Discordance Between Invasive and NonInvasive Oxygen Saturation in Critically Ill COVID-19 Patients.

OBJECTIVES: To investigate discordance in oxy-hemoglobin saturation measured both by pulse oximetry (SpO2) and arterial blood gas (ABG, SaO2) among critically ill coronavirus disease 2019 (COVID-19(+)) patients compared to COVID-19(-) patients. METHODS: Paired SpO2 and SaO2 readings were collected retrospectively from consecutive adult admissions to four critical care units in the United States between March and May 2020. The primary outcome was the rate of discordance (|SaO2-SpO2|>4%) in COVID-19(+) versus COVID-19(-) patients. The odds each cohort could have been incorrectly categorized as having a PaO2/FiO2 above or below 150 by their SpO2: Fractional inhaled oxygen ratio (pulse oximetry-derived oxyhemoglobin saturation:fraction of inspired oxygen ratio [SF]) was examined. A multivariate regression analysis assessed confounding by clinical differences between cohorts including pH, body temperature, renal replacement therapy at time of blood draw, and self-identified race. RESULTS: There were 263 patients (173 COVID-19(+)) included. The rate of saturation discordance between SaO2 and SpO2 in COVID-19(+) patients was higher than in COVID-19(-) patients (27.9% vs 16.7%, odds ratio [OR] 1.94, 95% confidence interval [CI]: 1.11 to 2.27). The average difference between SaO2 and SpO2 for COVID-19(+) patients was -1.24% (limits of agreement, -13.6 to 11.1) versus -0.11 [-10.3 to 10.1] for COVID-19(-) patients. COVID-19(+) patients had higher odds (OR: 2.61, 95% CI: 1.14-5.98) of having an SF that misclassified that patient as having a PaO2:FiO2 ratio above or below 150. There was not an association between discordance and the confounders of pH, body temperature, or renal replacement therapy at time of blood draw. After controlling for self-identified race, the association between COVID-19 status and discordance was lost. CONCLUSIONS: Pulse oximetry was discordant with ABG more often in critically ill COVID-19(+) than COVID-19(-) patients. However, these findings appear to be driven by racial differences between cohorts.

Care erosion in sedation assessment: A prospective comparison of usual care Richmond Agitation-Sedation Scale assessment with protocolized assessment for medical intensive care unit patients.

OBJECTIVES: To determine concordance between an explicit protocolized assessment of the Richmond Agitation-Sedation Scale and an assessment performed during usual care nursing practice. RESEARCH DESIGN: In an urban, safety-net hospital, intensive care nurses previously trained in sedation assessment recorded a bedside Richmond Agitation-Sedation Scale assessment, while study investigators used an explicit script to perform the assessment at a similar time point. Kappa indices determined concordance of the assessments. Bivariate analyses explored factors associated with discordance and unresponsiveness. RESULTS: Twenty-one subjects with 38 observations were analysed. Bedside nursing assessment was poorly concordant with protocolized assessment (ƙ = 0.21) with the former reporting significantly lighter sedation (median -2 vs. -5, p = .01). Bedside assessment was significantly less likely than protocolized assessment to categorize subjects as unresponsive (29 vs. 50%, p = .02). CONCLUSION: Methods used in usual clinical practice to assess adequacy of sedation frequently led to oversedation. We propose that care erosion, the deterioration of skills over time, may help explain this finding. IMPLICATIONS FOR NURSING MANAGEMENT: Results suggest sedation assessment may be particularly vulnerable to care erosion. Nurse managers should monitor for signs of care erosion and consider utilization of explicit scripts during sedation assessment and/or frequent education to ensure sedation assessment accuracy.

Effect of Interhospital ICU Relocation on Patient Physiology and Clinical Outcomes.

Relocation of large numbers of critically ill patients between hospitals is sometimes necessary and the risks associated with relocation may be high. In the setting of adherence to an interhospital intensive care unit (ICU) relocation protocol, we aimed to determine whether the interhospital relocation of all ICU patients in a single day is associated with changes in vital signs, device removal, and worse clinical outcomes. We conducted a prospective, observational, cohort study of all critically ill adults admitted to a tertiary medical center's ICUs on the day of a planned hospital relocation and exposed to interhospital ICU relocation compared with unexposed critically ill adults. Changes in vital signs were evaluated by the before-and-after interhospital relocation measurement of vital signs, and clinical outcomes were collected for all patients. A total of 699 patients were admitted to the ICU during the observation period, 24 of whom were exposed to interhospital ICU relocation on a single day. The median interhospital transport duration was 28 minutes (interquartile range: 24-35) and 29% of patients were receiving invasive mechanical ventilation. Patients exposed to interhospital ICU relocation had no significant change in any vital sign measurement and no devices were unintentionally removed. Inhospital mortality was similar (8.3%) to patients not exposed to interhospital ICU relocation (9.2%, P > .99). In the setting of adherence to an ICU relocation protocol, the interhospital ICU relocation of all critically ill adults during a single day is not associated with changes in vital signs, device removal, or worse clinical outcomes.

Microparticles in systemic sclerosis: Potential pro-inflammatory mediators and pulmonary hypertension biomarkers.

BACKGROUND AND OBJECTIVE: Endothelial microparticles (EMP) are submicron vesicles released from endothelial cells. We aimed to determine the utility of EMP as biomarkers of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) patients and the pathogenic role of microparticles (MP) in vascular inflammation. METHODS: Levels of EMP (CD144+, CD31+, CD62E+ and CD143+) were compared between three groups (10 SSc patients with PAH, 10 SSc patients without pulmonary hypertension (no-PH) and 10 healthy age- and sex-matched controls). Human pulmonary artery endothelial cells (HPAEC) were exposed in vitro to MP obtained from SSc patients or healthy controls, and levels of cytokines and inflammatory adhesion molecules were compared. RESULTS: CD144+ EMP were significantly higher in the SSc-PAH group compared to either the SSc-no PH or healthy controls (diagnostic accuracy 80%, P = 0.02). Compared to controls, SSc patients had higher CD31+/CD62E+ ratios, indicating larger contributions of apoptosis to EMP release (P = 0.04). Patients with limited SSc had significantly higher levels of CD143+ EMP compared to those with diffuse subtype (P = 0.008). When HPAEC were exposed to MP from SSc patients, there was a significant increase in inflammatory cytokines and adhesion molecules. Interestingly, exposure to healthy control MP caused a reduction in inflammatory markers. CONCLUSION: EMP (particularly CD144+) are promising biomarkers of PAH in SSc but require further study. MP isolated from SSc patients induced an increase in endothelial cell inflammation and may be an important pathogenic factor in SSc.

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial.

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.

Rosuvastatin for sepsis-associated acute respiratory distress syndrome.

BACKGROUND: In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS: We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. RESULTS: The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).

Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD.

Pulmonary endothelial prostacyclin appears to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The effect of treatment with a prostacyclin analog in animal models of previously established COPD is unknown. We evaluated the short- and long-term effect of iloprost on inflammation and airway hyperresponsiveness (AHR) in a murine model of COPD. Nineteen mice were exposed to LPS/elastase, followed by either three doses of intranasal iloprost or saline. In the long-term treatment experiment, 18 mice were exposed to LPS/elastase and then received 6 wk of iloprost or were left untreated as controls. In the short-term experiment, iloprost did not change AHR but significantly reduced serum IL-5 and IFN-γ. Long-term treatment with iloprost for both 2 and 6 wk significantly improved AHR. After 6 wk of iloprost, there was a reduction in bronchoalveolar lavage (BALF) neutrophils, serum IL-1ß (30.0 ± 9.2 vs. 64.8 ± 7.4 pg/ml, P = 0.045), IL-2 (36.5 ± 10.6 vs. 83.8 ± 0.4 pg/ml, P = 0.01), IL-10 (75.7 ± 9.3 vs. 96.5 ± 3.5 pg/ml, P = 0.02), and nitrite (15.1 ± 5.4 vs. 30.5 ± 10.7 µmol, P = 0.01). Smooth muscle actin (SMA) in the lung homogenate was also significantly reduced after iloprost treatment (P = 0.02), and SMA thickness was reduced in the small and medium blood vessels after iloprost (P < 0.001). In summary, short- and long-term treatment with intranasal iloprost significantly reduced systemic inflammation in an LPS/elastase COPD model. Long-term iloprost treatment also reduced AHR, serum nitrite, SMA, and BALF neutrophilia. These data encourage future investigations of prostanoid therapy as a novel treatment for COPD patients.

Missed Opportunities for Health Promotion Intervention in the Management of Alcohol Withdrawal Syndrome.

OBJECTIVE: We aimed to characterize utilization of evidence-based health promotion practices not included in Alcohol Withdrawal Syndrome (AWS) guidelines, such as vaccinations and counseling services, hypothesizing that missed opportunities for health promotion intervention would abound. METHODS: Retrospective medical record review of 99 patients presenting to a safety-net academic medical center with AWS between August 1, 2012 and March 31, 2013. RESULTS: Thiamine replacement (70%), tobacco cessation counseling (28%), influenza or pneumonia vaccination (25% and 28% respectively), psychiatric counseling (70%), referral to alcohol support group or treatment center(40%), and screening for viral hepatitis and HIV (39% and 44%, respectively) were documented by healthcare providers at lower than optimal frequency. CONCLUSIONS: Provision of health promotion interventions was not consistent with evidence-based practices. Integration of these measures into AWS protocols and guidelines could help clinicians provide consistent, cost-effective, evidence- based care.

Ghrelin in Critical Illness.

Ghrelin, a recently described peptide, has attracted significant attention in recent years, primarily in the context of its endocrine- and appetite-regulating effects. The versatility of this peptide is manifested in a rapidly expanding body of literature highlighting its nonendocrine functions. This review summarizes the available data on the immunomodulatory as well as the non-immune-mediated effects of ghrelin that form the scientific basis of its role in critical illness.

Infective Endocarditis-Induced Lung Injury Mimicking Acute Vanishing Lung Syndrome.

Infective endocarditis is the infection of the endocardial surface of the heart valve. The right-sided endocarditis can be complicated by pulmonary injury. The pulmonary complications of infective endocarditis include pulmonary embolism, empyema, pleural effusion, lung abscess, and, in rare cases, pneumothorax. We present a case of bilateral pneumatoceles mimicking vanishing lung syndrome, a very rare pulmonary complication of right-sided infective endocarditis.

Implementation of a Longitudinal Critical Care Fellowship Ultrasound Curriculum.

Background: The use of point-of-care ultrasound as a diagnostic and interventional tool is rapidly becoming standard of care in critical care medicine; a standardized training curriculum is needed to ensure provider proficiency. Objective: This study aimed to describe a longitudinal critical care ultrasound (CCUS) curriculum in a pulmonary critical care medicine (PCCM) fellowship training program. It evaluated the curriculum's impact on fellows' knowledge, skills, and self-reported confidence and retention of these attributes. Methods: We conducted a prospective observational study of a longitudinal CCUS training program within a single PCCM fellowship training program. Knowledge, skills, and confidence of 22 fellows were assessed at baseline; after initial training; and at 6, 12, and 18 months in five domains (ultrasound basics, vascular, lung/pleural, abdomen, and cardiac). We quantified changes in CCUS knowledge, confidence, and skills by fellowship class and assessed for longitudinal retention of these three attributes. The difference in scores between new first-year fellows undergoing formal training and second-year fellows with previous informal training was compared at matched time points. Results: After the initial formal training, there was a significant increase in knowledge, skills, and confidence scores, which were maintained or continued to increase up to 18 months. Fellows with 1 year of formal training also had a higher level of knowledge and skills than fellows with 1 year of informal training, although they had similar levels of self-reported confidence in their skills. Conclusion: A formal, longitudinal CCUS curriculum implemented in a PCCM fellowship program improves trainees' knowledge and skills in various ultrasound domains in addition to their confidence in using ultrasound for patient care. A longitudinal curriculum results in retention of all three attributes and appeared to be more effective than an informal training program based on teaching during rounds, but this needs to be replicated in a larger cohort.

Use of Handheld Ultrasound to Estimate Right Atrial Pressure in a Pulmonary Hypertension Clinic.

Rationale: Point-of-care ultrasonography is an invaluable asset for inpatient decision-making. Whether handheld ultrasound can be used in the outpatient management of pulmonary hypertension is unknown. Objectives: We investigated whether a handheld ultrasound estimate of right atrial pressure correlates with B-type natriuretic peptide (BNP) and clinical outcome over time in outpatients with pulmonary hypertension. Methods: This prospective study included outpatients in a Pulmonary Hypertension Comprehensive Care Center clinic who had a same-day BNP concentration. We used a handheld ultrasound to measure inferior vena cava size and collapsibility, which were used to estimate right atrial pressure (eRAP) and categorize it as normal, intermediate, or high. Correlation analysis was used to compare these ultrasound measurements with BNP at baseline and over time. Cox regression was used to determine whether these measurements were associated with time to clinical worsening. Results: Ninety patients (60% Group 1 pulmonary hypertension) were enrolled. Patients with an intermediate or high eRAP category at baseline had higher BNP concentrations than patients with normal eRAP. For every transition in eRAP category (e.g., from normal to intermediate) between clinic visits, BNP changed by an average of 155 pg/ml (95% confidence interval [CI], 84-227). Higher baseline eRAP category was independently associated with more than twofold increased risk for clinical worsening (hazard ratio, 2.44; 95% CI, 1.47-4.07). Conclusions: Right atrial pressure estimated by portable handheld ultrasound correlates with BNP at baseline and serially over time. Furthermore, eRAP is independently associated with clinical worsening. The use of portable handheld ultrasound to estimate right atrial pressure should be considered in pulmonary hypertension clinics. Clinical trial registered at clinicaltrials.gov (NCT02873039).

Computer clinical decision support that automates personalized clinical care: a challenging but needed healthcare delivery strategy.

How to deliver best care in various clinical settings remains a vexing problem. All pertinent healthcare-related questions have not, cannot, and will not be addressable with costly time- and resource-consuming controlled clinical trials. At present, evidence-based guidelines can address only a small fraction of the types of care that clinicians deliver. Furthermore, underserved areas rarely can access state-of-the-art evidence-based guidelines in real-time, and often lack the wherewithal to implement advanced guidelines. Care providers in such settings frequently do not have sufficient training to undertake advanced guideline implementation. Nevertheless, in advanced modern healthcare delivery environments, use of eActions (validated clinical decision support systems) could help overcome the cognitive limitations of overburdened clinicians. Widespread use of eActions will require surmounting current healthcare technical and cultural barriers and installing clinical evidence/data curation systems. The authors expect that increased numbers of evidence-based guidelines will result from future comparative effectiveness clinical research carried out during routine healthcare delivery within learning healthcare systems.

Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury.

CONTEXT: The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. OBJECTIVE: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. DESIGN, SETTING, AND PARTICIPANTS: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. INTERVENTIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. MAIN OUTCOME MEASURE: Ventilator-free days to study day 28. RESULTS: The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001). CONCLUSIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609180.

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.

BACKGROUND AND OBJECTIVE: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH). METHODS: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 µg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime. RESULTS: Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost. CONCLUSIONS: A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure.

OBJECTIVE: : Adiponectin, an anti-inflammatory cytokine produced by adipose tissue, has been shown to modulate survival in animal models of critical illness. We examined the association between plasma adiponectin and clinical outcomes in critically ill patients with acute respiratory failure. DESIGN: : Secondary analysis of a single-center, randomized controlled trial. SETTING: : Medical intensive care unit of a university-based, tertiary medical center. PATIENTS: : One hundred seventy-five subjects with acute respiratory failure enrolled in randomized, controlled pilot trial of Early versus Delayed Enternal Nutrition (EDEN pilot study). INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : Adiponectin measured within 48 hrs of respiratory failure (Apn1) was inversely correlated with body mass index (r=-0.25, p=.007) and was higher in females (median, 12.6 µg/mL; interquartile range, 7.6-17.1) than males (9.45 µg/mL; 6.2-14.2; p=.02). Adiponectin increased at day 6 (Apn1: 11.4 µg/mL [6.6-15.3] vs. Apn6: 14.1 µg/mL [10.3-18.6], p<.001). This increase was significant only in survivors (Δ adiponectin in survivors: 3.9±6 µg/mL, n=80, p<.001 vs. Δ in nonsurvivors: 1.69±4.6 µg/mL, n=14, p=.19). Higher Apn1 was significantly associated with 28-day mortality (odds ratio 1.59 per 5-µg/mL increase; 95% confidence interval 1.15-2.21; p=.006). No measured demographic, clinical, or cytokine covariates, including interleukin-6, interleukin-8, interleukin-10, interleukin-1ß, interleukin-12, tumor necrosis factor-α, and interferon-γ, were confounders or effect modifiers of this association between adiponectin and mortality. CONCLUSIONS: : Independent of measured covariates, increased plasma adiponectin levels measured within 48 hrs of respiratory failure are associated with mortality. This finding suggests that factors derived from adipose tissue play a role in modulating the response to critical illness.