Nursing in Critical Care

Light affects heart rate 24-hour rhythmicity of Intensive

Care Unit patients

Journal: Nursing in Critical Care

Manuscript ID NCR-2018-1078.R1

Manuscript Type: Research

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Keywords: ICU Follow-Up, Critical Care Nursing, Adult Intensive Care
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Page 1 of 17 Nursing in Critical Care

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3 Abstract
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5 Background: ICU patients experience two affronts to normal 24-hour rhythms: largely internal
6 events such as medication, and external factors such as light, noise and nursing interventions.
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8 Aim: We investigate the impact of light on 24-hour rhythmicity of three key physiological
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parameters: heart rate (HR), mean arterial blood pressure (MAP) and body temperature (BT) in
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11 this patient population.
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13 Study design: Patients were assigned to beds either in the “light” or “dark” side within a single
14 ICU. An actigraph, attached to subjects' arm, continuously recorded light intensity for at least
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16 one 24-hour period.
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Methods: Measurements of HR, MAP, and BT were recorded every 30 minutes.
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19 Results: HR, MAP, and BT did not follow 24-hour rhythmicity in all patients. Higher light
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21 exposure in the light side of the ICU (122.3 lux vs 50.6 lux) was related to higher heart rate
22 (89.4 bpm vs 79.8 bpm), which may translate to clinically relevant outcomes in a larger sample.
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24 The one clinical outcome measured in this study, duration of stay, showed no significant
25 variation between the groups (p=0.147).
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27 Conclusion: ICU patients are exposed to varying light intensities depending on bed positioning
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relative to natural sunlight, affecting the 24-hour rhythm of heart rate. Larger well-controlled
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32 Relevance to Clinical Practice: Light offers a variable that can be manipulated in the highly
33 structured and constrained environment of an ICU, and thus offers an avenue for relatively
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35 unobtrusive intervention.
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 Nursing in Critical Care Page 2 of 17

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3 1. Introduction
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5 The internal states of patients in an intensive care unit (ICU), due to medication (sedation,
6 opioids) and physiological parameters (organ dysfunction and failure), are geared toward
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8 suppressed 24-hour rhythms (McKenna et al., 2018; Paul and Lemmer, 2007). On the other
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hand, external cycles (light, environmental noise, medical and nursing interventions) tend
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11 towards 24-hour activity (Korompeli et al., 2017; McKenna et al., 2017; Weiss et al., 2016). The
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13 mismatch between internal states and external cycles in the ICU environment thus offers a
14 unique challenge to circadian timing. Artificial lighting afforded to patients only loosely conforms
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16 to ‘normal’ 24-hour cycles. The rhythm abnormalities are often expressed in patients at ICU with
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altered rhythmic 24-hour profiles of physiological parameters such as sleep/wake cycles, mean
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19 arterial blood pressure (MAP), heart rate (HR), body temperature (BT), spontaneous motor
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21 activity, and levels of melatonin and cortisol (Engwall et al., 2017). In addition, admission for an
22 acute illness is itself a major risk factor for rest-activity rhythm disturbance and the illness profile
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24 may itself mitigate through alterations in meals, daily physical activity and confinement to bed
25 (Sunderram et al., 2014). These conditions may induce sleep disorders that amplify
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27 disturbances of the circadian timing system. Durrington et al additionally found that ICUs offer a
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paradoxical mixture of suboptimal light and bursts of bright light during nighttime, together
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30 representing a major challenge to good quality sleep (Durrington et al., 2017).

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33 2. Background
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35 Bright light treatment during daytime of the day adjusted sleep-wakefulness cycles and reduced
36 postoperative delirium (Ono et al., 2011; Simons et al., 2016; Taguchi, 2013; Taguchi et al.,
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38 2007). On the other hand, light at night (LAN) affects the circadian system, diminishes
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Light/Dark (L/D) differences and can be harmful to other physiological systems (Fonken and
41 Nelson, 2014; Gaston et al., 2015). Patients at ICU demonstrate dampened L/D differences.
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43 This dampening could be because of LAN in ICUs, however, pain and acute inflammation can
44 also alter 24-hour oscillations (Touitou et al., 2017). There is limited evidence on the therapeutic
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46 implications of ICU lighting. Evidence from previous studies suggests that patients assigned to
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well-lit positions in cardiac ICUs had shorter lengths of stay and lower mortality rates (Vinzio et
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49 al., 2003), and better outcomes (lower pain and stress) were observed for patients exposed to
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51 greater sunlight, however the current study offers greater control and makes use of a more
52 homogenous sample than previous studies (Ritchie et al., 2015).
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3 3. Aims and objectives of study
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5 The purpose of the present study was to examine the impact of light exposure (assignment to a
6 bed in either the ‘light’ or the ‘dark’ side within a single ICU), over a continuous 24-72-hour
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8 period on 24-hour rhythmicity of three key physiological parameters: HR, MAP and BT. These
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parameters are continuously measured and monitored during the normal course of operation of
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11 most ICUs and used as predictors to mortality rates in patients at ICU; their 24-hour rhythm can
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13 be altered by the influence of light (Bourcier et al., 2016; McKenna et al., 2017).
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16 4. Design and methods
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4.1 ICU design
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19 This observational study was conducted in a single ward University Intensive Care Unit at a
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21 Greek general hospital, in Athens. The windows offered access to natural lighting in the ICU.
22 Artificial lighting consisting of overhead panels containing bright white fluorescent lights
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24 illuminated the ICU. The arrangement of beds in the ICU led to a distinction between an array of
25 three fully equipped beds close to the windows in a “light” side, and six otherwise identical beds
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27 bounded by a corridor in a “dark” side, in the same large room. Patients were randomly
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assigned to either a dark or light side of the ICU, like in a previous study (Durrington et al.,
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30 2017). The same nursing staff attended both sets of patients. Daytime was set 8 am to 8 pm
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32 and nighttime was set 8 pm to 8 am. Notably, this study did not manipulate light exposure, but
33 took advantage of natural fluctuations of light within the existing ICU design.
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36 4.2 Patients
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38 Totally 86 subjects were admitted to the ICU during the period between May and November
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2016. The study site was a general ICU, thus it included critically ill patients with respiratory and
41 cardiovascular disease, as well as surgical patients. To ensure a high degree of homogeneity,
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43 patients were enrolled according to the following inclusion criteria, which had to be met at least
44 48 hours prior to study entry and maintained throughout the whole 72 hours of study period: 18–
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46 87 years of age, afebrile (body temperature <38.3), cessation of analog-sedation and
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mechanical ventilation and/or other disturbance necessitating analog-sedation.
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49 The exclusion criteria of patients were: participation in another clinical study in the past 30 days,
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51 use of glucocorticoid medication during the last 14 days, use of b-adrenergic receptor blockers
52 or MAO inhibitors less than one week before study entry, delirium, sleep disorders, clinical
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54 depression, craniocerebral injury, thyroid disorders, liver cirrhosis, renal failure, hemodialysis,
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3 coronary heart disease, sepsis, multi-organ failure or severe coagulopathy. All patients were
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5 evaluated within 24 hours of admission calculating the APACHE II score, a severity-of-disease
6 classification system, and the SOFA score, used to predict hospital mortality based on six organ
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8 dysfunction factors. To avoid implications of hormonal changes in female participants, only post-
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menopausal patients were included. Of the 86 patients admitted to the ICU, 35 met the inclusion
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11 criteria. Data from 13 participants were not used due to a high proportion of missing data
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13 relating to light exposure. This was found to be associated with sensors being obscured by
14 clothes and bed linen. In total, 22 patients entered the study protocol and were monitored for
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16 24-72 hours. On the conclusion of the recording period, the patients either continued to be
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treated in the ICU or were transferred elsewhere.
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21 4.3 Activity and light parameters
22 Light exposure (lux levels) and the rest-activity rhythm of the patients were monitored for 24
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24 consecutive hours and analyzed separately for daytime and nighttime using the MotionWatch
25 8© actigraphy system (MW8, CamNtech, Cambridge, UK). Activity and light data were recorded
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27 with a one-minute epoch and tracked with MotionWare 1.1.20 software. Since patients were
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treated exclusively in bed during the study period, the measured activity levels of the first
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30 enrolled patients were found below the detection limit of the actigraph, thus activity was no
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32 longer recorded thereafter.
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35 4.4 Physiological parameters

36 The physiological parameters heart rate (HR) (beats per minute, bpm) and mean arterial
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38 pressure (MAP) (millimeter of mercury, mmHg) were recorded automatically every 30 minutes
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with a Philips IntelliVue MP60 Monitor. Additionally, body temperature (BT) (°C) was measured
41 with a body thermometer automatically every 30 minutes (Motohashi et al., 1987). All
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43 parameters (HR, MAP and BT) were measured at the same time for each patient, and at the
44 same interval of 30 minutes for a 24-72-hour period.
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4.5 Data analysis
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49 As the length of data collection period varied between patients, HR, MAP and BT data of each
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51 patient were combined for analysis purposes to a single 24-hour period and the significance of
52 this period using the cosinor model (Refinetti et al., 2007) was evaluated. Specifically, if patient
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54 data exceeded the minimum 24-hour period, rather than discarding the data, or choosing a 24-
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3 hour period from a longer period for these patients, the full patient data was integrated into a
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5 single 24-hour unit. Due to the absence of 24-hour rhythms in some patients and some
6 parameters (Table 2), we further analyzed only the mesor (average value around which the
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8 variable oscillates).
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11 4.6 Statistical Analysis
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13 SPSS Statistics 22 (IBM, Armonk, New York) was used for all analyses. Shapiro Wilk test of
14 normality was applied, and proved non-significant (p>0.05), showing that the distribution of all
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16 depending variables was normal. Therefore, the independent 2-group t-test was used for
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comparison. The statistical tests were considered statistically significant if p-value was less than
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19 0.05. Data in the text are expressed as the arithmetic mean ± SEM. The distribution of data is
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21 displayed by box plots. The bottom and top of the box represent the first and third quartiles,
22 respectively; the band near the middle of the box is the median and the lines above and below
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24 the box show the locations of the minimum and maximum value.
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27 5. Ethical and research approvals

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The study was conducted in full accordance with ethical principles, including the World Medical
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30 Association Declaration of Helsinki (version, 2002), followed the protocols set out by Portaluppi
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32 et al (Portaluppi et al., 2010) and was independently reviewed and approved by the ethical
33 committee of the hospital. Informed consent forms were signed by all patients or, when patients
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35 were unable to sign, these were obtained from their legal representatives.
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3 6. Results
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5 6.1 Clinical variables
6 Based on their bed positioning, ICU patients were divided into “Light Side” and “Dark Side”
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8 groups. Table 1 presents the characteristics of all patients as well as of the groups.
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Baseline values of all variables, including length of stay in the ICU, were comparable between
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11 the groups.
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13 In line with the literature, the patients displayed less prominent 24-hour rhythms; a portion of
14 patients in both “Light Side” and “Dark Side” groups did not reveal significant 24-hour rhythms of
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16 HR, MAP and BT (data not shown).
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For this reason, we decided to further investigate other outputs independent of 24-hour rhythm
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19 presence (curve fitting). For the subsequent analyses we evaluated the mean values of all
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21 measured variables for daytime and nighttime separately and their difference (delta) in the
22 “Light Side” and “Dark Side” groups.
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25 6.2 Light exposure of patients in the “Light Side” and “Dark Side” of the ICU
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27 In order to investigate the difference in exposure to light between the “Light Side” and “Dark
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Side" group of patients at ICU, we measured light intensity (lux) and compared the mean values
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30 for the whole 24-hour period, daytime and nighttime between the “Light Side” and “Dark Side”
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32 groups.
33 Average light intensity was higher during the whole 24-hour in the “Light Side” group than in the
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35 “Dark Side” group of patients at ICU, a results that approached statistical significance (p=0.053)
36 (Table 1). Moreover, average light intensity was statistically higher during daytime (p=0.011) in
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38 the “Light Side” group compared to the “Dark Side” group of patients at ICU (Table 1). Similarly,
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average light intensity was statistically higher during nighttime (p=0.009) in the “Light Side”
41 group compared to the “Dark Side” group of ICU patients (Table 1).
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43 Notably, the ratio between daytime and nighttime light intensity (relative intensity) was found
44 similar between the “Dark Side” (3.4±0.3 lux) and “Light Side” (4.2±0.7 lux) groups (p=0.39, data
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46 not shown).
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49 6.3 Light impact on heart rate, arterial pressure and body temperature of ICU patients
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51 In order to investigate the effect of light on the measured physiological parameters, we
52 evaluated and compared mean values of HR, MAP and BT for the whole 24-hour period,
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54 daytime and nighttime separately, as well as and their difference (delta) between the “Light
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3 Side” and “Dark Side” groups.
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5 Statistically higher HR values were observed during daytime (Figure 1A) in patients allocated to
6 the “Light Side” (89.4±2.8 bpm) in comparison to patients in the “Dark Side” of the ICU
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8 (79.8±2.2 bpm) (p=0.024) (Figure 1B).
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Nonetheless, the light did not significantly affect HR during nighttime, neither did it affect MAP or
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11 BT during either daytime or nighttime (data not shown).
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3 7. Discussion
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5 This study demonstrates that ICU bed positioning relative to natural sunlight may have
6 direct measurable impacts on patient’s 24-hour rhythms. A significantly lower heart rate was
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8 observed during daytime in the “Dark Side” group compared to “Light Side” group of ICU
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patients. In contrast, such differences did not emerge during nighttime or in other parameters
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11 such as mean arterial pressure or body temperature.
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13 This study provides evidence of 24-hour rhythmicity disruption in this cohort of patients
14 at ICU, in line with studies over the past 3 decades examining circadian deregulation in ICU
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16 patients (Brainard et al., 2015; Madrid-Navarro et al., 2015). A shorter duration of light exposure
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prior to stress has been shown to promote survival (Castro et al., 2012). Indeed the rhythm of
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19 the parameters included in this study can be altered by the influence of light and are used as
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21 predictors to mortality rates in patients at ICU (Bourcier et al., 2016).
22 Our observational study demonstrates no significant difference between the light and
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24 dark side groups in terms of duration of stay in the ICU. This finding is not consistent with
25 previous evidence showing that patients assigned to well-lit positions in cardiac ICUs
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27 experience stay of shorter duration (Vinzio et al., 2003), and this inconsistency may be
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attributed to the small number of patients in the current study and misallocation to the “Light
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30 Side” and “Dark Side” groups.

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32 In this ICU, illumination levels during daytime (115±29 lux) and nighttime (35±7 lux) were
33 within the normal range (Engwall et al., 2017), in contrast to other previous studies showing a
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35 greater range in ICU lighting. For example, Hu et al. recorded levels ranging from 62-790 lux
36 during daytime, 15-489 lux during the evening and 10-239 lux during nighttime (Hu et al., 2016),
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38 while Elliott et al. observed median daytime levels of 74 lux and nighttime levels of 2 lux (Elliott
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et al., 2014). Another study reported that 52.2% of the assessed hospitals had illumination
41 levels below the 2011 recommended European Standards ranging from 100 lux for general
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43 lighting to 100,000 lux for some operating areas (Dianat et al., 2013).
44 Our data demonstrate that critically ill patients are exposed to varying light intensities
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46 depending on bed positioning. The “Light Side” group was exposed to significantly higher
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average light intensity during all day in comparison with the “Dark Side” group. When examined
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49 separately, mean light exposure was higher in the “Light Side” group versus “Dark Side” group
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51 during daytime, as well as during nighttime. The finding of overall higher mean illumination in
52 the “Light Side” group of patients at ICU is consistent with previous studies (Durrington et al.,
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54 2017; Fan et al., 2017) and can be explained to an extent by the fact that, besides artificial ICU
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3 lighting, beds near the windows are further exposed to natural sunlight during daytime and to
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5 street light and moonlight.
6 Besides the light intensities, physiological variables such as HR, its variability, BT
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8 (Litscher et al., 2013), MAP, arterial stiffness and endothelial function (Stern et al., 2018) can be
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affected by colored light exposition.
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11 It is interesting to note that, despite the difference in absolute values of daytime and
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13 nighttime light intensity in “Light Side” and “Dark Side” groups, the relative light intensity was
14 very similar between the two groups. This finding indicates that not only the absolute value of
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16 light but also its relative nighttime decrease may be of significant importance, but this remains
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open for further exploration. If relative light intensity is proven important for circadian rhythm
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19 normalization, since nighttime artificial light in a working ward cannot easily be reduced below
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21 current levels, clinically significant outcomes may be achieved by increasing daytime light. In
22 favor of this speculation, increased daytime light is proposed to result in improvement in
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24 circadian modulated physiologic parameters in both translational and human studies (Fan et al.,
25 2017).
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8. Limitations
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30 The results of this study need to be considered in the context of a number of limitations.
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32 The sample size was relatively small, with unbalanced allocation to the “Light Side” and “Dark
33 Side” groups, because less beds in the “Light Side” were fully equipped, and thus
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35 accommodated fewer patients. Overnight light interruptions were not recorded, although those
36 interruptions were likely to have been distributed randomly between patients and conditions.
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38 Bright light at night can eliminate 24-hour rhythms (Durrington et al., 2017), although such high-
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intensity light interruptions are necessary to enable delivery of 24-hour care to critically ill
41 patients. It is worth noting that patients were monitored with the MotionWatch actigraphy
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43 system. While this system did not interfere with intravascular lines, as it was attached to the
44 opposite arm, the data showed no meaningful activity variation (Mistraletti et al., 2009), with
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46 patients largely immobile. Lastly, body temperature was used as a proxy for what is the ‘gold
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standard’ of establishing core BT but probably offers a good approximation as a circadian
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49 marker (Motohashi et al., 1987). However, it would have been valuable to include cortisol and
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51 melatonin measurements (Van Dycke et al., 2015).
52 Critically ill patients are clearly an unusual subject pool for circadian studies. They were
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54 partly chosen for this study to ensure that their differences in their responses as patients could
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3 be, to a significant degree, attributed to differences in bed positioning, as other aspects of their
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5 cases were randomly assigned and controlled. As such, cardiovascular variables may change
6 due to differences between groups in age, diagnoses, medication use, smoking history, level of
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8 fitness etc. As another limitation, such differences were not considered in this study.
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While larger randomized controlled trials are needed to establish the parameters, studies
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11 with relatively more homogenous samples, such as the current study, can begin to address the
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13 question of the role of light in the critically ill patients. In particular, a larger sample, as well as
14 the analysis of the main circadian biomarker, melatonin, will offer greater insight into the impact
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16 of relatively minor changes of lighting on outcomes (such as time to discharge) in this highly
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vulnerable population.
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21 9. Implications and recommendations for practice
22 This observational study points towards a need to better simulate daily variability of light
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24 intensities in the ICU setting. This could probably adjust physiological variables, including heart
25 rate.
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10. Conclusion
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30 Differential light exposure depending on ICU bed positioning seems to have a significant
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32 impact on heart rate in patients. Decreased light intensity was connected with decreased HR.
33 Light exposure is one factor present in the highly structured and constrained environment of
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35 hospitals that can be relatively easily modulated and is thus a promising avenue for relatively
36 unobtrusive interventions.
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3 What is known about this topic
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5  ICU patients often exhibit dysregulated 24-hour profiles of physiological parameters such
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as sleep/wake cycles, mean arterial blood pressure, heart rate, spontaneous motor
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8 activity. Moreover, acute illness is itself a major risk factor for 24-hour rhythm.
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10  Although there is limited evidence on the therapeutic implications of ICU lighting,
11 evidence from previous studies suggests that patients assigned to well-lit positions in
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13 cardiac ICUs had shorter lengths of stay and lower mortality rates.
14 What this paper adds
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16  ICU patients are exposed to varying light intensities depending on bed positioning.
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18  Bed positioning relative to natural sunlight affects the 24-hour rhythm of heart rate.
19  Apart from the absolute levels of light, its nighttime decrease may be important.
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21  Light levels can be modulated as an intervention for circadian rhythm normalization
22
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3 References
4
5 Bourcier, S., Pichereau, C., Boelle, P.-Y., Nemlaghi, S., Dubée, V., Lejour, G., Baudel, J.-L.,
6 Galbois, A., Lavillegrand, J.-R., Bigé, N., Tahiri, J., Leblanc, G., Maury, E., Guidet, B., Ait-
7
8 Oufella, H., 2016. Toe-to-room temperature gradient correlates with tissue perfusion and
9
predicts outcome in selected critically ill patients with severe infections. Ann. Intensive
10
11 Care 6, 63. https://doi.org/10.1186/s13613-016-0164-2
12
13 Brainard, J., Gobel, M., Scott, B., Koeppen, M., Eckle, T., 2015. Health implications of disrupted
14 circadian rhythms and the potential for daylight as therapy. Anesthesiology 122, 1170–5.
15
16 https://doi.org/10.1097/ALN.0000000000000596
17
Castro, R.A., Angus, D.C., Hong, S.Y., Lee, C., Weissfeld, L.A., Clermont, G., Rosengart, M.R.,
18
19 2012. Light and the outcome of the critically ill: an observational cohort study. Crit. Care 16,
Fo
20
21 R132. https://doi.org/10.1186/cc11437
22 Dianat, I., Sedghi, A., Bagherzade, J., Jafarabadi, M.A., Stedmon, A.W., 2013. Objective and
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23
24 subjective assessments of lighting in a hospital setting: implications for health, safety and
25 performance. Ergonomics 56, 1535–45. https://doi.org/10.1080/00140139.2013.820845
26
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27 Durrington, H.J., Clark, R., Greer, R., Martial, F.P., Blaikley, J., Dark, P., Lucas, R.J., Ray, D.W.,
28
2017. “In a dark place, we find ourselves”: light intensity in critical care units. Intensive care
29
iew

30 Med. Exp. 5, 9. https://doi.org/10.1186/s40635-017-0122-9

31
32 Elliott, R., Rai, T., McKinley, S., 2014. Factors affecting sleep in the critically ill: an observational
33 study. J. Crit. Care 29, 859–63. https://doi.org/10.1016/j.jcrc.2014.05.015
34
On

35 Engwall, M., Fridh, I., Jutengren, G., Bergbom, I., Sterner, A., Lindahl, B., 2017. The effect of
36 cycled lighting in the intensive care unit on sleep, activity and physiological parameters: A
37
38 pilot study. Intensive Crit. care Nurs. 41, 26–32. https://doi.org/10.1016/j.iccn.2017.01.009
ly

39
40
Fan, E.P., Abbott, S.M., Reid, K.J., Zee, P.C., Maas, M.B., 2017. Abnormal environmental light
41 exposure in the intensive care environment. J. Crit. Care 40, 11–14.
42
43 https://doi.org/10.1016/j.jcrc.2017.03.002
44 Fonken, L.K., Nelson, R.J., 2014. The effects of light at night on circadian clocks and
45
46 metabolism. Endocr. Rev. 35, 648–70. https://doi.org/10.1210/er.9013-1051
47
Gaston, K.J., Visser, M.E., Hölker, F., 2015. The biological impacts of artificial light at night: the
48
49 research challenge. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 370, 20140133–20140133.
50
51 https://doi.org/10.1098/rstb.2014.0133
52 Hu, R., Hegadoren, K.M., Wang, X., Jiang, X., 2016. An investigation of light and sound levels
53
54 on intensive care units in China. Aust. Crit. Care 29, 62–67.
55
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57
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Page 13 of 17 Nursing in Critical Care

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3 https://doi.org/10.1016/j.aucc.2015.08.001
4
5 Korompeli, A., Muurlink, O., Kavrochorianou, N., Katsoulas, T., Fildissis, G., Baltopoulos, G.,
6 2017. Circadian disruption of ICU patients: A review of pathways, expression, and
7
8 interventions. J. Crit. Care 38, 269–277. https://doi.org/10.1016/j.jcrc.2016.12.006
9
Litscher, D., Wang, L., Gaischek, I., Litscher, G., 2013. The influence of new colored light
10
11 stimulation methods on heart rate variability, temperature, and well-being: results of a pilot
12
13 study in humans. Evid. Based. Complement. Alternat. Med. 2013, 674183.
14 https://doi.org/10.1155/2013/674183
15
16 Madrid-Navarro, C.J., Sanchez-Galvez, R., Martinez-Nicolas, A., Marina, R., Garcia, J.A.,
17
Madrid, J.A., Rol, M.A., 2015. Disruption of Circadian Rhythms and Delirium, Sleep
18
19 Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for
Fo
20
21 Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment. Curr.
22 Pharm. Des. 21, 3453–68.
rR
23
24 McKenna, H., van der Horst, G.T.J., Reiss, I., Martin, D., 2018. Clinical chronobiology: a timely
25 consideration in critical care medicine. Crit. Care 22, 124. https://doi.org/10.1186/s13054-
26
ev

27 018-2041-x
28
McKenna, H.T., Reiss, I.K., Martin, D.S., 2017. The significance of circadian rhythms and
29
iew

30 dysrhythmias in critical illness. J. Intensive Care Soc. 18, 121–129.

31
32 https://doi.org/10.1177/1751143717692603
33 Mistraletti, G., Taverna, M., Sabbatini, G., Carloni, E., Bolgiaghi, L., Pirrone, M., Cigada, M.,
34
On

35 Destrebecq, A.L.L., Carli, F., Iapichino, G., 2009. Actigraphic monitoring in critically ill
36 patients: preliminary results toward an &quot;observation-guided sedation&quot;. J. Crit.
37
38 Care 24, 563–7. https://doi.org/10.1016/j.jcrc.2009.05.006
ly

39
40
Motohashi, Y., Reinberg, A., Levi, F., Nougier, J., Benoit, O., Foret, J., Bourdeleau, P., 1987.
41 Axillary temperature: a circadian marker rhythm for shift workers. Ergonomics 30, 1235–47.
42
43 https://doi.org/10.1080/00140138708966019
44 Ono, H., Taguchi, T., Kido, Y., Fujino, Y., Doki, Y., 2011. The usefulness of bright light therapy
45
46 for patients after oesophagectomy. Intensive Crit. care Nurs. 27, 158–66.
47
https://doi.org/10.1016/j.iccn.2011.03.003
48
49 Paul, T., Lemmer, B., 2007. Disturbance of circadian rhythms in analgosedated intensive care
50
51 unit patients with and without craniocerebral injury. Chronobiol. Int. 24, 45–61.
52 https://doi.org/10.1080/07420520601142569
53
54 Portaluppi, F., Smolensky, M.H., Touitou, Y., 2010. Ethics and methods for biological rhythm
55
56
57
58
59
60
 Nursing in Critical Care Page 14 of 17

1
2
3 research on animal and human beings. Chronobiol. Int. 27, 1911–1929.
4
5 https://doi.org/10.3109/07420528.2010.516381
6 Refinetti, R., Lissen, G.C., Halberg, F., 2007. Procedures for numerical analysis of circadian
7
8 rhythms. Biol. Rhythm Res. 38, 275–325. https://doi.org/10.1080/09291010600903692
9
Ritchie, H.K., Stothard, E.R., Wright, K.P., 2015. Entrainment of the Human Circadian Clock to
10
11 the Light-Dark Cycle and its Impact on Patients in the ICU and Nursing Home Settings.
12
13 Curr. Pharm. Des. 21, 3438–42.
14 Simons, K.S., Laheij, R.J.F., van den Boogaard, M., Moviat, M.A.M., Paling, A.J., Polderman,
15
16 F.N., Rozendaal, F.W., Salet, G.A.M., van der Hoeven, J.G., Pickkers, P., de Jager,
17
C.P.C., 2016. Dynamic light application therapy to reduce the incidence and duration of
18
19 delirium in intensive-care patients: a randomised controlled trial. Lancet. Respir. Med. 4,
Fo
20
21 194–202. https://doi.org/10.1016/S2213-2600(16)00025-4
22 Stern, M., Broja, M., Sansone, R., Gröne, M., Skene, S.S., Liebmann, J., Suschek, C. V, Born,
rR
23
24 M., Kelm, M., Heiss, C., 2018. Blue light exposure decreases systolic blood pressure,
25 arterial stiffness, and improves endothelial function in humans. Eur. J. Prev. Cardiol. 25,
26
ev

27 1875–1883. https://doi.org/10.1177/2047487318800072
28
Sunderram, J., Sofou, S., Kamisoglu, K., Karantza, V., Androulakis, I.P., 2014. Time-restricted
29
iew

30 feeding and the realignment of biological rhythms: translational opportunities and

31
32 challenges. J. Transl. Med. 12, 79. https://doi.org/10.1186/1479-5876-12-79
33 Taguchi, T., 2013. Bright light treatment for prevention of perioperative delirium in elderly
34
On

35 patients. J. Nurs. Educ. Pract. 3, 10. https://doi.org/10.5430/jnep.v3n10p10

36 Taguchi, T., Yano, M., Kido, Y., 2007. Influence of bright light therapy on postoperative patients:
37
38 A pilot study. Intensive Crit. Care Nurs. 23, 289–297.
ly

39
40
https://doi.org/10.1016/j.iccn.2007.04.004
41 Touitou, Y., Reinberg, A., Touitou, D., 2017. Association between light at night, melatonin
42
43 secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of
44 circadian disruption. Life Sci. 173, 94–106. https://doi.org/10.1016/j.lfs.2017.02.008
45
46 Van Dycke, K.C.G., Pennings, J.L.A., van Oostrom, C.T.M., van Kerkhof, L.W.M., van Steeg,
47
H., van der Horst, G.T.J., Rodenburg, W., 2015. Biomarkers for circadian rhythm disruption
48
49 independent of time of day. PLoS One 10, e0127075.
50
51 https://doi.org/10.1371/journal.pone.0127075
52 Vinzio, S., Ruellan, A., Perrin, A.-E., Schlienger, J.-L., Goichot, B., 2003. Actigraphic
53
54 assessment of the circadian rest-activity rhythm in elderly patients hospitalized in an acute
55
56
57
58
59
60
Page 15 of 17 Nursing in Critical Care

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3 care unit. Psychiatry Clin. Neurosci. 57, 53–8. https://doi.org/10.1046/j.1440-
4
5 1819.2003.01079.x
6 Weiss, B., Spies, C., Piazena, H., Penzel, T., Fietze, I., Luetz, A., 2016. Exposure to light and
7
8 darkness and its influence on physiological measures of intensive care unit patients-a
9
systematic literature review. Physiol. Meas. 37, R73-87. https://doi.org/10.1088/0967-
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3 Table 1. Patients’ characteristics and group assignment (mean ± SEM)
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5 Total ICU Dark side Light side
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7 Number of patients (n) 22 17 5
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9 Male (n, %) 14 (63.6%) 10 (58.8%) 4 (80%)
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11 Female (n, %) 8 (36.4%) 7 (41.2%) 1 (20%)
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13 Age (years) 71.3 ± 3.2 69.2 ± 3.6 78.4 ± 6.1
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15 APACHE-II score 21 ± 2 19.9 ± 2.2 25 ± 4
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17 SOFA score 8.4 ± 0.6 8.2 ± 0.7 8.8 ± 1.5
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19 Length of ICU stay (days) 17.8 ± 3.7 20.7 ± 4.5 8.2 ± 1.7
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Length of ICU stay before inclusion 16.6 ± 3.6 19.4 ± 4.5 7.2 ± 1.7
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Light exposure during 24-hour period 66.9 ± 10.4 50.6 ± 7.7 122.3 ±26.7
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(lux)
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Daytime light exposure (lux) 108.2 ± 17.6 78.8 ± 12.2 233.2 ± 31.7
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28 Nighttime light exposure (lux) 31.1 ± 5.2 24.7 ± 5.1 58.3 ± 6.6
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32 Figure 1. Average heart rate (beats/min, bpm) of patients during daytime (A) and nighttime (B) of the
33 24-hour period, by allocation to the light (n=17) or dark (n=5) sides of the ICU. The difference of daytime
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35 and nighttime for each ICU group is expressed as delta (C). Mesor represents the middle value of the
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