An Approach to Diversifying the Selection of a Guideline Panel-The Process Utilized for the Updated Adult Critical Care Ultrasound Guidelines.

OBJECTIVES: Clinical practice guidelines are essential for promoting evidence-based healthcare. While diversification of panel members can reduce disparities in care, processes for panel selection lack transparency. We aim to share our approach in forming a diverse expert panel for the updated Adult Critical Care Ultrasound Guidelines. DESIGN: This process evaluation aims to understand whether the implementation of a transparent and intentional approach to guideline panel selection would result in the creation of a diverse expert guideline panel. SETTING: This study was conducted in the setting of creating a guideline panel for the updated Adult Critical Care Ultrasound Guidelines. PATIENTS: Understanding that family/patient advocacy in guideline creations can promote the impact of a clinical practice guideline, patient representation on the expert panel was prioritized. INTERVENTIONS: Interventions included creation of a clear definition of expertise, an open invitation to the Society of Critical Care Medicine membership to apply for the panel, additional panel nomination by guideline leadership, voluntary disclosure of pre-identified diversity criteria by potential candidates, and independent review of applications including diversity criteria. This resulted in an overall score per candidate per reviewer and an open forum for discussion and final consensus. MEASUREMENTS AND MAIN RESULTS: The variables of diversity were collected and analyzed after panel selection. These were compared with historical data on panel composition. The final guideline panel comprised of 33 panelists from six countries: 45% women and 79% historically excluded people and groups. The panel has representation from nonphysician professionals and patients advocates. Of the healthcare professionals, there is representation from early, mid, and late career stages. CONCLUSIONS: Our intentional and transparent approach resulted in a panel with improved gender parity and robust diversity along ethnic, racial, and professional lines. We hope it can serve as a starting point as we strive to become a more inclusive and diverse discipline that creates globally representative guidelines.

Society of Critical Care Medicine Guidelines on Glycemic Control for Critically Ill Children and Adults 2024.

RATIONALE: Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target blood levels, monitoring frequency, and methods. OBJECTIVES: The purpose was to update the 2012 Society of Critical Care Medicine and American College of Critical Care Medicine (ACCM) guidelines with a new systematic review of the literature and provide actionable guidance for clinicians. PANEL DESIGN: The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting. METHODS: We conducted a systematic review for each Population, Intervention, Comparator, and Outcomes question related to glycemic management in critically ill children (≥ 42 wk old adjusted gestational age to 18 yr old) and adults, including triggers for initiation of insulin therapy, route of administration, monitoring frequency, role of an explicit decision support tool for protocol maintenance, and methodology for glucose testing. We identified the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as a good practice statement. In addition, "In our practice" statements were included when the available evidence was insufficient to support a recommendation, but the panel felt that describing their practice patterns may be appropriate. Additional topics were identified for future research. RESULTS: This guideline is an update of the guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. It is intended for adult and pediatric practitioners to reassess current practices and direct research into areas with inadequate literature. The panel issued seven statements related to glycemic control in unselected adults (two good practice statements, four conditional recommendations, one research statement) and seven statements for pediatric patients (two good practice statements, one strong recommendation, one conditional recommendation, two "In our practice" statements, and one research statement), with additional detail on specific subset populations where available. CONCLUSIONS: The guidelines panel achieved consensus for adults and children regarding a preference for an insulin infusion for the acute management of hyperglycemia with titration guided by an explicit clinical decision support tool and frequent (≤ 1 hr) monitoring intervals during glycemic instability to minimize hypoglycemia and against targeting intensive glucose levels. These recommendations are intended for consideration within the framework of the patient's existing clinical status. Further research is required to evaluate the role of individualized glycemic targets, continuous glucose monitoring systems, explicit decision support tools, and standardized glycemic control metrics.

Implementation of Lung-Protective Ventilation in Patients With Acute Respiratory Failure.

OBJECTIVES: We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS). DESIGN: Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial. SETTING: Twelve hospitals in an integrated healthcare system over a 2-year period. PATIENTS: Patients greater than or equal to 18 years old who had initiation of mechanical ventilation in the emergency department or ICU. We excluded patients who died or transitioned to comfort care on the day of admission to the ICU. We defined a subgroup of patients with ARDS for analysis. INTERVENTIONS: Implementation of ventilator protocols for LTVV in the ICU. MEASUREMENTS AND MAIN RESULTS: Our primary clinical outcome was ventilator-free days (VFDs) to day 28. Our primary process outcome was median initial set tidal volume. We included 8,692 mechanically ventilated patients, 3,282 (38%) of whom had ARDS. After implementation, set tidal volume reported as mL/kg predicted body weight decreased from median 6.1 mL/kg (interquartile range [IQR], 6.0-6.8 mL/kg) to 6.0 mL/kg (IQR, 6.0-6.6 mL/kg) ( p = 0.009). The percent of patients receiving LTVV (tidal volume ≤ 6.5 mL/kg) increased from 69.8% ( n = 1,721) to 72.5% ( n = 1,846) ( p = 0.036) after implementation. The percent of patients receiving greater than 8 mL/kg initial set tidal volume was reduced from 9.0% ( n = 222) to 6.7% ( n = 174) ( p = 0.005) after implementation. Among patients with ARDS, day 1 positive end-expiratory pressure increased from 6.7 to 8.0 cm H 2 O ( p < 0.001). We observed no difference in VFD (adjusted odds ratio, 1.06; 95% CI, 0.91-1.24; p = 0.44), or in secondary outcomes of length of stay or mortality, either within the main cohort or the subgroup of patients with ARDS. CONCLUSIONS: We observed improved adherence to optimal ventilator management with implementation of a computerized protocol and reduction in the number of patients receiving tidal volumes greater than 8 mL/kg. We did not observe improvement in clinical outcomes.

Alveolar macrophages from EVALI patients and e-cigarette users: a story of shifting phenotype.

Exposure to e-cigarette vapors alters important biologic processes including phagocytosis, lipid metabolism, and cytokine activity in the airways and alveolar spaces. Little is known about the biologic mechanisms underpinning the conversion to e-cigarette, or vaping, product use-associated lung injury (EVALI) from normal e-cigarette use in otherwise healthy individuals. We compared cell populations and inflammatory immune populations from bronchoalveolar lavage fluid in individuals with EVALI to e-cigarette users without respiratory disease and healthy controls and found that e-cigarette users with EVALI demonstrate a neutrophilic inflammation with alveolar macrophages skewed towards inflammatory (M1) phenotype and cytokine profile. Comparatively, e-cigarette users without EVALI demonstrate lower inflammatory cytokine production and express features associated with a reparative (M2) phenotype. These data indicate macrophage-specific changes are occurring in e-cigarette users who develop EVALI.

Initial Derivation of a Predictive Model for Left Ventricular Longitudinal Strain (LS) in Early Sepsis.

Septic shock is a common deadly disease often associated with cardiovascular dysfunction. Left ventricular longitudinal strain (LV LS) has been proposed as a sensitive marker to measure cardiovascular function; however, it is not available universally in standard clinical echocardiograms. We sought to derive a predictive model for LV LS, using machine learning techniques with the hope that we may uncover surrogates for LV LS. We found that left ventricular ejection fraction, tricuspid annular plane systolic excursion, sepsis source, height, mitral valve Tei index, LV systolic dimension, aortic valve ejection time, and peak acceleration rate were all predictive of LV LS in this initial exploratory model. Future modeling work may uncover combinations of these variables which may be powerful surrogates for LV LS and cardiovascular function.

Long-Term Implications of Abnormal Left Ventricular Strain During Sepsis.

OBJECTIVES: Septic cardiomyopathy develops frequently in patients with sepsis and likely increases short-term mortality. However, whether septic cardiomyopathy is associated with long-term outcomes after sepsis is unknown. We investigated whether septic patients with septic cardiomyopathy have worse long-term outcomes than septic patients without septic cardiomyopathy. DESIGN: Retrospective cohort study. SETTING: Adult ICU. PATIENTS: Adult ICU patients with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Left ventricular global longitudinal systolic strain was our primary measure of septic cardiomyopathy. We employed a suite of multivariable survival analyses to explore linear and nonlinear associations between left ventricular global longitudinal systolic strain and major adverse cardiovascular events, which included death, stroke, and myocardial infarction. Our primary outcome was major adverse cardiovascular event through 24 months after ICU discharge. Among 290 study patients, median left ventricular global longitudinal systolic strain was -16.8% (interquartile range, -20.4% to -12.6%), and 38.3% of patients (n = 111) experienced a major adverse cardiovascular event within 24 months after discharge. On our primary, linear analysis, there was a trend (p = 0.08) toward association between left ventricular global longitudinal systolic strain and major adverse cardiovascular event (odds ratio, 1.03; CI, < 1 to 1.07). On our nonlinear analysis, the association was highly significant (p < 0.001) with both high and low left ventricular global longitudinal systolic strain associated with major adverse cardiovascular event among patients with pre-existing cardiac disease. This association was pronounced among patients who were younger (age < 65 yr) and had Charlson Comorbidity Index greater than 5. CONCLUSIONS: Among patients with sepsis and pre-existing cardiac disease who survived to ICU discharge, left ventricular global longitudinal systolic strain demonstrated a U-shaped association with cardiovascular outcomes through 24 months. The relationship was especially strong among younger patients with more comorbidities. These observations are likely of use to design of future trials.

Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study.

BACKGROUND: An ongoing outbreak of lung injury associated with e-cigarettes or vaping (also known as E-VALI or VALI) started in March, 2019, in the USA. The cause, diagnosis, treatment, and course of this disease remains unknown. METHODS: In this multicentre, prospective, observational, cohort study, we collected data on all patients with lung injury associated with e-cigarettes or vaping seen in Intermountain Healthcare, an integrated health system based in Utah, USA, between June 27 and Oct 4, 2019. Telecritical care, based in Salt Lake City, UT, USA, was used as the central repository for case validation, public reporting, and system-wide dissemination of expertise, which included a proposed diagnosis and treatment guideline for lung injury associated with e-cigarettes or vaping. We extracted data on patient presentation, treatment, and short-term follow-up (2 weeks after discharge) from chart review and interviews with patients undertaken by the Utah Department of Health (Salt Lake City, UT, USA). FINDINGS: 60 patients presented with lung injury associated with e-cigarettes or vaping at 13 hospitals or outpatient clinics in the integrated health system. 33 (55%) of 60 were admitted to an intensive care unit (ICU). 53 (88%) of 60 patients presented with constitutional symptoms, 59 (98%) with respiratory symptoms, and 54 (90%) with gastrointestinal symptoms. 54 (90%) of 60 were given antibiotics and 57 (95%) were given steroids. Six (10%) of 60 patients were readmitted to an ICU or hospital within 2 weeks, three (50%) of whom had relapsed with vaping or e-cigarette use. Of 26 patients who were followed up within 2 weeks, despite clinical and radiographic improvement in all, many had residual abnormalities on chest radiographs (ten [67%] of 15) and pulmonary function tests (six [67%] of nine). Two patients died and lung injury associated with e-cigarettes or vaping was thought to be a contributing factor, but not the cause of death, for both. INTERPRETATION: Lung injury associated with e-cigarettes or vaping is an emerging illness associated with severe lung injury and constitutional and gastrointestinal symptoms. Increased awareness has led to identification of a broad spectrum of severity of illness in patients who were treated with antibiotics and steroids. Despite improvement, at short-term follow-up many patients had residual abnormalities. Lung injury associated with e-cigarettes or vaping remains a clinical diagnosis with symptoms that overlap infectious and other lung diseases. Maintaining a high index of suspicion for this disease is important as work continues in understanding the cause or causes, optimal therapy, and long-term outcomes of these patients. FUNDING: Intermountain Healthcare.

Driving pressure is not associated with mortality in mechanically ventilated patients without ARDS.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), low tidal volume ventilation has been associated with reduced mortality. Driving pressure (tidal volume normalized to respiratory system compliance) may be an even stronger predictor of ARDS survival than tidal volume. We sought to study whether these associations hold true in acute respiratory failure patients without ARDS. METHODS: This is a retrospectively cohort analysis of mechanically ventilated adult patients admitted to ICUs from 12 hospitals over 2 years. We used natural language processing of chest radiograph reports and data from the electronic medical record to identify patients who had ARDS. We used multivariable logistic regression and generalized linear models to estimate associations between tidal volume, driving pressure, and respiratory system compliance with adjusted 30-day mortality using covariates of Acute Physiology Score (APS), Charlson Comorbidity Index (CCI), age, and PaO2/FiO2 ratio. RESULTS: We studied 2641 patients; 48% had ARDS (n = 1273). Patients with ARDS had higher mean APS (25 vs. 23, p < .001) but similar CCI (4 vs. 3, p = 0.6) scores. For non-ARDS patients, tidal volume was associated with increased adjusted mortality (OR 1.18 per 1 mL/kg PBW increase in tidal volume, CI 1.04 to 1.35, p = 0.010). We observed no association between driving pressure or respiratory compliance and mortality in patients without ARDS. In ARDS patients, both ΔP (OR1.1, CI 1.06-1.14, p < 0.001) and tidal volume (OR 1.17, CI 1.04-1.31, p = 0.007) were associated with mortality. CONCLUSIONS: In a large retrospective analysis of critically ill non-ARDS patients receiving mechanical ventilation, we found that tidal volume was associated with 30-day mortality, while driving pressure was not.

Septic Cardiomyopathy.

OBJECTIVES: To describe, with an emphasis on clinical applications, what is known about the pathophysiology, management, and implications of septic cardiomyopathy in the adult ICU. DATA SOURCES AND STUDY SELECTION: A PubMed literature review was performed for relevant articles. Only articles in English that studied human adults with sepsis were included. DATA EXTRACTION AND DATA SYNTHESIS: Multiple competing definitions for septic cardiomyopathy hinder understanding of this entity. Although many patients with sepsis develop cardiac dysfunction, the impact of septic cardiomyopathy on prognosis and therapy remains to be demonstrated. Treatment of septic cardiomyopathy is aimed at treating the underlying sepsis and providing specific supportive care for cardiogenic shock when present. CONCLUSIONS: Septic cardiomyopathy is an important contributor to organ dysfunction in sepsis. Guided treatment of septic cardiomyopathy may affect patients' prognosis, especially when their cardiac index is substantially decreased. The implication of septic cardiomyopathy for both short- and long-term outcomes is an important area for future investigation.

Randomized Feasibility Trial of a Low Tidal Volume-Airway Pressure Release Ventilation Protocol Compared With Traditional Airway Pressure Release Ventilation and Volume Control Ventilation Protocols.

OBJECTIVES: Low tidal volume (= tidal volume ≤ 6 mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable and can exceed tidal volume breaths of low tidal volume-volume control. We evaluate the application of a low tidal volume-compatible airway pressure release ventilation protocol that manages release volumes on both clinical and feasibility endpoints. DESIGN: We designed a prospective randomized trial in patients with acute hypoxemic respiratory failure. We randomized patients to low tidal volume-volume control, low tidal volume-airway pressure release ventilation, and traditional airway pressure release ventilation with a planned enrollment of 246 patients. The study was stopped early because of low enrollment and inability to consistently achieve tidal volumes less than 6.5 mL/kg in the low tidal volume-airway pressure release ventilation arm. Although the primary clinical study endpoint was PaO2/FIO2 on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms. SETTING: Four Intermountain Healthcare tertiary ICUs. PATIENTS: Adult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation. INTERVENTIONS: Low tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation. MEASUREMENTS AND MAIN RESULTS: We observed wide variability and higher tidal (release for airway pressure release ventilation) volumes in both airway pressure release ventilation (8.6 mL/kg; 95% CI, 7.8-9.6) and low tidal volume-airway pressure release ventilation (8.0; 95% CI, 7.3-8.9) than volume control (6.8; 95% CI, 6.2-7.5; p = 0.005) with no difference between airway pressure release ventilation and low tidal volume-airway pressure release ventilation (p = 0.58). Recognizing the limitations of small sample size, we observed no difference in 52 patients in day 3 PaO2/ FIO2 (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax. CONCLUSIONS: Airway pressure release ventilation resulted in release volumes often exceeding 12 mL/kg despite a protocol designed to target low tidal volume ventilation. Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway pressure release ventilation is not feasible at this time in the absence of an explicit, generalizable, and reproducible low tidal volume-airway pressure release ventilation protocol.

Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy.

OBJECTIVES: Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate, < 80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock. DESIGN: Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013. SETTING: One large academic referral hospital and two community hospitals. PATIENTS: Adult patients with septic shock requiring vasopressors. INTERVENTION: None. MEASUREMENTS: Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score. RESULTS: We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p < 0.001). Relatively bradycardic patients were older (65 vs 60 yr; p < 0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p < 0.001). CONCLUSIONS: Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.

Multi-complexity measures of heart rate variability and the effect of vasopressor titration: a prospective cohort study of patients with septic shock.

BACKGROUND: Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known. METHODS: We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min. RESULTS: We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20-37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8-17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12-0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration. CONCLUSIONS: Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols.

Application of a simplified definition of diastolic function in severe sepsis and septic shock.

BACKGROUND: Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. METHODS: In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. RESULTS: We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. CONCLUSIONS: A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

Sildenafil and Exercise Capacity in the Elderly at Moderate Altitude.

OBJECTIVE: Hypobaric hypoxia decreases exercise capacity and causes hypoxic pulmonary vasoconstriction and pulmonary hypertension. The phosphodiesterase-5 inhibitor sildenafil is a pulmonary vasodilator that may improve exercise capacity at altitude. We aimed to determine whether sildenafil improves exercise capacity, measured as maximal oxygen consumption (peak V̇o2), at moderate altitude in adults 60 years or older. METHODS: The design was a randomized, double-blind, placebo-controlled, crossover study. After baseline cardiopulmonary exercise testing at 1400 m, 12 healthy participants (4 women) aged 60 years or older, who reside permanently at approximately 1400 m and are regularly active in self-propelled mountain recreation above 2000 m, performed maximal cardiopulmonary cycle exercise tests in a hypobaric chamber at a simulated altitude of 2750 m after ingesting sildenafil and after ingesting a placebo. RESULTS: After placebo, mean peak V̇o2 was significantly lower at 2750 m than 1400 m: 37.0 mL · kg(-1) · min(-1) (95% CI, 32.7 to 41.3) vs 39.1 mL · kg(-1) · min(-1) (95% CI, 33.5 to 44.7; P = .020). After placebo, there was no difference in heart rate (HR) or maximal workload at either altitude (z = 0.182; P = .668, respectively). There was no difference between sildenafil and placebo at 2750 m in peak V̇o2 (P = .668), O2 pulse (P = .476), cardiac index (P = .143), stroke volume index (z = 0.108), HR (z = 0.919), or maximal workload (P = .773). Transthoracic echocardiography immediately after peak exercise at 2750 m showed tricuspid annular plane systolic velocity was significantly higher after sildenafil than after placebo (P = .019), but showed no difference in tricuspid annular plane systolic excursion (P = .720). CONCLUSIONS: Sildenafil (50 mg) did not improve exercise capacity in adults 60 years or older at moderate altitude in our study. This might be explained by a "dosing effect" or insufficiently high altitude.

Fluid management with a simplified conservative protocol for the acute respiratory distress syndrome*.

OBJECTIVES: In the Fluid and Catheter Treatment Trial (FACTT) of the National Institutes of Health Acute Respiratory Distress Syndrome Network, a conservative fluid protocol (FACTT Conservative) resulted in a lower cumulative fluid balance and better outcomes than a liberal fluid protocol (FACTT Liberal). Subsequent Acute Respiratory Distress Syndrome Network studies used a simplified conservative fluid protocol (FACTT Lite). The objective of this study was to compare the performance of FACTT Lite, FACTT Conservative, and FACTT Liberal protocols. DESIGN: Retrospective comparison of FACTT Lite, FACTT Conservative, and FACTT Liberal. Primary outcome was cumulative fluid balance over 7 days. Secondary outcomes were 60-day adjusted mortality and ventilator-free days through day 28. Safety outcomes were prevalence of acute kidney injury and new shock. SETTING: ICUs of Acute Respiratory Distress Syndrome Network participating hospitals. PATIENTS: Five hundred three subjects managed with FACTT Conservative, 497 subjects managed with FACTT Liberal, and 1,124 subjects managed with FACTT Lite. INTERVENTIONS: Fluid management by protocol. MEASUREMENTS AND MAIN RESULTS: Cumulative fluid balance was 1,918 ± 323 mL in FACTT Lite, -136 ± 491 mL in FACTT Conservative, and 6,992 ± 502 mL in FACTT Liberal (p < 0.001). Mortality was not different between groups (24% in FACTT Lite, 25% in FACTT Conservative and Liberal, p = 0.84). Ventilator-free days in FACTT Lite (14.9 ± 0.3) were equivalent to FACTT Conservative (14.6 ± 0.5) (p = 0.61) and greater than in FACTT Liberal (12.1 ± 0.5, p < 0.001 vs Lite). Acute kidney injury prevalence was 58% in FACTT Lite and 57% in FACTT Conservative (p = 0.72). Prevalence of new shock in FACTT Lite (9%) was lower than in FACTT Conservative (13%) (p = 0.007 vs Lite) and similar to FACTT Liberal (11%) (p = 0.18 vs Lite). CONCLUSIONS: FACTT Lite had a greater cumulative fluid balance than FACTT Conservative but had equivalent clinical and safety outcomes. FACTT Lite is an alternative to FACTT Conservative for fluid management in Acute Respiratory Distress Syndrome.

Clinical study replicability and the pursuit of excellence.

Comparisons of processes of care are common in critical care research. Often, these processes are neither explicit nor replicable and this can result in seemingly irreconcilable results. Here, we briefly review the article by Taniguchi and colleagues, who studied liberation from mechanical ventilation by using either a computerized weaning protocol or one driven by respiratory therapists. We discuss the implications of explicit protocols increasing replicability in clinical research.

Association of left ventricular longitudinal strain with central venous oxygen saturation and serum lactate in patients with early severe sepsis and septic shock.

INTRODUCTION: In septic shock, assessment of cardiac function often relies on invasive central venous oxygen saturation (ScvO2). Ventricular strain is a non-invasive method of assessing ventricular wall deformation and may be a sensitive marker of heart function. We hypothesized that it may have a relationship with ScvO2 and lactate. METHODS: We prospectively performed transthoracic echocardiography in patients with severe sepsis or septic shock and measured (1) left ventricular longitudinal strain from a four-chamber view and (2) ScvO2. We excluded patients for whom image quality was inadequate or for whom ScvO2 values were unobtainable. We determined the association between strain and ScvO2 with logistic and linear regression, using covariates of mean arterial pressure, central venous pressure, and vasopressor dose. We determined the association between strain and lactate. We considered strain greater than -17% as abnormal and strain greater than -10% as severely abnormal. RESULTS: We studied 89 patients, 68 of whom had interpretable images. Of these patients, 42 had measurable ScvO2. Sixty percent of patients had abnormal strain, and 16% had severely abnormal strain. Strain is associated with low ScvO2 (linear coefficient -1.05, p =0.006; odds ratio 1.23 for ScvO2 <60%, p =0.016). Patients with severely abnormal strain had significantly lower ScvO2 (56.1% vs. 67.5%, p <0.01) and higher lactate (2.7 vs. 1.9 mmol/dl, p =0.04) than those who did not. Strain was significantly different between patients, based on a threshold ScvO2 of 60% (-13.7% vs. -17.2%, p =0.01) but not at 70% (-15.0% vs. -18.2%, p =0.08). CONCLUSIONS: Left ventricular strain is associated with low ScvO2 and hyperlactatemia. It may be a non-invasive surrogate for adequacy of oxygen delivery during early severe sepsis or septic shock.

Coefficient of Variation of Coarsely Sampled Heart Rate is Associated With Early Vasopressor Independence in Severe Sepsis and Septic Shock.

PURPOSE: To determine whether variability of coarsely sampled heart rate and blood pressure early in the course of severe sepsis and septic shock predicts successful resuscitation, defined as vasopressor independence at 24 hours after admission. METHODS: In an observational study of patients admitted with severe sepsis or septic shock from 2009 to 2011 to either of 2 intensive care units (ICUs) at a tertiary-care hospital, in whom blood pressure was measured via an arterial catheter, we sampled heart rate and blood pressure every 30 seconds over the first 6 hours of ICU admission and calculated the coefficient of variability of those measurements. Primary outcome was vasopressor independence at 24 hours; and secondary outcome was 28-day mortality. RESULTS: We studied 165 patients, of which 97 (59%) achieved vasopressor independence at 24 hours. Overall, 28-day mortality was 15%. Significant predictors of vasopressor independence at 24 hours included the coefficient of variation of heart rate, age, Acute Physiology and Chronic Health Evaluation II, the number of increases in vasopressor dose, mean vasopressin dose, mean blood pressure, and time-pressure integral of mean blood pressure less than 60 mm Hg. Lower sampling frequencies (up to once every 5 minutes) did not affect the findings. CONCLUSIONS: Increased variability of coarsely sampled heart rate was associated with vasopressor independence at 24 hours after controlling for possible confounders. Sampling frequencies of once in 5 minutes may be similar to once in 30 seconds.