Cecile Aubron

Predicting Survival after Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score

RATIONALE Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. OBJECTIVES To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. METHODS Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction (RESP) score using bootstrapping methodology with internal and external validation. MEASUREMENTS AND MAIN RESULTS Of the 2,355 patients included in the study, 1,338 patients (57%) were discharged alive from hospital. The RESP score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression, which included age, immunocompromised status, duration of mechanical ventilation before ECMO, diagnosis, central nervous system dysfunction, acute associated nonpulmonary infection, neuromuscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2, and peak inspiratory pressure. The receiver operating characteristics curve analysis of the RESP score was c = 0.74 (95% confidence interval, 0.72-0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c = 0.92; 95% confidence interval, 0.89-0.97). CONCLUSIONS The RESP score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure.

Age of red blood cells and transfusion in critically ill patients

Red blood cells (RBC) storage facilitates the supply of RBC to meet the clinical demand for transfusion and to avoid wastage. However, RBC storage is associated with adverse changes in erythrocytes and their preservation medium. These changes are responsible for functional alterations and for the accumulation of potentially injurious bioreactive substances. They also may have clinically harmful effects especially in critically ill patients. The clinical consequences of storage lesions, however, remain a matter of persistent controversy. Multiple retrospective, observational, and single-center studies have reported heterogeneous and conflicting findings about the effect of blood storage duration on morbidity and/or mortality in trauma, cardiac surgery, and intensive care unit patients. Describing the details of this controversy, this review not only summarizes the current literature but also highlights the equipoise that currently exists with regard to the use of short versus current standard (extended) storage duration red cells in critically ill patients and supports the need for large, randomized, controlled trials evaluating the clinical impact of transfusing fresh (short duration of storage) versus older (extended duration of storage) red cells in critically ill patients.

Extracorporeal Membrane Oxygenation—Hemostatic Complications

The use of extracorporeal membrane oxygenation (ECMO) support for cardiac and respiratory failure has increased in recent years. Improvements in ECMO oxygenator and pump technologies have aided this increase in utilization. Additionally, reports of successful outcomes in supporting patients with respiratory failure during the 2009 H1N1 pandemic and reports of ECMO during cardiopulmonary resuscitation have led to increased uptake of ECMO. Patients requiring ECMO are a heterogenous group of critically ill patients with cardiac and respiratory failure. Bleeding and thrombotic complications remain a leading cause of morbidity and mortality in patients on ECMO. In this review, we describe the mechanisms and management of hemostatic, thrombotic and hemolytic complications during ECMO support.

Plasma-induced endothelial oxidative stress is related to the severity of septic shock.

Objective:To estimate the capacity of plasma from septic shock patients to induce in vitro reactive oxygen species (ROS) production by endothelial cells and to analyze whether ROS production is related to the severity of the septic shock. Design:Prospective, observational study. Setting:Medical intensive care unit in a university hospital. Patients:Twenty-one patients with septic shock. Interventions:The in vitro capacity of plasma from septic shock patients to induce ROS production by naive human umbilical vein endothelial cells (HUVEC) was quantified by using a fluorescent probe (2′,7′-dichlorodihydrofluorescein diacetate). Measurements and Main Results:Blood samples were collected on day 1, day 3, and day 5 from 21 consecutive septic shock adult patients and from ten healthy volunteers. Patients mean age was 58 yrs old, mean Sequential Organ Failure Assessment (SOFA) score at admission was 12, mean severity illness assessed by Simplified Acute Physiology Score (SAPS) II was 53, and the mortality rate was 47%. In addition to assessment of in vitro ROS generation by HUVEC, oxidative stress in blood was evaluated by measuring lipid peroxidation products and enzymatic and nonenzymatic antioxidants. Septic shock was associated with oxidative stress and an imbalance in antioxidant status. As compared with controls, plasma-induced ROS production by naïve HUVEC was significantly higher in septic shock. Moreover ROS production was significantly correlated with SAPS II (p = .028) and SOFA values (p = .0012) and was higher in nonsurvivors than in survivors. In contrast, no correlation was found between the severity of the septic shock and any of the levels of lipid peroxidation products or enzymatic and nonenzymatic antioxidants. Conclusion:Plasma from septic shock patients induces ROS formation by naive HUVEC, and the extent of ROS formation correlates with mortality and with criteria of the severity of septic shock as SOFA score and SAPS II.

Infections Acquired by Adults Who Receive Extracorporeal Membrane Oxygenation: Risk Factors and Outcome

OBJECTIVES To analyze infectious complications that occur in patients who receive extracorporeal membrane oxygenation (ECMO), associated risk factors, and consequences on patient outcome. DESIGN Retrospective observational survey from 2005 through 2011. PARTICIPANTS AND SETTING Patients who required ECMO in an Australian referral center. METHODS Cases of bloodstream infection (BSI), catheter-associated urinary tract infection (CAUTI), and ventilator-associated pneumonia (VAP) that occurred in patients who received ECMO were analyzed. RESULTS A total of 146 ECMO procedures were performed for more than 48 hours in 139 patients, and 36 patients had a total of 46 infections (30.1 infectious episodes per 1,000 days of ECMO). They included 24 cases of BSI, 6 of them secondary to VAP; 23 cases of VAP; and 5 cases of CAUTI. The most frequent pathogens were Enterobacteriaceae (found in 16 of 46 cases), and Candida was the most common cause of BSI (in 9 of 24 cases). The Sequential Organ Failure Assessment score before ECMO initiation and the number of days of support were independently associated with a risk of BSI, with odds ratios of 1.23 (95% confidence interval [CI], 1.03-1.47; [Formula: see text]) and 1.08 (95% CI, 1.03-1.19]; [Formula: see text]), respectively. Infected patients did not have a significantly higher mortality compared with uninfected patients (41.7% vs 32%; [Formula: see text]), but intensive care unit length of stay (16 days [interquartile range, 8-26 days] vs 11 days [IQR, 4-19 days]; [Formula: see text]) and hospital length of stay (33.5 days [interquartile range, 15.5-55.5] vs 24 days [interquartile range, 9-42 days]; [Formula: see text]) were longer. CONCLUSION The probability of infection increased with the duration of support and the severity of illness before initiation of ECMO. Infections affected length of stay but did not have an impact on mortality.

A pilot feasibility trial of allocation of freshest available red blood cells versus standard care in critically ill patients

BACKGROUND: Prolonged storage of red blood cells (RBCs) may increase posttransfusion adverse events in critically ill patients. We aimed to evaluate in intensive care unit (ICU) patients 1) the feasibility of allocating freshest available compatible RBCs versus standard care and 2) the suitability of this approach in the design of a large randomized controlled trial (RCT).

Vancomycin Dosing: Assessment of Time to Therapeutic Concentration and Predictive Accuracy of Pharmacokinetic Modeling Software

BACKGROUND: Therapeutic drug monitoring is usually required for safe and effective administration of vancomycin. However, dosing recommendations from published guidelines are not suitable in achieving therapeutic vancomycin concentrations in a timely manner in patients with normal renal function. OBJECTIVE: To audit vancomycin dosing and concentrations at our institution and evaluate the predictive accuracy of a pharmacokinetic simulation program, with a view to implementing a pharmacy-based pharmacokinetic service for vancomycin monitoring. METHODS: Patients receiving vancomycin were identified prospectively through the therapeutic drug monitoring archives. Patient information was obtained from medication charts and medical records that were located on wards. Data were entered into the MM-USC*Pack program (Jelliffe R, University of Southern California, 2008, version 12.10). This software was used to predict initial and subsequent concentrations of vancomycin based on patient parameters. The predictive accuracy of this software was evaluated by comparing the predicted concentrations to the observed concentrations. RESULTS: During a 6-week period, 204 concentrations were measured in 77 patients. The most common dosing regimen was 1 g every 12 hours. Overall, initial trough concentrations were subtherapeutic (<10 mg/L) in 58% of patients and trough concentrations did not become therapeutic at any stage throughout therapy in 25% of patients. The pharmacokinetic modeling software demonstrated little systematic bias (−3.1%), but the precision (median prediction error) was 23% (interquartile range, 11-45%). Predictions were poorer in obese patients (body mass index >35 kg/m2) and in patients with unstable renal function. CONCLUSIONS: A delay in attaining target trough concentrations was observed in a significant proportion of patients. Pharmacokinetic modeling software is a potential tool to improve the timeliness of achieving adequate dosing by allowing concentrations to be determined prior to steady-state. The program was able to predict vancomycin concentrations across a heterogeneous patient population with little systematic bias, but only moderate precision.

Efficacy and safety of fibrinogen concentrate in trauma patients-a systematic review

PURPOSE Uncontrolled bleeding is the main preventable cause of death in severe trauma patients. Fibrinogen is the first coagulation factor to decrease during trauma-induced coagulopathy, suggesting that pharmacological replacement might assist early hemorrhage control. Several sources of fibrinogen are available; however, fibrinogen concentrate (FC) is not routinely used in trauma settings in most countries. The aim of this review is to summarize the available literature evaluating the use of FC in the management of severe trauma. METHODS Studies reporting the administration of FC in trauma patients published between January 2000 and April 2013 were identified from MEDLINE and from the Cochrane Library. RESULTS The systematic review identified 12 articles reporting FC usage in trauma patients: 4 case reports, 7 retrospective studies, and 1 prospective observational study. Three of these were not restricted to trauma patients. CONCLUSIONS Despite methodological flaws, some of the available studies suggested that FC administration may be associated with a reduced blood product requirement. Randomized trials are warranted to determine whether FC improves outcomes in prehospital management of trauma patients or whether FC is superior to another source of fibrinogen in early hospital management of trauma patients.

Ensuring animal welfare while meeting scientific aims using a murine pneumonia model of septic shock.

ABSTRACT With animal models, death as an intentional end point is ethically unacceptable. However, in the study of septic shock, death is still considered the only relevant end point. We defined eight humane end points into four stages of severity (from healthy to moribund) and used to design a clinically relevant scoring tool, termed “the mouse clinical assessment score for sepsis” (M-CASS). The M-CASS was used to enable a consistent approach to the assessment of disease severity. This allowed an ethical and objective assessment of disease after which euthanasia was performed, instead of worsening suffering. The M-CASS displayed a high internal consistency (Cronbach &agr; = 0.97) with a high level of agreement and an intraclass correlation coefficient equal to 0.91. The plasma levels of cytokines and markers of oxidative stress were all associated with the M-CASS score (Kruskal-Wallis test, P < 0.05). The M-CASS allows tracking of disease progression and animal welfare requirements.

Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults

BACKGROUND It is uncertain whether the duration of red‐cell storage affects mortality after transfusion among critically ill adults. METHODS In an international, multicenter, randomized, double‐blind trial, we assigned critically ill adults to receive either the freshest available, compatible, allogeneic red cells (short‐term storage group) or standard‐issue (oldest available), compatible, allogeneic red cells (long‐term storage group). The primary outcome was 90‐day mortality. RESULTS From November 2012 through December 2016, at 59 centers in five countries, 4994 patients underwent randomization and 4919 (98.5%) were included in the primary analysis. Among the 2457 patients in the short‐term storage group, the mean storage duration was 11.8 days. Among the 2462 patients in the long‐term storage group, the mean storage duration was 22.4 days. At 90 days, there were 610 deaths (24.8%) in the short‐term storage group and 594 (24.1%) in the long‐term storage group (absolute risk difference, 0.7 percentage points; 95% confidence interval [CI], ‐1.7 to 3.1; P=0.57). At 180 days, the absolute risk difference was 0.4 percentage points (95% CI, ‐2.1 to 3.0; P=0.75). Most of the prespecified secondary measures showed no significant between‐group differences in outcome. CONCLUSIONS The age of transfused red cells did not affect 90‐day mortality among critically ill adults. (Funded by the Australian National Health and Medical Research Council and others; TRANSFUSE Australian and New Zealand Clinical Trials Registry number, ACTRN12612000453886; ClinicalTrials.gov number, NCT01638416.)