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Objective To examine patient-ventilator asynchrony and sleep quality in non-sedated critically ill patients ventilated with proportional assist ventilation with load adjustable gain factors (PAV+) and pressure support (PSV). Methods This was a randomized crossover physiological study conducted in an adult ICU at a tertiary hospital. Patients who exhibited patient-ventilator asynchrony on PSV were selected. Polysomnography was performed in these patients over 24 h, during which respiratory variables were continuously recorded. During the study period, each patient was randomized to receive alternating 4-h periods of PSV and PAV+ equally distributed during the day and night. Sleep architecture was analyzed manually using predetermined criteria. Patient-ventilator asynchrony was evaluated breath by breath using the flow-time and airway pressure-time waveforms. Results Fourteen patients were studied. The majority (85.7 %) had either acute exacerbation of COPD as admission diagnosis or COPD as comorbidity. During sleep, compared to PSV, PAV+ significantly reduced the patient-ventilator asynchrony events per hour of sleep [5 (1-17) vs. 40 (4-443), p = 0.02, median (25-75th interquartile range)]. Compared to PSV, PAV+ was associated with slightly but significantly greater sleep fragmentation [18.8 (13.1-33.1) versus 18.1 (7.0-22.8) events/h, p = 0.01] and less REM sleep [0.0 % (0.0-8.4) vs. 5.8 % (0.0-21.9), p = 0.02). Conclusions PAV+ failed to improve sleep in mechanically ventilated patients despite the fact that this mode was associated with better synchrony between the patient and ventilator. These results do not support the hypothesis that patient-ventilator synchrony plays a central role in determining sleep quality in this group of patients., Author(s): C. Alexopoulou [sup.1], E. Kondili [sup.1], M. Plataki [sup.1], D. Georgopoulos [sup.1] Author Affiliations: (1) grid.8127.c, 0000000405763437, Department of Intensive Care Medicine, University Hospital of Heraklion, School of Medicine, [...]

AbstractPurpose: To assess the presence and extent of air trapping (AT) on chest high-resolution CT (HRCT) in sarcoidosis and to correlate such findings with patterns, lesion extent on inspiratory CT and pulmonary function tests (PFT). Material and Methods: Thirty patients with sarcoidosis underwent inspiratory and expiratory HRCT and PFT. HRCT images were evaluated for presence, distribution and AT extent as well as the predominant HRCT pattern and the extent of lesions at inspiration. Attenuation difference in the AT regions at expiration and at inspiration were calculated. The presence and extent of AT were correlated with PFT, extent of involvement and predominant inspiratory patterns. Results: AT was present in 25/30 patients with no lung zone predilection. AT was the only CT indication of pulmonary sarcoidosis in 3/30 patients who also had normal PFT. Attenuation difference between inspiration and expiration ranged from -40 HU to 106 HU. In 2 patients, a paradoxical decrease of lung attenuation was observed at expiration. A significant correlation was found between AT extent at expiration, with residual volume–total lung capacity ratio and residual volume. Conclusion: AT is an additional HRCT finding in sarcoidosis. AT may involve any lung zone, including costophrenic angles and may be the only CT feature of pulmonary sarcoidosis. Strong correlation is only found with PFT values that are specific for incomplete lung emptying at expiration. [ABSTRACT FROM AUTHOR]

We examined associations between objective sleep duration and cognitive status in older adults initially categorized as cognitively non-impaired (CNI, n  = 57) or diagnosed with mild cognitive impairment (MCI, n  = 53). On follow-up, 8 years later, all participants underwent neuropsychiatric/neuropsychological evaluation and 7-day 24-h actigraphy. On re-assessment 62.7% of participants were cognitively declined. Patients who developed dementia had significantly longer night total sleep time (TST) than persons with MCI who, in turn, had longer night TST than CNI participants. Objective long sleep duration is a marker of worse cognitive status in elderly with MCI/dementia and this association is very strong in older adults., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Adolescents often experience insufficient sleep and have unhealthy sleep habits. Our aim was to investigate the sleep patterns of secondary education students in Heraklion, Crete, Greece and their association with school performance and health habits. We conducted a community-based cross-sectional study with 831 students aged 13-19 years who completed an online self-reported questionnaire related to sleep and health habits. The data are mostly numerical or categorical, and an analysis was performed using t -tests, chi-square tests and multiple logistic regression. During weekdays, the students slept for an average of 7 ± 1.1 h, which is significantly lower than the 7.8 ± 1.5 h average on weekends ( p < 0.001). Nearly 79% reported difficulty waking up and having insufficient sleep time, while 73.8% felt sleepy at school at least once a week. Having sufficient sleep time ≥ 8 h) was positively correlated with better academic performance (OR: 1.48, CI: 1.06-2.07, p = 0.022) and frequent physical exercise (never/rarely: 13.5%, sometimes: 21.2%, often: 65.3%; p = 0.002). Conversely, there was a negative correlation between adequate sleep and both smoking (OR: 0.29, CI: 0.13-0.63) and alcohol consumption (OR: 0.51, CI: 0.36-0.71, p = 0.001). In conclusion, this study shows that students in Heraklion, Crete frequently experience sleep deprivation, which is associated with compromised academic performance, reduced physical activity and an increased likelihood of engaging in unhealthy behaviors like smoking and alcohol consumption.

Rationale: Sleep abnormalities are very frequent in critically ill patients during and after intensive care unit (ICU) stays. Their mechanisms are poorly understood. The odds ratio product (ORP) is a continuous metric (range, 0.0-2.5) of sleep depth measured in 3-second intervals and derived from the relationship of powers of different electroencephalographic frequencies to one another. When expressed as the percentage of epochs within 10 ORP deciles covering the entire ORP range, it provides information about the mechanism(s) of abnormal sleep. Objectives: To determine ORP architecture types in critically ill patients and survivors of critical illness who had previously undergone sleep studies. Methods: Nocturnal polysomnograms from 47 unsedated critically ill patients and 23 survivors of critical illness at hospital discharge were analyzed. Twelve critically ill patients were monitored also during the day, and 15 survivors underwent subsequent polysomnography 6 months after hospital discharge. In all polysomnograms, each 30-second epoch was characterized by the mean ORP of the 10 3-second epochs. The number of 30-second epochs with mean ORP within each of 10 ORP deciles covering the entire ORP range (0.0-2.5) was calculated and expressed as a percentage of total recording time. Thereafter, each polysomnogram was characterized using a two-digit ORP type, with the first digit (range, 1-3) reflecting increasing degrees of deep sleep (ORP < 0.5, deciles 1 and 2) and the second digit (range, 1-3) reflecting increasing degrees of full wakefulness (ORP > 2.25, decile 10). Results from patients were compared with those from 831 age- and gender-matched community dwellers free of sleep disorders. Results: In critically ill patients, types 1,1 and 1,2 (little deep sleep and little or average full wakefulness) dominated (46% of patients). In the community, these types are uncommon (<15%) and seen primarily in disorders that preclude progression to deep sleep (e.g., very severe obstructive sleep apnea). Next in frequency (22%) was type 1,3, consistent with hyperarousal. Day ORP sleep architecture was similar to night results. Survivors had similar patterns, with little improvement after 6 months. Conclusions: Sleep abnormalities in critically ill patients and survivors of critical illness result primarily from stimuli that preclude progression to deep sleep or from the presence of a hyperarousal state.

Introduction: Although the link between sleep and memory function is well established, associations between sleep macrostructure and memory function in normal cognition and Mild Cognitive Impairment remain unclear. We aimed to investigate the longitudinal associations of baseline objectively assessed sleep quality and duration, as well as time in bed, with verbal memory capacity over a 7-9 year period. Participants are a well-characterized subsample of 148 persons (mean age at baseline: 72.8 ± 6.7 years) from the Cretan Aging Cohort. Based on comprehensive neuropsychiatric and neuropsychological evaluation at baseline, participants were diagnosed with Mild Cognitive Impairment (MCI; n  = 79) or found to be cognitively unimpaired (CNI; n  = 69). Sleep quality/quantity was estimated from a 3-day consecutive actigraphy recording, whereas verbal memory capacity was examined using the Rey Auditory Verbal Learning Test (RAVLT) and the Greek Passage Memory Test at baseline and follow-up. Panel models were applied to the data using AMOS including several sociodemographic and clinical covariates., Results: Sleep efficiency at baseline directly predicted subsequent memory performance in the total group (immediate passage recall: β = 0.266, p  = 0.001; immediate word list recall: β = 0.172, p  = 0.01; delayed passage retrieval: β = 0.214, p  = 0.002) with the effects in Passage Memory reaching significance in both clinical groups. Wake after sleep onset time directly predicted follow-up immediate passage recall in the total sample (β = -0.211, p  = 0.001) and in the MCI group (β = -0.235, p  = 0.02). In the total sample, longer 24-h sleep duration was associated with reduced memory performance indirectly through increased sleep duration at follow-up (immediate passage recall: β = -0.045, p  = 0.01; passage retention index: β = -0.051, p  = 0.01; RAVLT-delayed recall: β = -0.048, p  = 0.009; RAVLT-retention index:β = -0.066, p  = 0.004). Similar indirect effects were found for baseline 24-h time in bed. Indirect effects of sleep duration/time in bed were found predominantly in the MCI group., Discussion: Findings corroborate and expand previous work suggesting that poor sleep quality and long sleep duration predict worse memory function in elderly. Timely interventions to improve sleep could help prevent or delay age-related memory decline among non-demented elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Skourti, Simos, Zampetakis, Koutentaki, Zaganas, Alexopoulou, Vgontzas and Basta.)

Identifying modifiable factors that may predict long-term cognitive decline in the elderly with adequate daily functionality is critical. Such factors may include poor sleep quality and quantity, sleep-related breathing disorders, inflammatory cytokines and stress hormones, as well as mental health problems. This work reports the methodology and descriptive characteristics of a long-term, multidisciplinary study on modifiable risk factors for cognitive status progression, focusing on the 7-year follow-up. Participants were recruited from a large community-dwelling cohort residing in Crete, Greece (CAC; Cretan Aging Cohort). Baseline assessments were conducted in 2013-2014 (Phase I and II, circa 6-month time interval) and follow-up in 2020-2022 (Phase III). In total, 151 individuals completed the Phase III evaluation. Of those, 71 were cognitively non-impaired (CNI group) in Phase II and 80 had been diagnosed with mild cognitive impairment (MCI). In addition to sociodemographic, lifestyle, medical, neuropsychological, and neuropsychiatric data, objective sleep was assessed based on actigraphy (Phase II and III) and home polysomnography (Phase III), while inflammation markers and stress hormones were measured in both phases. Despite the homogeneity of the sample in most sociodemographic indices, MCI persons were significantly older (mean age = 75.03 years, SD = 6.34) and genetically predisposed for cognitive deterioration (APOE ε4 allele carriership). Also, at follow-up, we detected a significant increase in self-reported anxiety symptoms along with a substantial rise in psychotropic medication use and incidence of major medical morbidities. The longitudinal design of the CAC study may provide significant data on possible modifiable factors in the course of cognitive progression in the community-dwelling elderly.

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer-BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38-54) years and body mass index of 24·84 (22.6-28.51) kg/m 2 were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6-7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = -0.178, p < 0.001), poor sleep quality (r = -0.094, p < 0.05), insomnia (r = -0.098, p < 0.05), and nap frequency per week (r = -0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination., (© 2022 European Sleep Research Society.)

Background: Chronic respiratory conditions are a prominent public health issue and thus, building a patient registry might facilitate both policy decision making and improvement of clinical management processes. Hellenic Registry of patients with Home Mechanical Ventilation (HR-HMV) was initiated in 2017 and a web-based platform is used to support patient data collection. Eighteen hospital departments (including sleep labs) across Greece participate in this initiative, focusing on recording data for both children and adult patients supported by mechanical ventilation at home, including patients with Sleep Apnea-Hypopnea Syndrome (SAHS) under Positive Airway Pressure (PAP) therapy., Methods: The HR-HMV initiative ultimately aims to provide a database for evidence-based care and policy making in this specific domain. To this end, a web information system was developed and data were manually collected by clinics and hospital departments. Legal and privacy issues (such as General Data Protection Rule compliance and technical information security measures) have been considered while designing the web application. Based on the collected data, an exploratory statistical report of SAHS patients in Greece is presented., Results: Eleven out of the eighteen participating clinics and hospital departments have contributed with data by the time of the current study. More than 5000 adult and children patient records have been collected so far, the vast majority of which (i.e., 4900 patients) diagnosed with SAHS., Conclusion: The development and maintenance of patient registries is a valuable tool for policy decision making, observational/epidemiological research and beyond (e.g., health technology assessment procedures). However, as all data collection and processing approaches, registries are also related with potential biases. Along these lines, strengths and limitations must be considered when interpreting the collected data, and continuous validation of the collected clinical data per se should be emphasized. Especially for Greece, where the lack of national registries is eminent, we argue that HR-HMV could be a useful tool for the development and the update of related policies regarding the healthcare services for patients with home mechanical ventilation support and SAHS patients, which could be useful for related initiatives at a European level as well., (© 2022. The Author(s).)

Introduction: Isolation of Candida spp. from bronchial samples of patients on mechanical ventilation is common. Even though it may not always reflect infection, it may induce immunological changes that can facilitate bacterial pneumonia. In this case, antifungal treatment is of uncertain value. This study examined the impact of antifungal treatment on the outcome of intensive care unit (ICU)-acquired respiratory tract infection (RTI) of critically ill, immunocompetent patients, with Candida isolation from their respiratory tract., Methods: This is a retrospective cohort study of adult patients hospitalized in the ICU of the University Hospital of Heraklion, Greece, from 2014 through 2016 with ICU-acquired RTI and Candida spp. isolated from their bronchial secretions. Data regarding medical history, demographics (gender, age), reason for ICU admission, previous antimicrobial use or hospitalization, SOFA and APACHE II score, clinical outcomes (primary clinical outcome: overall mortality during hospitalization; secondary clinical outcome: mortality during the ICU stay and duration of ICU and hospital stay) at the end of their ICU stay and at the end of their hospital stay were recorded and consequently evaluated. A logistic regression analysis model evaluated the effect of the recorded parameters in association with ICU mortality and overall mortality during hospitalization., Results: A total of 90 individuals were enrolled. Of them, 47 (52.2%) were treated with antifungals during their hospitalization around the time of Candida isolation. Patients treated with antifungals had higher SOFA and APACHE II scores, longer duration of stay in the ICU, more days on ventilator and higher total mortality during hospitalization. Multivariate logistic regression analysis identified antifungal use to be independently associated with total mortality during hospitalization., Conclusions: Antifungal use in patients with ICU-acquired RTI was associated with higher overall mortality as compared to those not receiving such agents., Competing Interests: Conflicts of interest: All authors - none to declare., (GERMS.)

Evaluation of sleep quality in critically ill patients is difficult using conventional scoring criteria. The aim of this study was to examine sleep in critically ill patients with and without light sedation using the odds ratio product, a validated continuous metric of sleep depth (0 = deep sleep; 2.5 = full wakefulness) that does not rely on the features needed for conventional staging., Design: Retrospective study., Settings: A 16-bed medical-surgical ICU., Patients: Twenty-three mechanically ventilated patients who had previously undergone two nocturnal sleep studies, one without and one with sedation (propofol, n = 12; dexmedetomidine, n = 11)., Interventions: None., Measurements and Main Results: Sleep architecture was evaluated with odds ratio product analysis by the distribution of 30-second epochs with different odds ratio product values. Electroencephalogram spectral patterns and frequency of wake intrusions (3-s odds ratio product > 1.75) were measured at different odds ratio product levels. Thirty-seven normal sleepers were used as controls. Compared with normal sleepers, unsedated critically ill patients spent little time in stable sleep (percent odds ratio product < 1.0: 31% vs 63%; p < 0.001), whereas most of the time were either in stage wake (odds ratio product > 1.75) or in a transitional state (odds ratio product 1.0-1.75), characterized by frequent wake intrusions. Propofol and dexmedetomidine had comparable effects on sleep. Sedation resulted in significant shift in odds ratio product distribution toward normal; percent odds ratio product less than 1.0 increased by 54% ( p = 0.006), and percent odds ratio product greater than 1.75 decreased by 48% ( p = 0.013). In six patients (26%), sedation failed to improve sleep., Conclusions: In stable critically ill unsedated patients, sleep quality is poor with frequent wake intrusions and little stable sleep. Light sedation with propofol or dexmedetomidine resulted in a shift in sleep architecture toward normal in most, but not all, patients., Competing Interests: Dr. Younes developed the odds ratio product used in this study and has a patent on this technology. The technology is licensed to Cerebra Health (Winnipeg). He owns shares in Cerebra and receives royalties from this license. The remaining authors have disclosed that they do not have any conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The present study investigated the clinical course, treatment pattern, prognostic factors, and outcome of patients with pun-drug resistant (PDR) infections. This was a retrospective single-center cohort study including consecutive eligible patients with a PDR infection hospitalized at the University Hospital of Heraklion, Crete, Greece, between January 2010 and June 2018. In total, 65 patients with infections due to PDR gram-negative pathogens were identified. The median age was 64 years (interquartile range, IQR: 45.5-74.5) and the median Charlson comorbidity index 3.0 (IQR: 1.0-5.75). Of the 65 PDR isolates, 31 (48%) were Klebsiella pneumoniae, 28 (43%) Acinetobacter baumannii, and 6 (9%) Pseudomonas aeruginosa. The most common empirical therapy was colistin-based combination (n = 32; 49%), followed by non-colistin, non-tigecycline combination (n = 25; 39%), and carbapenemes + tigecycline (n = 8; 12%). The empirical therapy was effective in 50%, 37.5%, and 8% of patients receiving colistin combination, carbapenemes - tigecycline, and non-colistin, non-tigecycline combination, respectively (p value = 0.003). The infection-related in-hospital mortality was 32% (95% confidence interval, CI: 21-45%). Three factors were significantly associated with infection-related in-hospital mortality in multivariate analysis: Charlson comorbidity index (odds ratio, OR: 1.5, 95% CI: 1.0-2.3, p value = 0.030), prior steroid use (OR: 4.1, 95% CI: 1.0-17.0, p value = 0.049), and empirical treatment with non-colistin, non-tigecycline combination (OR: 7.5; 95% CI: 1.7-32.8, p value = 0.008). Infections due to PDR pathogens are associated with considerable mortality. Our results support the use of colistin and/or tigecycline-based combinations as empirical therapy when infection due to PDR pathogens is suspected.

Background: The present study aimed to validate a recently proposed algorithm for assistance titration during proportional assist ventilation with load-adjustable gain factors, based on a noninvasive estimation of maximum inspiratory pressure (peak P mus ) and inspiratory effort (pressure-time product [PTP] peak P mus )., Methods: Retrospective analysis of the recordings obtained from 26 subjects ventilated on proportional assist ventilation with load-adjustable gain factors under different conditions, each considered as an experimental case. The estimated inspiratory output (peak P mus ) and effort (PTP-peak P mus ) were compared with the actual-determined by the measurement of transdiaphragmatic pressure- and the derived PTP. Validation of the algorithm was performed by assessing the accuracy of peak P mus in predicting the actual inspiratory muscle effort and indicating the appropriate level of assist., Results: In the 63 experimental cases analyzed, a limited agreement was observed between the estimated and the actual inspiratory muscle pressure (-11 to 10 cm H 2 O) and effort (-82 to 125 cm H 2 O × s/min). The sensitivity and specificity of peak P mus to predict the range of the actual inspiratory effort was 81.2% and 58.1%, respectively. In 49% of experimental cases, the level of assist indicated by the algorithm differed from that indicated by the transdiaphragmatic pressure and PTP., Conclusions: The proposed algorithm had limited accuracy in estimating inspiratory muscle effort and with indicating the appropriate level of assist., Competing Interests: Drs Amargiannitakis and Gialamas contributed equally to this work. Drs Kondili, Vaporidi, and Georgopoulos have received lecture fees (honoraria) from Covidien., (Copyright © 2020 by Daedalus Enterprises.)

Purpose: There is limited data regarding the sleep quality in survivors of critical illness, while the time course of the sleep abnormalities observed after ICU discharge is not known. The aim of this study was to assess sleep quality and the time course of sleep abnormalities in survivors of critical illness., Methods: Eligible survivors of critical illness without hypercapnia and hypoxemia were evaluated within 10 days (1st evaluation, n = 36) and at 6 months after hospital discharge (2nd evaluation, n = 29). At each visit, all patients underwent an overnight full polysomnography and completed health-related quality of life questionnaires (HRQL). Lung function and electro-diagnostic tests (ED) were performed in 24 and 11 patients, respectively., Results: At 1st evaluation, sleep quality and HRQL were poor. Sleep was characterised by high percentages of N1, low of N3 and REM stages, and high apnea-hypopnea index (AHI, events/h). Twenty-two out of 36 patients (61%) exhibited AHI ≥ 15 (21 obstructive, 1 central). None of the patients' characteristics, including HRQL and lung function, predicted the occurrence of AHI ≥ 15. At 6 months, although sleep quality remained poor (high percentages of N1 and low of REM), sleep architecture had improved as indicated by the significant increase in N3 [4.2% (0-12.5) vs. 9.8% (3.0-20.4)] and decrease in AHI [21.5 (6.5-29.4) vs. 12.8 (4.7-20.4)]. HRQL improved slightly but significantly at 6 months. Neither the changes in HRQL nor in lung function tests were related to these of sleep architecture. Six out of eight patients with abnormal ED at 1st evaluation continued to exhibit abnormal results at 6 months., Conclusions: Survivors of critical illness exhibited a high prevalence of obstructive sleep-disordered breathing and poor sleep architecture at hospital discharge, which slightly improved 6 months later, indicating that reversible factors are partly responsible for these abnormalities.

Gastrointestinal (GI) motility disorders are commonly present in critical illness. Up to 60% of critically ill patients have been reported to experience GI dysmotility of some form necessitating therapeutic intervention. It has been attributed to various factors, related to both the underlying disease and the therapeutic interventions undertaken. The assessment of motility disturbances can be challenging in critically ill patients, as the available tests used to detect abnormal motility have major limitations in the setting of an Intensive Care Unit. Critically ill patients with GI dysmotility require a multifaceted treatment approach that addresses multiple causes and utilizes multiple pharmacological pathways. In this review, we discuss the pathophysiology, assessment and management of GI dysmotility in critically ill patients., Competing Interests: Conflict of interest: None

Background: Dexmedetomidine, a potent α-2-adrenergic agonist, is widely used as sedative in critically ill patients. This pilot study was designed to assess the effect of dexmedetomidine administration on sleep quality in critically ill patients., Methods: Polysomnography was performed on hemodynamically stable critically ill patients for 57 consecutive hours, divided into three night-time (9:00 PM to 6:00 AM) and two daytime (6:00 AM to 9:00 PM) periods. On the second night, dexmedetomidine was given by a continuous infusion targeting a sedation level -1 to -2 on the Richmond Agitation Sedation Scale. Other sedatives were not permitted., Results: Thirteen patients were studied. Dexmedetomidine was given in a dose of 0.6 μg kg(-1) h(-1) (0.4 to 0.7) (median [interquartile range]). Compared to first and third nights (without dexmedetomidine), sleep efficiency was significantly higher during the second night (first: 9.7% [1.6 to 45.1], second: 64.8% [51.4 to 79.9], third: 6.9% [0.0 to 17.1], P < 0.002). Without dexmedetomidine, night-time sleep fragmentation index (7.6 events per hour [4.8 to 14.2]) and stage 1 of sleep (48.0% [30.1 to 66.4]) were significantly higher (P = 0.023 and P = 0.006, respectively), and stage 2 (47.0% [27.5 to 61.2]) showed values lower (P = 0.006) than the corresponding values (2.7 events per hour [1.6 to 4.9], 13.1% [6.2 to 23.6], 80.2% [68.9 to 92.8]) observed with dexmedetomidine. Without sedation, sleep was equally distributed between day and night, a pattern that was modified significantly (P = 0.032) by night-time dexmedetomidine infusion, with more than three quarters of sleep occurring during the night (79% [66 to 87])., Conclusion: In highly selected critically ill patients, dexmedetomidine infusion during the night to achieve light sedation improves sleep by increasing sleep efficiency and stage 2 and modifies the 24-h sleep pattern by shifting sleep mainly to the night.

Purpose: To access the effect of propofol administration on sleep quality in critically ill patients ventilated on assisted modes., Methods: This was a randomized crossover physiological study conducted in an adult ICU at a tertiary hospital. Two nights' polysomnography was performed in mechanically ventilated critically ill patients with and without propofol infusion, while respiratory variables were continuously recorded. Arterial blood gasses were measured in the beginning and at the end of the study. The rate of propofol infusion was adjusted to maintain a sedation level of 3 on the Ramsay scale. Sleep architecture was analyzed manually using predetermined criteria. Patient-ventilator asynchrony was evaluated breath by breath using the flow-time and airway pressure-time waveforms., Results: Twelve patients were studied. Respiratory variables, patient-ventilator asynchrony, and arterial blood gasses did not differ between experimental conditions. With or without propofol all patients demonstrated abnormal sleep architecture, expressed by lack of sequential progression through sleep stages and their abnormal distribution. Sleep efficiency, sleep fragmentation, and sleep stage distribution (1, 2, and slow wave) did not differ with or without propofol. Compared to without propofol, both the number of patients exhibiting REM sleep (p = 0.02) and the percentage of REM sleep (p = 0.04) decreased significantly with propofol., Conclusions: In critically ill patients ventilated on assisted modes, propofol administration to achieve the recommended level of sedation suppresses the REM sleep stage and further worsens the poor sleep quality of these patients.

Objectives: The incidence of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) organisms is increasing. Intravenous (IV) colistin or aerosolized (AS) plus IV colistin have been recently used to treat these life-threatening infections. The purpose of this study was to compare the efficacy and safety of AS plus IV colistin versus IV colistin alone for patients with MDR VAP due to gram-negative bacteria., Methods: A retrospective matched case-control study was performed at the Intensive Care Unit of the University Hospital of Heraklion, Greece, from January 2005 through December 2008. Forty-three patients with VAP due gram-negative MDR pathogens received AS plus IV colistin and were matched on the basis of age and Acute Physiology and Chronic Health Evaluation II score with 43 control patients who had received IV colistin alone., Results: Demographic characteristics, clinical status, and gram-negative isolated pathogens were similar between the 2 treatment groups. Acinetobacter baumannii (66 cases [77%]) was the most common pathogen, followed by Klebsiella pneumoniae (12 cases [14%]) and Pseudomonas aeruginosa (8 cases [9.3%]). No colistin-resistant strains were isolated from patients in either group. No significant differences between the 2 groups were observed regarding eradication of pathogens (P = .679), clinical cure (P = .10), and mortality (P = .289). Eight patients (19%) in each treatment group developed reversible renal dysfunction. No AS colistin-related adverse events were recorded., Conclusions: Addition of AS colistin to IV colistin did not provide additional therapeutic benefit to patients with MDR VAP due to gram-negative bacteria.

The aim of the study was to investigate Propofol's effect on breathing stability in brain damage patients, as quantified by the Loop Gain (LG) of the respiratory system (breathing stability increases with decreasing LG). In 11 stable brain damage patients full polysomnography was performed before, during and after propofol sedation, titrated to achieve stage 2 or slow wave sleep. During each period, patients were ventilated with proportional assist ventilation and the % assist was increased in steps, until either periodic breathing (PB) occurred or the highest assist (95%) was achieved. The tidal volume amplification factor (VT(AF)) at the highest assist level reached just before PB occurred was used to calculate LG (LG=1/VT(AF)). In all but one patient, PB was observed. With propofol, the assist level at which PB occurred (73 + or - 19%) was significantly higher, than that before (43 + or - 35%) and after propofol sedation (49 + or - 29%). As a result, with propofol LG (0.49 + or - 0.2) was significantly lower than that before (0.74 + or - 0.2) and after propofol sedation (0.69 + or - 0.2) (p<0.05). We conclude that Propofol decreases LG. Therefore it exerts an overall stabilizing effect on control of breathing., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Recently, a new technology has been introduced aiming to monitor and improve patient ventilator interaction (PVI monitor). With the PVI monitor, a signal representing an estimation of the patient's total inspiratory muscle pressure (Pmus(PVI)) is calculated from the equation of motion, utilizing estimated values of resistance and elastance of the respiratory system., Objective: The aim of the study was to prospectively examine the accuracy of Pmus(PVI) to quantify inspiratory muscle pressure., Methods and Interventions: Eleven critically ill patients mechanically ventilated on proportional assist ventilation with load-adjustable gain factors were studied at three levels of assist (30, 50 and 70%). Airway, esophageal, gastric and transdiaphragmatic (Pdi) pressures, volume and flow were measured breath by breath, whereas the total inspiratory muscle pressure (Pmus) was calculated using the Campbell diagram., Results: For a given assist, Pmus(PVI) throughout inspiration did not differ from the corresponding values calculated using the Pdi and Pmus signals. Inspiratory and expiratory time did not differ among the various methods of calculation. Inspiratory muscle pressure decreased with increasing assist, and the magnitude of this decrease did not differ among the various methods of pressure calculation., Conclusions: A signal generated from flow, volume and airway pressure may be used to provide breath-by-breath quantitative information of inspiratory muscle pressure.

Patient-ventilator asynchrony refers to the uncoupling between the mechanically delivered breath and the patient's respiratory effort. It is common during assisted mechanical ventilation and may affect the morbidity of critically ill patients. Close inspection of pressure, volume and flow waveforms - displayed by modern ventilators - may help the physician to recognize and act appropriately to minimize patient-ventilator asynchrony. During the last two decades new modes of assisted mechanical ventilation have been introduced, aiming to improve patient ventilator synchrony by modulating the triggering function and the variables that control the flow delivery and the cycling off.

Objectives: It is not known if proportional assist ventilation with load-adjustable gain factors (PAV+) may be used as a mode of support in critically ill patients. The aim of this study was to examine the effectiveness of sustained use of PAV+ in critically ill patients and compare it with pressure support ventilation (PS)., Design and Setting: Randomized study in the intensive care unit of a university hospital., Methods: A total of 208 critically ill patients mechanically ventilated on controlled modes for at least 36 h and meeting certain criteria were randomized to receive either PS (n = 100) or PAV+ (n = 108). Specific written algorithms were used to adjust the ventilator settings in each mode. PAV+ or PS was continued for 48 h unless the patients met pre-defined criteria either for switching to controlled modes (failure criteria) or for breathing without ventilator assistance., Results: Failure rate was significantly lower in PAV+ than that in PS (11.1 vs. 22.0%, P = 0.040, OR 0.443, 95% CI 0.206-0.952). The proportion of patients exhibiting major patient-ventilator dyssynchronies at least during one occasion and after adjusting the initial ventilator settings, was significantly lower in PAV+ than in PS (5.6 vs. 29.0%, P < 0.001, OR 0.1, 95% CI 0.06-0.4). The proportion of patients meeting criteria for unassisted breathing did not differ between modes., Conclusions: PAV+ may be used as a useful mode of support in critically ill patients. Compared to PS, PAV+ increases the probability of remaining on spontaneous breathing, while it considerably reduces the incidence of patient-ventilator asynchronies.

Rationale: In mechanically ventilated patients respiratory system impedance may vary from time to time, resulting, with pressure modalities of ventilator support, in changes in the level of assistance. Recently, implementation of a closed-loop adjustment to continuously adapt the level of assistance to changes in respiratory mechanics has been designed to operate with proportional assist ventilation (PAV+)., Objectives: The aim of this study was to assess, in critically ill patients, the short-term steady-state response of respiratory motor output to added mechanical respiratory load during PAV+ and during pressure support (PS)., Patients and Interventions: In 10 patients respiratory workload was increased and the pattern of respiratory load compensation was examined during both modes of support., Measurements and Results: Airway and transdiaphragmatic pressures, volume and flow were measured breath by breath. Without load, both modes provided an equal support as indicated by a similar pressure-time product of the diaphragm per breath, per minute and per litre of ventilation. With load, these values were significantly lower (p<0.05) with PAV+ than those with PS (5.1+/-3.7 vs 6.1+/-3.4 cmH2O.s, 120.9+/-77.6 vs 165.6+/-77.5 cmH2O.s/min, and 18.7+/-15.1 vs 24.4+/-16.4 cmH2O.s/l, respectively). Contrary to PS, with PAV+ the ratio of tidal volume (VT) to pressure-time product of the diaphragm per breath (an index of neuroventilatory coupling) remained relatively independent of load. With PAV+ the magnitude of load-induced VT reduction and breathing frequency increase was significantly smaller than that during PS., Conclusion: In critically ill patients the short-term respiratory load compensation is more efficient during proportional assist ventilation with adjustable gain factors than during pressure support.

Background: Angiogenesis is an adaptation mechanism of skeletal muscles to increased load. Animal data have shown increased vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in the diaphragm as a result of increased minute ventilation, but there are no data concerning the human diaphragm., Objectives: The purpose of this study was to investigate the VEGF, bFGF, TGF-beta(1) mRNA levels in the human diaphragm of normal subjects and patients with altered respiratory mechanics., Methods: We studied 9 patients with chronic obstructive pulmonary disease (COPD), 4 obese patients and 12 controls. We performed multiplex semiquantitative reverse transcription polymerase chain reaction to determine the VEGF, bFGF and TGF-beta(1) mRNA levels in specimens taken from their diaphragm., Results: VEGF mRNA levels were 18% higher in COPD patients compared with controls (p = 0.04), while for the obese patients, these levels were not statistically significantly different. bFGF and TGF-beta(1) mRNA levels in COPD patients or obese individuals compared with controls did not differ significantly either., Conclusions: The results of our study showed that TGF-beta(1), VEGF and bFGF mRNA was detected in the human diaphragm. The VEGF levels were higher in COPD patients than in normal subjects. This upregulation of VEGF may suggest an enhancement of angiogenesis in the diaphragm in COPD patients.

Introduction: The cuff-leak test has been proposed as a simple method to predict the occurrence of post-extubation stridor. The test is performed by cuff deflation and measuring the expired tidal volume a few breaths later (VT). The leak is calculated as the difference between VT with and without a deflated cuff. However, because the cuff remains deflated throughout the respiratory cycle a volume of gas may also leak during inspiration and therefore this method (conventional) measures the total leak consisting of an inspiratory and expiratory component. The aims of this physiological study were, first, to examine the effects of various variables on total leak and, second, to compare the total leak with that obtained when the inspiratory component was eliminated, leaving only the expiratory leak., Methods: In 15 critically ill patients mechanically ventilated on volume control mode, the cuff-leak volume was measured randomly either by the conventional method (Leakconv) or by deflating the cuff at the end of inspiration and measuring the VT of the following expiration (Leakpause). To investigate the effects of respiratory system mechanics and inspiratory flow, cuff-leak volume was studied by using a lung model, varying the cross-sectional area around the endotracheal tube and model mechanics., Results: In patients Leakconv was significantly higher than Leakpause, averaging 188 +/- 159 ml (mean +/- SD) and 61 +/- 75 ml, respectively. In the model study Leakconv increased significantly with decreasing inspiratory flow and model compliance. Leakpause and Leakconv increased slightly with increasing model resistance, the difference being significant only for Leakpause. The difference between Leakconv and Leakpause increased significantly with decreasing inspiratory flow (V'I) and model compliance and increasing cross-sectional area around the tube., Conclusion: We conclude that the cross-sectional area around the endotracheal tube is not the only determinant of the cuff-leak test. System compliance and inspiratory flow significantly affect the test, mainly through an effect on the inspiratory component of the total leak. The expiratory component is slightly influenced by respiratory system resistance.

Objectives: To study the pattern of lung emptying and expiratory resistance in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD)., Design: A prospective physiological study., Setting: A 12-bed Intensive Care Unit., Patients: Ten patients with acute exacerbation of COPD., Interventions: At three levels of positive end-expiratory pressure (PEEP, 0, 5 and 10 cm H(2)O) tracheal (Ptr) and airway pressures, flow (V') and volume (V) were continuously recorded during volume control ventilation and airway occlusions at different time of expiration., Measurements and Results: V-V' curves during passive expiration were obtained, expired volume was divided into five equal volume slices and the time constant (tau) and dynamic deflation compliance (Crs(dyn)) of each slice was calculated by regression analysis of V-V' and post-occlusion V-Ptr relationships, respectively. In each volume slice the existence or not of flow limitation was examined by comparing V-V' curves with and without decreasing Ptr. For a given slice total expiratory resistance was calculated as tau/Crs(dyn), whereas expiratory resistance (Rrs) and time constant (tau(rs)) of the respiratory system were subsequently estimated taken into consideration the presence of flow limitation. At zero PEEP, tau(rs) increased significantly toward the end of expiration due to an increase in Rrs. PEEP significantly decreased Rrs at the end of expiration and resulted in a faster and relatively constant rate of lung emptying., Conclusions: Patients with COPD exhibit a decrease in the rate of lung emptying toward the end of expiration due to an increase in Rrs. PEEP decreases Rrs, resulting in a faster and uniform rate of lung emptying.

Objective: Scleroderma is characterized by the presence of 3 predominant, yet almost mutually exclusive, antibodies: anticentromere antibody (ACA), antitopoisomerase antibody, and anti-RNA polymerase antibody. The purpose of this study was to investigate tumor necrosis factor (TNF) polymorphisms in scleroderma, with the specific aim of determining whether TNF polymorphisms would prove to be stronger markers for ACA than class II major histocompatibility complex (MHC)., Methods: We studied 214 UK white scleroderma patients and 354 healthy controls. All subjects were investigated for 5 TNF promoter region polymorphisms by sequence-specific polymerase chain reaction., Results: We showed that an NF-kappaB binding site polymorphism (known to be functionally relevant) in the TNF promoter region was present in 51.8% of patients with ACA and 16.3% of patients without ACA (chi(2) = 25.1, P = 0.000004 [corrected P = 0.00002]). Using haplotype mapping, we showed that this was a primary TNF association that could explain the previous weak links between ACA production and class II MHC alleles. In marked contrast to our ACA results, HLA class II (especially DRB1*11) appeared to be primary in that it could explain the weaker TNF association with antitopoisomerase production. Further, we observed a separate TNF haplotype to be associated with scleroderma per se, although the level of significance was much lower (chi(2) = 8.7, P = 0.003 [corrected P = 0.02])., Conclusion: We believe these findings may have importance both for the directional pathogenesis of scleroderma progression and for the treatment of scleroderma with anti-TNF agents.

This review reports evidence showing that the function of the respiratory muscles (RMs) is affected in endocrinopathies and emphasizes that clinicians should look for RM weakness in hormone inbalances. Although there is a potential pathophysiological mechanism for affecting RM in diabetes insipidus, hypoparathyroidism, Cushing's disease, pheochromocytoma, adrenalin deficiency or androgen disorder, no study was found in the available literature. Therefore, investigations are urgently needed in these diseases. Controversial results have been reported in acromegaly, hypopituitarism, diabetes mellitus and steroid-induced (iatrogenic) RM myopathy. Obviously, these are areas for further research. Respiratory muscle dysfunction has been well documented in thyroid disease and there is general agreement that both hypo- and hyperthyroidism are associated with reversible respiratory muscle weakness.