We examined the prevalence and recognition of pre-existing obstructive sleep apnea (OSA) among MICU patients. Analyses to date identified known OSA in 19% of patients and high clinical suspicion for OSA in an additional 6%, while information regarding OSA severity was frequently unavailable, suggesting that OSA may be both common and under-recognized in critically ill patients. (Funding Yale School of Medicine Office of Student Research; selected publication Sleep Abstract 2023)

• Evaluating Sleep Deficiency in Aging Populations. Dr. Knauert serves as a mentor on this K76-funded program investigating sleep deficiency and approaches to sleep assessment in older adults. This work has demonstrated that insomnia with objectively short sleep duration is common and multifactorial in older adults. More recent work showed that a home EEG-measuring headband provided better agreement with polysomnography than actigraphy for several important sleep measures, including among individuals with the poorest sleep. (Funding K76 AG074905; selected publications PMID: 36524599; 41757511)
• The Collaboration Linking Opioid Use Disorder and Sleep (“CLOUDS”) Study. Dr. Knauert is a co-investigator on this multidisciplinary study examining biological, behavioral, social, and environmental pathways linking sleep and circadian disruption with opioid use disorder and treatment outcomes. Recent work demonstrated blunted daily light-exposure amplitudes among individuals with opioid use disorder, suggesting weaker circadian light cues and identifying light exposure as a potentially modifiable target. (Funding U01 HL150596; selected publication PMID: 42509283)