Protocols and Hospital Mortality in Critically Ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

OBJECTIVE: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. DESIGN: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. PATIENTS: A total of 6,179 critically ill patients. SETTING: Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15-21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). CONCLUSIONS: Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

Structure, process, and annual ICU mortality across 69 centers: United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

OBJECTIVE: Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs. DESIGN: We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality. SETTING: ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. SUBJECTS: Sixty-nine intensivists completed the survey. MEASUREMENTS AND MAIN RESULTS: We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4-8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4-8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6-10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25-3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality. CONCLUSIONS: In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.

How soon should we start interventional feeding in the ICU?

PURPOSE OF REVIEW: Nutrition in the critically ill patient remains a controversial topic. Most clinicians have viewed nutrition as part of patient care but not as a therapeutic intervention. Recent studies have looked at type and timing of nutrition to determine whether they affect important clinical outcomes. RECENT FINDINGS: Large-scale, multicentre randomized trials have found that supplemental parenteral nutrition has a deleterious effect in comparison to enteral nutrition alone. Use of early parenteral nutrition in critically ill patients in whom enteral nutrition was contraindicated did not significantly improve clinical outcomes. Also, low-dose or trophic enteral nutrition has similar benefits with less gastrointestinal complications compared with early full dose caloric feedings. The timing of early nutrition has been defined in most large-scale studies as beginning within 48 h of intubation, though some earlier studies used a 24-h cut-off point with some improved outcomes. SUMMARY: Although not strong, the best available data suggest that critically ill patients should be started on enteral tube feeds within 48 h of intubation whenever possible. The use of parenteral nutrition should be limited within the first 6 days, and not used to augment caloric intake. Finally, similar benefits are seen in patients receiving minimal enteral feeds versus full caloric enteral nutrition.

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use.

OBJECTIVES: To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. DESIGN: Prospective cohort study. SETTING: Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. PATIENTS: Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. INTERVENTIONS: All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. MEASUREMENTS AND MAIN RESULTS: Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5-15.7%) in band 1, 28.1% (95% CI, 21.3-35.8%) in band 2, and 49.4% (95% CI, 41.4-57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. CONCLUSIONS: Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.

Bath salts intoxication: a case series.

BACKGROUND: Bath salts commonly contain multiple synthetic drugs, and their toxic effects are largely the same as those seen in patients who have taken large doses of amphetamines. Bath salts can be ingested, smoked, or administered intravenously. Their use is on the rise and is responsible for a large number of emergency department visits. CASE REPORT: Our case series involved five patients (six hospital courses) who presented after ingesting bath salts. The presentations involved signs and symptoms of intense sympathetic response. All patients had a history of drug abuse, and most had psychiatric disorders as well. Treatments included benzodiazepines, mechanical ventilation, and intravenous hydration. CONCLUSION: Bath salts are available for approximately $20 (USD) in packets at truck stops and on the Internet, usually marketed with the disclaimer, "not for human consumption." Their presentation mimics other sympathetic drugs and causes a significant amount of delirium, hallucinogenic-delusional symptoms, extreme agitation, combativeness, and rhabdomyolysis, often leading to hospitalizations and intensive care unit (ICU) stays. Management is largely supportive and includes aggressive intravenous hydration, dampening of the excessive sympathetic outflow with benzodiazepines, and close monitoring in the ICU setting. The U.S. Drug Enforcement Administration (DEA) recently invoked its emergency scheduling authority to control these synthetic stimulants. The DEA plans to make possessing and selling these chemicals, or products that contain them, illegal in the United States.

Antibiotic use in acute upper respiratory tract infections.

Upper respiratory tract infections account for millions of visits to family physicians each year in the United States. Although warranted in some cases, antibiotics are greatly overused. This article outlines the guidelines and indications for appropriate antibiotic use for common upper respiratory infections. Early antibiotic treatment may be indicated in patients with acute otitis media, group A beta-hemolytic streptococcal pharyngitis, epiglottitis, or bronchitis caused by pertussis. Persistent cases of rhinosinusitis may necessitate the use of antibiotics if symptoms persist beyond a period of observation. Antibiotics should not be considered in patients with the common cold or laryngitis. Judicious, evidence-based use of antibiotics will help contain costs and prevent adverse effects and drug resistance.

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

BACKGROUND: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy. RESEARCH QUESTION: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19? STUDY DESIGN AND METHODS: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473). The primary outcome was clinical status (disease severity) 14 days following study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) < 1.0 indicating more favorable outcomes with convalescent plasma than with placebo. In secondary analyses, trial participants were stratified according to the presence of endogenous anti-SARS-CoV-2 antibodies ("serostatus") at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality. RESULTS: Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR, 1.04; one-seventh support interval [1/7 SI], 0.82-1.33), in patients without endogenous antibodies (aOR, 1.15; 1/7 SI, 0.74-1.80), or in patients with endogenous antibodies (aOR, 0.96; 1/7 SI, 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89 of 482 (18.5%) patients in the convalescent plasma group and 80 of 465 (17.2%) patients in the placebo group had died (aOR, 1.04; 1/7 SI, 0.69-1.58). INTERPRETATION: Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04362176; URL: www. CLINICALTRIALS: gov.

Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome.

OBJECTIVES: To determine whether prehospital statin use is associated with a lower risk of sepsis, acute lung injury/acute respiratory distress syndrome, and mortality in critically ill patients. We also investigated the effect of combined prehospital use of both statins and aspirin. DESIGN: Cross-sectional analysis of a prospective cohort. PATIENTS: A total of 575 critically ill patients admitted to the medical or surgical intensive care unit of an academic tertiary-care hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 575 patients, 149 (26%) were on statin therapy before hospitalization. A multivariable analysis including age, gender, current tobacco use, prehospital aspirin use, race, and Acute Physiology and Chronic Health Evaluation II score revealed that patients on statin therapy before hospitalization were less likely to have or develop severe sepsis (odds ratio 0.62, 95% confidence interval 0.40-0.96) or acute lung injury/acute respiratory distress syndrome (odds ratio 0.60, 95% confidence interval 0.36-0.99) during the first four intensive care unit days. In-hospital mortalities for patients with and without prehospital statin use (odds ratio 1.06, 95% confidence interval 0.62-1.83) were similar. Patients who had prehospital use of both statins and aspirin had the lowest rates of severe sepsis, acute lung injury/acute respiratory distress syndrome, and mortality. CONCLUSIONS: Prehospital use of statins may be protective against sepsis and acute lung injury. This effect may be potentiated by prehospital aspirin use.

Gender and acute respiratory distress syndrome in critically injured adults: a prospective study.

BACKGROUND: The acute respiratory distress syndrome (ARDS) is a proinflammatory condition that often complicates trauma and critical illness. Animal studies have shown that both gender and sex hormones play an important role in inflammatory regulation. Human data are scant regarding the role of gender and sex hormones in developing ARDS. Our objective was to describe gender and hormonal differences in patients who develop ARDS in a large cohort of critically injured adults. METHODS: A prospective cohort study of adult trauma patients requiring intensive care unit admission for at least 48 hours was performed. Demographic and clinical data were collected prospectively, and sex hormones were assayed at study entry (48 hours). The primary outcome was the development of ARDS. Multivariate logistic regression was used to determine the adjusted odds of death associated with differences in gender. RESULTS: Six hundred forty-eight patients met entry criteria, and 180 patients developed ARDS (31%). Women were more likely to develop ARDS (35% vs. 25%, p=0.02). This association remained after adjusting for age, mechanism of injury, injury severity, and blood product transfusion (odds ratio, 1.6; 95% confidence interval: 1.1-2.4; p=0.02). Of patients with ARDS, there was no difference in mortality related to gender (22% mortality in women with ARDS vs. 20% in men; p=not significant). A proinflammatory sex hormone profile (low testosterone and high estradiol) was associated with ARDS in both men and women. CONCLUSION: Women are more likely than men to develop ARDS after critical injury. Despite the increased incidence in ARDS, the mortality in patients with ARDS does not differ according to gender. The inflammatory properties of sex hormones may contribute to ARDS, but they do not fully explain observed gender differences.

Acute lung injury in patients with traumatic injuries: utility of a panel of biomarkers for diagnosis and pathogenesis.

BACKGROUND: The diagnosis of acute lung injury (ALI) is based on a consensus clinical definition. Despite the simplicity of this definition, ALI remains underdiagnosed and undertreated. Severe trauma is a well-described cause of ALI that represents a relatively homogeneous subset of patients with ALI. The aims of this study were to develop a panel of plasma biomarkers to facilitate diagnosis of trauma-induced ALI and to enhance our understanding of the pathogenesis of human ALI. METHODS: A retrospective nested case control of 192 patients admitted to the trauma intensive care unit at a university hospital between 2002 and 2006. We compared 107 patients with ALI to 85 patients without ALI. Plasma was collected within 72 hours of intensive care unit admission. Twenty-one plasma biomarkers were measured in duplicate in each plasma sample. RESULTS: Patients with ALI had higher severity of illness scores, more days of mechanical ventilation, longer hospital stays, and higher mortality versus controls. Seven biomarkers (receptor for advanced glycation end products, procollagen peptide III, brain natriuretic peptide, angiopoietin-2, interleukin-10, tumor necrosis factor alpha, and interleukin-8) had a high diagnostic accuracy as reflected by the area under the receiver operating characteristic curve of 0.86 (95% confidence interval, 0.82-0.92) in differentiating ALI from controls. CONCLUSIONS: A model using seven plasma biomarkers had a high diagnostic accuracy in differentiating patients with trauma-induced ALI from trauma patients without ALI. In addition, use of a panel of biomarkers provides insight into the likely importance of alveolar epithelial injury in the pathogenesis of early ALI.

Six-minute walk distance in healthy young adults.

BACKGROUND: The 6-min walk test (6MWT) is a commonly used clinical assessment of exercise capacity in patients with cardiopulmonary or neuromuscular disease, but normal values are lacking for young adults, who are frequent subjects of testing. METHODS: In a two-center study, 272 young adults, ages 18-50, underwent American Thoracic Society protocolized 6-min walk testing, and 56 underwent repeat testing. A linear regression model was developed based on anthropomorphic data. This model was compared to existing prediction equations. RESULTS: Median 6MWD for the cohort was 637 m (IQR 584-686 m) and was not significantly impacted by age. This is in contrast to existing equations extrapolated from older subjects that predict increasing 6MWD in younger subjects. We found weak correlation of 6MWD with height, weight, BMI, and resting heart rate. Heart rate at completion correlated most strongly with 6MWD (rho 0.53 p < 0.0001). Repeat 6MWD was surprisingly variable, with a median difference between tests of 32.5 ± 31.9 m. Established reference equations performed poorly in this population, largely because age has much less effect on 6MWD in this group than in older adults. CONCLUSIONS: Established reference equations should be reconfigured to include data from young adults, as age has minimal effect on 6MWD in this population. Heart rate response may be a valuable measure of effort in normal subjects. Six-minute walk distance, as with pulmonary function and exercise testing, should have predictive equations across the spectrum of age to allow for accurate assessment of exercise limitation.

Procoagulant alveolar microparticles in the lungs of patients with acute respiratory distress syndrome.

Coagulation and fibrinolysis abnormalities are observed in acute lung injury (ALI) in both human disease and animal models and may contribute to ongoing inflammation in the lung. Tissue factor (TF), the main initiator of the coagulation cascade, is upregulated in the lungs of patients with ALI/acute respiratory distress syndrome (ARDS) and likely contributes to fibrin deposition in the air space. The mechanisms that govern TF upregulation and activation in the lung are not well understood. In the vascular space, TF-bearing microparticles (MPs) are central to clot formation and propagation. We hypothesized that TF-bearing MPs in the lungs of patients with ARDS contribute to the procoagulant phenotype in the air space during acute injury and that the alveolar epithelium is one potential source of TF MPs. We studied pulmonary edema fluid collected from patients with ARDS compared with a control group of patients with hydrostatic pulmonary edema. Patients with ARDS have higher concentrations of MPs in the lung compared with patients with hydrostatic edema (25.5 IQR 21.3-46.9 vs. 7.8 IQR 2.3-27.5 micromol/l, P = 0.009 by Mann-Whitney U-test). These MPs are enriched for TF, have procoagulant activity, and likely originate from the alveolar epithelium [as measured by elevated levels of RAGE (receptor for advanced glycation end products) in ARDS MPs compared with hydrostatic MPs]. Furthermore, alveolar epithelial cells in culture release procoagulant TF MPs in response to a proinflammatory stimulus. These findings suggest that alveolar epithelial-derived MPs are one potential source of TF procoagulant activity in the air space in ARDS and that epithelial MP formation and release may represent a unique therapeutic target in ARDS.

Postobstructive pulmonary edema: a case for hydrostatic mechanisms.

BACKGROUND: Postobstructive pulmonary edema is a well-recognized complication of upper airway obstruction. The mechanisms of edema formation are unclear and may be due to increased hydrostatic forces generated by high negative inspiratory pressure or by increased permeability of the alveolar capillary membrane. Measurement of the edema fluid/plasma protein ratio and the rate of net alveolar fluid clearance are two well-validated methods for classifying the underlying mechanism of edema formation. The goal of the current study was to investigate the mechanisms of pulmonary edema formation in patients with postobstructive pulmonary edema by serial sampling of undiluted pulmonary edema fluid. METHODS: A retrospective review of 341 patients who had pulmonary edema fluid collected prospectively after the acute onset of pulmonary edema. All patients had serial samples of edema fluid and plasma collected over the first 8 h after intubation. RESULTS: Ten of the 341 patients with acute pulmonary edema were identified as having postobstructive pulmonary edema. The mean (+/- SD) edema fluid/plasma protein ratio in these patients was 0.54 +/- 0.15. The mean rate of alveolar fluid clearance over 8 h was 14.0 +/- 17.4% per hour. Nine of the 10 patients survived the hospitalization. CONCLUSION: Measurement of the edema fluid/plasma protein ratio and the presence of net alveolar fluid clearance in 10 patients with postobstructive pulmonary edema supports a hydrostatic mechanism for edema fluid formation. The predominantly fast rates of alveolar fluid clearance may explain the rapid resolution of clinical postobstructive pulmonary edema that is typically described.

Derivation and validation of a two-biomarker panel for diagnosis of ARDS in patients with severe traumatic injuries.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is common after severe traumatic injuries but is underdiagnosed and undertreated. We hypothesized that a panel of plasma biomarkers could be used to diagnose ARDS in severe trauma. To test this hypothesis, we derived and validated a biomarker panel in three independent cohorts and compared the diagnostic performance to clinician recognition of ARDS. METHODS: Eleven plasma biomarkers of inflammation, lung epithelial and endothelial injury were measured in a derivation cohort of 439 severe trauma patients. ARDS status was analyzed by two-investigator consensus, and cases were required to meet Berlin criteria on intensive care unit (ICU) day 1. Controls were subjects without ARDS during the first 4 days of study enrollment. A multivariable logistic regression model was used to generate probabilities for ARDS. A reduced model with the top two performing markers was then tested in two independent validation cohorts. To assess clinical diagnosis of ARDS, medical records in the derivation cohort were systematically searched for documentation of ARDS diagnosis made by a clinical provider. RESULTS: Among 11 biomarkers, the combination of the endothelial injury marker angiopoietin-2 (Ang-2) and the lung epithelial injury marker receptor for advanced glycation endproducts (RAGE) provided good discrimination for ARDS in the derivation cohort (area under the curve (AUC)=0.74 (95% CI 0.67 to 0.80). In the validation cohorts, the AUCs for this model were 0.70 (0.61 to 0.77) and 0.78 (0.71 to 0.84). In contrast, provider assessment demonstrated poor diagnostic accuracy for ARDS, with AUC of 0.55 (0.51 to 0.60). DISCUSSION: A two-biomarker panel consisting of Ang-2 and RAGE performed well across multiple patient cohorts and outperformed clinical providers for diagnosing ARDS in severe trauma. Clinical application of this model could improve both diagnosis and treatment of ARDS in patients with severe trauma. LEVEL OF EVIDENCE: Diagnostic study, level II.

Pros and cons of feeding the septic intensive care unit patient.

Sepsis is a common disease seen in critically ill patients. Many patients with sepsis are unable to provide nutrition for themselves, and therefore initiating artificial nutrition has become part of routine care for these patients. However, studies investigating the optimal route, composition, volume, and duration of nutrition in critically ill patients with sepsis are lacking. The best recommendations have to be extrapolated from studies in heterogeneous populations of critically ill patients or in those with syndromes such as acute lung injury or acute respiratory distress syndrome (ARDS) where sepsis is a common predisposing etiology. In this review, we summarize pertinent studies that inform clinical practice on providing artificial nutrition to critically ill patients with severe sepsis and make recommendations as to how these studies influence clinical care of these patients.

Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury.

BACKGROUND: Acute lung injury (ALI) and ARDS are common clinical syndromes that are underdiagnosed. Clara cell secretory protein (CC16) is an antiinflammatory protein secreted by the Clara cells of the distal respiratory epithelium that has been proposed as a biomarker of lung epithelial injury. We tested the diagnostic and prognostic utility of CC16 in patients with non-trauma-related ALI/ARDS compared to a control group of patients with acute cardiogenic pulmonary edema (CPE). METHODS: Plasma and pulmonary edema fluid samples were obtained from medical and surgical patients with ALI/ARDS or CPE requiring intubation for mechanical ventilation. The etiology of pulmonary edema was determined using consensus clinical criteria for ALI/ARDS and CPE and the edema fluid-to-plasma protein ratio. Plasma and edema fluid CC16 levels were measured by sandwich enzyme-linked immunosorbent assay. CC16 levels were log transformed for analysis, and comparisons were made by the Student t test or Chi(2) as appropriate. RESULTS: Compared to patients with CPE (n = 9), patients with ALI/ARDS (n = 23) had lower median CC16 levels in plasma (22 ng/mL [interquartile range (IQR), 9 to 44 ng/mL] vs 55 ng/mL [IQR, 18 to 123 ng/mL], respectively; p = 0.053) and pulmonary edema fluid (1,950 ng/mL [IQR, 1,780 to 4,024 ng/mL] vs 4,835 ng/mL [IQR, 2,006 to 6,350 ng/mL], respectively; p = 0.044). Relative to total pulmonary edema fluid protein concentration, the median CC16 level was significantly lower in patients with ALI/ARDS (45 ng CC16/mg total protein [IQR, 4 to 64 ng CC16/mg total protein] vs 120 ng CC16/mg total protein [IQR, 87 to 257 ng CC16/mg total protein], respectively; p = 0.005). Neither plasma nor edema fluid CC16 levels predicted mortality, the number of days of unassisted ventilation, or ICU length of stay. CONCLUSION: CC16 is a promising diagnostic biomarker for helping to discriminate ALI from CPE. Larger scale validation is warranted to better characterize the utility of CC16 in the diagnosis of this underrecognized syndrome.

Association of the metabolic syndrome with pulmonary venous hypertension.

BACKGROUND: Pulmonary venous hypertension (PVH) is a well-described cause of pulmonary hypertension (PH) in patients with left heart disease associated with elevated left heart filling pressure. PVH results from a number of processes, including left-sided valvular disease, constrictive pericardial disease, restrictive cardiomyopathies, and left ventricular (LV) systolic dysfunction. PVH in patients with normal LV systolic function, commonly referred to as diastolic dysfunction, is not well characterized. We observed that many patients with PH due to PVH have obesity, hypertension, diabetes mellitus, and hypercholesterolemia, which are clinical features of the metabolic syndrome (MS), a previously identified cause for systemic vascular disease. METHODS: We evaluated 122 consecutive patients referred for diagnosis and treatment of PH and compared the prevalence of features of the MS between patients with PVH and those with pulmonary arterial hypertension (PAH). We also compared clinical and hemodynamic characteristics between these two groups. RESULTS: Compared to patients with PAH, patients with PVH had a higher frequency of hypertension, obesity, diabetes mellitus, and hyperlipidemia. Two or more features of the MS were found in 16 of 17 patients with PVH (94.1%) compared with 34.3% of patients with PAH (p < 0.001; odds ratio, 30.7; 95% confidence interval, 3.6 to 260.0). PH was substantial, but less severe overall, in patients with PVH compared to those with PAH (mean pulmonary artery pressure, 45 +/- 17 mm Hg [range, 26 to 71 mm Hg] vs 53 +/- 10 [range, 33 to 72 mm Hg], respectively [p = 0.041]; and pulmonary vascular resistance, 4.4 +/- 2.9 units [range, 1.2 to 10.8 units] vs 10.8 +/- 4.7 units [range, 4.8 to 21.9 units], respectively [p < 0.001]). CONCLUSION: PVH is highly associated with the MS. Our results suggest that the MS may predispose patients to develop pulmonary vascular disease.