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1.
Am J Respir Crit Care Med ; 209(1): 37-47, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37487152

ABSTRACT

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.


Subject(s)
Respiratory Distress Syndrome , Humans , Prospective Studies , Reproducibility of Results , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Oximetry , Oxygen
2.
Am J Respir Crit Care Med ; 209(11): 1304-1313, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38477657

ABSTRACT

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproved. The NHLBI of the NIH assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and well-being of ARDS survivors.


Subject(s)
Respiratory Distress Syndrome , Survivors , Humans , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/physiopathology , United States , National Heart, Lung, and Blood Institute (U.S.) , Quality of Life , Brain/physiopathology
3.
Crit Care Med ; 52(5): 743-751, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38214566

ABSTRACT

OBJECTIVES: Ventilator dyssynchrony may be associated with increased delivered tidal volumes (V t s) and dynamic transpulmonary pressure (ΔP L,dyn ), surrogate markers of lung stress and strain, despite low V t ventilation. However, it is unknown which types of ventilator dyssynchrony are most likely to increase these metrics or if specific ventilation or sedation strategies can mitigate this potential. DESIGN: A prospective cohort analysis to delineate the association between ten types of breaths and delivered V t , ΔP L,dyn , and transpulmonary mechanical energy. SETTING: Patients admitted to the medical ICU. PATIENTS: Over 580,000 breaths from 35 patients with acute respiratory distress syndrome (ARDS) or ARDS risk factors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received continuous esophageal manometry. Ventilator dyssynchrony was identified using a machine learning algorithm. Mixed-effect models predicted V t , ΔP L,dyn , and transpulmonary mechanical energy for each type of ventilator dyssynchrony while controlling for repeated measures. Finally, we described how V t , positive end-expiratory pressure (PEEP), and sedation (Richmond Agitation-Sedation Scale) strategies modify ventilator dyssynchrony's association with these surrogate markers of lung stress and strain. Double-triggered breaths were associated with the most significant increase in V t , ΔP L,dyn , and transpulmonary mechanical energy. However, flow-limited, early reverse-triggered, and early ventilator-terminated breaths were also associated with significant increases in V t , ΔP L,dyn , and energy. The potential of a ventilator dyssynchrony type to increase V t , ΔP L,dyn , or energy clustered similarly. Increasing set V t may be associated with a disproportionate increase in high-volume and high-energy ventilation from double-triggered breaths, but PEEP and sedation do not clinically modify the interaction between ventilator dyssynchrony and surrogate markers of lung stress and strain. CONCLUSIONS: Double-triggered, flow-limited, early reverse-triggered, and early ventilator-terminated breaths are associated with increases in V t , ΔP L,dyn , and energy. As flow-limited breaths are more than twice as common as double-triggered breaths, further work is needed to determine the interaction of ventilator dyssynchrony frequency to cause clinically meaningful changes in patient outcomes.


Subject(s)
Respiration, Artificial , Respiratory Distress Syndrome , Humans , Respiration, Artificial/adverse effects , Prospective Studies , Ventilators, Mechanical , Tidal Volume , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/etiology , Biomarkers
4.
Crit Care Med ; 52(7): 1043-1053, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38506571

ABSTRACT

OBJECTIVES: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death. DESIGN: A retrospective multicenter cohort study. SETTING: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States. PATIENTS: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40). CONCLUSIONS: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice.


Subject(s)
Hypnotics and Sedatives , Noninvasive Ventilation , Humans , Noninvasive Ventilation/methods , Retrospective Studies , Male , Female , Middle Aged , Aged , United States , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/therapeutic use , Respiratory Insufficiency/therapy , Respiratory Insufficiency/mortality , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Adult , Analgesia/methods , Analgesia/statistics & numerical data , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/mortality , Benzodiazepines/therapeutic use , Benzodiazepines/administration & dosage
5.
Crit Care Med ; 51(10): 1373-1385, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37246922

ABSTRACT

OBJECTIVE: To explore if patient characteristics (pre-existing comorbidity, age, sex, and illness severity) modify the effect of physical rehabilitation (intervention vs control) for the coprimary outcomes health-related quality of life (HRQoL) and objective physical performance using pooled individual patient data from randomized controlled trials (RCTs). DATA SOURCES: Data of individual patients from four critical care physical rehabilitation RCTs. STUDY SELECTION: Eligible trials were identified from a published systematic review. DATA EXTRACTION: Data sharing agreements were executed permitting transfer of anonymized data of individual patients from four trials to form one large, combined dataset. The pooled trial data were analyzed with linear mixed models fitted with fixed effects for treatment group, time, and trial. DATA SYNTHESIS: Four trials contributed data resulting in a combined total of 810 patients (intervention n = 403, control n = 407). After receiving trial rehabilitation interventions, patients with two or more comorbidities had HRQoL scores that were significantly higher and exceeded the minimal important difference at 3 and 6 months compared with the similarly comorbid control group (based on the Physical Component Summary score (Wald test p = 0.041). Patients with one or no comorbidities who received intervention had no HRQoL outcome differences at 3 and 6 months when compared with similarly comorbid control patients. No patient characteristic modified the physical performance outcome in patients who received physical rehabilitation. CONCLUSIONS: The identification of a target group with two or more comorbidities who derived benefits from the trial interventions is an important finding and provides direction for future investigations into the effect of rehabilitation. The multimorbid post-ICU population may be a select population for future prospective investigations into the effect of physical rehabilitation.


Subject(s)
Critical Illness , Multimorbidity , Humans , Adult , Critical Illness/rehabilitation , Randomized Controlled Trials as Topic , Quality of Life , Critical Care
6.
Respir Res ; 24(1): 177, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37415141

ABSTRACT

BACKGROUND: Sepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis. METHODS: We genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets. RESULTS: Among AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P < 0.008-0.049). Two out of six SNPs (rs561525 and rs2163059) were associated with risk of sepsis-associated ARDS in an independent validation cohort (GEN-SEP) of 590 sepsis patients of European descent. Two common SNPs (rs1884725 and rs4952085) in tight linkage disequilibrium (LD) provided strong evidence for association with increased levels of serum creatinine (Padjusted<0.0005 and 0.0006, respectively), suggesting a role in increased risk of renal dysfunction. In contrast, among EA ARDS patients, the missense variant rs17011368 (I703V) was associated with enhanced mortality at 60-days (P < 0.038). We found higher serum XOR activity in 143 sepsis patients (54.5 ± 57.1 mU/mL) compared to 31 controls (20.9 ± 12.4 mU/mL, P = 1.96 × 10- 13). XOR activity was associated with the lead variant rs185925 among AA sepsis patients with ARDS (P < 0.005 and Padjusted<0.01). Multifaceted functions of prioritized XDH variants, as suggested by various functional annotation tools, support their potential causality in sepsis. CONCLUSIONS: Our findings suggest that XOR is a novel combined genetic and biochemical marker for risk and outcome in patients with sepsis and ARDS.


Subject(s)
Respiratory Distress Syndrome , Sepsis , Humans , Xanthine Dehydrogenase/genetics , Genotype , Polymorphism, Single Nucleotide/genetics , Sepsis/diagnosis , Sepsis/genetics , Sepsis/complications
7.
N Engl J Med ; 380(21): 1997-2008, 2019 05 23.
Article in English | MEDLINE | ID: mdl-31112383

ABSTRACT

BACKGROUND: The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS: We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS: The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS: Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).


Subject(s)
Atracurium/analogs & derivatives , Neuromuscular Blocking Agents/therapeutic use , Positive-Pressure Respiration , Respiratory Distress Syndrome/drug therapy , Adult , Aged , Atracurium/adverse effects , Atracurium/therapeutic use , Combined Modality Therapy , Conscious Sedation , Female , Hospital Mortality , Humans , Male , Middle Aged , Neuromuscular Blockade , Neuromuscular Blocking Agents/adverse effects , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Treatment Failure
8.
Crit Care Med ; 50(4): 644-654, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34605778

ABSTRACT

OBJECTIVES: Vasopressin is suggested as an adjunct to norepinephrine in patients with septic shock. However, after vasopressin was rebranded in November 2014, its cost exponentially increased. Utilization patterns of vasopressin after its rebranding are unclear. The objective of this study was to determine if there is an association between the rebranding of vasopressin in November 2014 and its utilization in vasopressor-dependent patients with severe sepsis or septic shock. DESIGN: Retrospective, multicenter, database study between January 2010 and March 2017. SETTING: Premier Healthcare Database hospitals. PATIENTS: Adult patients admitted to an ICU with severe sepsis or septic shock, who received at least one vasoactive agent for two or more calendar days were included. INTERVENTIONS: The proportion of patients who received vasopressin and vasopressin cost was assessed before and after rebranding, and evaluated with segmented regression. MEASUREMENTS AND MAIN RESULTS: Among 294,733 patients (mean age, 66 ± 15 yr), 27.8% received vasopressin, and ICU mortality was 26.5%. The proportion of patients receiving vasopressin was higher after rebranding (31.2% postrebranding vs 25.8% prerebranding). Before vasopressin rebranding, the quarterly proportion of patients who received vasopressin had an increasing slope (prerebranding slope 0.41% [95% CI, 0.35-0.46%]), with no difference in slope detected after vasopressin rebranding (postrebranding slope, 0.47% [95% CI, 0.29-0.64%]). After vasopressin rebranding, mean vasopressin cost per patient was higher ($527 ± 1,130 vs $77 ± 160), and the quarterly slope of vasopressin cost was higher (change in slope $77.18 [95% CI, $75.73-78.61]). Total vasopressin billed cost postrebranding continually increased by ~$294,276 per quarter from less than $500,000 in Q4 2014 to over $3,000,000 in Q1 2017. CONCLUSIONS: After vasopressin rebranding, utilization continued to increase quarterly despite a significant increase in vasopressin cost. Vasopressin appeared to have price inelastic demand in septic shock.


Subject(s)
Shock, Septic , Aged , Aged, 80 and over , Humans , Middle Aged , Norepinephrine/therapeutic use , Retrospective Studies , Vasoconstrictor Agents/therapeutic use , Vasopressins/therapeutic use
9.
Crit Care Med ; 50(12): 1689-1700, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36300945

ABSTRACT

OBJECTIVES: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic. DESIGN: Cross-sectional survey using four validated instruments. SETTING: Sixty-two sites in Canada and the United States. SUBJECTS: Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and self-reported moral distress (240 [56.9%]) and burnout (259 [63.8%]). Of the 10 top-ranked items that incited moral distress, most pertained to regulatory/organizational ( n = 6) or local/institutional ( n = 2) issues or both ( n = 2). Average moral distress (95.6 ± 66.9), professional fulfilment (6.5 ± 2.1), and burnout scores (3.6 ± 2.0) were moderate with 227 physicians (54.6%) meeting burnout criteria. A significant dose-response existed between COVID-19 patient volume and moral distress scores. Physicians who worked more days/mo and more scheduled in-house nightshifts, especially combined with more unscheduled in-house nightshifts, experienced significantly more moral distress. One in five physicians used at least one maladaptive coping strategy. We identified four coping profiles (active/social, avoidant, mixed/ambivalent, infrequent) that were associated with significant differences across all wellness measures. CONCLUSIONS: Despite moderate intrapandemic moral distress and burnout, physicians experienced moderate professional fulfilment. However, one in five physicians used at least one maladaptive coping strategy. We highlight potentially modifiable factors at individual, institutional, and regulatory levels to enhance physician wellness.


Subject(s)
Burnout, Professional , COVID-19 , Physicians , Adult , Male , Humans , Child , United States/epidemiology , Female , Cross-Sectional Studies , Pandemics , Burnout, Professional/epidemiology , Intensive Care Units , Adaptation, Psychological , Surveys and Questionnaires , North America
10.
BMC Health Serv Res ; 22(1): 627, 2022 May 11.
Article in English | MEDLINE | ID: mdl-35546236

ABSTRACT

BACKGROUND: Recently, there has been increasing evidence that reducing burnout in healthcare providers requires significant organizational efforts that include the integration of leadership strategies. METHODS: Focus groups were conducted across four health systems within the University of Colorado Department of Medicine in four affinity groups (administrative staff, medical trainees, research faculty, and clinical faculty). Authentic leadership theory was used for analysis to advance the understanding of the role of leadership style upon participants' work experiences and preferences, and to identify opportunities for translation of site-specific results to other academic medical settings. RESULTS: Study participants from each affinity group believed their clinical leaders lacked objectivity with decision-making (lacking "balancing processing"), which contributed to their overall feeling of powerlessness. The experience of increasing work demands was salient throughout all twelve focus groups, and participants identified leadership that interacted in a more open and self-disclosing manner ("relational transparency") as alleviating at least some of this burden. Strong preference discernable alignment between their leaders' decision-making and their internal moral compass of values (demonstrating "internalized moral perspective") was described, as was clinical leaders demonstrating "self-awareness" (having a self-reflective process that informs the leader's decision-making). Comparing affinity group experiences within each authentic leadership theory construct identified the relevance of contextual factors, such as work setting and roles, upon employees' perceptions and expectations of their leaders. CONCLUSIONS: Use of authentic leadership theory advanced the understanding of the association between leadership traits and experiences of burnout amongst a large group of academic clinicians, researchers, trainees, and administrative staff. Leadership styles that promoted relationship transparency, openness, and support were preferred and fostering these traits may help address the demands in academic medicine, including symptoms of burnout.


Subject(s)
Burnout, Professional , Leadership , Burnout, Professional/prevention & control , Burnout, Psychological , Humans , Organizations , Workplace
11.
Am J Respir Crit Care Med ; 202(11): 1520-1530, 2020 12 01.
Article in English | MEDLINE | ID: mdl-32663410

ABSTRACT

Rationale: Noninvasive ventilation decreases the need for invasive mechanical ventilation and mortality among patients with chronic obstructive pulmonary disease but has not been well studied in asthma.Objectives: To assess the association between noninvasive ventilation and subsequent need for invasive mechanical ventilation and in-hospital mortality among patients admitted with asthma exacerbation to the ICU.Methods: We performed a retrospective cohort study using administrative data collected during 2010-2017 from 682 hospitals in the United States. Outcomes included receipt of invasive mechanical ventilation and in-hospital mortality. Generalized estimating equations, propensity-matched models, and marginal structural models were used to assess the association between noninvasive ventilation and outcomes.Measurements and Main Results: The study population included 53,654 participants with asthma exacerbation. During the study period, 13,540 patients received noninvasive ventilation (25.2%; 95% confidence interval [CI], 24.9-25.6%), 14,498 underwent invasive mechanical ventilation (27.0%; 95% CI, 26.7-27.4%), and 1,291 died (2.4%; 95% CI, 2.3-2.5%). Among those receiving noninvasive ventilation, 3,013 patients (22.3%; 95% CI, 21.6-23.0%) required invasive mechanical ventilation after first receiving noninvasive ventilation, 136 of whom died (4.5%; 95% CI, 3.8-5.3%). Across all models, the use of noninvasive ventilation was associated with a lower odds of receiving invasive mechanical ventilation (adjusted generalized estimating equation odds ratio, 0.36; 95% CI, 0.32-0.40) and in-hospital mortality (odds ratio, 0.48; 95% CI 0.40-0.58). Those who received noninvasive ventilation before invasive mechanical ventilation were more likely to have comorbid pneumonia and severe sepsis.Conclusions: Noninvasive ventilation use during asthma exacerbation was associated with improved outcomes but should be used cautiously with acute comorbid conditions.


Subject(s)
Asthma/therapy , Hospital Mortality , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/methods , Respiratory Insufficiency/therapy , Adult , Aged , Asthma/epidemiology , Asthma/physiopathology , Cohort Studies , Comorbidity , Critical Care , Critical Care Outcomes , Critical Illness , Disease Progression , Female , Humans , Male , Middle Aged , Pneumonia/epidemiology , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/physiopathology , Retrospective Studies , Sepsis/epidemiology , Status Asthmaticus/epidemiology , Status Asthmaticus/physiopathology , Status Asthmaticus/therapy
12.
Am J Respir Crit Care Med ; 202(4): 511-523, 2020 Aug 15.
Article in English | MEDLINE | ID: mdl-32150460

ABSTRACT

Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the NHLBI. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising preclinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data," causal inference using observational data, novel clinical trial designs, preclinical disease modeling, and understanding of recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state of, research priorities for, and future directions in adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including 1) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment response with the goal of developing targeted, personalized interventions; 2) optimizing preclinical models by incorporating comorbidities, cointerventions, and organ support; 3) developing and applying novel clinical trial designs; and 4) advancing mechanistic understanding of injury and recovery to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.

13.
Dysphagia ; 36(5): 831-841, 2021 10.
Article in English | MEDLINE | ID: mdl-33156398

ABSTRACT

The mechanisms responsible for aspiration are relatively unknown in patients recovering from acute respiratory failure (ARF) who required mechanical ventilation. Though many conditions may contribute to swallowing dysfunction, alterations in laryngeal structure and swallowing function likely play a role in the development of aspiration. At four university-based tertiary medical centers, we conducted a prospective cohort study of ARF patients who required intensive care and mechanical ventilation for at least 48 h. Within 72 h after extubation, a Fiberoptic Flexible Endoscopic Evaluation of Swallowing (FEES) examination was performed. Univariate and multivariable analyses examined the relationship between laryngeal structure and swallowing function abnormalities. Aspiration was the primary outcome, defined as a Penetration- Aspiration Scale (PAS) score of 6 or greater. Two other salient signs of dysphagia-spillage and residue-were secondary outcomes. A total of 213 patients were included in the final analysis. Aspiration was detected in 70 patients (33%) on at least one bolus. The most commonly aspirated consistency was thin liquids (27%). In univariate analyses, several abnormalities in laryngeal anatomy and structural movement were significantly associated with aspiration, spillage, and residue. In a multivariable analysis, the only variables that remained significant with aspiration were pharyngeal weakness (Odds ratio = 2.57, 95%CI = 1.16-5.84, p = 0.019) and upper airway edema (Odds ratio = 3.24, 95%CI = 1.44-7.66, p = 0.004). These results demonstrated that dysphagia in ARF survivors is multifactorial and characterized by both anatomic and physiologic abnormalities. These findings may have important implications for the development of novel interventions to treat dysphagia in ARF survivors.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT02363686, Aspiration in Acute Respiratory Failure Survivors.


Subject(s)
Deglutition Disorders , Respiratory Insufficiency , Deglutition , Deglutition Disorders/etiology , Humans , Prospective Studies , Respiratory Aspiration/etiology , Respiratory Insufficiency/etiology , Survivors
14.
Dysphagia ; 36(2): 170-182, 2021 04.
Article in English | MEDLINE | ID: mdl-32654059

ABSTRACT

At the time of writing this paper, there are over 11 million reported cases of COVID-19 worldwide. Health professionals involved in dysphagia care are impacted by the COVID-19 pandemic in their day-to-day practices. Otolaryngologists, gastroenterologists, rehabilitation specialists, and speech-language pathologists are subject to virus exposure due to their proximity to the aerodigestive tract and reliance on aerosol-generating procedures in swallow assessments and interventions. Across the globe, professional societies and specialty associations are issuing recommendations about which procedures to use, when to use them, and how to reduce the risk of COVID-19 transmission during their use. Balancing safety for self, patients, and the public while maintaining adequate evidence-based dysphagia practices has become a significant challenge. This paper provides current evidence on COVID-19 transmission during commonly used dysphagia practices and provides recommendations for protection while conducting these procedures. The paper summarizes current understanding of dysphagia in patients with COVID-19 and draws on evidence for dysphagia interventions that can be provided without in-person consults and close proximity procedures including dysphagia screening and telehealth.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Deglutition Disorders/therapy , Infection Control/organization & administration , Telemedicine/organization & administration , COVID-19/transmission , Humans
15.
Am J Occup Ther ; 75(5)2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34780634

ABSTRACT

IMPORTANCE: Occupational therapy use in the neurological critical care unit (NCCU) may relate to patient factors, but data about these relationships remain unpublished. OBJECTIVE: To examine how patient factors predict NCCU occupational therapy use and intervention types. DESIGN: Retrospective cohort study of electronic health records data from adults admitted to the NCCU between May 2013 and September 2015. SETTING: NCCU in a large, urban academic hospital. PARTICIPANTS: Adults (age ≥18 yr; N = 1,134) admitted to the NCCU. MEASURES: Using length of stay (LOS), number of comorbidities, Glasgow Coma Scale (GCS) score, gender, age, and racial-ethnic minority status as independent variables, separate regression models identified predictors for each dependent variable: receipt of NCCU occupational therapy, occupational therapy onset (days after admission), and receipt of self-care or home management (ADL-Home); functional activities or cognitive training (Func-Cog); and therapeutic exercise (Ther-Ex). RESULTS: Four hundred twenty patients (37.0%) received occupational therapy in the NCCU. Receipt of occupational therapy was positively associated with LOS, number of comorbidities, GCS score, and age. Earlier occupational therapy onset was associated with higher GCS score and shorter LOS. Receipt of ADL-Home or Func-Cog interventions was significantly predicted by number of occupational therapy sessions, but patients with longer LOS were less likely to receive ADL-Home interventions. Receipt of Ther-Ex interventions became less likely as GCS score increased. CONCLUSIONS AND RELEVANCE: Patients are more likely to receive occupational therapy services if they are older and have a longer NCCU LOS, more comorbidities, and a higher level of consciousness. What This Article Adds: A patient's level of consciousness is clearly associated with occupational therapy utilization and hospital outcomes, but it should not be the only factor considered when prioritizing patients for NCCU occupational therapy services. Compared with patients who were more awake and alert, patients with a lower level of consciousness had a later onset of occupational therapy, which suggests an opportunity for NCCU occupational therapists to collaborate with physicians in the modification of sedation protocols to enable early rehabilitation.


Subject(s)
Ethnicity , Occupational Therapists , Adult , Critical Care , Humans , Length of Stay , Minority Groups , Retrospective Studies
17.
Crit Care Med ; 48(2): 249-253, 2020 02.
Article in English | MEDLINE | ID: mdl-31939795

ABSTRACT

OBJECTIVES: To summarize the results of expert discussions and recommendations from a National Summit and survey on the promoting wellness and preventing and managing burnout in the ICU. DATA SOURCES: Literature review; Critical Care Societies Collaborative (CCSC) Statement on Burnout Syndrome in Critical Care Healthcare Professionals: A Call for Action; CCSC's National Summit on Prevention and Management of Burnout in the ICU; and a descriptive survey on strategies for addressing burnout using Research Electronic Data Capture (REDCap) (project-redcap.org). DATA SYNTHESIS: Building on the CCSC call for action to address burnout among critical care professionals, the CCSC sponsored the National Summit on Prevention and Management of Burnout in the ICU with 55 invited experts in various fields including psychology, sociology, integrative medicine, psychiatry, suicide prevention, bereavement support, ethics, palliative care, meditation, mindfulness-based stress reduction, among others. Attendees joined breakout groups, to identify factors influencing burnout in ICU professionals and the value of organizational and individual interventions. As a follow-up to the Summit, a descriptive survey assessing strategies for addressing burnout was sent via email or newsletter blast with responses received from 680 CCSC members, including physicians, nurses, pharmacists, therapists, and others. CONCLUSIONS: The Summit attendees identified the importance of raising awareness among critical care clinicians and key stakeholders, advocating for workplace changes to promote healthy work environments, and promoting research to further explore practical strategies to address, mitigate, and prevent burnout. Critical care clinicians reported that a number of initiatives are being implemented both at their hospitals and at the unit level to build resilience and address burnout prevention. However, other respondents reported that no measures were being used within their organizations, and that colleagues were experiencing burnout. Dissemination and application of resiliency building measures and strategies to address burnout in critical care clinicians are needed.


Subject(s)
Burnout, Professional/prevention & control , Critical Care/psychology , Health Personnel/psychology , Humans , Intensive Care Units , Resilience, Psychological , Workplace/psychology
18.
Crit Care Med ; 48(8): 1103-1110, 2020 08.
Article in English | MEDLINE | ID: mdl-32697479

ABSTRACT

OBJECTIVES: The financial burdens and subsequent related distress of medical care, referred to as financial toxicity, may limit access to beneficial treatments. However, financial toxicity after acute care is less described-and may be an important but underexplored mechanism preventing full recovery after critical illnesses such as acute respiratory distress syndrome. We sought to identify the mechanisms by which financial toxicity manifested in patients with acute respiratory distress syndrome, protective factors against such toxicity, and the consequences of financial toxicity to survivors' lives following acute respiratory distress syndrome. DESIGN: We conducted semistructured interviews following patients' hospitalization and during recovery as an ancillary study to a multicenter randomized clinical trial in acute respiratory distress syndrome. Patients were 9-16 months post randomization at the time of interview. SETTING AND PARTICIPANTS: The Reevaluation Of Systemic Early Neuromuscular Blockade trial examined the use of early neuromuscular blockade in mechanically ventilated patients with moderate/severe acute respiratory distress syndrome. We recruited consecutive surviving patients who were English speaking, consented to follow-up, and were randomized between December 11, 2017, and May 4, 2018 (n = 79) from 29 U.S. sites. MEASUREMENTS AND MAIN RESULTS: We asked about patients' perceptions of financial burden(s) that they associated with their acute respiratory distress syndrome hospitalization. Forty-six of 79 eligible acute respiratory distress syndrome survivors (58%) participated (from 22 sites); their median age was 56 (interquartile range 47-62). Thirty-one of 46 reported at least one acute respiratory distress syndrome-related financial impact. Financial toxicity manifested via medical bills, changes in insurance coverage, and loss of employment income. Respondents reported not working prior to acute respiratory distress syndrome, using Medicaid or Medicare, or, conversely, generous work benefits as factors which may have limited financial burdens. Patients reported multiple consequences of acute respiratory distress syndrome-related financial toxicity, including harms to their mental and physical health, increased reliance on others, and specific material hardships. CONCLUSIONS: Financial toxicity related to critical illness is common and may limit patients' emotional, physical, and social recovery after acute respiratory distress syndrome hospitalization for at least a year.


Subject(s)
Cost of Illness , Financing, Personal/economics , Respiratory Distress Syndrome/economics , Female , Health Care Costs , Humans , Income , Insurance Coverage/economics , Insurance, Health/economics , Interviews as Topic , Male , Middle Aged
19.
Crit Care Med ; 48(11): 1604-1611, 2020 11.
Article in English | MEDLINE | ID: mdl-32804785

ABSTRACT

OBJECTIVES: To determine whether a modifiable risk factor, endotracheal tube size, is associated with the diagnosis of postextubation aspiration in survivors of acute respiratory failure. DESIGN: Prospective cohort study. SETTING: ICUs at four academic tertiary care medical centers. PATIENTS: Two hundred ten patients who were at least 18 years old, admitted to an ICU, and mechanically ventilated with an endotracheal tube for longer than 48 hours were enrolled. INTERVENTIONS: Within 72 hours of extubation, all patients received a flexible endoscopic evaluation of swallowing examination that entailed administration of ice, thin liquid, thick liquid, puree, and cracker boluses. Patient demographics, treatment variables, and hospital outcomes were abstracted from the patient's medical records. Endotracheal tube size was independently selected by the patient's treating physicians. MEASUREMENTS AND MAIN RESULTS: For each flexible endoscopic evaluation of swallowing examination, laryngeal pathology was evaluated, and for each bolus, a Penetration Aspiration Scale score was assigned. Aspiration (Penetration Aspiration Scale score ≥ 6) was further categorized into nonsilent aspiration (Penetration Aspiration Scale score = 6 or 7) and silent aspiration (Penetration Aspiration Scale score = 8). One third of patients (n = 68) aspirated (Penetration Aspiration Scale score ≥ 6) on at least one bolus, 13.6% (n = 29) exhibited silent aspiration, and 23.8% (n = 50) exhibited nonsilent aspiration. In a multivariable analysis, endotracheal tube size (≤ 7.5 vs ≥ 8.0) was significantly associated with patients exhibiting any aspiration (Penetration Aspiration Scale score ≥ 6) (p = 0.016; odds ratio = 2.17; 95% CI 1.14-4.13) and with risk of developing laryngeal granulation tissue (p = 0.02). CONCLUSIONS: Larger endotracheal tube size was associated with increased risk of aspiration and laryngeal granulation tissue. Using smaller endotracheal tubes may reduce the risk of postextubation aspiration.


Subject(s)
Deglutition , Intubation, Intratracheal/instrumentation , Respiratory Aspiration/etiology , Respiratory Insufficiency/therapy , Aged , Deglutition/physiology , Female , Humans , Intensive Care Units , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/methods , Male , Middle Aged , Prospective Studies , Respiration, Artificial/adverse effects , Respiration, Artificial/instrumentation , Respiration, Artificial/methods , Risk Factors , Survivors/statistics & numerical data
20.
JAMA ; 324(21): 2165-2176, 2020 12 01.
Article in English | MEDLINE | ID: mdl-33165621

ABSTRACT

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration: ClinicalTrials.gov: NCT04332991.


Subject(s)
COVID-19 Drug Treatment , Hydroxychloroquine/therapeutic use , Adult , Aged , Female , Humans , Hydroxychloroquine/administration & dosage , Male , Middle Aged , Treatment Failure
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