Improvement of neutrophil gelatinase-associated lipocalin sensitivity and specificity by two plasma measurements in predicting acute kidney injury after cardiac surgery

Introduction: Acute kidney injury (AKI) remains among the most severe complication after cardiac surgery. The aim of this study was to evaluate the neutrophil gelatinase-associated lipocalin (NGAL) as possible biomarker for the prediction of AKI in an adult cardiac population. Materials and methods: Sixty-nine consecutive patients who underwent cardiac surgeries in our hospital were prospectively evaluated. In the intensive care unit (ICU) NGAL was measured as a new biomarker of AKI besides serum creatinine (sCrea). Patients with at least two factors of AKI risk were selected and samples collected before the intervention and soon after the patient’s arrival in ICU. As reference standard, sCrea measurements and urine outputs were evaluated to define the clinical AKI. A Triage Meter for plasma NGAL fluorescence immunoassay was used. Results: Acute kidney injury occurred in 24 of the 69 patients (35%). Analysis of post-operative NGAL values demonstrated an AUC of 0.71, 95% CI (0.60 - 0.82) with a cut-off = 154 ng/mL (sensitivity = 76%, specificity = 59%). Moreover, NGAL after surgery had a good correlation with the AKI stage severity (P ≤ 0.001). Better diagnostic results were obtained with two consecutive tests: sensitivity 86% with a negative predictive value (NPV) of 87%. At 10-18 h after surgery sCrea measurement, as confirmatory test, allowed to reach a more sensitivity and specificity with a NPV of 96%. Conclusions: The assay results showed an improvement of NGAL diagnostic accuracy evaluating two tests. Consequently, NGAL may be useful for a timely treatment or for the AKI rule out in ICU patients

Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: Systematic Review and Individual Patient Data Meta-Analysis

Background: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle. Results: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08–1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04–1.76, I2 21%). Conclusions: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO

Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography

<div><p>Introduction</p><p>Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality.</p><p>Methods</p><p>This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge.</p><p>Results</p><p>UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6–13) vs 5 (4–7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93–0.98, p = 0.003).</p><p>Conclusions</p><p>Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality.</p></div

Coagulation and TEG parameters in healthy individuals, sepsis patients with “normal response to UK” and sepsis patients with “low response to UK”.

<p>*P value from Kruskal-Wallis rank test. Post-hoc multiple comparison analyses from Dunn’s test with Bonferroni correction,</p><p>^° low responders vs normal responders p<0.05;</p><p>^°° low responders vs normal responders p<0.001;</p><p>^§ low responders vs healthy individuals p<0.05;</p><p>^§§ low responders vs healthy individuals p<0.001;</p><p>^{^} normal responders vs healthy individuals p<0.05;</p><p>^{^^} normal responders vs healthy individuals p<0.001.</p><p>Numbers in table refer to median (25^th– 75^th). Low response to UK group is defined as those patients with UK-TEG_Ly30 value less than 64.9% (limits of normality of healthy individuals UK-TEG_Ly30 = 64.9%-100%).</p><p>Abbreviations: PT ratio, prothrombin time ratio; aPTT ratio, activated partial thromboplastin time ratio; PAI-1, Plasminogen Activator Inhibitor 1; TAFI, Thrombin Activatable Fibrinolysis Inhibitor; TEG, Thromboelastography; TEG_r, reaction time measured by TEG; TEG_angle, angle α measured by TEG; TEG_MA, maximum amplitude measured by TEG; TEG_Ly30, lysis at 30 minutes after MA measured by TEG; UK-TEG, urokinase kaolin activated thromboelastography, UK-TEG_r, reaction time measured by UK-TEG; UK-TEG_angle, angle α measured by UK-TEG; UK-TEG_MA, maximum amplitude measured by UK-TEG; UK-TEG_Ly30, lysis at 30 minutes after MA measured by UK-TEG.</p><p>Coagulation and TEG parameters in healthy individuals, sepsis patients with “normal response to UK” and sepsis patients with “low response to UK”.</p

Characteristics of healthy individuals and sepsis patients.

<p>*From Mann-Whitney (continuous variables) or Fisher’s exact test (categorical variables).</p><p>Numbers in table refer to median (25^th– 75^th) or N(%). Abbreviations: SOFA, Sequential Organ Failure Assessment; DIC, disseminated intravascular coagulation; ISTH, International Society of Thrombosis and Haemostasis; JAAM, Japanese Association for Acute Medicine. Gram-positive microorganisms were: Methicillin Resistant Staphilococcus Aureus, Methicillin Subsceptible Staphilococcus Aureus, Enterococcus, Streptococcus Pyogenes, Streptococcus Pneumoniae. Enterobacteriae were: Escherichia Coli, Enterobacter, Serratia Marcescens. Other gram-negative bacilli were: Acynetobacter, Legionella Pneumophila. Virus was H1N1 influenza A virus.</p><p>Characteristics of healthy individuals and sepsis patients.</p

Clinical and laboratory parameters of sepsis patients in “normal response to UK” group and in “low response to UK” group.

<p>*P value from Mann-Whitney (continuous variables) or Fisher’s exact test (categorical variables). Numbers in table refer to median (25^th– 75^th) or N(%). Low response to UK group is defined as those patients with UK-TEG_Ly30 value less than 64.9% (limits of normality of healthy individuals UK-TEG_Ly30 = 64.9%-100%).</p><p>Abbreviations: SOFA, Sequential Organ Failure Assessment; LDH, lactate dehydrogenase; DIC, disseminated intravascular coagulation; MAP, mean arterial pressure; Hb, hemoglobin; ScvO₂, central venous oxygen saturation; SpO2, pulse oximetry.</p><p>Clinical and laboratory parameters of sepsis patients in “normal response to UK” group and in “low response to UK” group.</p

Distribution of MA and Ly30 measured by TEG and UK-TEG in healthy individuals and sepsis patients.

<p>Column scatter-plot for TEG_MA (Panel A), UK-TEG_MA (Panel B), TEG_Ly30 (Panel C) and UK-TEG_Ly30 (Panel D) in healthy individuals (circles) and sepsis patients (squares). Filled squares represent sepsis patients with SOFA score ≤ 10 (lower severity of disease), clear squares represent sepsis patients with SOFA score > 10 (higher severity of disease). Horizontal lines represent median (25^th- 75^th). * p<0.05, *** p<0.001, p value from Mann-Whitney test. TEG_MA, MA measured by TEG, UK-TEG_MA, MA measured by UK-TEG, TEG_Ly30, Ly30 measured by TEG, UK-TEG_Ly30, Ly30 measured by UK-TEG.</p

Predicted probability (risk) of death in relation with UK-TEG_Ly30 (%).

<p>Predicted probability (risk) of death in relation with UK-TEG_Ly30 (%).</p

Odds ratios (OR) and 95% confidence interval (95% CI) of death for different lysis parameters using logistic regression analysis.

<p>Odds ratios (OR) and 95% confidence interval (95% CI) of death for different lysis parameters using logistic regression analysis.</p