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

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

The impact of sleep disordered breathing on cardiac troponin in acutely decompensated heart failure.

PURPOSE: Sleep disordered breathing in decompensated heart failure has physiological consequences (e.g., intermittent hypoxemia) that may predispose to subclinical myocardial injury, yet a temporal relationship between sleep apnea and troponin elevation has not been established. METHODS: We assessed the feasibility of performing respiratory polygraphy and measuring overnight high-sensitivity cardiac troponin T change in adults admitted to the hospital with acutely decompensated heart failure. Repeat sleep apnea tests (SATs) were performed to determine response to optimal medical heart failure therapy. Multivariable logistic regression was used to identify associations between absolute overnight troponin change and sleep apnea characteristics. RESULTS: Among the 19 subjects with acutely decompensated heart failure, 92% of SATs demonstrated sleep disordered breathing (apnea-hypopnea index [AHI] > 5 events/h). For those with repeat SATs, AHI increased in 67% despite medical management of heart failure. Overnight troponin increase was associated with moderate to severe sleep apnea (vs. no to mild sleep apnea, odds ratio (OR = 18.4 [1.51-224.18]), central apnea index (OR = 1.11 [1.01-1.22]), and predominantly central sleep apnea (vs. obstructive, OR = 22.9 [1.29-406.32]). CONCLUSIONS: Sleep apnea severity and a central apnea pattern may be associated with myocardial injury. Respiratory polygraphy with serial biomarker assessment is feasible in this population, and combining this approach with interventions (e.g., positive airway pressure) may help establish if a link exists between sleep apnea and subclinical myocardial injury.

Very Low Driving-Pressure Ventilation in Patients With COVID-19 Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation: A Physiologic Study.

OBJECTIVES: To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE). DESIGN: A single-center prospective physiologic study. SETTING: At a single university medical center. PARTICIPANTS: Adult patients with severe COVID-19 ARDS on VV ECMO. INTERVENTIONS: Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP = 1 cmH2O), and (5) 2 hours after returning to LDPV. MAIN MEASUREMENTS AND RESULTS: Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (Vt) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, Vt were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p = 0.481 and p = 0.065, respectively). There was no relationship found when accounting for Vt changes and biomarkers. CONCLUSIONS: Biomarkers did not significantly change with decreased ΔPs or Vt changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in Vt during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher Vt (ie, transpulmonary pressure) than desired despite low ΔPs or Vt.

Practices and Patterns of Hourly Neurochecks: Analysis of 8,936 Patients With Neurological Injury.

BACKGROUND: Patients experiencing acute neurological injury often receive hourly neurological assessments ("neurochecks") to capture signs of deterioration. While commonly utilized in the intensive care unit (ICU) setting, little is known regarding practices (i.e., variations by age and ordering services) and patterns (i.e., duration and post-discontinuation plans) of hourly neurochecks. To inform future quality improvement intervention efforts, we performed an analysis of hourly neurochecks using an electronic health record-based dataset. STUDY DESIGN AND METHODS: Our 75-month retrospective dataset consisted of all health system ICU patients who received hourly neurochecks. Variables included age, admission diagnosis category, ordering provider, post-discontinuation order, and discharge destination. Multivariable Cox regression was used to evaluate factors associated with hourly neurocheck duration. RESULTS: We evaluated 9,513 first admission hourly neurocheck orders in 8,936 patients. The trauma, neurosurgery, and neurocritical care services were responsible for 4,067 (43%), 2,071 (22%) and 1,697 (18%) hourly neurocheck orders, respectively. Median (interquartile range) hourly neurocheck duration was 1.09 (0.69, 2.35) days, and was greater than 3 and 7 days, respectively, for 1,773 (19%) and 640 (7%) patients. Median hourly neurocheck duration ranged from 0.87 (0.65, 1.68) to 1.60 (0.83, 2.97) days for neurosurgical and non-neurological ICU services, respectively. Upon discontinuation, 2,225 (23%) of hourly neurochecks were transitioned to no neurochecks. CONCLUSION: Substantial differences exist between ICU services and practice patterns surrounding hourly neurochecks. Understanding these differences will help inform intervention efforts aimed at streamlining hourly neurocheck practices and outcomes for patients with acute neurological injury.

Point-of-care prediction model of loop gain in patients with obstructive sleep apnea: development and validation.

BACKGROUND: High loop gain (unstable ventilatory control) is an important-but difficult to measure-contributor to obstructive sleep apnea (OSA) pathogenesis, predicting OSA sequelae and/or treatment response. Our objective was to develop and validate a clinical prediction tool of loop gain. METHODS: A retrospective cohort of consecutive adults with OSA (apnea-hypopnea index, AHI > 5/hour) based on in-laboratory polysomnography 01/2017-12/2018 was randomly split into a training and test-set (3:1-ratio). Using a customized algorithm ("reference standard") loop gain was quantified from raw polysomnography signals on a continuous scale and additionally dichotomized (high > 0.7). Candidate predictors included general patient characteristics and routine polysomnography data. The model was developed (training-set) using linear regression with backward selection (tenfold cross-validated mean square errors); the predicted loop gain of the final linear regression model was used to predict loop gain class. More complex, alternative models including lasso regression or random forests were considered but did not meet pre-specified superiority-criteria. Final model performance was validated on the test-set. RESULTS: The total cohort included 1055 patients (33% high loop gain). Based on the final model, higher AHI (beta = 0.0016; P < .001) and lower hypopnea-percentage (beta = -0.0019; P < .001) predicted higher loop gain values. The predicted loop gain showed moderate-to-high correlation with the reference loop gain (r = 0.48; 95% CI 0.38-0.57) and moderate discrimination of patients with high versus low loop gain (area under the curve = 0.73; 95% CI 0.67-0.80). CONCLUSION: To our knowledge this is the first prediction model of loop gain based on readily-available clinical data, which may facilitate retrospective analyses of existing datasets, better patient selection for clinical trials and eventually clinical practice.

Silent hypoxaemia in COVID-19 patients.

The clinical presentation of COVID-19 due to infection with SARS-CoV-2 is highly variable with the majority of patients having mild symptoms while others develop severe respiratory failure. The reason for this variability is unclear but is in critical need of investigation. Some COVID-19 patients have been labelled with 'happy hypoxia', in which patient complaints of dyspnoea and observable signs of respiratory distress are reported to be absent. Based on ongoing debate, we highlight key respiratory and neurological components that could underlie variation in the presentation of silent hypoxaemia and define priorities for subsequent investigation.

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).

Sleep Outcomes From AWAKE-HF: A Randomized Clinical Trial of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Heart failure and sleep-disordered breathing have been increasingly recognized as co-occurring conditions. Their bidirectional relationship warrants investigation into whether heart failure therapy improves sleep and sleep-disordered breathing. We sought to explore the effect of treatment with sacubitril/valsartan on sleep-related endpoints from the AWAKE-HF study. METHODS AND RESULTS: AWAKE-HF was a randomized, double-blind study conducted in 23 centers in the United States. Study participants with heart failure with reduced rejection fraction and New York Heart Association class II or III symptoms were randomly assigned to receive treatment with either sacubitril/valsartan or enalapril. All endpoints were assessed at baseline and after 8 weeks of treatment. Portable sleep-monitoring equipment was used to measure the apnea-hypopnea index, including obstructive and central events. Total sleep time, wake after sleep onset and sleep efficiency were exploratory measures assessed using wrist actigraphy. THE RESULTS WERE AS FOLLOWS: 140 patients received treatment in the double-blind phase (sacubitril/valsartan, n = 70; enalapril, n = 70). At baseline, 39% and 40% of patients randomly assigned to receive sacubitril/valsartan or enalapril, respectively, presented with undiagnosed, untreated, moderate-to-severe sleep-disordered breathing (≥ 15 events/h), and nearly all had obstructive sleep apnea. After 8 weeks of treatment, the mean 4% apnea-hypopnea index changed minimally from 16.3/h to 15.2/h in the sacubitril/valsartan group and from 16.8/h to 17.6/h in the enalapril group. Mean total sleep time was long at baseline and decreased only slightly in both treatment groups at week 8 (-14 and -11 minutes for sacubitril/valsartan and enalapril, respectively), with small changes in wake after sleep onset and sleep efficiency in both groups. CONCLUSIONS: In a cohort of patients with heart failure with reduced rejection fraction who met prescribing guidelines for sacubitril/valsartan, one-third had undiagnosed moderate-to-severe obstructive sleep apnea. The addition of sacubitril/valsartan therapy did not significantly improve sleep-disordered breathing or sleep duration or efficiency. Patients who meet indications for treatment with sacubitril/valsartan should be evaluated for sleep-disordered breathing.

Objectively measured sleep fragmentation is associated with incident delirium in older hospitalized patients: Analysis of data collected from an randomized controlled trial.

Delirium may lead to poor outcomes in hospitalized older adults, and sleep deprivation may contribute to its pathogenesis. Thus, we sought to measure sleep duration and fragmentation using wrist-worn actigraphy in older, hospitalized patients with and without delirium, and to determine if actigraphy-based parameters could be used to predict delirium prior to clinical recognition. We conducted a secondary analysis of data from a recent, randomized clinical trial aimed at preventing inpatient delirium. Participants (n = 70) were aged ≥ 65 years admitted to an internal medicine service. Delirium was defined by the Confusion Assessment Method, or altered mental status identified by a clinician. Sleep measurements were actigraphy-based, and included total sleep time, median sleep bout duration and other measures of sleep fragmentation. We found that total sleep duration was similar between patients with (n = 17) and without (n = 53) delirium (mean 384.9 ± SD 162.7 versus mean 456.6 ± SD 135.8 min; p = .081). Mean sleep bout times were shorter in delirious versus never-delirious patients (median 6.1 [interquartile range 4.3-8.9] versus 7.9 [interquartile range 5.7-11.3] min, p = .048). Patients with delirium had more short sleep bouts (< 10 min) and fewer longer sleep bouts (> 30 min) compared with those without delirium. Increased sleep fragmentation was present prior to the clinical recognition of delirium. Overall, delirium was associated with increased sleep fragmentation detected by actigraphy, and sleep fragmentation might be useful as a biomarker for delirium prediction in the future.

Long-Term Noninvasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations:1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.

Implementation and Outcomes of a Mobile Extracorporeal Membrane Oxygenation Program in the United States During the Coronavirus Disease 2019 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic began in the United States around March 2020. Because of limited access to extracorporeal membrane oxygenation (ECMO) in the authors' region, a mobile ECMO team was implemented by April 2020 to serve patients with COVID-19. Several logistical and operational needs were assessed and addressed to ensure a successful program, including credentialing, equipment management, and transportation. A multidisciplinary team was included in the planning, decision-making, and implementation of the mobile ECMO. From April 2020 to January 2021, mobile ECMO was provided to 22 patients in 13 facilities across four southern California counties. The survival to hospital discharge of patients with COVID-19 who received mobile ECMO was 52.4% (11 of 21) compared with 45.2% (14 of 31) for similar patients cannulated in-house. No significant patient or transportation complications occurred during mobile ECMO. Neither the ECMO nor transport teams experianced unprotected exposures to or infections with severe acute respiratory syndrome coronavirus 2. Herein, the implementation of the mobile ECMO team is reviewed, and patient characteristics and outcomes are described.

Endotypes and phenotypes in obstructive sleep apnea.

PURPOSE OF REVIEW: The purpose of this review is to describe the variability of obstructive sleep apnea (OSA), both from a standpoint of underlying mechanisms and in terms of clinical manifestations. RECENT FINDINGS: Recent data suggest that not all patients with sleep apnea get their disease for the same reason. As such, no one variable is effective at defining which patients do or do not have sleep apnea. Identifying the mechanism(s) underlying OSA for an individual is helpful as it can help to determine whether personalized therapy could be developed based on an individual's characteristics. In addition, these underlying mechanisms may be helpful in predicting response to therapy and prognosticating regarding future complications. SUMMARY: OSA is a heterogeneous disease with highly varying underlying mechanisms. OSA has variable clinical manifestations with definable subsets having risk of particular complications. Future studies will be helpful to identify mechanisms underlying OSA using clinically accessible tools and then using these data to focus individualized treatment approaches.

Equipoise in Appropriate Initial Volume Resuscitation for Patients in Septic Shock With Heart Failure: Results of a Multicenter Clinician Survey.

PURPOSE: International clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock. METHODS: We conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) <40%. Initial volume resuscitation preferences were captured as ordinal values, and additional testing for volume resuscitation preferences was performed using McNemar and Wilcoxon signed rank tests as indicated. Univariable logistic regression models were used to identify significant predictors of ≥30 mL/kg fluid administration. RESULTS: A total of 317 clinicians at 9 US hospitals completed the survey (response rate 47.3%). Most respondents were specialists in either internal medicine or emergency medicine. Substantial heterogeneity was found regarding sepsis resuscitation preferences for patients with concomitant HFrEF. The belief that patients with septic shock and HFrEF should be exempt from current sepsis bundle initiatives was shared by 39.4% of respondents. A minimum fluid challenge of ∼30 mL/kg or more was deemed appropriate in septic shock by only 56.4% of respondents for patients with concomitant HFrEF, compared to 89.1% of respondents for patients without HFrEF (P < .01). Emergency medicine physicians were most likely to feel that <30 mL/kg was most appropriate in patients with septic shock and HFrEF. CONCLUSIONS: Clinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.

More Than the Sum of the Respiratory Events: Personalized Medicine Approaches for Obstructive Sleep Apnea.

Traditionally, the presence and severity of obstructive sleep apnea (OSA) have been defined by the apnea-hypopnea index (AHI). Continuous positive airway pressure is generally first-line therapy despite low adherence, because it reliably reduces the AHI when used, and the response to other therapies is variable. However, there is growing appreciation that the underlying etiology (i.e., endotype) and clinical manifestation (i.e., phenotype) of OSA in an individual are not well described by the AHI. We define and review the important progress made in understanding and measuring physiological mechanisms (or endotypes) that help define subtypes of OSA and identify the potential use of genetics to further refine disease classification. This more detailed understanding of OSA pathogenesis should influence clinical treatment decisions as well as help inform research priorities and clinical study design. In short, treatments could be individualized on the basis of the underlying cause of OSA; patients could better understand which symptoms and outcomes will respond to OSA treatment and by how much; and researchers could select populations most likely to benefit from specific treatment approaches for OSA.

Impact of Sleep Deprivation in the Neurological Intensive Care Unit: A Narrative Review.

Sleep is fundamental for everyday functioning, yet it is often negatively impacted in critically ill patients by the intensive care setting. With a focus on the neurological intensive care unit (NeuroICU), this narrative review summarizes methods of measuring sleep and addresses common causes of sleep disturbance in the hospital including environmental, pharmacological, and patient-related factors. The effects of sleep deprivation on the cardiovascular, pulmonary, immune, endocrine, and neuropsychological systems are discussed, with a focus on short-term deprivation in critically ill populations. Where evidence is lacking in the literature, long-term sleep deprivation studies and the effects of sleep deprivation in healthy individuals are also referenced. Lastly, strategies for the promotion of sleep in the NeuroICU are presented.

Female Physician Leadership During Cardiopulmonary Resuscitation Is Associated With Improved Patient Outcomes.

OBJECTIVES: A recently published simulation study suggested that women are inferior leaders of cardiopulmonary resuscitation efforts. The aim of this study was to compare female and male code leaders in regard to cardiopulmonary resuscitation outcomes in a real-world clinical setting. DESIGN: Retrospective cohort review. SETTING: Two academic, urban hospitals in San Diego, California. SUBJECTS: One-thousand eighty-two adult inpatients who suffered cardiac arrest and underwent cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed whether physician code leader gender was independently associated with sustained return of spontaneous circulation and survival to discharge and with markers of quality cardiopulmonary resuscitation. Of all arrests, 327 (30.1%) were run by female physician code leaders with 251 (76.8%) obtaining return of spontaneous circulation, and 122 (37.3%) surviving to discharge. Male physicians ran 757 codes obtaining return of spontaneous circulation in 543 (71.7%) with 226 (29.9%) surviving to discharge. When adjusting for variables, female physician code leader gender was independently associated with a higher likelihood of return of spontaneous circulation (odds ratio, 1.36; 95% CI, 1.01-1.85; p = 0.049) and survival to discharge (odds ratio, 1.53; 95% CI, 1.15-2.02; p < 0.01). Additionally, the odds ratio for survival to discharge was 1.62 (95% CI, 1.13-2.34; p < 0.01) for female physicians with a female code nurse when compared with male physician code leaders paired with a female code nurse. Gender of code leader was not associated with cardiopulmonary resuscitation quality. CONCLUSIONS: In contrast to data derived from a simulated setting with medical students, real life female physician leadership of cardiopulmonary resuscitation is not associated with inferior outcomes. Appropriately, trained physicians can lead high-quality cardiopulmonary resuscitation irrespective of gender.

Ramelteon for Prevention of Postoperative Delirium: A Randomized Controlled Trial in Patients Undergoing Elective Pulmonary Thromboendarterectomy.

OBJECTIVES: To assess the efficacy of ramelteon in preventing delirium, an acute neuropsychiatric condition associated with increased morbidity and mortality, in the perioperative, ICU setting. DESIGN: Parallel-arm, randomized, double-blinded, placebo-controlled trial. SETTING: Academic medical center in La Jolla, California. PATIENTS: Patients greater than or equal to 18 years undergoing elective pulmonary thromboendarterectomy. INTERVENTIONS: Ramelteon 8 mg or matching placebo starting the night prior to surgery and for a maximum of six nights while in the ICU. MEASUREMENTS AND MAIN RESULTS: Incident delirium was measured twice daily using the Confusion Assessment Method-ICU. The safety outcome was coma-free days assessed by the Richmond Agitation-Sedation Scale. One-hundred twenty participants were enrolled and analysis completed in 117. Delirium occurred in 22 of 58 patients allocated to placebo versus 19 of 59 allocated to ramelteon (relative risk, 0.8; 95% CI, 0.5-1.4; p = 0.516). Delirium duration, as assessed by the number of delirium-free days was also similar in both groups (placebo median 2 d [interquartile range, 2-3 d] vs ramelteon 3 d [2-5 d]; p = 0.181). Coma-free days was also similar between groups (placebo median 2 d [interquartile range, 1-3 d] vs ramelteon 3 d [2-4 d]; p = 0.210). We found no difference in ICU length of stay (median 4 d [interquartile range, 3-5 d] vs 4 d [3-6 d]; p = 0.349), or in-hospital mortality (four vs three deaths; relative risk ratio, 0.7; 95% CI, 0.2-3.2; p = 0.717), all placebo versus ramelteon, respectively. CONCLUSIONS: Ramelteon 8 mg did not prevent postoperative delirium in patients admitted for elective cardiac surgery.

Sleep in the Intensive Care Unit: Strategies for Improvement.

Sleep in the intensive care unit (ICU) is considered to be subjectively poor, highly fragmented, and sometimes referred to as "atypical." Although sleep is felt to be crucial for patient recovery, little is known about the association of sleep with physiologic function among critically ill patients, or those with clinically important outcomes in the ICU. Research involving ICU-based sleep disturbance is challenging due to the lack of objective, practical, reliable, and scalable methods to measure sleep and the multifactorial etiologies of its disruption. Despite these challenges, research into sleep-promoting techniques is growing and has demonstrated a variety of causes leading to ICU-related sleep loss, thereby motivating multifaceted intervention efforts. Through a focused review of (1) sleep measurement in the ICU; (2) outcomes related to poor sleep in the ICU; and (3) ICU-based sleep promotion efforts including environmental, nonpharmacological, and pharmacological interventions, this paper examines research regarding sleep in the ICU and highlights the need for future investigation into this complex and dynamic field.

Automatic EPAP intelligent volume-assured pressure support is effective in patients with chronic respiratory failure: A randomized trial.

BACKGROUND AND OBJECTIVE: Patients with chronic respiratory failure are increasingly managed with domiciliary non-invasive ventilation (NIV). There may be limited ability to provide NIV titration for these complex patients, and ventilatory requirements and upper airway support needs may change over time. Therefore, an automatically adjusting expiratory positive airway pressure (AutoEPAP) algorithm may offer advantages over manually adjusted EPAP for treating these patients. This study compared 4% oxygen desaturation index (ODI4%) values during the use of an AutoEPAP algorithm versus manual EPAP titration with the intelligent volume-assured pressure support (iVAPS) algorithm. METHODS: This prospective, single-blind, randomized, crossover study was conducted at six US sites. Patients with chronic respiratory failure (neuromuscular disease, chronic obstructive pulmonary disease, obesity hypoventilation and other aetiologies) and an apnoea-hypopnoea index of >5/h who were already established NIV users underwent a single night of NIV with the iVAPS manual EPAP and iVAPS AutoEPAP in the sleep laboratory in random order. RESULTS: A total of 38 patients constituted the study population. Mean ODI4% was statistically non-inferior with AutoEPAP versus manual EPAP (P < 0.0001). There was no difference in the effect on ODI4% across respiratory failure subgroups. Ventilation parameters and gas exchange were similar with either NIV mode, indicating equally effective treatment of respiratory failure. Sleep parameters were improved during AutoEPAP versus manual EPAP. CONCLUSION: A single night of NIV using the iVAPS with AutoEPAP algorithm was non-inferior to a single night of iVAPS with manual EPAP titration in patients with respiratory failure. CLINICAL TRIAL REGISTRATION: NCT02683772 at clinicaltrials.gov.

Research Priorities in Pathophysiology for Sleep-disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Research Statement.

BACKGROUND: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are common conditions; the co-occurrence of these diseases, called the overlap syndrome (OVS), has been associated with poor health outcomes. PURPOSE: The purpose of this Official American Thoracic Society Research Statement is to describe pathophysiology, epidemiology, outcomes, diagnostic metrics, and treatment of OVS, as well as to identify important gaps in knowledge and make recommendations for future research. METHODS: Clinicians and researchers with expertise in sleep medicine, pulmonary medicine, or both were invited to participate. Topics were divided among the participants according to their interest and expertise. A literature search was conducted; the search was not a formal systematic review. Evidence was considered and supplemented with the panelists' nonsystematic clinical observations. Important knowledge gaps were identified. RESULTS: Recommendations for research to fill existing knowledge gaps were made. The recommendations were formulated by discussion and consensus. CONCLUSIONS: Many important questions about OVS exist. This American Thoracic Society Research Statement highlights the types of research that leading clinicians and researchers believe will have the greatest impact on better understanding the spectrum of disease, improving diagnosis, and optimizing therapy.