Impact of sleep disturbances on outcomes in intensive care units

Impact of sleep disturbances on outcomes in intensive care units | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of sleep disturbances on outcomes in intensive care units Laura Marchasson, Christophe Rault, Sylvain Le Pape, François Arrivé, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4687249/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2024 Read the published version in Critical Care → Version 1 posted 9 You are reading this latest preprint version Abstract Background Sleep deprivation is common in ICUs and may alter respiratory performance. Few studies have assessed the role of sleep disturbances on outcomes in critically ill patients. Objectives We hypothesized that sleep disturbances may be associated with poor outcomes in ICUs. Methods Post-hoc analysis pooling 3 studies assessing sleep by complete polysomnography in 131 conscious and non-sedated patients included at different times of their ICU stay. Sleep was assessed early in patients admitted for acute respiratory failure while breathing spontaneously (n = 34), or under mechanical ventilation in patients with weaning difficulties (n = 45), or immediately after extubation (n = 52). Patients admitted for acute respiratory failure who required intubation, those under mechanical ventilation who had prolonged weaning, and those who required reintubation after extubation were considered as having poor clinical outcomes. Durations of deep sleep, rapid eye movement (REM) sleep, and atypical sleep were compared according to the timing of polysomnography and the clinical outcomes. Results While deep sleep remained preserved in patients admitted for acute respiratory failure whereas it was markedly reduced under mechanical ventilation and after extubation (p < 0.01). Atypical sleep was significantly more frequent in patients under mechanical ventilation than in those breathing spontaneously (p < 0.01). REM sleep was uncommon at any time of their ICU stay. Patients with complete disappearance of REM sleep (50% of patients) were more likely to have poor clinical outcomes than those with persistent REM sleep (24% vs. 9%, p = 0.03). Conclusion Complete disappearance of REM sleep was significantly associated with poor clinical outcomes in critically ill patients. Sleep Rapid Eye Movement sleep Polysomnography Intensive care unit Ventilator weaning Endotracheal intubation Airway Extubation Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Sleep is an essential physiological periodic activity permitting physical and neurobehavioral restoration, which can be severely impaired during an ICU stay, especially in mechanically ventilated patients ( 1 – 5 ). In critically ill patients, sleep is characterized by a high proportion of light sleep (mainly stages N1 and N2), fragmented by numerous awakenings, and with loss of the circadian rhythm, with sleep occurring as well during the daytime as during the night ( 1 – 5 ). Deep sleep (sleep stage N3) and rapid eye movement (REM) sleep, which are two essential stages of sleep, may completely disappear in the ICU, even in patients conscious and not under sedation. In some patients, normal sleep architecture may completely disappear and be replaced by electroencephalogram (EEG) aspects suggesting atypical sleep recordings, characterized by the absence of stage-2 markers (absence of K complexes and sleep spindles) ( 1 , 6 – 9 ). Many factors may promote sleep disturbances, including underlying disease severity, mechanical ventilation, use of sedation, anxiety, but also aggressive environments including light exposure, noise, pain or factors related to nursing ( 1 – 5 ). Two studies have shown that sleep disturbances may impair ability to breathe without the ventilator in patients under mechanical ventilation, suggesting that brain dysfunction influences the ability to breathe spontaneously ( 6 , 7 ). In line with these findings, it has been shown in healthy subjects that sleep deprivation may alter respiratory endurance by altering cortical respiratory command ( 10 , 11 ), and may reduce response to hypoxia and hypercapnia ( 12 , 13 ). Consequently, sleep disturbances observed in ICU-patients such as atypical sleep or absence of restorative sleep such as deep sleep and REM sleep, may impair respiratory function and precipitate respiratory failure. Few studies have assessed the influence of sleep disturbances on outcomes in critically ill patients. Therefore, we aimed at assessing sleep quantity and quality, and the role of sleep disturbances on outcomes of critically ill patients at different times during their ICU stay, i.e. at the beginning of the ICU stay in patients who are breathing spontaneously, during the weaning period in patients still under mechanical ventilation, or in patients who have just been extubated. METHODS Study design and patients This is a post-hoc analysis pooling 3 prospective physiological studies assessing sleep by complete polysomnography in critically ill patients admitted to the University Hospital of Poitiers ( 6 , 14 , 15 ). All studies were approved by the independent ethics committee of Poitiers (CPP Ouest III). Patients and/or their next of kin were informed and gave their written consent before being included in studies. Sleep was assessed as early as possible at different times during the ICU stay: 1) at the beginning of the ICU stay in patients breathing spontaneously just after ICU admission for acute hypoxemic respiratory failure (defined as a respiratory rate above 25 breaths per minute or clinical signs suggesting respiratory distress and PaO 2 /FiO 2 below 300 mmHg while receiving high-flow nasal oxygen therapy) ( 15 ); 2) in patients still under mechanical ventilation and with difficult weaning ( i.e. after failure of at least one spontaneous breathing trial) ( 6 ); 3) in patients breathing spontaneously just after being extubated ( 14 ). All patients were awake and conscious on the day of polysomnography. Patients with altered consciousness, central nervous system or psychiatric disorders, or those receiving sedation or neuroleptic medication were excluded. Sleep assessment and EEG reactivity Sleep was evaluated by complete polysomnography (PSG) that started in the afternoon and was continuously performed until the next morning. A trained investigator positioned the electrodes, which consisted of six EEG channels (F3-A2, F4-A1, C4-A1, C3-A2, O2-A1 and O1-A2) referenced to the contralateral mastoid according to the international 10–20 system for electrode placement ( 16 ). Two electromyograms (EMGs) (chin) and two electro-oculograms (EOGs) were recorded to score REM and non-REM sleep. Sleep recordings were manually scored by a neurologist blinded to the patient’s status (XD). Duration of REM sleep and non-REM sleep stages including light sleep (sleep stages N1 and N2) and deep sleep (sleep stage N3) was assessed using the standard 2007 criteria of the American Academy of Sleep Medicine ( 17 ). The presence of atypical sleep was detected according to a modified classification ( 9 ). Indeed, due to the absence of stage 2 markers (absence of K complexes and sleep spindles), atypical sleep cannot be classified according to the standard criteria. To be able to differentiate atypical sleep from pathological wakefulness characterized by excessive slow wave activity, an eyes-open test was systematically performed by the neurophysiologist before PSG in order to assess EEG frequency in the wakefulness state. EMG and EOG were more active during wakefulness than during sleep, while decreased EMG was required as evidence of REM sleep. EEG reactivity at eyes-open test was assessed during wakefulness by the neurologist at the beginning of PSG according to the EEG rhythm on an O2-A1 electrode as previously described ( 9 ). Immediate disappearance or frank attenuation (> 90%) of the background EEG rhythm at eyes-open test, which was replaced by fast low-amplitude frequencies and maintained as long as the eyes were open, was considered as normal EEG reactivity. Moderate and brief attenuation (30–50% decrease in amplitude) was considered as altered EEG reactivity. Undetectable or a very small difference between EEG patterns with the eyes closed and the eyes open was considered as no EEG reactivity. Sleep quantity and quality Sleep quantity included measurement of total sleep time, duration of light, deep and REM sleep stages in minutes or hours, and sleep efficiency as the ratio of total sleep time divided by the total recording time in percentage. Sleep quality was assessed by measurement of atypical sleep, and deep sleep or REM sleep (the two most restorative sleep stages). Sleep fragmentation was defined as the number of arousals and awakenings per hour of sleep. Outcomes The primary endpoint was sleep quality according to the clinical outcomes in ICUs. Patients were considered to have poor clinical outcomes according to time of inclusion in the study. Poor patient clinical outcomes included: 1) need for intubation in patients admitted for acute respiratory failure while breathing spontaneously, 2) prolonged weaning defined according to the weaning classification as a duration of more than 7 days between the initial spontaneous breathing trial and extubation ( 18 ), and 3) need for reintubation in patients who were included after extubation while breathing spontaneously. Intubation and reintubation were decided according to pre-specified criteria including the following: cardiac or respiratory arrest, hemodynamic failure requiring vasopressors, altered consciousness defined as a Glasgow coma scale below 12, or severe respiratory failure defined by at least two criteria among the following; respiratory rate above 35 breaths per minute, clinical signs suggesting respiratory distress, hypoxemia defined as PaO 2 /FiO 2 below 100 mm Hg or FIO 2 at least 80% to maintain SpO 2 at least 92%, or respiratory acidosis defined as pH below 7.25 and PaCO 2 > 45 mmHg. Statistical analysis Continuous variables were expressed as mean ± standard deviation or median and interquartile range [IQR, 25th -75th percentiles] according to their distribution, and qualitative variables were expressed as number and percentage. Patient and sleep characteristics were compared according to the timing of inclusion in the ICU between the three groups of patients using ANOVA or Kruskal-Wallis as appropriate for continuous variables, and using the χ2 test for categorical variables. Comparison between patients with poor clinical outcomes and the others were compared using a Wilcoxon rank-sum test for continuous variables, and the Fisher exact test for categorical variables. A two-tailed p-value < 0,05 was considered as statistically significant. All analyses were performed using the R software version 4.2.1 ( www.R-project.org ). RESULTS One hundred and thirty-one patients had complete polysomnography in the ICU, including 34 patients breathing spontaneously with acute respiratory failure (26%), 45 mechanically ventilated patients with weaning difficulties (34%), and 52 patients breathing spontaneously after extubation (40%) ( Fig. 1 ). The proportion of patients considered as having poor outcomes in ICUs was similar between the three groups: 5 patients (15%) among the 34 patients included with acute respiratory failure required intubation, 9 patients among the 45 patients included under mechanical ventilation had prolonged weaning (20%), and 8 patients (15%) among the 52 patients included after extubation required reintubation (p = 0.77). Mortality in ICU was significantly higher in patients considered as having with poor outcomes than the others: 32% (7 out of 22 patients) vs. 3% (3 out of 109 patients), p < 0.01. Comparison of sleep characteristics between the different timings of sleep assessment in the ICU. Sleep characteristics significantly differed according to the timing of polysomnography in the ICU ( Table 1 and Fig. 2 ) . Table 1 Comparison of patients and sleep characteristics between the different times of inclusion. Acute respiratory failure (N = 34) Weaning failure (N = 45) After extubation (N = 52) P value Patient characteristics - Age, years 62 ± 11 65 ± 11 67 ± 11 0.14 - Male sex, n (%) 25 (74%) 32 (71%) 35 (67%) 0.82 - Body mass index, kg/m2 27 ± 4 32 ± 11 30 ± 7 0.04 - Underlying cardiac disease, n (%) 12 (35%) 15 (33%) 19 (37%) 0.95 - Underlying respiratory disease, n (%) 12 (35%) 18 (40%) 18 (35%) 0.84 - SAPS II at admission, points 31 ± 11 48 ± 16 50 ± 19 < 0.01 - SOFA at inclusion, points 4.5 ± 1.9 3.5 ± 1.9 3.4 ± 2.4 0.07 Sleep quantity - Total sleep time, hours 4.2 [2.9–6.8] 4.6 [2.1–7.3] 2.4 [1.1–4.1] < 0.01 - Sleep efficiency, % 30 ± 17 31 ± 26 18 ± 15 < 0.01 - Duration of light sleep (stage N1), min 12 [6–28] 2 [0–32] 8 [0–28] 0.19 - Duration of light sleep (stage N2), min 146 [60–227] 13 [0-151] 46 [5–79] < 0.01 - Duration of deep sleep (stage N3), min 70 [34–127] 4 [0–67] 17 [0–66] < 0.01 - Duration of REM sleep stage, min 9 [0–28] 3 [0–33] 0 [0–8] 0.01 - Duration of atypical sleep, min 0 [0–0] 0 [0-145] 0 [0–0] < 0.01 Sleep quality - Fragmentation index, events/hour 28 ± 15 35 ± 21 37 ± 20 0.09 - Absence of deep sleep stage, n (%) 2 (6%) 22 (49%) 15 (29%) < 0.01 - Absence of REM sleep stage, n (%) 13 (38%) 20 (44%) 33 (63%) 0.04 - Atypical sleep, n (%) 1 (3%) 20 (44%) 10 (19%) < 0.01 EEG reactivity at eyes-open test - Normal reactivity, n (%) 30 (88%) 21 (49%) 33 (69%) < 0.01 - Pathological wakefulness, n (%) 4 (12%) 22 (51%) 15 (31%) < 0.01 Outcomes - Poor outcomes, n (%) 5 (15%) 9 (20%) 8 (15%) 0.77 - Mortality, n (%) 4 (12%) 5 (11%) 1 (1.9%) 0.14 Values are given in mean ± standard deviation and median [25–75 percentiles] Patients admitted for acute respiratory failure had relatively well-preserved total sleep time (4.2 hours [IQR 2.9–6.8] in median) and deep sleep (31% of total sleep time). REM sleep was markedly short and represented only 4.9% of total sleep time. Complete disappearance of REM sleep was observed in 38% of patients (13/34). Patients included under mechanical ventilation with weaning difficulties had relatively well-preserved total sleep time (4.6 hours [IQR 2.1–7.3] in median). Deep sleep and REM sleep were markedly short and represented only 14% and 6% of total sleep time, respectively. Complete disappearance of REM sleep was observed in 44% of patients (20/45). Patients included after extubation had particularly short total sleep time (2.4 hours [IQR 1.1–4.1] in median). Deep sleep was relatively well preserved (24% of total sleep time) whereas REM sleep was markedly short (3% of total sleep time). Complete disappearance of REM sleep was observed in 63% of patients (33/52). By comparing the three groups, patients included after extubation were those with the shortest total sleep time and the shortest REM sleep duration (p < 0.01), whereas patients included under mechanical ventilation were those with the most impaired deep sleep (p < 0.01) ( Fig. 2 ) . In patients under mechanical ventilation, deep sleep was mainly replaced by atypical sleep. Atypical sleep occurred in 44% of patients under mechanical ventilation and occurred in only 19% of patients after extubation and in only one patient admitted for acute respiratory failure (p < 0.01 between the 3 groups). REM sleep was uncommon at any time of the ICU stay, and was completely abolished in 50% of patients (66 out of 131 patients). Complete disappearance of REM sleep occurred in 63% of patients after extubation, whereas it occurred in 44% of patients under mechanical ventilation, and 38% of patients admitted for acute respiratory failure (p < 0.01 between the 3 groups). Comparison of sleep characteristics between patients with poor outcomes and the others. Characteristics of the patients and severity scores (SAPS II at inclusion and SOFA at inclusion) did not significantly differ between patients with subsequent poor outcomes and those with good outcomes. Whereas sleep quantity indicated by total sleep time did not differ regardless of the outcomes, sleep quality was significantly more altered in patients with poor outcomes than in the others ( Table 2 ). Patients with poor outcomes had shorter duration of light sleep stage and shorter duration of REM sleep stage than those with good outcomes. Whereas duration of deep sleep did not differ between groups, patients with poor outcomes had longer duration of atypical sleep than the others. Patients with complete disappearance of REM sleep were more likely to have poor outcomes than those with persistent REM sleep (24% vs. 9%, p = 0.03) ( Fig. 3 ) . In-ICU mortality did not significantly differ between patients with complete disappearance of REM sleep and those with persistent REM sleep (12% vs. 3%, respectively, p = 0.11) Table 2 Characteristics, sleep and reactivity EEG comparison between patients who developed poor outcomes (intubation. prolonged weaning. or reintubation) and the others. Poor outcomes (N = 22) Good outcomes (N = 109) P value Patient characteristics - Age, years 63 ± 10 65 ± 11 0.30 - Male sex, n (%) 15 (68%) 77 (71%) 0.80 - Body mass index, kg/m2 29 ± 6 30 ± 9 0.43 - Underlying cardiac disease, n (%) 8 (36%) 38 (35%) > 0.99 - Underlying respiratory disease, n (%) 9 (41%) 39 (36%) 0.64 - SAPS II at admission, points 40 ± 16 45 ± 18 0.20 - SOFA at inclusion, points 4.0 ± 2.3 3.7 ± 2.1 0.49 Sleep quantity - Total sleep time, hours 3.7 [1.6–5.3] 3.6 [1.6-6] 0.91 - Sleep efficiency, % 26 ± 24 26 ± 20 0.92 - Duration of light sleep (stage N1 + N2), min 33[0–97] 100 [14–208] < 0,01 - Duration of deep sleep (stage N3), min 14 [0–51] 34 [0–99] 0.23 - Duration of REM sleep stage, min 0 [0–2] 2 [0–24] 0.02 - Duration of atypical sleep, min 0 [0-158] 0 [0–0] 0.02 Sleep quality, n (%) - Fragmentation index, events/hour 29 ± 18 35 ± 20 0.09 - Absence of deep sleep stage, n (%) 9 (41%) 30 (28%) 0.21 - Absence of REM sleep stage, n (%) 16 (73%) 50 (46%) 0.03 - Atypical sleep, n (%) 9 (41%) 22 (20%) 0.05 EEG reactivity at eyes-open test 0.18 - Normal reactivity, n (%) 10 (53%) 74 (70%) - Pathological wakefulness, n (%) 9 (47%) 32 (30%) Values are given in mean ± standard deviation and median [25–75 percentiles] DISCUSSION In this post-hoc analysis assessing sleep by complete polysomnography in conscious and non-sedated critically ill patients included at different times of the ICU stay, total sleep time and deep sleep remained well-preserved in patients admitted for acute respiratory failure, whereas it was frequently replaced by atypical sleep in patients under mechanical ventilation. By contrast, total sleep time was markedly reduced after extubation. REM sleep was uncommon at any time of the ICU stay and complete disappearance of REM sleep was significantly associated with poor outcomes. Sleep characteristics according to the timing of the ICU stay. To our knowledge, this is the first study comparing sleep characteristics in critically ill patients at different times during their ICU stay. Sleep is deeply altered in ICUs and it is common to observe complete disappearance of the restorative sleep stages of deep sleep and REM sleep, which are sometimes replaced by abnormal sleep called atypical sleep ( 1 – 3 , 5 – 8 ). However, sleep studies in ICUs have mainly explored patients under mechanical ventilation having previously received sedation. Sedation favors sleep disturbances and it has been shown that patients who had received high doses of sedation had reduced total sleep time and that they were more likely to exhibit atypical sleep ( 6 , 14 ). Sleep may also directly be altered by mechanical ventilation itself via patient-ventilator asynchronies or sleep apneas, especially those induced by excessive ventilation ( 4 , 5 , 19 – 21 ). By contrast, few studies have assessed sleep in patients breathing spontaneously either early upon ICU admission or after extubation ( 14 , 22 – 24 ). Among those studies, several have included patients treated with noninvasive ventilation and who had hypercapnic encephalopathy, which may have markedly altered sleep ( 22 , 23 ). Although all patients included in the present study were conscious and free of sedation, main sleep disturbances differed according to the timing of the ICU stay and to the course of acute respiratory failure. If atypical sleep was predominant under mechanical ventilation, it may have been because sedation had been stopped shortly before sleep recording. Atypical sleep was still observed after extubation but in a lesser proportion than under mechanical ventilation, probably because it was more distant from sedation cessation. By contrast, atypical sleep was almost non-existent in patients admitted for acute respiratory failure who had never received sedation. In these patients, total sleep time and deep sleep remained preserved, which was not the case in patients breathing spontaneously after extubation, reinforcing the hypothesis that sleep disturbances are mainly favored by sedation or by sleep deprivation after prolonged ICU length of stay. Nevertheless, the only constant sleep alteration observed, whatever the timing of sleep recordings, was frequent disappearance of REM sleep. REM sleep completely disappeared in half of patients, and could be the most reliable marker to assess sleep quality at any time of the ICU stay. During REM sleep, accessory inspiratory muscles are inhibited, and as a result, the diaphragm remains the only active inspiratory muscle ( 25 , 26 ). Several studies have reported a decreased ventilatory response to hypercapnia and hypoxia during REM sleep leading to hypoxemic episodes ( 12 , 13 ). Consequently, REM sleep is a sleep stage that may precipitate or worsen underlying respiratory failure, and it might be hypothesized that disappearance of REM sleep is a protective mechanism to cope respiratory failure. However, disappearance of REM sleep was associated with poor clinical outcomes and might be more deleterious on brain function than protective on respiratory muscle function. Role of sleep disturbances in ICU outcomes Only a few studies have assessed the role of sleep on the prognosis of critically ill patients ( 6 , 7 , 22 , 27 ).. Two of these studies showed that mechanically ventilated patients with sleep disturbances were more likely to exhibit prolonged weaning and delayed extubation ( 6 , 7 ). In both studies, atypical sleep, but also pathological wakefulness, were particularly frequent and were associated with more prolonged weaning and delayed extubation ( 6 , 7 ). One of these studies showed that respiratory muscle strength was not more altered in patients with atypical sleep, suggesting that sleep disturbances may be the evidence of brain dysfunction that may precipitate respiratory failure. In line with these findings, it has been shown that in healthy subjects sleep deprivation may reduce respiratory endurance by altering cortical respiratory command ( 10 , 11 ). In another prospective study including 52 conscious mechanically ventilated patients, atypical sleep was for the first time shown to be associated with an increased risk of death ( 27 ). All of these studies showing potential deleterious effects of atypical sleep on patient outcomes included only mechanically ventilated patients ( 6 , 7 , 27 ). Atypical sleep seems mainly observed in mechanically ventilated patients and does not contribute to assessment of sleep disturbances in all critically ill patients admitted to ICUs. In our study, only one-third of patients were under mechanical ventilation at time of inclusion whereas the others were breathing spontaneously. This could explain why we did not observe any significant impact of atypical sleep on poor clinical outcomes. By contrast, we showed that disappearance of REM sleep was significantly more frequent in patients with poor clinical outcomes. Even though atypical sleep and disappearance of REM sleep could both be predictors poor clinical outcomes, complete absence of REM sleep is probably easier to detect than atypical sleep, and may be assessed not only in mechanically ventilated patients, but also in all critically ill patients admitted in ICUs. A previous study showed that low REM sleep stage was associated with poor clinical outcomes in patients admitted to ICU for acute hypercapnic respiratory failure and who were breathing spontaneously ( 22 ). Similarly, a previous study showed that low REM sleep stage was associated with poor outcomes in patients admitted to ICU for acute hypercapnic respiratory failure and who were breathing spontaneously. Limitations Poor outcomes included different events according to the timing of sleep exploration. However, each event is well-established as being associated with poor prognosis. Intubation occurs in around 30 to 50% in patients admitted to ICU for acute hypoxemic respiratory failure and is associated with high mortality rates ( 28 ). Reintubation occurs in around 15% of cases after planned extubation, and is associated with an increased risk of death ( 29 – 31 ). Similarly, prolonged weaning, defined as a duration of more than 7 days between the initial spontaneous breathing trial and extubation attempt, is well defined in the literature, and also associated with increased risk of death as compared to more simple weaning ( 18 , 32 , 33 ). In our study, patients in whom these events occurred had significantly higher mortality than the others, confirming that they could be considered as being associated with a poor prognosis. This is obviously not a longitudinal analysis of sleep including several sleep explorations at different times of the ICU stay of the same patient. Even though we included three distinct populations, patients included under mechanical ventilation and those included after extubation had been admitted to ICU in more than 80% of cases for acute respiratory failure. Therefore, one may consider that sleep was explored in a similar population of patients with acute respiratory failure, and that the differences in sleep characteristics were mainly due to the timing of sleep assessment during the ICU stay. Another major limitation is that the study was performed in a single center. Consequently, the dramatically low duration of sleep recorded in the present study may be due to an environment not conducive to sleep in that unit. CONCLUSION In conclusion, complete disappearance of REM sleep was frequently observed in ICUs (50% of patients) and may occur at all times during the ICU stay, as well as in patients breathing spontaneously, after admission or after extubation. Complete disappearance of REM sleep was significantly associated with poor outcomes. Abbreviations REM Rapid Eye Movement EEG Electroencephalogram PSG Polysomnography EMGs Electromyograms EOGs Electro-oculograms Declarations Ethics approval and consent to participate: No applicable Consent for publication: No applicable Availability of data and materials: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests" in this section. Funding: The authors declare no source of funding Authors' contributions: LM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. AWT designed the study. LM and AWT wrote the manuscript. SLP performed statistical analysis. CR, QH and XD analyzed sleep recordings. 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Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Béduneau G, Delétage-Métreau C, Richard JC, Brochard L, Robert R. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. The New England journal of medicine 2015;372:2185–2196. Thille AW, Richard JC, Brochard L. The decision to extubate in the intensive care unit. American journal of respiratory and critical care medicine 2013;187:1294–1302. Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186–192. Frutos-Vivar F, Esteban A, Apezteguia C, González M, Arabi Y, Restrepo MI, Gordo F, Santos C, Alhashemi JA, Pérez F, Peñuelas O, Anzueto A. Outcome of reintubated patients after scheduled extubation. Journal of critical care 2011;26:502–509. Peñuelas O, Frutos-Vivar F, Fernández C, Anzueto A, Epstein SK, Apezteguía C, González M, Nin N, Raymondos K, Tomicic V, Desmery P, Arabi Y, Pelosi P, Kuiper M, Jibaja M, Matamis D, Ferguson ND, Esteban A. Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation. American journal of respiratory and critical care medicine 2011;184:430–437. Pham T, Heunks L, Bellani G, Madotto F, Aragao I, Beduneau G, Goligher EC, Grasselli G, Laake JH, Mancebo J, Peñuelas O, Piquilloud L, Pesenti A, Wunsch H, van Haren F, Brochard L, Laffey JG. Weaning from mechanical ventilation in intensive care units across 50 countries (wean safe): A multicentre, prospective, observational cohort study. The Lancet Respiratory medicine 2023;11:465–476. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Oct, 2024 Read the published version in Critical Care → Version 1 posted Editorial decision: Revision requested 11 Aug, 2024 Reviews received at journal 10 Aug, 2024 Reviews received at journal 06 Aug, 2024 Reviewers agreed at journal 25 Jul, 2024 Reviewers agreed at journal 18 Jul, 2024 Reviewers invited by journal 09 Jul, 2024 Editor assigned by journal 08 Jul, 2024 Submission checks completed at journal 08 Jul, 2024 First submitted to journal 04 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4687249","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":333869137,"identity":"44397b88-498f-4860-b89b-a119b111cbc0","order_by":0,"name":"Laura Marchasson","email":"data:image/png;base64,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","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":true,"prefix":"","firstName":"Laura","middleName":"","lastName":"Marchasson","suffix":""},{"id":333869138,"identity":"f3298157-cb19-427d-babe-fb1c4da8a6d3","order_by":1,"name":"Christophe Rault","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Christophe","middleName":"","lastName":"Rault","suffix":""},{"id":333869139,"identity":"bf7b16cc-cefc-482c-b984-4683cf528fc3","order_by":2,"name":"Sylvain Le Pape","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Sylvain","middleName":"Le","lastName":"Pape","suffix":""},{"id":333869140,"identity":"233cda29-0902-4569-8333-9f3d512b4997","order_by":3,"name":"François Arrivé","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"François","middleName":"","lastName":"Arrivé","suffix":""},{"id":333869141,"identity":"2aa2d6f0-d915-435a-8d08-1418ea655e4a","order_by":4,"name":"Rémi Coudroy","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Rémi","middleName":"","lastName":"Coudroy","suffix":""},{"id":333869142,"identity":"f6879d15-1122-4206-aa83-d2484b8a6898","order_by":5,"name":"Jean-Pierre Frat","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Jean-Pierre","middleName":"","lastName":"Frat","suffix":""},{"id":333869143,"identity":"c2abfbc8-3c58-47c2-b22c-d40980000627","order_by":6,"name":"Vanessa Bironneau","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Vanessa","middleName":"","lastName":"Bironneau","suffix":""},{"id":333869144,"identity":"51dd2fc8-7258-40e3-9efc-a899c628d212","order_by":7,"name":"Etienne-Marie Jutant","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Etienne-Marie","middleName":"","lastName":"Jutant","suffix":""},{"id":333869145,"identity":"56bf09e3-7406-475d-92a2-a2bf0972e5c6","order_by":8,"name":"Quentin Heraud","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Quentin","middleName":"","lastName":"Heraud","suffix":""},{"id":333869146,"identity":"7b17ca79-ab47-44d7-af4b-8fa5a0a53682","order_by":9,"name":"Xavier Drouot","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Xavier","middleName":"","lastName":"Drouot","suffix":""},{"id":333869147,"identity":"7d1f7902-5895-4ccb-8d23-40be5f681a26","order_by":10,"name":"Arnaud W Thille","email":"","orcid":"","institution":"INSERM CIC 1402, University of Poitiers","correspondingAuthor":false,"prefix":"","firstName":"Arnaud","middleName":"W","lastName":"Thille","suffix":""}],"badges":[],"createdAt":"2024-07-04 14:28:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4687249/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4687249/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13054-024-05118-4","type":"published","date":"2024-10-09T15:57:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62138846,"identity":"ceabc13d-e757-4539-a2df-acea548fde44","added_by":"auto","created_at":"2024-08-09 16:49:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34379,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the patients. Poor outcomes occurred in 22 out of the 131 patients (17%), including patients admitted for acute respiratory failure who needed intubation, patients under mechanical ventilation with prolonged weaning (\u0026gt; 7 days), and extubated patients who needed reintubation.\u003c/p\u003e","description":"","filename":"OnlineFig1FlowChart.png","url":"https://assets-eu.researchsquare.com/files/rs-4687249/v1/1c838bfd6751b6195236fac8.png"},{"id":62138848,"identity":"ebc30e53-dc70-49aa-a23a-9a89d8a1a476","added_by":"auto","created_at":"2024-08-09 16:49:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50376,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of sleep stages according to the timings of polysomnography recordings. From the top to the bottom, theoretical distribution of sleep stages in healthy volunteers with normal sleep, patients with acute respiratory failure explored upon ICU admission while breathing spontaneously, patients under mechanical ventilation with weaning difficulties, and patients explored after extubation while breathing spontaneously. TST= Total Sleep Time.\u003c/p\u003e","description":"","filename":"OnlineFIg2groups.png","url":"https://assets-eu.researchsquare.com/files/rs-4687249/v1/59c508ddbadfb872c8879d72.png"},{"id":62138847,"identity":"694a49a2-2298-43ce-9054-9bcd5d68e4f1","added_by":"auto","created_at":"2024-08-09 16:49:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":40424,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of sleep stages according to the clinical outcomes of included patients. Poor outcomes included the need for intubation in patients admitted for acute respiratory failure while breathing spontaneously, prolonged weaning defined (\u0026gt; 7 days) in patients under mechanical ventilation, and the need for reintubation in patients who were included after extubation while breathing spontaneously. TST= Total Sleep Time.\u003c/p\u003e","description":"","filename":"OnlineFigGoodpooroutcomes.png","url":"https://assets-eu.researchsquare.com/files/rs-4687249/v1/450d10de568ecc82b6734196.png"},{"id":66597120,"identity":"d572a7ce-d724-4c2b-8001-28506b0d1ce1","added_by":"auto","created_at":"2024-10-14 16:07:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1030605,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4687249/v1/6c435db4-4bfa-431f-88bf-559df4e3f2b8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of sleep disturbances on outcomes in intensive care units","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eSleep is an essential physiological periodic activity permitting physical and neurobehavioral restoration, which can be severely impaired during an ICU stay, especially in mechanically ventilated patients (\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In critically ill patients, sleep is characterized by a high proportion of light sleep (mainly stages N1 and N2), fragmented by numerous awakenings, and with loss of the circadian rhythm, with sleep occurring as well during the daytime as during the night (\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Deep sleep (sleep stage N3) and rapid eye movement (REM) sleep, which are two essential stages of sleep, may completely disappear in the ICU, even in patients conscious and not under sedation. In some patients, normal sleep architecture may completely disappear and be replaced by electroencephalogram (EEG) aspects suggesting atypical sleep recordings, characterized by the absence of stage-2 markers (absence of K complexes and sleep spindles) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Many factors may promote sleep disturbances, including underlying disease severity, mechanical ventilation, use of sedation, anxiety, but also aggressive environments including light exposure, noise, pain or factors related to nursing (\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Two studies have shown that sleep disturbances may impair ability to breathe without the ventilator in patients under mechanical ventilation, suggesting that brain dysfunction influences the ability to breathe spontaneously (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In line with these findings, it has been shown in healthy subjects that sleep deprivation may alter respiratory endurance by altering cortical respiratory command (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), and may reduce response to hypoxia and hypercapnia (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Consequently, sleep disturbances observed in ICU-patients such as atypical sleep or absence of restorative sleep such as deep sleep and REM sleep, may impair respiratory function and precipitate respiratory failure.\u003c/p\u003e \u003cp\u003eFew studies have assessed the influence of sleep disturbances on outcomes in critically ill patients. Therefore, we aimed at assessing sleep quantity and quality, and the role of sleep disturbances on outcomes of critically ill patients at different times during their ICU stay, \u003cem\u003ei.e.\u003c/em\u003e at the beginning of the ICU stay in patients who are breathing spontaneously, during the weaning period in patients still under mechanical ventilation, or in patients who have just been extubated.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patients\u003c/h2\u003e \u003cp\u003eThis is a post-hoc analysis pooling 3 prospective physiological studies assessing sleep by complete polysomnography in critically ill patients admitted to the University Hospital of Poitiers (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). All studies were approved by the independent ethics committee of Poitiers (CPP Ouest III). Patients and/or their next of kin were informed and gave their written consent before being included in studies.\u003c/p\u003e \u003cp\u003eSleep was assessed as early as possible at different times during the ICU stay: 1) at the beginning of the ICU stay in patients breathing spontaneously just after ICU admission for acute hypoxemic respiratory failure (defined as a respiratory rate above 25 breaths per minute or clinical signs suggesting respiratory distress and PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e below 300 mmHg while receiving high-flow nasal oxygen therapy) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e); 2) in patients still under mechanical ventilation and with difficult weaning (\u003cem\u003ei.e.\u003c/em\u003e after failure of at least one spontaneous breathing trial) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e); 3) in patients breathing spontaneously just after being extubated (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAll patients were awake and conscious on the day of polysomnography. Patients with altered consciousness, central nervous system or psychiatric disorders, or those receiving sedation or neuroleptic medication were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSleep assessment and EEG reactivity\u003c/h2\u003e \u003cp\u003eSleep was evaluated by complete polysomnography (PSG) that started in the afternoon and was continuously performed until the next morning. A trained investigator positioned the electrodes, which consisted of six EEG channels (F3-A2, F4-A1, C4-A1, C3-A2, O2-A1 and O1-A2) referenced to the contralateral mastoid according to the international 10\u0026ndash;20 system for electrode placement (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Two electromyograms (EMGs) (chin) and two electro-oculograms (EOGs) were recorded to score REM and non-REM sleep. Sleep recordings were manually scored by a neurologist blinded to the patient\u0026rsquo;s status (XD). Duration of REM sleep and non-REM sleep stages including light sleep (sleep stages N1 and N2) and deep sleep (sleep stage N3) was assessed using the standard 2007 criteria of the American Academy of Sleep Medicine (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The presence of atypical sleep was detected according to a modified classification (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Indeed, due to the absence of stage 2 markers (absence of K complexes and sleep spindles), atypical sleep cannot be classified according to the standard criteria. To be able to differentiate atypical sleep from pathological wakefulness characterized by excessive slow wave activity, an eyes-open test was systematically performed by the neurophysiologist before PSG in order to assess EEG frequency in the wakefulness state. EMG and EOG were more active during wakefulness than during sleep, while decreased EMG was required as evidence of REM sleep. EEG reactivity at eyes-open test was assessed during wakefulness by the neurologist at the beginning of PSG according to the EEG rhythm on an O2-A1 electrode as previously described (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Immediate disappearance or frank attenuation (\u0026gt;\u0026thinsp;90%) of the background EEG rhythm at eyes-open test, which was replaced by fast low-amplitude frequencies and maintained as long as the eyes were open, was considered as normal EEG reactivity. Moderate and brief attenuation (30\u0026ndash;50% decrease in amplitude) was considered as altered EEG reactivity. Undetectable or a very small difference between EEG patterns with the eyes closed and the eyes open was considered as no EEG reactivity.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSleep quantity and quality\u003c/h2\u003e \u003cp\u003eSleep quantity included measurement of total sleep time, duration of light, deep and REM sleep stages in minutes or hours, and sleep efficiency as the ratio of total sleep time divided by the total recording time in percentage. Sleep quality was assessed by measurement of atypical sleep, and deep sleep or REM sleep (the two most restorative sleep stages). Sleep fragmentation was defined as the number of arousals and awakenings per hour of sleep.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary endpoint was sleep quality according to the clinical outcomes in ICUs. Patients were considered to have poor clinical outcomes according to time of inclusion in the study. Poor patient clinical outcomes included: 1) need for intubation in patients admitted for acute respiratory failure while breathing spontaneously, 2) prolonged weaning defined according to the weaning classification as a duration of more than 7 days between the initial spontaneous breathing trial and extubation (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), and 3) need for reintubation in patients who were included after extubation while breathing spontaneously.\u003c/p\u003e \u003cp\u003eIntubation and reintubation were decided according to pre-specified criteria including the following: cardiac or respiratory arrest, hemodynamic failure requiring vasopressors, altered consciousness defined as a Glasgow coma scale below 12, or severe respiratory failure defined by at least two criteria among the following; respiratory rate above 35 breaths per minute, clinical signs suggesting respiratory distress, hypoxemia defined as PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e below 100 mm Hg or FIO\u003csub\u003e2\u003c/sub\u003e at least 80% to maintain SpO\u003csub\u003e2\u003c/sub\u003e at least 92%, or respiratory acidosis defined as pH below 7.25 and PaCO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026gt;\u0026thinsp;45 mmHg.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median and interquartile range [IQR, 25th -75th percentiles] according to their distribution, and qualitative variables were expressed as number and percentage. Patient and sleep characteristics were compared according to the timing of inclusion in the ICU between the three groups of patients using ANOVA or Kruskal-Wallis as appropriate for continuous variables, and using the χ2 test for categorical variables.\u003c/p\u003e \u003cp\u003eComparison between patients with poor clinical outcomes and the others were compared using a Wilcoxon rank-sum test for continuous variables, and the Fisher exact test for categorical variables. A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0,05 was considered as statistically significant. All analyses were performed using the R software version 4.2.1 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.R-project.org\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.R-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e).\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOne hundred and thirty-one patients had complete polysomnography in the ICU, including 34 patients breathing spontaneously with acute respiratory failure (26%), 45 mechanically ventilated patients with weaning difficulties (34%), and 52 patients breathing spontaneously after extubation (40%) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e The proportion of patients considered as having poor outcomes in ICUs was similar between the three groups: 5 patients (15%) among the 34 patients included with acute respiratory failure required intubation, 9 patients among the 45 patients included under mechanical ventilation had prolonged weaning (20%), and 8 patients (15%) among the 52 patients included after extubation required reintubation (p\u0026thinsp;=\u0026thinsp;0.77). Mortality in ICU was significantly higher in patients considered as having with poor outcomes than the others: 32% (7 out of 22 patients) vs. 3% (3 out of 109 patients), p\u0026thinsp;\u0026lt;\u0026thinsp;0.01.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison of sleep characteristics between the different timings of sleep assessment in the ICU.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eSleep characteristics significantly differed according to the timing of polysomnography in the ICU \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of patients and sleep characteristics between the different times of inclusion.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcute respiratory failure (N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWeaning failure\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;45)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAfter extubation\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePatient characteristics\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Age, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Male sex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Body mass index, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Underlying cardiac disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Underlying respiratory disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- SAPS II at admission, points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- SOFA at inclusion, points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSleep quantity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Total sleep time, hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.2 [2.9\u0026ndash;6.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6 [2.1\u0026ndash;7.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.4 [1.1\u0026ndash;4.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Sleep efficiency, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u0026thinsp;\u0026plusmn;\u0026thinsp;26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of light sleep (stage N1), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [6\u0026ndash;28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 [0\u0026ndash;32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 [0\u0026ndash;28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of light sleep (stage N2), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e146 [60\u0026ndash;227]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 [0-151]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 [5\u0026ndash;79]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of deep sleep (stage N3), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 [34\u0026ndash;127]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 [0\u0026ndash;67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 [0\u0026ndash;66]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of REM sleep stage, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 [0\u0026ndash;28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 [0\u0026ndash;33]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 [0\u0026ndash;8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of atypical sleep, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 [0\u0026ndash;0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 [0-145]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 [0\u0026ndash;0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSleep quality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Fragmentation index, events/hour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Absence of deep sleep stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Absence of REM sleep stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Atypical sleep, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEEG reactivity at eyes-open test\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Normal reactivity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (88%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Pathological wakefulness, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Poor outcomes, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Mortality, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eValues are given in mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and median [25\u0026ndash;75 percentiles]\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients admitted for acute respiratory failure had relatively well-preserved total sleep time (4.2 hours [IQR 2.9\u0026ndash;6.8] in median) and deep sleep (31% of total sleep time). REM sleep was markedly short and represented only 4.9% of total sleep time. Complete disappearance of REM sleep was observed in 38% of patients (13/34).\u003c/p\u003e \u003cp\u003ePatients included under mechanical ventilation with weaning difficulties had relatively well-preserved total sleep time (4.6 hours [IQR 2.1\u0026ndash;7.3] in median). Deep sleep and REM sleep were markedly short and represented only 14% and 6% of total sleep time, respectively. Complete disappearance of REM sleep was observed in 44% of patients (20/45).\u003c/p\u003e \u003cp\u003ePatients included after extubation had particularly short total sleep time (2.4 hours [IQR 1.1\u0026ndash;4.1] in median). Deep sleep was relatively well preserved (24% of total sleep time) whereas REM sleep was markedly short (3% of total sleep time). Complete disappearance of REM sleep was observed in 63% of patients (33/52).\u003c/p\u003e \u003cp\u003eBy comparing the three groups, patients included after extubation were those with the shortest total sleep time and the shortest REM sleep duration (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), whereas patients included under mechanical ventilation were those with the most impaired deep sleep (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. In patients under mechanical ventilation, deep sleep was mainly replaced by atypical sleep. Atypical sleep occurred in 44% of patients under mechanical ventilation and occurred in only 19% of patients after extubation and in only one patient admitted for acute respiratory failure (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 between the 3 groups).\u003c/p\u003e \u003cp\u003eREM sleep was uncommon at any time of the ICU stay, and was completely abolished in 50% of patients (66 out of 131 patients). Complete disappearance of REM sleep occurred in 63% of patients after extubation, whereas it occurred in 44% of patients under mechanical ventilation, and 38% of patients admitted for acute respiratory failure (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 between the 3 groups).\u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison of sleep characteristics between patients with poor outcomes and the others.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCharacteristics of the patients and severity scores (SAPS II at inclusion and SOFA at inclusion) did not significantly differ between patients with subsequent poor outcomes and those with good outcomes.\u003c/p\u003e \u003cp\u003eWhereas sleep quantity indicated by total sleep time did not differ regardless of the outcomes, sleep quality was significantly more altered in patients with poor outcomes than in the others \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Patients with poor outcomes had shorter duration of light sleep stage and shorter duration of REM sleep stage than those with good outcomes. Whereas duration of deep sleep did not differ between groups, patients with poor outcomes had longer duration of atypical sleep than the others. Patients with complete disappearance of REM sleep were more likely to have poor outcomes than those with persistent REM sleep (24% vs. 9%, p\u0026thinsp;=\u0026thinsp;0.03) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. In-ICU mortality did not significantly differ between patients with complete disappearance of REM sleep and those with persistent REM sleep (12% vs. 3%, respectively, p\u0026thinsp;=\u0026thinsp;0.11)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics, sleep and reactivity EEG comparison between patients who developed poor outcomes (intubation. prolonged weaning. or reintubation) and the others.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePoor outcomes\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGood outcomes\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;109)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePatient characteristics\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Age, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Male sex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Body mass index, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Underlying cardiac disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Underlying respiratory disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u0026nbsp;(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- SAPS II at admission, points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- SOFA at inclusion, points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSleep quantity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Total sleep time, hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7 [1.6\u0026ndash;5.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.6 [1.6-6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Sleep efficiency, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of light sleep (stage N1\u0026thinsp;+\u0026thinsp;N2), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33[0\u0026ndash;97]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 [14\u0026ndash;208]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0,01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of deep sleep (stage N3), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 [0\u0026ndash;51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 [0\u0026ndash;99]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of REM sleep stage, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 [0\u0026ndash;2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 [0\u0026ndash;24]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Duration of atypical sleep, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 [0-158]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 [0\u0026ndash;0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSleep quality, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Fragmentation index, events/hour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Absence of deep sleep stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Absence of REM sleep stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Atypical sleep, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEEG reactivity at eyes-open test\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Normal reactivity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Pathological wakefulness, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eValues are given in mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and median [25\u0026ndash;75 percentiles]\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this post-hoc analysis assessing sleep by complete polysomnography in conscious and non-sedated critically ill patients included at different times of the ICU stay, total sleep time and deep sleep remained well-preserved in patients admitted for acute respiratory failure, whereas it was frequently replaced by atypical sleep in patients under mechanical ventilation. By contrast, total sleep time was markedly reduced after extubation. REM sleep was uncommon at any time of the ICU stay and complete disappearance of REM sleep was significantly associated with poor outcomes.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSleep characteristics according to the timing of the ICU stay.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTo our knowledge, this is the first study comparing sleep characteristics in critically ill patients at different times during their ICU stay. Sleep is deeply altered in ICUs and it is common to observe complete disappearance of the restorative sleep stages of deep sleep and REM sleep, which are sometimes replaced by abnormal sleep called atypical sleep (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, sleep studies in ICUs have mainly explored patients under mechanical ventilation having previously received sedation. Sedation favors sleep disturbances and it has been shown that patients who had received high doses of sedation had reduced total sleep time and that they were more likely to exhibit atypical sleep (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Sleep may also directly be altered by mechanical ventilation itself via patient-ventilator asynchronies or sleep apneas, especially those induced by excessive ventilation (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). By contrast, few studies have assessed sleep in patients breathing spontaneously either early upon ICU admission or after extubation (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Among those studies, several have included patients treated with noninvasive ventilation and who had hypercapnic encephalopathy, which may have markedly altered sleep (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Although all patients included in the present study were conscious and free of sedation, main sleep disturbances differed according to the timing of the ICU stay and to the course of acute respiratory failure. If atypical sleep was predominant under mechanical ventilation, it may have been because sedation had been stopped shortly before sleep recording. Atypical sleep was still observed after extubation but in a lesser proportion than under mechanical ventilation, probably because it was more distant from sedation cessation. By contrast, atypical sleep was almost non-existent in patients admitted for acute respiratory failure who had never received sedation. In these patients, total sleep time and deep sleep remained preserved, which was not the case in patients breathing spontaneously after extubation, reinforcing the hypothesis that sleep disturbances are mainly favored by sedation or by sleep deprivation after prolonged ICU length of stay. Nevertheless, the only constant sleep alteration observed, whatever the timing of sleep recordings, was frequent disappearance of REM sleep. REM sleep completely disappeared in half of patients, and could be the most reliable marker to assess sleep quality at any time of the ICU stay. During REM sleep, accessory inspiratory muscles are inhibited, and as a result, the diaphragm remains the only active inspiratory muscle (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Several studies have reported a decreased ventilatory response to hypercapnia and hypoxia during REM sleep leading to hypoxemic episodes (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Consequently, REM sleep is a sleep stage that may precipitate or worsen underlying respiratory failure, and it might be hypothesized that disappearance of REM sleep is a protective mechanism to cope respiratory failure. However, disappearance of REM sleep was associated with poor clinical outcomes and might be more deleterious on brain function than protective on respiratory muscle function.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eRole of sleep disturbances in ICU outcomes\u003c/h2\u003e \u003cp\u003eOnly a few studies have assessed the role of sleep on the prognosis of critically ill patients (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).. Two of these studies showed that mechanically ventilated patients with sleep disturbances were more likely to exhibit prolonged weaning and delayed extubation (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In both studies, atypical sleep, but also pathological wakefulness, were particularly frequent and were associated with more prolonged weaning and delayed extubation (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). One of these studies showed that respiratory muscle strength was not more altered in patients with atypical sleep, suggesting that sleep disturbances may be the evidence of brain dysfunction that may precipitate respiratory failure. In line with these findings, it has been shown that in healthy subjects sleep deprivation may reduce respiratory endurance by altering cortical respiratory command (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In another prospective study including 52 conscious mechanically ventilated patients, atypical sleep was for the first time shown to be associated with an increased risk of death (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). All of these studies showing potential deleterious effects of atypical sleep on patient outcomes included only mechanically ventilated patients (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Atypical sleep seems mainly observed in mechanically ventilated patients and does not contribute to assessment of sleep disturbances in all critically ill patients admitted to ICUs. In our study, only one-third of patients were under mechanical ventilation at time of inclusion whereas the others were breathing spontaneously. This could explain why we did not observe any significant impact of atypical sleep on poor clinical outcomes. By contrast, we showed that disappearance of REM sleep was significantly more frequent in patients with poor clinical outcomes. Even though atypical sleep and disappearance of REM sleep could both be predictors poor clinical outcomes, complete absence of REM sleep is probably easier to detect than atypical sleep, and may be assessed not only in mechanically ventilated patients, but also in all critically ill patients admitted in ICUs. A previous study showed that low REM sleep stage was associated with poor clinical outcomes in patients admitted to ICU for acute hypercapnic respiratory failure and who were breathing spontaneously (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Similarly, a previous study showed that low REM sleep stage was associated with poor outcomes in patients admitted to ICU for acute hypercapnic respiratory failure and who were breathing spontaneously.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003ePoor outcomes included different events according to the timing of sleep exploration. However, each event is well-established as being associated with poor prognosis. Intubation occurs in around 30 to 50% in patients admitted to ICU for acute hypoxemic respiratory failure and is associated with high mortality rates (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Reintubation occurs in around 15% of cases after planned extubation, and is associated with an increased risk of death (\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Similarly, prolonged weaning, defined as a duration of more than 7 days between the initial spontaneous breathing trial and extubation attempt, is well defined in the literature, and also associated with increased risk of death as compared to more simple weaning (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). In our study, patients in whom these events occurred had significantly higher mortality than the others, confirming that they could be considered as being associated with a poor prognosis.\u003c/p\u003e \u003cp\u003eThis is obviously not a longitudinal analysis of sleep including several sleep explorations at different times of the ICU stay of the same patient. Even though we included three distinct populations, patients included under mechanical ventilation and those included after extubation had been admitted to ICU in more than 80% of cases for acute respiratory failure. Therefore, one may consider that sleep was explored in a similar population of patients with acute respiratory failure, and that the differences in sleep characteristics were mainly due to the timing of sleep assessment during the ICU stay.\u003c/p\u003e \u003cp\u003eAnother major limitation is that the study was performed in a single center. Consequently, the dramatically low duration of sleep recorded in the present study may be due to an environment not conducive to sleep in that unit.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn conclusion, complete disappearance of REM sleep was frequently observed in ICUs (50% of patients) and may occur at all times during the ICU stay, as well as in patients breathing spontaneously, after admission or after extubation. Complete disappearance of REM sleep was significantly associated with poor outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eREM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRapid Eye Movement\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectroencephalogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePSG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolysomnography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMGs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectromyograms\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEOGs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectro-oculograms\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch4\u003eEthics approval and consent to participate: \u0026nbsp;No applicable\u0026nbsp;\u003c/h4\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNo applicable\u003c/p\u003e\n\u003ch4\u003eAvailability of data and materials: \u0026nbsp;The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/h4\u003e\n\u003ch4\u003eCompeting interests:\u0026nbsp;The authors declare that they have no competing interests\u0026quot; in this section.\u003c/h4\u003e\n\u003ch4\u003eFunding:\u0026nbsp;The authors declare no source of funding\u003c/h4\u003e\n\u003ch4\u003eAuthors\u0026apos; contributions:\u003c/h4\u003e\n\u003cp\u003eLM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. AWT designed the study. LM and AWT wrote the manuscript. SLP performed statistical analysis. CR, QH and XD analyzed sleep recordings.\u0026nbsp;All authors (LM, CR, SLP, FA, RC, JPF, VB, EMJ, QH, XD, AWT)\u0026nbsp;contributed to drafting of the work, revising it critically for important intellectual content and approved the final version of the manuscript. All authors give their agreement to be accountable for all aspects of the work, and ensure the accuracy and integrity of any part of the work.\u003c/p\u003e\n\u003ch4\u003eAcknowledgements: Not applicable\u0026nbsp;\u003c/h4\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCooper AB, Thornley KS, Young GB, Slutsky AS, Stewart TE, Hanly PJ. Sleep in critically ill patients requiring mechanical ventilation. Chest 2000;117:809\u0026ndash;818.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreedman NS, Gazendam J, Levan L, Pack AI, Schwab RJ. Abnormal sleep/wake cycles and the effect of environmental noise on sleep disruption in the intensive care unit. American journal of respiratory and critical care medicine 2001;163:451\u0026ndash;457.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGabor JY, Cooper AB, Crombach SA, Lee B, Kadikar N, Bettger HE, Hanly PJ. Contribution of the intensive care unit environment to sleep disruption in mechanically ventilated patients and healthy subjects. American journal of respiratory and critical care medicine 2003;167:708\u0026ndash;715.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParthasarathy S, Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. American journal of respiratory and critical care medicine 2002;166:1423\u0026ndash;1429.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCabello B, Thille AW, Drouot X, Galia F, Mancebo J, d'Ortho MP, Brochard L. Sleep quality in mechanically ventilated patients: Comparison of three ventilatory modes. Critical care medicine 2008;36:1749\u0026ndash;1755.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThille AW, Reynaud F, Marie D, Barrau S, Rousseau L, Rault C, Diaz V, Meurice JC, Coudroy R, Frat JP, Robert R, Drouot X. Impact of sleep alterations on weaning duration in mechanically ventilated patients: A prospective study. The European respiratory journal 2018;51:1702465.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDres M, Younes M, Rittayamai N, Kendzerska T, Telias I, Grieco DL, Pham T, Junhasavasdikul D, Chau E, Mehta S, Wilcox ME, Leung R, Drouot X, Brochard L. Sleep and pathological wakefulness at the time of liberation from mechanical ventilation (sleewe). A prospective multicenter physiological study. 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The American review of respiratory disease 1983;128:984\u0026ndash;986.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRault C, Sangar\u0026eacute; A, Diaz V, Ragot S, Frat JP, Raux M, Similowski T, Robert R, Thille AW, Drouot X. Impact of sleep deprivation on respiratory motor output and endurance. A physiological study. American journal of respiratory and critical care medicine 2020;201:976\u0026ndash;983.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDouglas NJ, White DP, Weil JV, Pickett CK, Martin RJ, Hudgel DW, Zwillich CW. Hypoxic ventilatory response decreases during sleep in normal men. The American review of respiratory disease 1982;125:286\u0026ndash;289.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDouglas NJ, White DP, Weil JV, Pickett CK, Zwillich CW. Hypercapnic ventilatory response in sleeping adults. The American review of respiratory disease 1982;126:758\u0026ndash;762.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThille AW, Barrau S, Beuvon C, Marie D, Reynaud F, Bardin J, P\u0026eacute;pin-Lehalleur A, Bironneau V, Meurice JC, Coudroy R, Frat JP, Robert R, Rault C, Drouot X. Role of sleep on respiratory failure after extubation in the icu. Annals of intensive care 2021;11:71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThille AW, Marie D, Reynaud F, Barrau S, Beuvon C, Bironneau V, Jutant EM, Coudroy R, Frat JP, Rault C, Drouot X. Sleep assessment in critically ill patients with acute hypoxemic respiratory failure. Respiratory care 2023;68:1417\u0026ndash;1425.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRechtschaffen A, Kales A. A manual for standardized terminology, techniques and scoring system for sleep stages of human subjects. Washington, DC: Public Health Service, US Government Printing Office; 1968. p. 1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIber C. The aasm manual for the scoring of sleep and associated events: Rules, terminology and technical specifications. \u003cem\u003eAmerican Academy of Sleep Medicine\u003c/em\u003e 2007; Westchester, IL.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeduneau G, Pham T, Schortgen F, Piquilloud L, Zogheib E, Jonas M, Grelon F, Runge I, Nicolas T, Grange S, Barberet G, Guitard PG, Frat JP, Constan A, Chretien JM, Mancebo J, Mercat A, Richard JM, Brochard L, Group WS, the RNdd. Epidemiology of weaning outcome according to a new definition. The wind study. American journal of respiratory and critical care medicine 2017;195:772\u0026ndash;783.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBosma K, Ferreyra G, Ambrogio C, Pasero D, Mirabella L, Braghiroli A, Appendini L, Mascia L, Ranieri VM. Patient-ventilator interaction and sleep in mechanically ventilated patients: Pressure support versus proportional assist ventilation. Critical care medicine 2007;35:1048\u0026ndash;1054.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToublanc B, Rose D, Glerant JC, Francois G, Mayeux I, Rodenstein D, Jounieaux V. Assist-control ventilation vs. Low levels of pressure support ventilation on sleep quality in intubated icu patients. Intensive care medicine 2007;33:1148\u0026ndash;1154.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThille AW, Cabello B, Galia F, Lyazidi A, Brochard L. Reduction of patient-ventilator asynchrony by reducing tidal volume during pressure-support ventilation. Intensive care medicine 2008;34:1477\u0026ndash;1486.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoche Campo F, Drouot X, Thille AW, Galia F, Cabello B, d'Ortho MP, Brochard L. Poor sleep quality is associated with late noninvasive ventilation failure in patients with acute hypercapnic respiratory failure. Critical care medicine 2010;38:477\u0026ndash;485.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCordoba-Izquierdo A, Drouot X, Thille AW, Galia F, Roche-Campo F, Schortgen F, Prats-Soro E, Brochard L. Sleep in hypercapnic critical care patients under noninvasive ventilation: Conventional versus dedicated ventilators. Critical care medicine 2013;41:60\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRomagnoli S, Villa G, Fontanarosa L, Tofani L, Pinelli F, De Gaudio AR, Ricci Z. Sleep duration and architecture in non-intubated intensive care unit patients: An observational study. Sleep medicine 2020;70:79\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson MW, Remmers JE. Accessory muscle activity during sleep in chronic obstructive pulmonary disease. Journal of applied physiology: respiratory, environmental and exercise physiology 1984;57:1011\u0026ndash;1017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStradling JR, Kozar LF, Dark J, Kirby T, Andrey SM, Phillipson EA. Effect of acute diaphragm paralysis on ventilation in awake and sleeping dogs. The American review of respiratory disease 1987;136:633\u0026ndash;637.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoyko Y, Toft P, \u0026Oslash;rding H, Lauridsen JT, Nikolic M, Jennum P. Atypical sleep in critically ill patients on mechanical ventilation is associated with increased mortality. Sleep \u0026amp; breathing\u0026thinsp;=\u0026thinsp;Schlaf \u0026amp; Atmung 2019;23:379\u0026ndash;388.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, B\u0026eacute;duneau G, Del\u0026eacute;tage-M\u0026eacute;treau C, Richard JC, Brochard L, Robert R. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. The New England journal of medicine 2015;372:2185\u0026ndash;2196.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThille AW, Richard JC, Brochard L. The decision to extubate in the intensive care unit. American journal of respiratory and critical care medicine 2013;187:1294\u0026ndash;1302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEpstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186\u0026ndash;192.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrutos-Vivar F, Esteban A, Apezteguia C, Gonz\u0026aacute;lez M, Arabi Y, Restrepo MI, Gordo F, Santos C, Alhashemi JA, P\u0026eacute;rez F, Pe\u0026ntilde;uelas O, Anzueto A. Outcome of reintubated patients after scheduled extubation. Journal of critical care 2011;26:502\u0026ndash;509.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePe\u0026ntilde;uelas O, Frutos-Vivar F, Fern\u0026aacute;ndez C, Anzueto A, Epstein SK, Apeztegu\u0026iacute;a C, Gonz\u0026aacute;lez M, Nin N, Raymondos K, Tomicic V, Desmery P, Arabi Y, Pelosi P, Kuiper M, Jibaja M, Matamis D, Ferguson ND, Esteban A. Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation. American journal of respiratory and critical care medicine 2011;184:430\u0026ndash;437.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePham T, Heunks L, Bellani G, Madotto F, Aragao I, Beduneau G, Goligher EC, Grasselli G, Laake JH, Mancebo J, Pe\u0026ntilde;uelas O, Piquilloud L, Pesenti A, Wunsch H, van Haren F, Brochard L, Laffey JG. Weaning from mechanical ventilation in intensive care units across 50 countries (wean safe): A multicentre, prospective, observational cohort study. The Lancet Respiratory medicine 2023;11:465\u0026ndash;476.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cric","sideBox":"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)","snPcode":"13054","submissionUrl":"https://submission.nature.com/new-submission/13054/3","title":"Critical Care","twitterHandle":"@Crit_Care","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sleep, Rapid Eye Movement sleep, Polysomnography, Intensive care unit, Ventilator weaning, Endotracheal intubation, Airway Extubation","lastPublishedDoi":"10.21203/rs.3.rs-4687249/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4687249/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSleep deprivation is common in ICUs and may alter respiratory performance. Few studies have assessed the role of sleep disturbances on outcomes in critically ill patients.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eWe hypothesized that sleep disturbances may be associated with poor outcomes in ICUs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePost-hoc analysis pooling 3 studies assessing sleep by complete polysomnography in 131 conscious and non-sedated patients included at different times of their ICU stay. Sleep was assessed early in patients admitted for acute respiratory failure while breathing spontaneously (n\u0026thinsp;=\u0026thinsp;34), or under mechanical ventilation in patients with weaning difficulties (n\u0026thinsp;=\u0026thinsp;45), or immediately after extubation (n\u0026thinsp;=\u0026thinsp;52). Patients admitted for acute respiratory failure who required intubation, those under mechanical ventilation who had prolonged weaning, and those who required reintubation after extubation were considered as having poor clinical outcomes. Durations of deep sleep, rapid eye movement (REM) sleep, and atypical sleep were compared according to the timing of polysomnography and the clinical outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWhile deep sleep remained preserved in patients admitted for acute respiratory failure whereas it was markedly reduced under mechanical ventilation and after extubation (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Atypical sleep was significantly more frequent in patients under mechanical ventilation than in those breathing spontaneously (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). REM sleep was uncommon at any time of their ICU stay. Patients with complete disappearance of REM sleep (50% of patients) were more likely to have poor clinical outcomes than those with persistent REM sleep (24% vs. 9%, p\u0026thinsp;=\u0026thinsp;0.03).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eComplete disappearance of REM sleep was significantly associated with poor clinical outcomes in critically ill patients.\u003c/p\u003e","manuscriptTitle":"Impact of sleep disturbances on outcomes in intensive care units","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-09 16:49:16","doi":"10.21203/rs.3.rs-4687249/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-11T07:58:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-10T06:21:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-06T21:40:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"214795479072005897357230708345845135290","date":"2024-07-25T16:53:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"312830131352500884427884869974826777760","date":"2024-07-18T19:47:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-10T00:15:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-08T05:46:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-08T05:45:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Critical Care","date":"2024-07-04T14:27:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cric","sideBox":"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)","snPcode":"13054","submissionUrl":"https://submission.nature.com/new-submission/13054/3","title":"Critical Care","twitterHandle":"@Crit_Care","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"85437c55-9318-4665-bfbf-fb79be5c715b","owner":[],"postedDate":"August 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-14T16:01:06+00:00","versionOfRecord":{"articleIdentity":"rs-4687249","link":"https://doi.org/10.1186/s13054-024-05118-4","journal":{"identity":"critical-care","isVorOnly":false,"title":"Critical Care"},"publishedOn":"2024-10-09 15:57:28","publishedOnDateReadable":"October 9th, 2024"},"versionCreatedAt":"2024-08-09 16:49:16","video":"","vorDoi":"10.1186/s13054-024-05118-4","vorDoiUrl":"https://doi.org/10.1186/s13054-024-05118-4","workflowStages":[]},"version":"v1","identity":"rs-4687249","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4687249","identity":"rs-4687249","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}