Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department.

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

Antiplatelet drugs and outcome in mixed admissions to an intensive care unit.

OBJECTIVE: Platelet activation has been implicated in microvascular thrombosis and organ failure. We tested the hypothesis that antiplatelet drugs favorably affect outcome in patients nonelectively admitted to an intensive care unit. DESIGN: Retrospective cohort study. SETTING: A 22-bed intensive care unit of a tertiary care center. PATIENTS: Six hundred fifteen consecutive patients admitted to an intensive care unit within 24 hrs after hospitalization were enrolled, approximately 25% of whom received antiplatelet drugs (acetylsalicylic acid, clopidogrel) for secondary prevention of vascular disease. Impact of antiplatelet drugs and established risk factors on mortality were assessed by logistic regression and 2 x 2 table analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients on antiplatelet drugs were markedly older and presented higher Acute Physiology and Chronic Health Evaluation II scores on intensive care unit admission. There was no significant difference in injury severity scores in trauma patients with (21 [range, 13-29]) or without antiplatelet drugs (18 [range, 12-29]). Using logistic regression analysis, a significant reduction of mortality was estimated for the use of antiplatelet drugs in various subgroups of patients with normal or high bleeding risk (odds ratios, 0.04-0.34). Significant benefit was also estimated by 2 x 2 table analysis of Acute Physiology and Chronic Health Evaluation II-matched samples (Acute Physiology and Chronic Health Evaluation II >20) of internal medicine patients and/or patients receiving medical treatment. No significant benefit but also no harm of antiplatelet drugs was estimated in Acute Physiology and Chronic Health Evaluation II-matched samples of patients with increased bleeding risk: patients from surgery departments overall, patients with surgical treatment, trauma, active bleeding, or transfusion (odds ratios, 0.51-0.88). CONCLUSIONS: Our data are consistent with prevention of organ dysfunction by antiplatelet drugs, which may be masked in some patients by concomitant bleeding risk. Antiplatelet drugs might offer a novel therapeutic option to prevent organ failure, at least in the absence of active bleeding. This hypothesis warrants testing in a prospective trial.

Design and effectiveness of a membrane-pump-driven ventilator for mice.

To perform mechanical ventilation of mice in the absence of highly expensive commercially available devices, we developed a membrane-pump-driven respirator and studied its practicability. The continuous airflow generated by the membrane pump was changed into an intermittent flow by using a multifunction timer. Tidal volume was adjusted by a rotary dimmer regulating the electric power onto the pump. The expiration air left the circuit through openings at the tube connection. Mice were ventilated with room air for 5 h with a tidal volume of approximately 200 muL. In group 1 (n = 6), ventilation was performed with a frequency of 110 min-1, in group 2 (n = 6) with a frequency of 150 min-1. Spontaneously breathing anesthetized mice (n = 6) served as controls. In addition we performed single-lung open-chest ventilation for 1 h in two animals. The parameters of arterial blood gas analyses were within the normal range except for moderate hyperventilation in group 2. Single-lung ventilation led to a significant decline (P < 0.05) of pO2 and SO2, whereas the pCO2 remained within the normal range. Respiratory rate, tidal volume and pressure limitation can be adjusted for optimal ventilation. In addition, the device provides a minimalized dead space and impedes potential alveolar damage caused by negative pressure generated by spontaneous inspiration during positive-pressure ventilation.