Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission

Purpose

The soluble form of the urokinase-type plasminogen activator receptor (suPAR) and proadrenomedullin (proADM) are two new and promising sepsis biomarkers. We assessed the prognostic value of a single determination of proADM and suPAR, comparing them with C-reactive protein (CRP) and procalcitonin (PCT), and evaluating whether their addition to severity scores (APACHE II and SOFA) could improve their prognostic accuracy.

Methods

A single-centre prospective observational study conducted in an adult intensive care department at Marques de Valdecilla University Hospital in Spain. APACHE II and SOFA scores, CRP, PCT, suPAR and proADM levels on the day of ICU admission were collected.

Results

A total of 137 consecutive septic patients were studied. The best area under the curve (AUC) for the prediction of in-hospital mortality was for APACHE II (0.82) and SOFA (0.75) scores. The ROC curve for suPAR yielded an AUC of 0.67, higher than proADM (0.62), CRP (0.50) and PCT (0.44). Significant dose-response trends were found between hospital mortality and suPAR (OR Q4 = 4.83, 95 % CI 1.60–14.62) and pro-ADM (OR Q4 = 3.00, 95 % CI 1.06–8.46) quartiles. Non-significant associations were found for PCT and CRP. The combination of severity scores and each biomarker did not provide superior AUCs.

Conclusions

SuPAR and, to a lesser extent, proADM levels on ICU admission were better tools in prognosticating in-hospital mortality than CRP or PCT. However, neither of the two new biomarkers has been demonstrated to be excessively useful in the current setting. The prognostic accuracy was better for severity scores than for any of the biomarkers.     

Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients with acute lung injury

Purpose

Deposition of fibrin in the alveolar space is a hallmark of acute lung injury (ALI). Plasminogen activator inhibitor-1 (PAI-1) is an antifibrinolytic agent that is activated during inflammation. Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI. This relationship has not been examined in children. The objective of this study was to test whether increased plasma PAI-1 levels are associated with worse clinical outcomes in pediatric patients with ALI.

Design/methods

We measured plasma PAI-1 levels on the first day of ALI among 94 pediatric patients enrolled in two separate prospective, multicenter investigations and followed them for clinical outcomes. All patients met American European Consensus Conference criteria for ALI.

Results

A total of 94 patients were included. The median age was 3.2 years (range 16 days–18 years), the PaO₂/F_iO₂ was 141 ± 72 (mean ± SD), and overall mortality was 14/94 (15%). PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01). The adjusted odds of mortality doubled for every log increase in the level of plasma PAI-1 after adjustment for age and severity of illness.

Conclusions

Higher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI. These findings suggest that impaired fibrinolysis may play a role in the pathogenesis of ALI in pediatric patients and suggest that PAI-1 may serve as a useful biomarker of prognosis in patients with ALI.     

The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood: multicenter evaluation and expert consensus

Purpose

A new acute respiratory distress syndrome (ARDS) definition has been recently issued: the so-called Berlin definition (BD) has some characteristics that could make it suitable for pediatrics. The European Society for Pediatric Neonatal Intensive Care (ESPNIC) Respiratory Section started a project to evaluate BD validity in early childhood. A secondary aim was reaching a consensus on clinical tools (risk factors list and illustrative radiographs) to help the application of BD.

Methods

This was an international, multicenter, retrospective study enrolling 221 children [aged greater than 30 days and less than 18 months; median age 6 (range 2–13) months], admitted to seven European pediatric intensive care units (PICU) with acute lung injury (ALI) or ARDS diagnosed with the earlier definition.

Results

Patients were categorized according to the two definitions, as follows: ALI, 36; ARDS, 185 (for the American–European Consensus Conference (AECC) definition); mild, 36; moderate, 97; severe ARDS, 88 (for BD). Mortality (13.9 % for mild ARDS; 11.3 % for moderate ARDS; 25 % for severe ARDS, p = 0.04) and the composite outcome extracorporeal membrane oxygenation (ECMO)/mortality (13.9 % for mild ARDS; 11.3 % for moderate ARDS; 28.4 % for severe ARDS, p < 0.01) were different across the BD classes, whereas they were similar using the previous definition. Mortality [HR 2.7 (95 % CI 1.1–7.1)] and ECMO/mortality [HR 3 (95 % CI 1.1–7.9)] were increased only for the severe ARDS class and remained significant after adjustment for confounding factors. PICU stay was not different across severity classes, irrespective of the definition used. There was significant concordance between raters evaluating radiographs [ICC 0.6 (95 % CI 0.2–0.8)] and risk factors [ICC 0.92 (95 % CI 0.8–0.97)].

Conclusions

BD validity for children is similar to that already reported in adults and mainly due to the introduction of a “severe ARDS” category. We provided clinical tools to use BD for clinical practice, research, and health services planning in pediatric critical care.     

Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock

Purpose

To assess changes in peroxisome proliferator-activated receptor-γ (PPARγ) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARγ, 15-deoxy-?^12,14-PGJ₂ (15d-PGJ₂), and the downstream targets of PPARγ activity, adiponectin and resistin.

Methods

Single-center, prospective case–control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock.

Results

PPARγ nuclear protein expression was decreased but PPARγ activity was increased in PBMC from children with septic shock compared with controls. PPARγ activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) ± standard error of the mean (SEM) 0.03 versus 0.12 OD ± 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARγ ligand, 15d-PGJ₂, compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 ± 21.7 versus 58 ± 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585–833 ng/ml versus 143 ng/ml, IQR 66–342 ng/ml; p < 0.05].

Conclusions

Sepsis is associated with altered PPARγ expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARγ in sepsis.     

Prevalence and prognosis of cor pulmonale during protective ventilation for acute respiratory distress syndrome

Purpose

Pulmonary vascular dysfunction is common during acute respiratory distress syndrome (ARDS), but there is controversy concerning prevalence and prognosis of cor pulmonale during protective ventilation for ARDS.

Methods

This was a prospective observational study in an academic medical intensive care unit in France. Two hundred and twenty-six consecutive patients with moderate to severe ARDS (Berlin definition) ventilated with plateau pressure limited at 30 cmH₂O (mean PEEP of 8.8 ± 3.6 cmH₂O) underwent transesophageal echocardiography (TEE) within the first 3 days after the diagnosis of ARDS. Cor pulmonale was defined as a dilated right ventricle associated with septal dyskinesia.

Results

Cor pulmonale was detected in 49 patients (prevalence of 22 %; 95 % confidence interval, 16–27 %). Multivariate logistic regression identified infectious causes of lung injury and higher driving pressures as independent factors associated with cor pulmonale. Patients with cor pulmonale exhibited a higher incidence of shock (need for vasoactive drug) at the time of TEE and were more often managed with prone positioning and/or nitric oxide as adjunctive therapy for severe hypoxemia during ARDS course. The 28-day mortality rate was significantly higher in the group with cor pulmonale (60 vs. 36 %, p < 0.01). Multivariate logistic regression identified McCabe and Jackson class, lung injury not related to pneumonia, aspiration, or sepsis, lactic acidosis, driving pressure, and cor pulmonale as independent risk factors for 28-day mortality.

Conclusion

Cor pulmonale occurrence is not negligible in ARDS patients ventilated with airway pressure limitation. Cor pulmonale was associated with sepsis and higher values of driving pressure and was an independent risk factor for 28-day mortality in our series.     

Pancreatic stone protein as a novel marker for neonatal sepsis

Purpose

Early-onset sepsis (EOS) is one of the main causes for the admission of newborns to the neonatal intensive care unit. However, traditional infection markers are poor diagnostic markers of EOS. Pancreatic stone protein (PSP) is a promising sepsis marker in adults. The aim of this study was to investigate whether determining PSP improves the diagnosis of EOS in comparison with other infection markers.

Methods

This was a prospective multicentre study involving 137 infants with a gestational age of >34 weeks who were admitted with suspected EOS. PSP, procalcitonin (PCT), soluble human triggering receptor expressed on myeloid cells-1 (sTREM-1), macrophage migration inhibitory factor (MIF) and C-reactive protein (CRP) were measured at admission. Receiver-operating characteristic (ROC) curve analysis was performed.

Results

The level of PSP in infected infants was significantly higher than that in uninfected ones (median 11.3 vs. 7.5 ng/ml, respectively; p = 0.001). The ROC area under the curve was 0.69 [95 % confidence interval (CI) 0.59–0.80; p < 0.001] for PSP, 0.77 (95 % CI 0.66–0.87; p < 0.001) for PCT, 0.66 (95 % CI 0.55–0.77; p = 0.006) for CRP, 0.62 (0.51–0.73; p = 0.055) for sTREM-1 and 0.54 (0.41–0.67; p = 0.54) for MIF. PSP independently of PCT predicted EOS (p < 0.001), and the use of both markers concomitantly significantly increased the ability to diagnose EOS. A bioscore combining PSP (>9 ng/ml) and PCT (>2 ng/ml) was the best predictor of EOS (0.83; 95 % CI 0.74–0.93; p < 0.001) and resulted in a negative predictive value of 100 % and a positive predictive value of 71 %.

Conclusions

In this prospective study, the diagnostic performance of PSP and PCT was superior to that of traditional markers and a combination bioscore improved the diagnosis of sepsis. Our findings suggest that PSP is a valuable biomarker in combination with PCT in EOS.     

One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome

Purpose

Advances in supportive care and ventilator management for acute respiratory distress syndrome (ARDS) have resulted in declines in short-term mortality, but risks of death after survival to hospital discharge have not been well described. Our objective was to quantify the difference between short-term and long-term mortality in ARDS and to identify risk factors for death and causes of death at 1 year among hospital survivors.

Methods

This multi-intensive care unit, prospective cohort included patients with ARDS enrolled between January 2006 and February 2010. We determined the clinical characteristics associated with in-hospital and 1-year mortality among hospital survivors and utilized death certificate data to identify causes of death.

Results

Of 646 patients hospitalized with ARDS, mortality at 1 year was substantially higher (41 %, 95 % CI 37–45 %) than in-hospital mortality (24 %, 95 % CI 21–27 %), P < 0.0001. Among 493 patients who survived to hospital discharge, the 110 (22 %) who died in the subsequent year were older (P < 0.001) and more likely to have been discharged to a nursing home, other hospital, or hospice compared to patients alive at 1 year (P < 0.001). Important predictors of death among hospital survivors were comorbidities present at the time of ARDS, and not living at home prior to admission. ARDS-related measures of severity of illness did not emerge as independent predictors of mortality in hospital survivors.

Conclusions

Despite improvements in short-term ARDS outcomes, 1-year mortality is high, mostly because of the large burden of comorbidities, which are prevalent in patients with ARDS.     

Increased plasma levels of heparin-binding protein in patients with acute respiratory distress syndrome

Introduction

Heparin-binding protein (HBP) is an antimicrobial protein stored in neutrophil granules and plays a role in endothelial permeability regulation. The aim was to assess the diagnostic and prognostic value of measuring HBP in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).

Methods

Plasma HBP was collected from 78 patients with ALI/ARDS, 28 patients with cardiogenic pulmonary edema (CPE) and 20 healthy volunteers at enrollment. Levels of HBP were measured by ELISA.

Results

Patients with ALI/ARDS had significantly higher median levels of HBP compared with patients with CPE (17.15 (11.95 to 24.07) ng/ml vs. 9.50 (7.98 to 12.18) ng/ml, P <0.001) at enrollment. There was no significant difference between CPE patients and healthy subjects in terms of HBP value (P = 0.372). The HBP levels of nonsurvivors was significantly higher than that of survivors (23.90 (14.81 to 32.45) ng/ml vs. 16.01 (10.97 to 21.06) ng/ml, P = 0.012) and multivariate logistic regression showed HBP (odds ratio =1.52, P = 0.034) was the independent predictor for 30-day mortality in patients with ALI/ARDS.

Conclusions

Plasma HBP levels of ALI/ARDS patients were significantly higher than that of CPE patients. HBP was a strong prognostic marker for short-term mortality in ALI/ARDS.     

Acute respiratory distress syndrome in patients with malignancies

Purpose

Little attention has been given to ARDS in cancer patients, despite their high risk for pulmonary complications. We sought to describe outcomes in cancer patients with ARDS meeting the Berlin definition.

Methods

Data from a cohort of patients admitted to 14 ICUs between 1990 and 2011 were used for a multivariable analysis of risk factors for hospital mortality.

Results

Of 1,004 included patients (86 % with hematological malignancies and 14 % with solid tumors), 444 (44.2 %) had neutropenia. Admission SOFA score was 12 (10–13). Etiological categories were primary infection-related ARDS (n = 662, 65.9 %; 385 bacterial infections, 213 invasive aspergillosis, 64 Pneumocystis pneumonia); extrapulmonary septic shock-related ARDS (n = 225, 22.4 %; 33 % candidemia); noninfectious ARDS (n = 76, 7.6 %); and undetermined cause (n = 41, 4.1 %). Of 387 (38.6 %) patients given noninvasive ventilation (NIV), 276 (71 %) subsequently required endotracheal ventilation. Hospital mortality was 64 % overall. According to the Berlin definition, 252 (25.1 %) patients had mild, 426 (42.4 %) moderate and 326 (32.5 %) severe ARDS; mortality was 59, 63 and 68.5 %, respectively (p = 0.06). Mortality dropped from 89 % in 1990–1995 to 52 % in 2006–2011 (p < 0.0001). Solid tumors, primary ARDS, and later admission period were associated with lower mortality. Risk factors for higher mortality were allogeneic bone-marrow transplantation, modified SOFA, NIV failure, severe ARDS, and invasive fungal infection.

Conclusions

In cancer patients, 90 % of ARDS cases are infection-related, including one-third due to invasive fungal infections. Mortality has decreased over time. NIV failure is associated with increased mortality. The high mortality associated with invasive fungal infections warrants specific studies of early treatment strategies.     

Outcome of acute respiratory distress syndrome patients treated with extracorporeal membrane oxygenation and brought to a referral center

Purpose

Patients with severe acute respiratory distress syndrome (ARDS) are candidates for extracorporeal membrane oxygenation (ECMO) therapy. The evaluation of organ severity is difficult in patients considered for cannulation in a distant hospital. This study was designed to identify early factors associated with hospital mortality in ARDS patients treated with ECMO and retrieved from referring hospitals.

Methods

Data from 85 consecutive ARDS patients equipped with ECMO by our mobile team and consequently admitted to our ICU were prospectively collected and analyzed.

Results

The main ARDS etiologies were community-acquired bacterial pneumonia (35 %), influenza pneumonia (23 %) (with 12 patients having been treated during the first half of the study period), and nosocomial pneumonia (14 %). The median (interquartile range) time between contact from the referring hospital and patient cannulation was 3 (1–4) h. ECMO was venovenous in 77 (91 %) patients. No complications occurred during transport by our mobile unit. Forty-eight patients died at the hospital (56 %). Based on a multivariate logistic regression, a score including age, SOFA score, and a diagnosis of influenza pneumonia was constructed. The probability of hospital mortality following ECMO initiation was 40 % in the 0–2 score class (n = 58) and 93 % in the 3–4 score class (n = 27). Patients with an influenza pneumonia diagnosis and a SOFA score before ECMO of less than 12 had a mortality rate of 22 %.

Conclusions

Age, SOFA score, and a diagnosis of influenza may be used to accurately evaluate the risk of death in ARDS patients considered for retrieval under ECMO from distant hospitals.     

Prognostic impact of the serum heart-type fatty acid-binding protein (H-FABP) levels in patients admitted to the non-surgical intensive care unit

Background

Biomarkers predicting adverse outcomes in non-surgical intensive care patients have not been reported.

Methods and results

Data for 1,006 emergency department patients were prospectively analyzed. The serum heart-type fatty acid-binding protein (s-H-FABP) level was measured within 10 min of admission. The patients were assigned to intensive care (n = 835) or other departments (n = 171). The intensive care patients were divided into survivors (n = 745) and non-survivors (n = 90) according to the in-hospital mortality and assigned to four groups according to the quartiles of s-H-FABP (Q1, Q2, Q3 and Q4). The s-H-FABP levels were significantly higher in the intensive care patients (12.7 [6.1–38.8] ng/ml versus 5.3 [3.1–9.4] ng/ml) and in the non-survivors (44.9 [23.2–87.6] ng/ml versus 11.5 [5.6–32.6] ng/ml). A Kaplan–Meier curve showed a significantly higher survival rate in Q3 than in Q1 and Q2 and in Q4 than in the other groups. The multivariate Cox regression model identified Q3 (HR 4.646, 95 % CI 1.526–14.146) and Q4 (HR 9.483, 95 % CI 3.152–28.525) as independent predictors of 90-day mortality. The sensitivity and specificity of H-FABP for in-hospital mortality were 81.1 and 66.0 % (AUC 0.775) at 20.95 ng/ml. The in-hospitality rate was significantly higher in the high s-H-FABP patients than in the low s-H-FABP patients in each etiology group.

Conclusions

The s-H-FABP level is an effective biomarker for risk stratification in non-surgical intensive care patients.     

Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis

Purpose

Prone positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials.

Methods

Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (>8 ml/kg predicted body weight) or low (≤8 ml/kg PBW) mean baseline tidal volume was planned a priori.

Results

Seven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95 % CI 0.68–1.02; p = 0.073; I ²  = 64 %). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95 % CI 0.50–0.86; p = 0.002; I ²  = 25 %). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis.

Conclusions

Prone positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume.     

Randomised trials of 6 % tetrastarch (hydroxyethyl starch 130/0.4 or 0.42) for severe sepsis reporting mortality: systematic review and meta-analysis

Purpose

To assess the impact of 6 % tetrastarch [hydroxyethyl starch (HES) 130/0.4 and 130/0.42] in severe sepsis patients. The primary outcome measure was 90-day mortality.

Methods

A structured literature search was undertaken to identify prospective randomised controlled trials (RCTs) in adult patients with severe sepsis receiving 6 % tetrastarch (of potato or waxy maize origin) as part of fluid resuscitation in comparison with other non-HES fluids after randomisation in the critical care setting. A systematic review and meta-analysis were performed.

Results

Six RCTs were included (n = 3,033): three from 2012 (n = 2,913) had low risk of bias. Median tetrastarch exposure was 37.4 ml/kg (range 30–43 ml/kg). Ninety-day mortality was associated with tetrastarch exposure [relative risk (RR) 1.13; 95 % confidence interval (CI) 1.02–1.25; p = 0.02] compared with crystalloid. The number needed to harm (NNH) was 28.8 (95 % CI 14.6–942.5). Publication bias and statistical heterogeneity (I ² = 0 %) were not present. Tetrastarch exposure was also associated with renal replacement therapy (p = 0.01; NNH 15.7) and allogeneic transfusion support (p = 0.001; NNH 9.9). No difference between groups was observed for 28-day mortality, for comparison with colloid as control, or for waxy maize-derived tetrastarch, but power was lacking. Overall mortality was associated with tetrastarch exposure (RR 1.13; 95 % CI 1.02–1.25; p = 0.02).

Conclusions

In our analysis, 6 % tetrastarch as part of initial fluid resuscitation for severe sepsis was associated with harm and, as alternatives exist, in our view should be avoided.     

Laminin γ2 fragments are increased in the circulation of patients with early phase acute lung injury

Objective

Laminin-5, a cell adhesive molecule expressed solely by epithelium, is known to enhance epithelial cell migration and repair of injured epithelium, after its essential component γ2-chain is processed proteolytically. Our previous study revealed circulating levels of amino-terminal fragment of laminin γ2-chain (G2F) reflect epithelial tumor invasiveness in carcinoma patients, but its physiological role in alveolar epithelial injury remains unknown.

Design

Sampling of epithelial lining fluids or pulmonary edema fluids from patients with acute lung injury (ALI) or related diseases was performed. Plasma samples were obtained from them at the time of disease onset or later. G2F concentrations were determined by immunoassay constructed by ourselves.

Results

We found a significantly higher amount of G2F in pulmonary edema and epithelial lining fluids of patients with ALI, as compared with those with the other respiratory diseases. Their plasma levels were also elevated significantly early at the onset of ALI (mean ± SD; 147 ± 82 ng/ml in non-surviving and 90 ± 56 in surviving patients) as compared with those in the patients with cardiogenic pulmonary edema (59 ± 36) or idiopathic pulmonary fibrosis (37 ± 17), indicating alveolar epithelium rapidly secrete laminin-5 in ALI. At 5 days after onset, non-surviving patients maintained higher plasma concentrations (152 ± 84), but in contrast, the levels in surviving patients declined (71 ± 35), suggesting secretion of laminin-5 was suppressed, associated with recovery from ALI.

Conclusion

Circulating G2F may be a biomarker for alveolar laminin-5 secreted early at disease onset in ALI, potentially regulating alveolar re-epithelialization.     

A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting—a prospective, multicenter validation study

Purpose

The PaO₂/FiO₂ is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO₂/FiO₂ calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification.

Methods

We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO₂/FiO₂ ≤ 200. In the derivation cohort (n = 170), we measured PaO₂/FiO₂ with two levels of positive end-expiratory pressure (PEEP) (≥5 and ≥10 cmH₂O) and two levels of FiO₂ (≥0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO₂ response, patients were reclassified into three groups: mild (PaO₂/FiO₂ > 200), moderate (PaO₂/FiO₂ 101–200), and severe (PaO₂/FiO₂ ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282).

Results

The only standard ventilatory setting that identified the three PaO₂/FiO₂ risk categories in the derivation cohort was PEEP ≥ 10 cmH₂O and FiO₂ ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001).

Conclusions

Our method for assessing PaO₂/FiO₂ greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials.     

Diagnostic utility of B-type natriuretic peptide in critically ill patients with pulmonary edema: a prospective cohort study

Introduction

Distinguishing pulmonary edema due to acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) from hydrostatic or cardiogenic edema is challenging in critically ill patients. B-type natriuretic peptide (BNP) can effectively identify congestive heart failure in the emergency room setting but, despite increasing use, its diagnostic utility has not been validated in the intensive care unit (ICU).

Methods

We performed a prospective, blinded cohort study in the medical and surgical ICUs at the University of Chicago Hospitals. Patients were eligible if they were admitted to the ICU with respiratory distress, bilateral pulmonary edema and a central venous catheter suggesting either high-pressure (cardiogenic) or low-pressure (ALI/ARDS) pulmonary edema. BNP levels were measured within 48 hours of ICU admission and development of pulmonary edema and onward up to three consecutive days. All levels were drawn simultaneously with the measurement of right atrial or pulmonary artery wedge pressure. The etiology of pulmonary edema – cardiogenic or ALI/ARDS – was determined by three intensivists blinded to BNP levels.

Results

We enrolled a total of 54 patients (33 with ALI/ARDS and 21 with cardiogenic edema). BNP levels were lower in patients with ALI/ARDS than in those with cardiogenic edema (496 ± 439 versus 747 ± 476 pg/ml, P = 0.05). At an accepted cutoff of 100 pg/ml, specificity for the diagnosis of ALI/ARDS was high (95.2%) but sensitivity was poor (27.3%). Cutoffs at higher BNP levels improved sensitivity at considerable cost to specificity. Invasive measures of filling pressures correlated poorly with initial BNP levels and subsequent day BNP values fluctuated unpredictably and without correlation with hemodynamic changes and net fluid balance.

Conclusion

BNP levels drawn within 48 hours of admission to the ICU do not reliably distinguish ALI/ARDS from cardiogenic edema, do not correlate with invasive hemodynamic measurements, and do not track predictably with changes in volume status on consecutive daily measurements.     

Effect of the use of low and high potency statins and sepsis outcomes

Introduction

Although statins have been shown to have cholesterol-lowering effects, their pleiotropic benefits on sepsis remain a matter of debate. In addition, the influence of statin potency on sepsis-related mortality has never been explored. The aim of our study was to determine the sepsis outcomes of low- and high-potency statin users and non-users.

Methods

This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan’s National Health Insurance program. Patients were hospitalized for sepsis between 2000 and 2010. All-cause mortality and major adverse consequences of sepsis, such as in-hospital death, intensive care unit admission, shock events, and the use of mechanical ventilation, were assessed. Patients were divided into high-potency statin users (at least 10 mg rosuvastatin, at least 20 mg atorvastatin, or at least 40 mg simvastatin), low-potency statin users (all other statin treatments), and non-users.

Results

A propensity score-matched cohort of 27,792 statin users and 27,792 non-users was included. Of 27,792 statin users, 9,785 (35.2 %) were treated with high-potency statins and 18,007 (64.8 %) were treated with low-potency statins. The 1-year mortality risk was significantly lower among both low-potency [adjusted hazard ratio (aHR) 0.89, 95 % confidence interval (CI) 0.85–0.93] and high-potency (aHR 0.80, 95 % CI 0.75–0.86) statin users compared with non-users. The risks of mortality and adverse consequences of sepsis were lower among high-potency than among low-potency statin users.

Conclusions

High-potency statin use is associated with a lower risk of sepsis-related mortality compared with low-potency statin use.     

Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality

Purpose

Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis.

Methods

This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F₁₊₂)] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90.

Results

Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F₁₊₂ concentration and with PAI-1 activity and concentration (p < 0.05 for all).

Conclusions

Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.     

The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome

Purpose

This study was designed to identify factors associated with death by 6 months post-intensive care unit (ICU) discharge and to develop a practical mortality risk score for extracorporeal membrane oxygenation (ECMO)-treated acute respiratory distress syndrome (ARDS) patients. We also assessed long-term survivors’ health-related quality of life (HRQL), respiratory symptoms, and anxiety, depression and post-traumatic stress disorder (PTSD) frequencies.

Methods

Data from 140 ECMO-treated ARDS patients admitted to three French ICUs (2008–2012) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQL, psychological and PTSD status.

Results

Main ARDS etiologies were bacterial (45 %), influenza A[H₁N₁] (26 %) and post-operative (17 %) pneumonias. Six months post-ICU discharge, 84 (60 %) patients were still alive. Based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0–14 points) was constructed with eight pre-ECMO parameters, i.e. age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure. Six-month post-ECMO initiation cumulative probabilities of survival were 97, 79, 54 and 16 % for PRESERVE classes 0–2, 3–4, 5–6 and ≥7 (p < 0.001), respectively. HRQL evaluation in 80 % of the 6-month survivors revealed satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety, depression or PTSD symptoms reported, by 34, 25 or 16 %, respectively.

Conclusions

The PRESERVE score might help ICU physicians select appropriate candidates for ECMO among severe ARDS patients. Future studies should also focus on physical and psychosocial rehabilitation that could lead to improved HRQL in this population.