MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study.

BACKGROUND: The MUC5B promoter variant (rs35705950) and telomere length are linked to pulmonary fibrosis and CT-based qualitative assessments of interstitial abnormalities, but their associations with longitudinal quantitative changes of the lung interstitium among community-dwelling adults are unknown. METHODS: We used data from participants in the Multi-Ethnic Study of Atherosclerosis with high-attenuation areas (HAAs, Examinations 1-6 (2000-2018)) and MUC5B genotype (n=4552) and telomere length (n=4488) assessments. HAA was defined as the per cent of imaged lung with attenuation of -600 to -250 Hounsfield units. We used linear mixed-effects models to examine associations of MUC5B risk allele (T) and telomere length with longitudinal changes in HAAs. Joint models were used to examine associations of longitudinal changes in HAAs with death and interstitial lung disease (ILD). RESULTS: The MUC5B risk allele (T) was associated with an absolute change in HAAs of 2.60% (95% CI 0.36% to 4.86%) per 10 years overall. This association was stronger among those with a telomere length below an age-adjusted percentile of 5% (p value for interaction=0.008). A 1% increase in HAAs per year was associated with 7% increase in mortality risk (rate ratio (RR)=1.07, 95% CI 1.02 to 1.12) for overall death and 34% increase in ILD (RR=1.34, 95% CI 1.20 to 1.50). Longer baseline telomere length was cross-sectionally associated with less HAAs from baseline scans, but not with longitudinal changes in HAAs. CONCLUSIONS: Longitudinal increases in HAAs were associated with the MUC5B risk allele and a higher risk of death and ILD.

Fibrotic-Like Pulmonary Radiographic Patterns Are Not Associated With Adverse Outcomes in COVID-19 Chronic Critical Illness.

OBJECTIVES: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness. DESIGN: Single-center prospective cohort study. SETTING: We examined chest CT scans performed between ICU discharge and 30 days after hospital discharge using established methods to quantify nonfibrotic and fibrotic-like patterns. PATIENTS: Adults hospitalized with COVID-19-related ARDS and chronic critical illness (> 21 d of mechanical ventilation, tracheostomy, and survival to ICU discharge) between March 2020 and May 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested associations of fibrotic-like patterns with clinical characteristics and biomarkers, and with time to mechanical ventilator liberation and 6-month survival, controlling for demographics, comorbidities, and COVID-19 therapies. A total of 141 of 616 adults (23%) with COVID-19-related ARDS developed chronic critical illness, and 64 of 141 (46%) had a chest CT a median (interquartile range) 66 days (42-82 d) after intubation. Fifty-five percent had fibrotic-like patterns characterized by reticulations and/or traction bronchiectasis. In adjusted analyses, interleukin-6 level on the day of intubation was associated with fibrotic-like patterns (odds ratio, 4.40 per quartile change; 95% CI, 1.90-10.1 per quartile change). Other inflammatory biomarkers, Sequential Organ Failure Assessment score, age, tidal volume, driving pressure, and ventilator days were not. Fibrotic-like patterns were not associated with longer time to mechanical ventilator liberation or worse 6-month survival. CONCLUSIONS: Approximately half of adults with COVID-19-associated chronic critical illness have fibrotic-like patterns that are associated with higher interleukin-6 levels at intubation. Fibrotic-like patterns are not associated with longer time to liberation from mechanical ventilation or worse 6-month survival.

Risks and Benefits of Ultra-Lung-Protective Invasive Mechanical Ventilation Strategies with a Focus on Extracorporeal Support.

Lung-protective ventilation strategies are the current standard of care for patients with acute respiratory distress syndrome in an effort to provide adequate ventilatory requirements while minimizing ventilator-induced lung injury. Some patients may benefit from ultra-lung-protective ventilation, a strategy that achieves lower airway pressures and Vt than the current standard. Specific physiological parameters beyond severity of hypoxemia, such as driving pressure and respiratory system elastance, may be predictive of those most likely to benefit. Because application of ultra-lung-protective ventilation is often limited by respiratory acidosis, extracorporeal membrane oxygenation or extracorporeal carbon dioxide removal, which remove carbon dioxide from blood, is an attractive option. These strategies are associated with hematological complications, especially when applied at low blood-flow rates with devices designed for higher blood flows, and a recent large randomized controlled trial failed to show a benefit from an extracorporeal carbon dioxide removal-facilitated ultra-lung-protective ventilation strategy. Only in patients with very severe forms of acute respiratory distress syndrome has the use of an ultra-lung-protective ventilation strategy-accomplished with extracorporeal membrane oxygenation-been suggested to have a favorable risk-to-benefit profile. In this critical care perspective, we address key areas of controversy related to ultra-lung-protective ventilation, including the trade-offs between minimizing ventilator-induced lung injury and the risks from strategies to achieve this added protection. In addition, we suggest which patients might benefit most from an ultra-lung-protective strategy and propose areas of future research.

Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation.

OBJECTIVES: In mechanically ventilated patients, deep sedation is often assumed to induce "respirolysis," that is, lyse spontaneous respiratory effort, whereas light sedation is often assumed to preserve spontaneous effort. This study was conducted to determine validity of these common assumptions, evaluating the association of respiratory drive with sedation depth and ventilator-free days in acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Patients were enrolled during 2 month-long periods in 2016-2017 from five ICUs representing medical, surgical, and cardiac specialties at a U.S. academic hospital. PATIENTS: Eligible patients were critically ill adults receiving invasive ventilation initiated no more than 36 hours before enrollment. Patients with neuromuscular disease compromising respiratory function or expiratory flow limitation were excluded. INTERVENTIONS: Respiratory drive was measured via P0.1, the change in airway pressure during a 0.1-second airway occlusion at initiation of patient inspiratory effort, every 12 ± 3 hours for 3 days. Sedation depth was evaluated via the Richmond Agitation-Sedation Scale. Analyses evaluated the association of P0.1 with Richmond Agitation-Sedation Scale (primary outcome) and ventilator-free days. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients undergoing 197 bedside evaluations across five ICUs were included. P0.1 ranged between 0 and 13.3 cm H2O (median [interquartile range], 0.1 cm H2O [0.0-1.3 cm H2O]). P0.1 was not significantly correlated with the Richmond Agitation-Sedation Scale (RSpearman, 0.02; 95% CI, -0.12 to 0.16; p = 0.80). Considering P0.1 terciles (range less than 0.2, 0.2-1.0, and greater than 1.0 cm H2O), patients in the middle tercile had significantly more ventilator-free days than the lowest tercile (incidence rate ratio, 0.78; 95% CI, 0.65-0.93; p < 0.01) or highest tercile (incidence rate ratio, 0.58; 95% CI, 0.48-0.70; p < 0.01). CONCLUSIONS: Sedation depth is not a reliable marker of respiratory drive during critical illness. Respiratory drive can be low, moderate, or high across the range of routinely targeted sedation depth.

Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis.

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.

A Time-Motion Study of ICU Workflow and the Impact of Strain.

OBJECTIVE: Understanding ICU workflow and how it is impacted by ICU strain is necessary for implementing effective improvements. This study aimed to quantify how ICU physicians spend time and to examine the impact of ICU strain on workflow. DESIGN: Prospective, observational time-motion study. SETTING: Five ICUs in two hospitals at an academic medical center. SUBJECTS: Thirty attending and resident physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 137 hours of field observations, the most time-84 hours (62% of total observation time)-was spent on professional communication. Reviewing patient data and documentation occupied a combined 52 hours (38%), whereas direct patient care and education occupied 24 hours (17%) and 13 hours (9%), respectively. The most frequently used tool was the computer, used in tasks that occupied 51 hours (37%). Severity of illness of the ICU on day of observation was the only strain factor that significantly impacted work patterns. In a linear regression model, increase in average ICU Sequential Organ Failure Assessment was associated with more time spent on direct patient care (ß = 4.3; 95% CI, 0.9-7.7) and education (ß = 3.2; 95% CI, 0.7-5.8), and less time spent on documentation (ß = -7.4; 95% CI, -11.6 to -3.2) and on tasks using the computer (ß = -7.8; 95% CI, -14.1 to -1.6). These results were more pronounced with a combined strain score that took into account unit census and Sequential Organ Failure Assessment score. After accounting for ICU type (medical vs surgical) and staffing structure (resident staffed vs physician assistant staffed), results changed minimally. CONCLUSION: Clinicians spend the bulk of their time in the ICU on professional communication and tasks involving computers. With the strain of high severity of illness and a full unit, clinicians reallocate time from documentation to patient care and education. Further efforts are needed to examine system-related aspects of care to understand the impact of workflow and strain on patient care.

Practices surrounding antimicrobial use in patients managed with extracorporeal membrane oxygenation: An international survey.

PURPOSE: This study aimed to survey critical care clinicians and characterize their perception of antimicrobial dosing strategies in patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: International, cross-sectional survey distributed to members of the Society of Critical Care Medicine in October 2022. RESULTS: Respondents were primarily physicians (45%), with 92% practicing in North America. Ninety-seven percent of respondents reported antimicrobial dosing in critically ill patients to be challenging, due to physiological derangements seen in the patient population. Eighty-seven percent reported consideration of physicochemical drug properties when dosing antimicrobials in ECMO-supported patients, with lipophilicity (83%) and degree of protein binding (74%) being the two most common. Respondents' approach to antimicrobial dosing strategies did not significantly differ in critically ill ECMO-supported patients, compared to patients with equal severity of illness not receiving ECMO support. CONCLUSION: Approaches to antimicrobial dosing strategies do not significantly differ among respondents between critically ill patients on ECMO support, compared to patients with equal severity of illness not receiving ECMO support. These findings were unexpected considering the added physiologic complexity of the ECMO circuit to critically ill adult patients and the need for well designed and adequately powered studies to inform empiric dosing guidance for ECMO-supported patients.

Approach to the Physiologically Challenging Endotracheal Intubation in the Intensive Care Unit.

Endotracheal intubation for airway management is a common procedure in the ICU. Intubation may be difficult due to anatomic airway abnormalities but also due to physiologic derangements that predispose patients to cardiovascular collapse during the procedure. Results of studies demonstrate a high incidence of morbidity and mortality associated with airway management in the ICU. To reduce the likelihood of complications, medical teams must be well versed in the general principles of intubation and be prepared to manage physiologic derangements while securing the airway. In this review, we present relevant literature on the approach to endotracheal intubation in the ICU and provide pragmatic recommendations relevant to medical teams performing intubations in patients who are physiologically unstable.

Age and associated outcomes among patients receiving venoarterial extracorporeal membrane oxygenation-analysis of the Extracorporeal Life Support Organization registry.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (V-A ECMO) can be used to support severely ill patients with cardiogenic shock. While age is commonly used in patient selection, little is known regarding its association with outcomes in this population. We sought to evaluate the association between increasing age and outcomes following V-A ECMO. METHODS: We used individual-level patient data from 440 centers in the international Extracorporeal Life Support Organization registry. We included all adult patients receiving V-A ECMO from 2017 to 2019. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of V-A ECMO. We conducted Bayesian analyses of the relationship between increasing age and outcomes of interest. RESULTS: We included 15,172 patients receiving V-A ECMO. Of these, 8172 (53.9%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18-29, the age bracket of 30-39 (odds ratio [OR] 0.94, 95% credible interval [CrI] 0.79-1.10) was not associated with hospital mortality, but age brackets 40-49 (odds ratio [OR] 1.26, 95% CrI: 1.08-1.47), 50-59 (OR 1.78, 95% CrI: 1.55-2.06), 60-69 (OR 2.24, 95% CrI: 1.94-2.59), 70-79 (OR 2.90, 95% CrI: 2.49-3.39) and ≥ 80 (OR 4.02, 95% CrI: 3.13-5.20) were independently associated with increasing hospital mortality. Similar results were found in the analysis conducted with an informative prior, as well as between increasing age and post-ECMO complications. CONCLUSIONS: Among patients receiving V-A ECMO for cardiogenic shock, increasing age is strongly associated with increasing odds of death and complications, and this association emerges as early as 40 years of age.

Early Mobilization during Extracorporeal Membrane Oxygenation for Cardiopulmonary Failure in Adults: Factors Associated with Intensity of Treatment.

Rationale: Early mobilization of extracorporeal membrane oxygenation (ECMO)-supported patients is increasingly common, but it remains unknown whether there are factors predictive of achieving higher intensity mobilization among those able to participate in physical therapy. Additionally, data regarding the safety and feasibility of early mobilization with femoral cannulation, particularly ambulation, are sparse. Objectives: To determine whether there are factors associated with achieving out-of-bed versus in-bed physical therapy in ECMO-supported patients participating in physical therapy, and whether mobilization with femoral cannulation is safe and feasible. Methods: This large, single-center, retrospective study evaluated adult patients who performed active physical therapy while receiving ECMO. Mixed effects modeling was used to identify predictors of out-of-bed versus in-bed activity. Rates of mobilization with femoral cannulation and adverse events were also reported. Results: Between April 2009 and January 2020, 511 patients were supported with ECMO in a single medical intensive care unit, of whom 177 (35%) underwent active physical therapy and were included in the analysis, including 124 of 141 (88%) bridge to lung transplantation and 53 of 370 (14%) bridge to recovery. These 177 patients accounted for 2,706 active physical therapy sessions, with 138 patients (78%) achieving out-of-bed activity. In total, 108 (61%) patients ambulated (1,284 sessions), 34 of whom had femoral cannulae (250 sessions). Bridge-to-transplant (odds ratio [OR], 17.2; 95% confidence interval [CI], 4.12-72.1), venovenous ECMO (OR, 2.83; 95% CI, 1.29-6.22), later cannulation year (OR, 1.65; 95% CI, 1.37-1.98) and higher Charlson comorbidity index (OR, 1.53; 95% CI, 1.07-2.19) were associated with increased odds of achieving out-of-bed versus in-bed physical therapy, whereas invasive mechanical ventilation (OR, 0.11; 95% CI, 0.05-0.25) and femoral cannulation (OR, 0.19; 95% CI, 0.04-0.92) were associated with decreased odds of performing out-of-bed activities. Adverse events occurred in 2% of sessions. Conclusions: Several patient- and ECMO-related factors were associated with achieving higher intensity of early mobilization in patients participating in rehabilitation. Physical therapy with femoral cannulation was safe and feasible, and complications related to mobilization were uncommon.

Real time three-dimensional stress echocardiography: a new approach for assessing diastolic function.

OBJECTIVE: To assess the feasibility of utilizing real time three-dimensional echocardiography (RT3DE) for assessment of diastolic function during stress. METHODS: Rest and stress volumes were acquired in 24 patients and parameters of diastolic function-peak ventricular filling rate (PFR) and time to peak filling rate (TPFR)-were calculated. RESULTS: Calculation of diastolic parameters was feasible in all patients. Resting PFR correlated with end-diastolic (EDV) and stroke volumes and inversely with TPFR (r = 0.53, 0.66, -0.5). With stress, PFR increased by 93% and TPFR decreased by 23% (P < 0.001). Stress PFR correlated with stress heart rate, EDV and stroke volume (r = 0.52, 0.50, 0.62) while TPFR correlated inversely with heart rate (r =-0.71). The change in PFR with stress correlated with the change in stroke volume (r = 0.42), while the change in TPFR correlated with the change in end-systolic volume (ESV) (r = 0.43) and inversely with the change in diastolic blood pressure (r =-0.41). Rest and stress PFR and TPFR are independent of age, gender and blood pressure and the change in PFR is independent of stress heart rate or blood pressure. E/E' correlated with stress TPFR (r = 0.72) and change in TPFR (r = 0.67) and inversely with change in PFR (r =-0.67). CONCLUSIONS: RT3DE can assess diastolic function during stress by detecting changes in PFR and TPFR, independent of gender, age, and blood pressure. The changes in these parameters with stress are influenced by baseline filling pressures. Larger studies are required to validate the clinical significance of these observations.

Clinical trials in critical care: can a Bayesian approach enhance clinical and scientific decision making?

Recent Bayesian reanalyses of prominent trials in critical illness have generated controversy by contradicting the initial conclusions based on conventional frequentist analyses. Many clinicians might be sceptical that Bayesian analysis, a philosophical and statistical approach that combines prior beliefs with data to generate probabilities, provides more useful information about clinical trials than the frequentist approach. In this Personal View, we introduce clinicians to the rationale, process, and interpretation of Bayesian analysis through a systematic review and reanalysis of interventional trials in critical illness. In the majority of cases, Bayesian and frequentist analyses agreed. In the remainder, Bayesian analysis identified interventions where benefit was probable despite the absence of statistical significance, where interpretation depended substantially on choice of prior distribution, and where benefit was improbable despite statistical significance. Bayesian analysis in critical care medicine can help to distinguish harm from uncertainty and establish the probability of clinically important benefit for clinicians, policy makers, and patients.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019: Crisis Standards of Care.

The coronavirus disease 2019 (COVID-19) pandemic has placed extraordinary strain on global healthcare systems. Use of extracorporeal membrane oxygenation (ECMO) for patients with severe respiratory or cardiac failure attributed to COVID-19 has been debated due to uncertain survival benefit and the resources required to safely deliver ECMO support. We retrospectively investigated adult patients supported with ECMO for COVID-19 at our institution during the first 80 days following New York City's declaration of a state of emergency. The primary objective was to evaluate survival outcomes in patients supported with ECMO for COVID-19 and describe the programmatic adaptations made in response to pandemic-related crisis conditions. Twenty-two patients with COVID-19 were placed on ECMO during the study period. Median age was 52 years and 18 (81.8%) were male. Twenty-one patients (95.4%) had severe ARDS and seven (31.8%) had cardiac failure. Fifteen patients (68.1%) were managed with venovenous ECMO while 7 (31.8%) required arterial support. Twelve patients (54.5%) were transported on ECMO from external institutions. Twelve patients were discharged alive from the hospital (54.5%). Extracorporeal membrane oxygenation was used successfully in patients with respiratory and cardiac failure due to COVID-19. The continued use of ECMO, including ECMO transport, during crisis conditions was possible even at the height of the COVID-19 pandemic.

Mitral annular velocities generated by speckle tracking imaging: reproducibility and correlation with tissue Doppler velocities.

BACKGROUND: Early diastolic mitral annular velocities (E') are routinely generated by tissue Doppler imaging (TDI), an angle-dependent technique. Velocity vector imaging (VVI) lacks this limitation. Normal VVI E' values and their correlation with TDI E' are unknown. METHODS: E' by VVI and TDI were compared in 100 patients. RESULTS: VVI velocities are lower and correlate moderately with TDI velocities for medial E' (r = 0.405) and mildly for lateral E' (r = 0.278) and are image quality dependent. In patients with diastolic or systolic dysfunction, no correlation was found. E' < 0.06 m/s by VVI for the medial and lateral annulus can detect abnormal diastolic function with sensitivity of 90% and 77%, respectively, and with specificity of 56% and 52%, respectively. CONCLUSIONS: E' by VVI is lower than by TDI with a poor agreement between the measurements, which are therefore not interchangeable. Although VVI can be performed offline, this method is dependent on image quality.

Segmental contribution to left ventricular systolic function at rest and stress: a quantitative real time three-dimensional echocardiographic study.

OBJECTIVE: To assess the relative contribution of each myocardial segment to global systolic function during stress using real time three-dimensional echocardiography (RT3DE). BACKGROUND: During stress, global augmentation in contractility results in an increased stroke volume. The relative contribution of each myocardial segment to these volumetric changes is unknown. METHODS: Full volume was acquired using RT3DE at rest and following peak exercise in 22 patients who had no ischemia and no systolic dyssynchrony on two-dimensional (2D) stress echocardiography. The following were calculated at rest and peak stress: end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), relative SV, and relative EF. RESULTS: With stress, an increase in global EDV from 90.8 to 101.1 ml (P < 0.001), SV from 59 to 78.4 ml (P = 0.01), and EF from 65.6 to 78.4% (P = 0.001) was observed. ESV decreased from 31.8 to 22.7 ml (P < 0.001). Segmental analysis revealed significantly higher SV, relative SV, and relative EF for the basal anterior, basal anterolateral, and basal inferolateral segments compared with the apical septum and apical inferior segments at both rest and stress (P < 0.001). The SV, relative SV, and relative EF increased significantly from apex to mid to base at both rest and stress (P < 0.001). CONCLUSIONS: The relative volumetric contribution of each myocardial segment to global left ventricular systolic function at rest and stress is not uniform. The basal segments contribute more than the mid and apical segments. Specifically, the basal anterior, basal anterolateral, and basal inferolateral segments contribute the most to augmentation of left ventricular systolic function with exercise.

Emerging concepts in ventilation-induced lung injury.

Ventilation-induced lung injury results from mechanical stress and strain that occur during tidal ventilation in the susceptible lung. Classical descriptions of ventilation-induced lung injury have focused on harm from positive pressure ventilation. However, injurious forces also can be generated by patient effort and patient-ventilator interactions. While the role of global mechanics has long been recognized, regional mechanical heterogeneity within the lungs also appears to be an important factor propagating clinically significant lung injury. The resulting clinical phenotype includes worsening lung injury and a systemic inflammatory response that drives extrapulmonary organ failures. Bedside recognition of ventilation-induced lung injury requires a high degree of clinical acuity given its indistinct presentation and lack of definitive diagnostics. Yet the clinical importance of ventilation-induced lung injury is clear. Preventing such biophysical injury remains the most effective management strategy to decrease morbidity and mortality in patients with acute respiratory distress syndrome and likely benefits others at risk.

Regional distribution of high-attenuation areas on chest computed tomography in the Multi-Ethnic Study of Atherosclerosis.

High-attenuation areas (HAA) are a computed tomography-based quantitative measure of subclinical interstitial lung disease (ILD). We aimed to validate HAA in lung regions that are less subject to artefacts, such as extravascular lung water or dependent atelectasis. We examined the associations of HAA within six lung regions (basilar, non-basilar, peel, core, basilar peel, basilar core) with serum biomarkers of lung remodelling, forced vital capacity (FVC), visually-assessed interstitial lung abnormalities (ILA), and all-cause and ILD-specific mortality. We performed cross-sectional and longitudinal analyses of participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort of 6814 adults aged 45-84 years without known cardiovascular disease who underwent cardiac computed tomography. Median regional HAA ranged from 3.8% in the peel to 4.8% in the basilar core. Doubling of regional HAA was associated with greater serum matrix metalloproteinase-7 (range 3.8% to 10.3%; p≤0.01), higher odds of ILA (OR 1.42 to 2.20; p≤0.03), and a higher risk of all-cause mortality (hazard ratio 1.20 to 1.47; p≤0.001). Doubling of regional HAA was associated with greater serum interleukin-6 (4.9% to 10.3%; p≤0.005) and higher risk of ILD-specific mortality (hazard ratio 3.30 to 3.98; p<0.001), except in the basilar core. Doubling of regional HAA was associated with lower FVC in the non-basilar, core and basilar core (113 mL to 186 mL; p<0.001). Associations of HAA with lung remodelling biomarkers, ILA risk and all-cause mortality were consistent across all regions of the lung, including dependent areas where atelectasis may be present. These findings support the validity of HAA as a measure of pathologic subclinical ILD.

Current practice and perceptions regarding pain, agitation and delirium management in patients receiving venovenous extracorporeal membrane oxygenation.

PURPOSE: To characterize monitoring of pain, agitation, and delirium; investigate opioid and sedative choices; and describe prevention and treatment of delirium in adults receiving venovenous extracorporeal membrane oxygenation (vv-ECMO) for respiratory failure. MATERIALS AND METHODS: International, cross-sectional survey distributed January 2018 to members of the Society of Critical Care Medicine. RESULTS: Respondents were predominately physicians (58%) from North America (89%). Fentanyl (77%) and hydromorphone (48%) were the most common intravenous opioids used to manage pain. A deep level of sedation was targeted in the first 24-h after initiation of vv-ECMO 64% of the time. When deep sedation was targeted, propofol (70%) and benzodiazepines (41%) were the most common sedatives. The most common sedatives for light sedation were dexmedetomidine (45%) and propofol (39%). Delirium prevention included avoidance of benzodiazepines (73%), whereas the most common treatment strategy was scheduled atypical antipsychotics (83%). Centers that extubated patients during vv-ECMO used dexmedetomidine as the second preferred sedative as compared to benzodiazepines at non-extubating centers (p = 0.04). CONCLUSIONS: Most respondents use validated scales and protocols to assess and manage pain, agitation/sedation, and delirium. The majority of respondents reported targeting a deep level of sedation with propofol being used for both deep and light levels of sedation.