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.

Electronic Health Record-Driven Approaches in Primary Care to Strengthen Hypertension Management Among Racial and Ethnic Minoritized Groups in the United States: Systematic Review.

BACKGROUND: Managing hypertension in racial and ethnic minoritized groups (eg, African American/Black patients) in primary care is highly relevant. However, evidence on whether or how electronic health record (EHR)-driven approaches in primary care can help improve hypertension management for patients of racial and ethnic minoritized groups in the United States remains scarce. OBJECTIVE: This review aims to examine the role of the EHR in supporting interventions in primary care to strengthen the hypertension management of racial and ethnic minoritized groups in the United States. METHODS: A search strategy based on the PICO (Population, Intervention, Comparison, and Outcome) guidelines was utilized to query and identify peer-reviewed articles on the Web of Science and PubMed databases. The search strategy was based on terms related to racial and ethnic minoritized groups, hypertension, primary care, and EHR-driven interventions. Articles were excluded if the focus was not hypertension management in racial and ethnic minoritized groups or if there was no mention of health record data utilization. RESULTS: A total of 29 articles were included in this review. Regarding populations, Black/African American patients represented the largest population (26/29, 90%) followed by Hispanic/Latino (18/29, 62%), Asian American (7/29, 24%), and American Indian/Alaskan Native (2/29, 7%) patients. No study included patients who identified as Native Hawaiian/Pacific Islander. The EHR was used to identify patients (25/29, 86%), drive the intervention (21/29, 72%), and monitor results and outcomes (7/29, 59%). Most often, EHR-driven approaches were used for health coaching interventions, disease management programs, clinical decision support (CDS) systems, and best practice alerts (BPAs). Regarding outcomes, out of 8 EHR-driven health coaching interventions, only 3 (38%) reported significant results. In contrast, all the included studies related to CDS and BPA applications reported some significant results with respect to improving hypertension management. CONCLUSIONS: This review identified several use cases for the integration of the EHR in supporting primary care interventions to strengthen hypertension management in racial and ethnic minoritized patients in the United States. Some clinical-based interventions implementing CDS and BPA applications showed promising results. However, more research is needed on community-based interventions, particularly those focusing on patients who are Asian American, American Indian/Alaskan Native, and Native Hawaiian/Pacific Islander. The developed taxonomy comprising "identifying patients," "driving intervention," and "monitoring results" to classify EHR-driven approaches can be a helpful tool to facilitate this.

Evaluating maternal health capacity building in rural and underserved areas: a research protocol.

INTRODUCTION: The US is currently experiencing a maternal health crisis. Maternal morbidity and mortality in the US are higher than in other developed nations and continue to rise. Infant mortality, likewise, is higher in the US than in other developed nations. Limited availability of maternal health services, particularly in rural areas, contributes to this crisis. Maternal health outcomes are poorer, and maternal care workforce shortages are more severe in rural areas of the US. In rural areas where obstetric specialists are rare, many patients rely on family medicine physicians for maternity care. However, the number of family medicine physicians who provide maternal care services is decreasing, aggravating shortages. Calls have been made to build maternal care capacity in rural areas. The role family medicine will play in addressing the maternal health crisis is not clear. Maternal care shortages are complex issues resulting from multiple factors; likewise, efforts to build maternal health capacity are challenging and require multifaceted approaches. METHODS: With funding from the Health Resources and Services Administration (HRSA), the University of Utah seeks to address the shortage of quality maternity care in rural and underserved areas of Utah by strengthening partnerships, enhancing maternal care training of family medicine residents and obstetrics fellows, and improving the transition from training to rural practice for residents and fellows. This protocol describes the evaluation of the HRSA-funded project. The evaluation includes three components. Component 1 consists of qualitative interviews with a diverse group of maternal health providers, administrators, educators and academics, patients, and others. Interviews will be analyzed using qualitative content analysis. Component 2 is a survey of family medicine residents and obstetrics fellows, which aims to increase understanding of the factors and circumstances influencing intention to practice in rural or underserved areas and to provide maternal health services. Component 3 involves surveying fellowship alumni and tracking graduates to assess effectiveness of training programs in producing physicians who provide maternal health services in rural and underserved areas. Surveys will be analyzed with descriptive statistics including means, frequencies, and cross-tabulations. If sample size and participation provide sufficient power, statistical tests will be included in analyses. RESULTS: Evaluation results will help to fill an important gap in research literature concerning outcomes of projects and initiatives designed to build maternal care capacity in rural areas of the US. In addition, results will provide valuable information regarding effective practices for building capacity, which can be adopted elsewhere to address maternal care shortages. Finally, results will help to define the role of family medicine in addressing the maternal health crisis. Amid maternal care shortages, fewer and fewer family medicine physicians are providing maternal care in their practice. Evaluation results will clarify the role of training and preparation of family medicine residents in addressing workforce shortages. CONCLUSION: This evaluation will provide important contributions, but additional research is needed, including research protocols and studies of project outcomes, to understand how best to resolve the maternal care crisis in the US.

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.

Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer.

BACKGROUND: The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS: Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors. RESULTS: Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76-21.32) months compared to 11.3 (95% CI 9.86-15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04-8.65; p = 0.037). CONCLUSIONS: CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer. CLINICAL TRIAL REGISTRATION: The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).

ICTV Virus Taxonomy Profile: Pospiviroidae.

Members of the family Pospiviroidae have single-stranded circular RNA genomes that adopt a rod-like or a quasi-rod-like conformation. These genomes contain a central conserved region that is involved in replication in the nucleus through an asymmetric RNA-RNA rolling-circle mechanism. Members of the family Pospiviroidae lack the hammerhead ribozymes that are typical of viroids classified in the family Avsunviroidae. The family Pospiviroidae includes the genera Apscaviroid, Cocadviroid, Coleviroid, Hostuviroid and Pospiviroid, with >25 species. This is a summary of the ICTV Report on the family Pospiviroidae, which is available at ictv.global/report/pospiviroidae.

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 .).

Silencing of transcription factor encoding gene StTCP23 by small RNAs derived from the virulence modulating region of potato spindle tuber viroid is associated with symptom development in potato.

Viroids are small, non-protein-coding RNAs which can induce disease symptoms in a variety of plant species. Potato (Solanum tuberosum L.) is the natural host of Potato spindle tuber viroid (PSTVd) where infection results in stunting, distortion of leaves and tubers and yield loss. Replication of PSTVd is accompanied by the accumulation of viroid-derived small RNAs (sRNAs) proposed to play a central role in disease symptom development. Here we report that PSTVd sRNAs direct RNA silencing in potato against StTCP23, a member of the TCP (teosinte branched1/Cycloidea/Proliferating cell factor) transcription factor family genes that play an important role in plant growth and development as well as hormonal regulation, especially in responses to gibberellic acid (GA). The StTCP23 transcript has 21-nucleotide sequence complementarity in its 3' untranslated region with the virulence-modulating region (VMR) of PSTVd strain RG1, and was downregulated in PSTVd-infected potato plants. Analysis using 3' RNA ligase-mediated rapid amplification of cDNA ends (3' RLM RACE) confirmed cleavage of StTCP23 transcript at the expected sites within the complementarity with VMR-derived sRNAs. Expression of these VMR sRNA sequences as artificial miRNAs (amiRNAs) in transgenic potato plants resulted in phenotypes reminiscent of PSTVd-RG1-infected plants. Furthermore, the severity of the phenotypes displayed was correlated with the level of amiRNA accumulation and the degree of amiRNA-directed down-regulation of StTCP23. In addition, virus-induced gene silencing (VIGS) of StTCP23 in potato also resulted in PSTVd-like phenotypes. Consistent with the function of TCP family genes, amiRNA lines in which StTCP23 expression was silenced showed a decrease in GA levels as well as alterations to the expression of GA biosynthesis and signaling genes previously implicated in tuber development. Application of GA to the amiRNA plants minimized the PSTVd-like phenotypes. Taken together, our results indicate that sRNAs derived from the VMR of PSTVd-RG1 direct silencing of StTCP23 expression, thereby disrupting the signaling pathways regulating GA metabolism and leading to plant stunting and formation of small and spindle-shaped tubers.

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.