Plasma neurofilament light is a predictor of neurological outcome 12 h after cardiac arrest

Background: Previous studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24–72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes. Methods: Observational multicentre cohort study in adults admitted to intensive care after cardiac arrest. NfL was retrospectively analysed in plasma collected on admission to intensive care, 12 and 48 h after cardiac arrest. The outcome was assessed at two to six months using the Cerebral Performance Category (CPC) scale, where CPC 1–2 was considered a good outcome and CPC 3–5 a poor outcome. Predictive performance was measured with the area under the receiver operating characteristic curve (AUROC). Results: Of 428 patients, 328 (77%) suffered OHCA and 100 (23%) IHCA. Poor outcome was found in 68% of OHCA and 55% of IHCA patients. The overall prognostic performance of NfL was excellent at 12 and 48 h after OHCA, with AUROCs of 0.93 and 0.97, respectively. The predictive ability was lower after IHCA than OHCA at 12 and 48 h, with AUROCs of 0.81 and 0.86 (p ≤ 0.03). AUROCs on admission were 0.77 and 0.67 after OHCA and IHCA, respectively. At 12 and 48 h after OHCA, high NfL levels predicted poor outcome at 95% specificity with 70 and 89% sensitivity, while low NfL levels predicted good outcome at 95% sensitivity with 71 and 74% specificity and negative predictive values of 86 and 88%. Conclusions: The prognostic accuracy of NfL for predicting good and poor outcomes is excellent as early as 12 h after OHCA. NfL is less reliable for the prediction of outcome after IHCA

Effects of inhibition of PAF, ICAM-1, and PECAM-1 on gut barrier failure caused by intestinal ischemia and reperfusion.

BACKGROUND: The role of cell adhesion molecules and transmigration of PMNs through the endothelial barrier is probably essential in intestinal ischemia and reperfusion (I/R)-induced gut barrier dysfunction. Although cytokines are released in I/R, it is unclear whether cytokines directly increase permeability or if this phenomenon requires both expression of cell adhesion molecules and PMN adhesion-activation. Endothelial barrier dysfunction plays an important role in the pathogenesis of multiple organ dysfunction syndrome, inducing gut barrier failure, but the mechanisms are not fully understood. The purpose of this study was to evaluate the potential therapeutic value of inhibition of platelet activating factor (PAF), intercellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) in gut barrier dysfunction induced by intestinal I/R. METHODS: A PAF antagonist (lexipafant, BB-882) and monoclonal antibodies against rat ICAM-1 (anti-ICAM-1-MAb) an

Sepsis Is Underreported in Swedish Intensive Care Units: A Retrospective Observational Multicentre Study

BackgroundSepsis is a common indication for admission to the intensive care unit (ICU). Since definitions vary across studies, comparisons of prevalence and outcomes have been challenging. We aimed to compare sepsis according to ICU discharge codes with sepsis according to Sepsis‐3 criteria and to investigate the epidemiology of sepsis in the ICU. We hypothesized that sepsis using discharge codes is underreported.MethodsAdult ICU admissions to four ICUs in Sweden between 2015 and 2017 were screened for sepsis according to the Sepsis‐3 criteria. Medical records were reviewed and data extracted from the Swedish Intensive Care Registry.ResultsOf 5990 adult ICU patients, 28% fulfilled the Sepsis‐3 criteria on admission, but only 31% of them had sepsis as the registered main diagnosis at ICU discharge. Of the 1654 Sepsis‐3 patients, 38% met the septic shock criteria. The Sepsis‐3 in‐hospital mortality was 26% compared to 33% in patients with septic shock. The incidence rate for ICU‐treated sepsis was 81 cases per 100 000 person‐years. One in four had a positive blood culture, and 44% were culture negative.ConclusionThis large Swedish multicentre study showed that 28% of adult ICU patients fulfilled the Sepsis‐3 criteria, but only one third of them had sepsis according to ICU discharge codes. We could confirm our hypothesis, that sepsis is severely underreported in Swedish ICUs, and we conclude that discharge codes should not be used for quality control or research purposes

Hemodynamics and Vasopressor Support During Targeted Temperature Management at 33\ub0C Versus 36\ub0C After Out-of-Hospital Cardiac Arrest: A Post Hoc Study of the Target Temperature Management Trial

OBJECTIVE:: To investigate the hemodynamic profile associated with different target temperatures and to assess the prognostic implication of inotropic/vasopressor support and mean arterial pressure after out-of-hospital cardiac arrest. There is a lack of information how different target temperatures may affect hemodynamics. DESIGN:: Post hoc analysis of a prospective randomized study. SETTING:: Thirthy-six ICUs in 10 countries. PATIENTS:: Nine hundred twenty patients (97%) with available vasopressor data out of 950 patients from the Target Temperature Management trial randomly assigned patients to a targeted temperature management at 33\ub0C or 36\ub0C. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Mean arterial pressure, heart rate, and lactate were registered at prespecified time points. The population was stratified according to cardiovascular Sequential Organ Failure Assessment = 4 defining the high vasopressor group and cardiovascular Sequential Organ Failure Assessment less than or equal to 3 defining the low vasopressor group. The targeted temperature management 33 (TTM33) group had a hemodynamic profile with lower heart rate (-7.0 min [95% confidence limit, -8.7, -5.1]; pgroup < 0.0001), similar mean arterial pressure (-1.1 mm Hg [95% confidence limit, -2.3, 0.2]; pgroup = 0.10), and increased lactate (0.6 mmol/L [95% confidence limit, 0.3, 0.8]; pgroup < 0.0001) compared with the targeted temperature management 36 (TTM36) group. A cardiovascular Sequential Organ Failure Assessment score = 4 was recorded in 54% versus 45%, p = 0.03 in the TTM33 and the TTM36 group, respectively. The high vasopressor group carried a 53% mortality rate when compared with a 34% in the low vasopressor group, plog-rank less than 0.0001, with an adjusted hazard ratio of 1.38 (95% CI, 1.11-1.71; p = 0.004). There was no interaction between vasopressor group and allocated target temperature group (p = 0.40). An inverse relationship between mean arterial pressure and mortality was identified (p = 0.0008). CONCLUSIONS:: Targeted temperature management at 33\ub0C was associated with hemodynamic alterations with decreased heart rate, elevated levels of lactate, and need for increased vasopressor support compared with targeted temperature management at 36\ub0C. Low mean arterial pressure and need for high doses of vasopressors were associated with increased mortality independent of allocated targeted temperature managemen

Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography:a post hoc analysis from the TTM trial

To investigate whether early coronary angiography (CAG) after out-of-hospital cardiac arrest of a presumed cardiac cause is associated with improved outcomes in patients without acute ST elevation