Early goal enteral nutrition associated with decreased in-hospital death in mechanically ventilated critically ill adults: a retrospective cohort study.

INTRODUCTION: Early enteral nutrition (EN) in critically ill adult patients is thought to improve mortality and morbidity; expert guidelines recommend early initiation of EN in critically ill adults. However, the ideal schedule and dose of EN remain understudied. STUDY OBJECTIVE: Our objective was to evaluate the relationship between achieving 70% of recommended EN within 2 days of intubation ('early goal EN') and clinical outcomes in mechanically ventilated medically critically ill adults. We hypothesised that early goal EN would be associated with reduced in-hospital death. METHODS: We conducted a retrospective cohort study of mechanically ventilated adult patients admitted to our medical intensive care unit during 2013-2019. We assessed the proportion of recommended total EN provided to the patient each day following intubation until extubation, death or 7 days whichever was shortest. Patients who received 70% or more of their recommended total daily EN within 2 days of intubation (ie, 'baseline period') were considered to have achieved 'early goal EN'; these patients were compared with patients who did not ('low EN'). The primary outcome was in-hospital death; secondary outcomes were successful extubation and discharge alive. RESULTS: 938 patients met eligibility criteria and survived the baseline period. During the 7-day postintubation period, 64% of all patients reached 70% of recommended daily calories; 33% of patients achieved early goal EN. In unadjusted and adjusted models, early goal EN versus low EN was associated with a lower incidence of in-hospital death (subdistribution HR (SHR) unadjusted=0.63, p=0.0003, SHR adjusted=0.73, p=0.02). Early goal EN was also associated with a higher incidence of successful extubation (SHR unadjusted=1.41, p<0.00001, SHR adjusted=1.27, p=0.002) and discharge alive (SHR unadjusted=1.54, p<0.00001, SHR adjusted=1.24, p=0.02). CONCLUSIONS: Early goal EN was associated with significant improvement in clinical metrics of decreased in-hospital death, increased extubation and increased hospital discharge alive.

Intensive care unit interventions to promote sleep and circadian biology in reducing incident delirium: a scoping review.

RATIONALE/OBJECTIVES: Despite plausible pathophysiological mechanisms, research is needed to confirm the relationship between sleep, circadian rhythm and delirium in patients admitted to the intensive care unit (ICU). The objective of this review is to summarise existing studies promoting, in whole or in part, the normalisation of sleep and circadian biology and their impact on the incidence, prevalence, duration and/or severity of delirium in ICU. METHODS: A sensitive search of electronic databases and conference proceedings was completed in March 2023. Inclusion criteria were English-language studies of any design that evaluated in-ICU non-pharmacological, pharmacological or mixed intervention strategies for promoting sleep or circadian biology and their association with delirium, as assessed at least daily. Data were extracted and independently verified. RESULTS: Of 7886 citations, we included 50 articles. Commonly evaluated interventions include care bundles (n=20), regulation or administration of light therapy (n=5), eye masks and/or earplugs (n=5), one nursing care-focused intervention and pharmacological intervention (eg, melatonin and ramelteon; n=19). The association between these interventions and incident delirium or severity of delirium was mixed. As multiple interventions were incorporated in included studies of care bundles and given that there was variable reporting of compliance with individual elements, identifying which components might have an impact on delirium is challenging. CONCLUSIONS: This scoping review summarises the existing literature as it relates to ICU sleep and circadian disruption (SCD) and delirium in ICU. Further studies are needed to better understand the role of ICU SCD promotion interventions in delirium mitigation.

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

Morning Chronotype Is Associated with Improved Adherence to Continuous Positive Airway Pressure among Individuals with Obstructive Sleep Apnea.

Rationale: Poor adherence limits the effectiveness of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). A better understanding of CPAP adherence is needed to develop novel strategies to improve it. Objectives: To determine if the chronotype (morning, evening, or intermediate) of patients with OSA is associated with differences in CPAP adherence. If such an association exists, determine the mechanisms underlying this association. Methods: We performed a secondary analysis of the APPLES (Apnea Positive Pressure Long-term Efficacy Study) clinical trial. We assessed chronotype using the Morningness-Eveningness Questionnaire (MEQ) among participants randomized to the CPAP arm with daily adherence data (n = 469). Evening (MEQ ⩽ 41), intermediate (41 < MEQ < 59), and morning type (MEQ ⩾ 59) categories were the exposures. We modeled daily CPAP use (hours per night) over a 6-month period, using a linear mixed model, adjusted for covariates (e.g., age, sex, marital status). To assess mechanisms of the association, we performed mediation analyses using sleep duration, weekend catch-up sleep, depression, and other factors. Results: Most participants were obese men with severe OSA (body mass index of 32.3 ± 7.3 kg/m2, 65% male, and apnea-hypopnea index 39.8 ± 24.6/h). Participants were 44% morning, 47% intermediate, and 8% evening chronotype. Participants with the morning chronotype reported the shortest sleep duration on weekends (7.3 vs. 7.6 and 7.9 h/night) compared with the intermediate and evening types. Participants with the morning chronotype exhibited a 40-min/night higher CPAP use (P = 0.001) than persons with the intermediate chronotype. This relationship was mildly attenuated (32.8 min/night; P = 0.011) after adjustment for covariates. None of the selected factors (e.g., sleep duration, weekend catch-up sleep) exhibited a significant mediation effect. Conclusions: Morning chronotype is associated with a clinically meaningful increase in CPAP adherence compared with other chronotypes. Mechanisms of this association require further study. Chronotype may be a novel predictor of CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT00051363).

Keeping an eye on circadian time in clinical research and medicine.

BACKGROUND: Daily rhythms are observed in humans and almost all other organisms. Most of these observed rhythms reflect both underlying endogenous circadian rhythms and evoked responses from behaviours such as sleep/wake, eating/fasting, rest/activity, posture changes and exercise. For many research and clinical purposes, it is important to understand the contribution of the endogenous circadian component to these observed rhythms. CONTENT: The goal of this manuscript is to provide guidance on best practices in measuring metrics of endogenous circadian rhythms in humans and promote the inclusion of circadian rhythms assessments in studies of health and disease. Circadian rhythms affect all aspects of physiology. By specifying minimal experimental conditions for studies, we aim to improve the quality, reliability and interpretability of research into circadian and daily (i.e., time-of-day) rhythms and facilitate the interpretation of clinical and translational findings within the context of human circadian rhythms. We describe protocols, variables and analyses commonly used for studying human daily rhythms, including how to assess the relative contributions of the endogenous circadian system and other daily patterns in behaviours or the environment. We conclude with recommendations for protocols, variables, analyses, definitions and examples of circadian terminology. CONCLUSION: Although circadian rhythms and daily effects on health outcomes can be challenging to distinguish in practice, this distinction may be important in many clinical settings. Identifying and targeting the appropriate underlying (patho)physiology is a medical goal. This review provides methods for identifying circadian effects to aid in the interpretation of published work and the inclusion of circadian factors in clinical research and practice.

Enhancing cosinor analysis of circadian phase markers using the gamma distribution.

The cosinor model, in which a cosine curve is fitted to periodic data within a regression model, is a frequently used method for describing patterns of cyclical activity such as circadian rhythms. For circadian variables of interest (eg, melatonin and heart rate) that do not take on negative values, the assumption of normally distributed residuals required by the general linear model, which is most commonly used for cosinor analysis, may not be appropriate. Alternatively, a generalized linear model with the gamma distribution (GZLM-gamma) is specifically defined to accommodate non-negative outcomes. Herein, we demonstrate the improved fit and gains of efficiency in detection of circadian rhythm afforded by using the GZLM-gamma in cosinor models of heart rate, actigraphic activity, and urinary 6-sulfatoxymelatonin. Notably, this improved detection of circadian rhythm allows retention of additional patients for downstream analyses, further improving study power.

A SAS macro for modelling periodic data using cosinor analysis.

BACKGROUND AND OBJECTIVE: Cosinor analysis, developed by Franz Hallberg and colleagues in the 1960s, allows for the fitting of a cosine curve to data of a known period. Cosinor analysis is frequently used in the analysis of biological rhythm data. While software exists to perform these analyses, we are not aware of any published SAS procedures or macros which would facilitate them. METHODS: To meet this gap, we herein describe SAS macros which perform cosinor analyses that assume either normally or gamma distributed outcomes and fixed period. The macros can 1) produce datasets with cosinor parameters including acrophase, mesor, amplitude, nadir and test for rhythmicity 2) output datasets with fitted and observed values from the model, and 3) plot the resulting curve and underlying data. RESULTS: We demonstrate the use of these macros with data from our research on circadian rhythms of heart rate and sleep in critically ill patients. CONCLUSIONS: Cosinor analysis provides a parsimonious and intuitive set of estimates to summarize periodic data. We are hopeful that the publication of our macro will allow a wider spectrum of users to avail themselves of this technique.

Light Levels in ICU Patient Rooms: Dimming of Daytime Light in Occupied Rooms.

One-third of patients report disruption of sleep by overnight light. Importantly, light causes both immediate sleep disturbance and influences circadian function, a fundamental process underpinning high-quality sleep. Short bursts of light at night and/or lack of bright daytime light disrupt circadian alignment, leading to sleep deficiency. To improve understanding of 24-hour light patterns, we conducted a longitudinal study of light levels in intensive care unit (ICU) rooms. Over 450 room-days, we observed high variability, dim daytime light, and active dimming of natural sunlight in occupied rooms. Such noncircadian light patterns have multifactorial influences on sleep and are a key target for sleep improvement in the ICU.

A Clinic Blueprint for Post-Coronavirus Disease 2019 RECOVERY: Learning From the Past, Looking to the Future.

The severe acute respiratory syndrome coronavirus 2 pandemic poses extraordinary challenges. The tremendous number of coronavirus disease 2019 (COVID-19) cases in the United States has resulted in a large population of survivors with prolonged postinfection symptoms. The creation of multidisciplinary post-COVID-19 clinics to address both persistent symptoms and potential long-term complications requires an understanding of the acute disease and the emerging data regarding COVID-19 outcomes. Experience with severe acute respiratory syndrome and Middle East respiratory syndrome, post-acute respiratory distress syndrome complications, and post-intensive care syndrome also informs anticipated sequelae and clinical program design. Post-COVID-19 clinical programs should be prepared to care for individuals previously hospitalized with COVID-19 (including those who required critical care support), nonhospitalized individuals with persistent respiratory symptoms following COVID-19, and individuals with preexisting lung disease complicated by COVID-19. Effective multidisciplinary collaboration models leverage lessons learned during the early phases of the pandemic to overcome the unique logistical challenges posed by pandemic circumstances. Collaboration between physicians and researchers across disciplines will provide insight into survivorship that may shape the treatment of both acute disease and chronic complications. In this review, we discuss the aims, general principles, elements of design, and challenges of a successful multidisciplinary model to address the needs of COVID-19 survivors.

Pilot Observational Study to Detect Diurnal Variation and Misalignment in Heart Rate Among Critically Ill Patients.

Circadian disruption is common in critically ill patients admitted to the intensive care unit (ICU). Understanding and treating circadian disruption in critical illness has significant potential to improve critical illness outcomes through improved cognitive, immune, cardiovascular, and metabolic function. Measurement of circadian alignment (i.e., circadian phase) can be resource-intensive as it requires frequent blood or urine sampling over 24 or more hours. Less cumbersome methods of assessing circadian alignment would advance investigations in this field. Thus, the objective of this study is to examine the feasibility of using continuous telemetry to assess diurnal variation in heart rate (HR) among medical ICU patients as a proxy for circadian alignment. In exploratory analyses, we tested for associations between misalignment of diurnal variation in HR and death during hospital admission. This was a prospective observational cohort study embedded within a prospective medical ICU biorepository. HR data were continuously collected (every 5 s) via telemetry systems for the duration of the medical ICU admission; the first 24 h of this data was analyzed. Patients were extensively characterized via medical record chart abstraction and patient interviews. Of the 56 patients with complete HR data, 48 (86%) had a detectable diurnal variation. Of these patients with diurnal variation, 39 (81%) were characterized as having the nadir of their HR outside of the normal range of 02:00-06:00 ("misalignment"). Interestingly, no deaths occurred in the patients with normally aligned diurnal variation; in contrast, there were seven deaths (out of 39 patients) in patients who had misaligned diurnal variation in HR. In an exploratory analysis, we found that the odds ratio of death for misaligned vs. aligned patients was increased at 4.38; however, this difference was not statistically significant (95% confidence interval 0.20-97.63). We conclude that diurnal variation in HR can be detected via continuous telemetric monitoring of critically ill patients. A majority of these patients with diurnal variation exhibited misalignment in their first 24 h of medical ICU admission. Exploratory analyses suggest possible associations between misalignment and death.

Circadian Biology and Its Importance to Intensive Care Unit Care and Outcomes.

Circadian rhythms are an integral part of life on earth. Circadian rhythms play a fundamental role in homeostasis as they ensure coordination between the environment and an organism's behavior and physiology. This coordination is called entrainment. Entrainment depends on environmental cues known as zeitgebers. Human zeitgebers include light (primary zeitgeber), sleep, eating, exercise, and activity. Circadian rhythms are disrupted in critically-ill patients due to both critical illness and current intensive care unit (ICU) practices. Disruptions in circadian rhythms are tightly linked with ICU sleep disruption. Together these entities potentiate numerous adverse outcomes including delirium, metabolic derangements, cardiovascular instability, and immune compromise. Herein, we will highlight potential areas for care improvement via chronobundles. We suggest bright light during the day, maintaining darkness, and protecting sleep at night, intermittent rather than continuous feeds, and activity via mobilization during the day. Optimizing circadian rhythms is a low-risk intervention that is underutilized in current ICU practice. This optimization could be a powerful tool in helping to improve outcomes in the critically-ill patient.

Pilot study: an intensive care unit sleep promotion protocol.

Purpose: Disturbances, such as in-room activity and sound, are significant sources of sleep disruption among critically ill patients. These factors are potentially modifiable. We tested the impact of an intensive care unit (ICU) sleep promotion protocol on overnight in-room disturbance. Methods: Our protocol restricted non-urgent bedside care from 00:00 to 03:59. Patients were assigned to usual care (n=30) or the sleep protocol (n=26). The primary outcomes were measures of in-room activity, sound and light. These three types of disturbance were compared between arms during a baseline time block (20:00-23:59) and a rest time block (00:00-03:59). We assessed the sleep protocol effect with generalised linear models. Results: Usual care and sleep protocol patients had equivalent levels of in-room activity, sound and light during the baseline time block (20:00-23:59). In contrast, during the rest time block (00:00-03:59), the sleep protocol arm had 32% fewer room entries (rate ratio (RR) 0.68, p=0.001) and 9.1 fewer minutes of in-room activity (p=0.0002). Also, the length of time between room entrances increased from 26.4 to 45.8 min (p=0.0004). The sleep protocol arm also had lower sound during the rest time block. Mean A-weighted sound was 2.5 decibels lower (p=0.02), and there were 36% fewer peaks (RR 0.64, p=0.02). Light levels were highly variable and not changed by the sleep protocol. Conclusions: Sleep promotion protocols can improve in-room activity and sound. This provides a better sleep opportunity and may, therefore, improve ICU sleep. Trial registration number: 1112009428.

Association between death and loss of stage N2 sleep features among critically Ill patients with delirium.

PURPOSE: Critically ill patients experience significant sleep disruption. In this study of ICU patients with delirium, we evaluated associations between the loss of stage N2 features (K-complexes, sleep spindles), grade of encephalopathy based on electroencephalography (EEG), and intensive care unit (ICU) outcomes. We hypothesized that loss of stage N2 features is associated with more severe grades of encephalopathy and worse ICU outcomes including death. MATERIALS AND METHODS: This was an observational cohort study of 93 medical ICU patients without primary acute brain injury who underwent continuous EEG. Type and severity of critical illness, sedative-hypnotic use, length of stay, modified Rankin Scale at hospital discharge, and death during hospitalization were abstracted from the medical record. EEG was evaluated for grade of encephalopathy and sleep features. RESULTS: Patients without K-complexes or without sleep spindles had more severe encephalopathy and higher odds of death. The odds ratio for patients without K-complexes was 18.8 (p = .046). The odds ratio for patients without sleep spindles was 6.3 (p = .036). CONCLUSIONS: Loss of stage N2 features is common and associated with more severe encephalopathy and higher odds of death. The absence of either Stage N2 feature, K complexes or sleep spindles, may have important prognostic value.

Creating Naptime: An Overnight, Nonpharmacologic Intensive Care Unit Sleep Promotion Protocol.

INTRODUCTION: Patients in the intensive care unit (ICU) have significantly disrupted sleep. Sleep disruption is believed to contribute to ICU delirium, and ICU delirium is associated with increased mortality. Experts recommend sleep promotion as a means of preventing or shortening the duration of delirium. ICU Sleep promotion protocols are highly complex and difficult to implement. Our objective is to describe the development, pilot implementation, and revision of a medical ICU sleep promotion protocol. METHODS: Naptime is a clustered-care intervention that provides a rest period between 00:00 and 04:00. We used literature review, medical chart review, and stakeholder interviews to identify sources of overnight patient disturbance. With stakeholder input, we developed an initial protocol that we piloted on a small scale. Then, using protocol monitoring and stakeholder feedback, we revised Naptime and adapted it for unitwide implementation. RESULTS: We identified sound, patient care, and patient anxiety as important sources of overnight disturbance. The pilot protocol altered the timing of routine care with a focus on medications and laboratory draws. During the pilot, there were frequent protocol violations for laboratory draws and for urgent care. Stakeholder feedback supported revision of the protocol with a focus on providing 60- to 120-minute rest periods interrupted by brief clusters of care between 00:00 and 04:00. DISCUSSION: Four-hour blocks of rest may not be possible for all medical ICU patients, but interruptions can be minimized to a significant degree. Involvement of all stakeholders and frequent protocol reevaluation are needed for successful adoption of an overnight rest period.

Non-circadian signals in the intensive care unit: Point prevalence morning, noon and night.

BACKGROUND: Intensive care unit (ICU) sleep disturbance is severe and potentially related to abnormal light and sound exposure. OBJECTIVES: To assess the prevalence of measures of light and sound disturbance in ICU patient rooms, and whether these could be modified by a sleep-promotion intervention. METHODS: This observational study with a before and after design for a quality improvement initiative surveyed environmental factors in ICU rooms at 01:00 08:00, and 12:00. Surveys assessed light usage, television usage, window shade position, and room door/curtain position. Factors were compared before and after an ICU sleep-promotion intervention. RESULTS: 990 (pre-intervention) and 819 (post-intervention) occupied rooms were surveyed. Pre-intervention, the prevalence of night-time factors included: bright lights on (21%), television on (46%), and room door open (94%). Post-intervention, more rooms had all lights off at night (41% v 50%, p = 0.04), and fewer rooms had open door curtains (57% v 42%, p = 0.001) and window shades (78% v 62%, p = 0.002). CONCLUSIONS: Disruptive environmental factors are common in the ICU. Some factors improve with sleep-promotion interventions.

Association of intensive care unit delirium with sleep disturbance and functional disability after critical illness: an observational cohort study.

BACKGROUND: In medical intensive care unit (MICU) patients, the predictors of post-discharge sleep disturbance and functional disability are poorly understood. ICU delirium is a risk factor with a plausible link to sleep disturbance and disability. This study evaluated the prevalence of self-reported post-ICU sleep disturbance and increased functional disability, and their association with MICU delirium and other ICU factors. METHODS: This was an observational cohort study of MICU patients enrolled in a biorepository and assessed upon MICU admission by demographics, comorbidities, and baseline characteristics. Delirium was assessed daily using the Confusion Assessment Method for the ICU. Telephone follow-up interview instruments occurred after hospital discharge and included the Pittsburgh Sleep Quality Index (PSQI), and basic and instrumental activities of daily living (BADLs, IADLs) for disability. We define sleep disturbance as a PSQI score > 5 and increased disability as an increase in composite BADL/IADL score at follow-up relative to baseline. Multivariable regression modeled the associations of delirium and other MICU factors on follow-up PSQI scores and change in disability scores. RESULTS: PSQI and BADL/IADL instruments were completed by 112 and 122 participants, respectively, at mean 147 days after hospital discharge. Of those surveyed, 63% had sleep disturbance by PSQI criteria, and 37% had increased disability by BADL/IADL scores compared to their pre-MICU baseline. Total days of MICU delirium (p = 0.013), younger age (p = 0.013), and preexisting depression (p = 0.025) were significantly associated with higher PSQI scores at follow-up. Lower baseline disability (p < 0.001), older age (p = 0.048), and less time to follow-up (p = 0.024) were significantly associated with worsening post-ICU disability, while the occurrence of MICU delirium showed a trend toward association (p = 0.077). CONCLUSIONS: After adjusting for important covariates, total days of MICU delirium were significantly associated with increased post-discharge sleep disturbance. Delirium incidence showed a trend toward association with increased functional disability in the year following discharge.

Factors Influencing Patients' Sleep in the Intensive Care Unit: Perceptions of Patients and Clinical Staff.

BACKGROUND: Multiple factors are believed to contribute to disruption of patients' sleep and negatively affect clinical outcomes in the intensive care unit. Achieving restorative sleep for critically ill patients remains a challenge. OBJECTIVES: To explore the perceptions and beliefs of staff, patients, and surrogates regarding the environmental and nonenvironmental factors in the medical intensive care unit that affect patients' sleep. METHODS: This qualitative study included 24 medical intensive care unit staff (7 physicians, 5 respiratory therapists, 10 nurses, and 2 patient-care assistants), 8 patients, and 6 patient surrogates. Semistructured interviews were conducted, and qualitative analysis of content was used to code, categorize, and identify interview themes. RESULTS: Interview responses revealed 4 themes with related subthemes: (1) The overnight medical intensive care unit environment does affect sleep, (2) nonenvironmental factors such as difficult emotions and anxiety also affect sleep, (3) respondents' perceptions about sleep quality in the medical intensive care unit were highly variable, and (4) suggestions for sleep improvement included reassuring patients and care-clustering strategies. CONCLUSIONS: Results of this study suggest that environment is not the only factor influencing patients' sleep. Decreases in environmental sources of disturbance are necessary but not sufficient for sleep improvement. Guideline-recommended clustered care is needed to provide adequate sleep opportunity, but patients' emotions and anxiety also must be addressed.