Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation - A sub-analysis of Prague-OHCA study.

BACKGROUND: Limited evidence exists for prognostic performance of biomarkers in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with extracorporeal CPR (ECPR). We hypothesized that (1) the time course and (2) prognostic performance of biomarkers might differ between CPR and ECPR in a sub-analysis of Prague-OHCA study. METHODS: Patients received either CPR (n = 164) or ECPR (n = 92). The primary outcome was favorable neurologic survival at 180 days [cerebral performance category (CPC) 1-2]. Secondary outcomes included biomarkers of neurologic injury, inflammation and hemocoagulation. RESULTS: Favorable neurologic outcome was not different between groups: CPR 29.3% vs. ECPR 21.7%; p = 0.191. Biomarkers exhibited similar trajectories in both groups, with better values in patients with CPC 1-2. Procalcitonin (PCT) was higher in ECPR group at 24-72 h (all p < 0.01). Neuron-specific enolase (NSE), C-reactive protein and neutrophil-to-lymphocyte ratio did not differ between groups. Platelets, D-dimers and fibrinogen were lower in ECPR vs. CPR groups at 24-72 h (all p < 0.001). ROC analysis (24-48-72 h) showed the best performance of NSE in both CPR and ECPR groups (AUC 0.89 vs. 0.78; 0.9 vs. 0.9; 0.91 vs. 0.9). PCT showed good performance specifically in ECPR (0.72 vs. 0.84; 0.73 vs. 0.87; 0.73 vs. 0.86). Optimal cutoff points of NSE and PCT were higher in ECPR vs. CPR. CONCLUSIONS: Biomarkers exhibited similar trajectories although absolute values tended to be higher in ECPR. NSE had superior performance in both groups. PCT showed a good performance specifically in ECPR. Additional biomarkers may have modest incremental value. Prognostication algorithms should reflect the resuscitation method.

Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial.

BACKGROUND AND OBJECTIVES: EEG is widely used for prediction of neurologic outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explored the association between EEG and neurofilament light (NfL) as a marker of neuroaxonal injury, evaluated whether highly malignant EEG patterns are reflected by high NfL levels, and explored the association of EEG backgrounds and EEG discharges with NfL. METHODS: We performed a post hoc analysis of the Target Temperature Management After Out-of-Hospital Cardiac Arrest trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours postarrest. Patients who awoke or died prior to 36 hours postarrest were excluded. EEG experts blinded to clinical information classified EEG background, amount of discharges, and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NfL after trial completion. The highest available concentration at 48 or 72 hours postarrest was used. RESULTS: A total of 262/939 patients with EEG and NfL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NfL levels than patients with malignant patterns and NfL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI 1.4-6.1 and 6.5-26.2, respectively; effect size 0.47; p < 0.001). Both background and the amount of discharges were independently strongly associated with NfL levels (p < 0.001). The EEG background had a stronger association with NfL levels than EEG discharges (R2 = 0.30 and R2 = 0.10, respectively). NfL levels in patients with a continuous background were lower than for any other background (95% CI for discontinuous, burst-suppression, and suppression, respectively: 2.26-18.06, 3.91-41.71, and 5.74-41.74; effect size 0.30; p < 0.001 for all). NfL levels did not differ between suppression and burst suppression. Superimposed discharges were only associated with higher NfL levels if the EEG background was continuous. DISCUSSION: Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NfL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NfL may be useful to better identify patients misclassified by single methods. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT01020916.

Dynamic changes in arterial blood gas during cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

We aimed to investigate the prognostic value of dynamic changes in arterial blood gas analysis (ABGA) measured after the start of cardiopulmonary resuscitation (CPR) for return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). This prospective observational study was conducted at the emergency department of a university hospital from February 2018 to February 2020. All blood samples for gas analysis were collected from a radial or femoral arterial line, which was inserted during CPR. Changes in ABGA parameters were expressed as delta (Δ), defined as the values of the second ABGA minus the values of the initial ABGA. The primary outcome was sustained ROSC. Out of the 80 patients included in the analysis, 13 achieved sustained ROSC after in-hospital resuscitation. Multivariable logistic analysis revealed that ΔpaO2 (odds ratio [OR] = 1.023; 95% confidence interval [CI] = 1.004-1.043, p = 0.020) along with prehospital shockable rhythm (OR = 84.680; 95% CI = 2.561-2799.939, p = 0.013) and total resuscitation duration (OR = 0.881; 95% CI = 0.805-0.964, p = 0.006) were significant predictors for sustained ROSC. Our study suggests a possible association between ΔpaO2 in ABGA during CPR and an increased rate of sustained ROSC in the late phase of OHCA.

Prognostic role of serum neutrophil gelatinase-associated lipocalin in cardiac arrest patients: A prospective observational study.

ABSTRACT: Accurate neurological prognostication is of the utmost importance to avoid futile treatments in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). This study aimed to investigate the prognostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) by comparing with neuron-specific enolase (NSE), which is currently recommended by international guidelines in patients treated with TTM after OHCA.The study included 85 comatose adult patients with OHCA who underwent TTM between May 2018 and December 2020. Serum NGAL and NSE were measured at 24-hour intervals until 72 hours after return of spontaneous circulation (ROSC). The primary outcome was their prognostic performance for poor neurological outcome at 3 months after OHCA.Forty-nine patients (57.6%) had a poor neurological outcome; NGAL levels at all time points measured were significantly higher in these patients than in those with a good outcome (P < .01). NGAL showed lower maximal sensitivity (95% confidence interval [CI]) under a false-positive rate of 0% for the primary outcome compared with NSE (18.2% [95% CI 8.2-32.7] vs 66.7% [95% CI 50.5-80.4]). The combination of NGAL with NSE at 48 h showed the highest sensitivity (69.1% [95% CI 52.9-82.4]) and had the highest area under the curve (0.91 [95% CI 0.81-0.96]) for a poor outcome. The prognostic performance of NGAL alone was inadequate at all time points. However, NGAL combined with NSE at 24 and 28 hours after ROSC showed improved sensitivity compared to NGAL alone.NGAL should be considered a supplementary biomarker in combination with NSE for prognostication in patients with OHCA treated with TTM.

Admission biomarkers among patients with acute myocardial-infarction related cardiogenic shock with or without out-of-hospital cardiac arrest an exploratory study.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMICS) with or without out-of-hospital cardiac arrest (OHCA) have some pathophysiological differences and could potentially be considered as two individual clinical entities. Thus, there may also be differences in terms of blood borne biomarkers. PURPOSE: To explore potential differences in concentrations of the biomarkers lactate, mid-regional proadrenomedullin (MRproADM), Copeptin, pro-atrial natriuretic peptide (proANP), Syndecan-1, soluble thrombomodulin (sTM), soluble suppression of tumorigenicity 2 (sST2) and neutrophil gelatinase-associated lipocalin (NGAL), in patients with AMICS with or without OHCA. METHOD: Patients admitted for acute coronary angiography due to suspected ST-elevation myocardial infarction were enrolled during a 1-year period. In the present study 86 patients with confirmed AMICS at admission were included. RESULTS: In the adjusted analysis OHCA patients had higher levels of lactate (p = 0.008), NGAL (p = 0.03) and sTM (p = 0.011) while the level of sST2 was lower (p = 0.029). There was little difference in 30-day mortality between the OHCA and non-OHCA groups (OHCA 37% vs. non-OHCA 38%). CONCLUSION: AMICS patients with or without OHCA had similar 30-day mortality but differed in terms of Lactate, NGAL, sTM and sST2 levels. These findings support that non-OHCA and OHCA patients with CS could be considered as two individual clinical entities.

Prognostic value of admission serum magnesium in acute myocardial infarction complicated by malignant ventricular arrhythmias.

OBJECTIVES: Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients. METHODS: We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death. RESULTS: Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (Fine & Gray's test; p < 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p < 0.001), tracheal intubation (p < 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level. CONCLUSIONS: In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.

Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE).

BACKGROUND: Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined. METHODS: We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC). RESULTS: Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33µg/l [16-94] vs. 119µg/l [25-406]; p<0.001, for survivors vs. non-survivors, and 21µg/l [16-29] vs. 40µg/l [23-98], p<0.001 for good vs. poor neurological outcome. S-100b was 0.127µg/l [0.063-0.360] vs. 0.772µg/l [0.121-2.710], p<0.001 and 0.086µg/l [0.061-0.122] vs. 0.138µg/l [0.090-0.271], p = 0.009, respectively. For mortality, thresholds of 36µg/l for NSE and 0.128µg/l for S-100b could be determined; for poor neurological outcome 33µg/l (NSE) and 0.123µg/l (S-100b), respectively. Positive predictive value for NSE was 81% (74-88) and 79% (71-85) for S-100b. CONCLUSIONS: Thresholds for NSE and S-100b predicting mortality and poor neurological outcome are similar in OHCA patients receiving therapeutic hypothermia as in those reported before the era of hypothermia. However, both biomarkers do not have enough specificity to predict mortality or poor neurological outcome on their own and should only be additively used in clinical decision making.

The title: serum neutrophil Gelatinase-associated Lipocalin at 3 hours after return of spontaneous circulation in patients with cardiac arrest and therapeutic hypothermia: early predictor of acute kidney injury.

BACKGROUND: Serum neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary from immediately after ROSC to several days later. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 h after ROSC (3 h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge. METHODS: This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. The serum NGAL level was measured both immediately and 3 h after ROSC. Univariate and multivariate analyses were performed to identify the associations between AKI, poor neurologic outcome, and NGAL. RESULTS: Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3 h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009-1.035; p = 0.001). The area under the receiver operating characteristic curve of 3 h-NGAL for AKI was 0.910 (95% CI 0.830-0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3 h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis (ROSC-NGAL; OR 1.017; 95% CI 0.998-1.036; p = 0.084, 3 h-NGAL; OR 0.997; 95% CI 0.992-1.001; p = 0.113). CONCLUSIONS: The serum NGAL concentration measured 3 h after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research.

Low dose Iloprost effect on platelet aggregation in comatose out-of-hospital cardiac arrest patients: A predefined sub-study of the ENDO-RCA randomized -phase 2- trial.

PURPOSE: This is a predefined sub-study of the Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA) trial. We aim to investigate Iloprost, a prostacyclin analogue, safety by evaluating change in whole blood platelet aggregometry (Multiplate) in out of hospital cardiac arrest (OHCA) patients from baseline to 96-h post randomization. METHODS: A randomized, placebo controlled double-blinded trial in 46 OHCA patients. Patients were allocated 1:2 to 48 h Iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Platelet aggregation was determined by platelet aggregation tests ASPI-test (arachidonic acid); TRAP-test (thrombin-receptor activating peptide (TRAP)-6; RISTO test (Ristocetin); ADP test (adenosin diphosphat). RESULTS: There was no significant difference between the iloprost and placebo groups according to ASPI, TRAP, RISTO and ADP platelet aggregation assays. Further, no significant differences regarding risk of bleeding were found between groups (Risk of bleeding: ASPI <40 U; TRAP <92 U; RISTO <35 U; ADP <50 U). CONCLUSIONS: In conclusion, the iloprost infusion did not influence platelet aggregation as evaluated by the ASPI, TRAP, RISTO and ADP assays. There was no increased risk of bleeding or transfusion therapy. A decline in platelet aggregation was observed for the ASPI and ADP assays during the initial 96 h after OHCA. TRIAL REGISTRATION: Trial registration at clinicaltrials.gov (identifier NCT02685618) on 18-02-2016.

Serum neprilysin and the risk of death in patients with out-of-hospital cardiac arrest of non-traumatic origin.

BACKGROUND: Early risk stratification remains an unmet clinical need in patients with in out-of-hospital cardiac arrest. We hypothesised that soluble neprilysin may represent a promising biomarker in patients with out-of-hospital cardiac arrest of non-traumatic origin and provide new pathobiological insight. METHODS: This pilot study was a biomarker analysis from the Heidelberg Resuscitation Registry. Serum soluble neprilysin levels on admission were measured in 144 patients with successful return of spontaneous circulation after out-of-hospital cardiac arrest of non-traumatic origin. The primary endpoint was time to all-cause mortality. KM Event Rates are reported. Cox models were adjusted for age, bystander resuscitation, initial ECG rhythm, baseline estimated glomerular filtration rate, baseline lactate, left ventricular function at baseline, and targeted temperature management. RESULTS: In total, 90 (62.5%) patients died over a follow-up of at least 30 days. Soluble neprilysin correlated weakly with high-sensitivity troponin T (r=0.18, P=0.032) but did not correlate significantly with estimated glomerular filtration rate (r=-0.12) or lactate (r=0.11). Patients with elevated soluble neprilysin levels on admission were at significantly higher risk of all-cause mortality (Q4 69.1% vs. Q1 48.4%). After multivariable adjustment, soluble neprilysin in the top quartile (Q4) was significantly associated with all-cause mortality (Q4 vs. Q1: adjusted hazard ratio 2.48 (1.20-5.12)). In an adjusted multimarker model including high-sensitivity troponin T and high-sensitivity C-reactive protein, soluble neprilysin and high-sensitivity troponin T remained independently associated with all-cause mortality (soluble neprilysin: adjusted hazard ratio 2.27 (1.08-4.78); high-sensitivity troponin T: adjusted hazard ratio 3.40 (1.63-7.09)). CONCLUSION: Soluble neprilysin, measured as early as on hospital admission, was independently associated with all-cause mortality in patients with out-of-hospital cardiac arrest of non-traumatic origin and may prove to be useful in the estimation of risk in these patients.

Prognostic value of blood gas parameters and end-tidal carbon dioxide values in out-of-hospital cardiopulmonary arrest patients

Background/aim: This study aimed to evaluate the usefulness of blood gas and end-tidal carbon dioxide (EtCO2) measurements for predicting return of spontaneous circulation (ROSC) and for evaluating post-ROSC neurological survival. Materials and methods: This was a prospective case control study utilizing Atatürk University's database of adult nontraumatic patients (over 18 years old) with out-of-hospital cardiac arrest (OHCA) over the course of a year. The neurological status of the patients was evaluated after 1 h at ROSC and at hospital discharge, as defined by the cerebral performance category score. The blood gas parameters pH, PO2, PCO2, lactate, and BE were compared with EtCO2 from capnography and arteriol/alveolar carbon dioxide difference (AaDCO2) by using both blood gas and capnography upon admission to the emergency department and at ROSC. Results: A total of 155 patients were included in the study to form the control group with ROSC. The PO2, PCO2, and AaDCO2 values showed a prognostic marker for the supply of ROSC (P < 0.05). The EtCO2,lactate, and BE values measured by the blood gas were found to be insignificant in the prediction of ROSC (P > 0.05). Conversely, AaDCO2 was found to be significant in ROSC estimation (P < 0.05), but not in neurological evaluation (P > 0.05). Conclusion: Blood gas parameters and EtCO2 are sufficient in predicting ROSC. The value of AaDCO2 calculated using EtCO2 and PO2may be used in predicting the prognosis of OHCA patients, but this value does not provide any conclusions concerning neurological survival.

Predictive performance of plasma neutrophil gelatinase-associated lipocalin for neurologic outcomes in out-of-hospital cardiac arrest patients treated with targeted temperature management: A prospective observational study.

Few studies have demonstrated the prognostic potential of neutrophil gelatinase-associated lipocalin (NGAL) in post-cardiac arrest patients. This study evaluated the usefulness of plasma NGAL in predicting neurologic outcome and mortality in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). A prospective observational study was conducted between October 2013 and April 2016 at a single tertiary hospital. We enrolled 75 patients treated with TTM and collected their demographic data, cardiopulmonary resuscitation-related information, data on plasma NGAL concentration, and prognostic test results. Plasma NGAL was measured at 4 hours after return of spontaneous circulation (ROSC). The primary endpoint was the neurologic outcome at discharge and the secondary outcome was 28-day mortality. Neurologic outcomes were analyzed using a stepwise multivariate logistic regression while 28-day mortality was analyzed using a stepwise Cox regression. The predictive performance of plasma NGAL for neurologic outcome was measured by the area under the receiver operating characteristic curve and the predictability of 28-day mortality was measured using Harrell C-index. We also compared the predictive performance of plasma NGAL to that of other traditional prognostic modalities for outcome variables. Thirty patients (40%) had good neurologic outcomes and 53 (70.7%) survived for more than 28 days. Plasma NGAL in patients with good neurologic outcomes was 122.7 ±â€Š146.7 ng/ml, which was significantly lower than that in the poor neurologic outcome group (307.5 ±â€Š269.6 ng/ml; P < .001). The probability of a poor neurologic outcome was more than 3.3-fold in the NGAL >124.3 ng/ml group (odds ratio, 3.321; 95% confidence interval [CI], 1.265-8.721]). Plasma NGAL in the survived group was significantly lower than that in the non-survived group (172.7 ±â€Š191.6 vs 379.9 ±â€Š297.8 ng/ml; P = .005). Plasma NGAL was significantly correlated with 28-day mortality (hazard ratio 1.003, 95% CI 1.001-1.004; P < .001). The predictive performance of plasma NGAL was not inferior to that of other prognostic modalities except electroencephalography. Plasma NGAL is valuable for predicting the neurologic outcome and 28-day mortality of patients with OHCA at an early stage after ROSC.This study was registered at ClinicalTrials.gov on November 19, 2013 (Identifier: NCT01987466).

Presepsin As a Biomarker for Evaluating Prognosis and Early Innate Immune Response of Out-of-Hospital Cardiac Arrest Patients After Return of Spontaneous Circulation.

OBJECTIVES: After return of spontaneous circulation, patients who experienced out-of-hospital cardiac arrest present an impaired innate immune response that resembles sepsis. Presepsin, a new biomarker for sepsis, has not been studied in out-of-hospital cardiac arrest patients. This study explored the role of presepsin in evaluating the prognosis and early innate immune alteration of out-of-hospital cardiac arrest patients after return of spontaneous circulation by observing presepsin levels, CD14, and human leukocyte antigen-DR expression on monocytes. DESIGN: Retrospective analysis. SETTING: The emergency department of an urban university tertiary hospital. PARTICIPANTS: One hundred sixty-five out-of-hospital cardiac arrest patients with return of spontaneous circulation more than 12 hours, and 100 healthy individuals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma presepsin and procalcitonin levels were tested after resuscitation (day 0) and on days 1 and 3 after return of spontaneous circulation. Presepsin levels were higher in out-of-hospital cardiac arrest patients than in healthy individuals. In the first 3 days, presepsin and procalcitonin levels were persistently lower in 28-day survivors and patients with favorable neurologic outcome patients than in 28-day nonsurvivors and patients with unfavorable neurologic outcome. On days 0, 1, and 3, different cut-off values of presepsin showed prognostic value for 28-day mortality and favorable neurologic outcomes similar to procalcitonin. CD14 and human leukocyte antigen-DR expression on monocytes were analyzed by flow cytometry. Compared with controls, CD14 expression in out-of-hospital cardiac arrest patients increased on day 1 and began to decrease on day 3, whereas human leukocyte antigen-DR+ monocyte percentages decreased on days 1 and 3. Presepsin and procalcitonin had a low positive correlation with CD14 expression and a strong negative correlation with human leukocyte antigen-DR+ monocyte percentages on day 1. CONCLUSIONS: Plasma presepsin concentrations are independent prognostic factors for out-of-hospital cardiac arrest patients after return of spontaneous circulation and are correlated with abnormal CD14 and human leukocyte antigen-DR expression on monocytes. Monitoring presepsin levels may be helpful for evaluating the prognosis and impaired innate immune response in the early period after return of spontaneous circulation.

Procalcitonin as a prognostic marker for outcomes in post-cardiac arrest patients: A systematic review and meta-analysis.

AIM: This study aimed to seek evidence for the usefulness of the procalcitonin as a prognostic blood biomarker for outcomes in post-cardiac arrest patients. METHODS: We systematically searched MEDLINE, EMBASE, and the Cochrane Library (search date: 8 January, 2019). Studies on patients who experienced return of spontaneous circulation, who had out of hospital cardiac arrest and had their level of procalcitonin measured and outcomes assessed at and after hospital discharge, were included. We additionally performed subgroup analyses for confounding factors affecting patients' outcomes. To assess the risk of bias of each included study, the Quality in Prognosis Studies tool was used. RESULTS: A total of 1065 patients from 10 studies were finally included. Elevated procalcitonin level during hospital admission (at 0-24 h) was associated with in-hospital mortality (standardized mean difference (SMD) 0.64, 95% confidence interval (CI) 0.33-0.95, I2 = 26%). The elevation of procalcitonin level (at 0-48 h) was also associated with poor neurologic outcomes (at 0-24 h, SMD 0.61; 95% CI 0.44-0.79, I2 = 0%; at 24-48 h, SMD 0.58, 95% CI 0.35-0.82, I2 = 0%) as well as at 1-6 months (at 24-48 h, SMD 0.62; 95% CI 0.36-0.88, I2 = 0%). CONCLUSIONS: Overall, the findings suggested that an elevated procalcitonin level measured at 0-48 h of post-cardiac arrest syndrome was associated with poor outcomes.

Predicting long-term outcomes after cardiac arrest by using serum neutrophil gelatinase-associated lipocalin.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by various tissues in pathologic states. Previous studies reported that post-cardiac arrest serum NGAL levels correlate with short-term neurologic outcomes and survival. The aim of this study was to examine the associations between NGAL levels post-cardiac arrest and long-term outcomes and survival. METHODS: This prospective observational study and retrospective review included adult out-of-hospital cardiac arrest survivors who were treated by hypothermia-targeted temperature management. Serum NGAL was assessed at 0, 24, 48, and 72h after return of spontaneous circulation. The primary outcome was poor outcome at six months after cardiac arrest, defined as cerebral performance category score of 3-5. The secondary outcome was six-month mortality. RESULTS: In total, 76 patients were analyzed. The patients with poor outcomes showed significantly higher NGAL levels at 24, 48 and 72h after cardiac arrest than the patients with good outcomes. Long-term survival rates were significantly lower in the high-NGAL group than in the low-NGAL group at each time point. Subgroup analysis of patients who survived 72h showed that only serum NGAL 72h after cardiac arrest had prognostic value for long-term outcomes (area under the receiver operating characteristic curve=0.72; p=0.02). CONCLUSIONS: Post-cardiac arrest serum NGAL is associated with long-term outcomes and survival; particularly, three days post-cardiac arrest is the optimal time point for predicting long-term outcomes. However, the predictive power of NGAL is unsatisfactory, and it should be regarded as an additional prognostic modality.

Platelet aggregation during targeted temperature management after out-of-hospital cardiac arrest: A randomised clinical trial.

Some studies conclude that mild hypothermia causes platelet dysfunction leading to an increased bleeding risk, whereas others state that platelet aggregation is enhanced during mild hypothermia. Therefore, the aim of this study was to clarify whether standard or prolonged duration of targeted temperature management affected platelet aggregation. We randomised 82 comatose patients resuscitated after out-of-hospital cardiac arrest to either 24 hours (standard group) or 48 hours (prolonged group) of targeted temperature management at 33±1°C. Blood samples were collected 22 hours, 46 hours and 70 hours after reaching target temperature. Platelet aggregation was assessed by impedance aggregometry employing a Multiplate®Analyser, using the COLtest®, TRAPtest®, ADPtest® and ASPItest® as agonists, and with the results reported as area under the curve (AUC, AU*min). The platelet aggregation was below the normal range in all blood samples. No differences were observed between the standard group and the prolonged group in either of the blood samples (all p ≥ 0.11), except for a 24% decreased aggregation (95% confidence interval (CI) (10%;37%), p = 0.002) when using the COLtest® in the 46-hour sample. Comparing the 22-hour sample with the 46-hour sample in the prolonged group separately, we found no differences when employing the COLtest®, the ASPItest® or the ADPtest® in patients without the use of adenosine diphosphate receptor inhibitors (all p values ≥0.21), but aggregation induced by the TRAPtest® decreased by 14% (95% CI -8%;-20%), p < 0.001). We concluded that the platelet aggregation post cardiac arrest was below the normal range independent of the core temperature. Moreover, no substantial difference was found in platelet aggregation between standard and prolonged targeted temperature management.

Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest.

BACKGROUND: Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest. METHODS: As a subcohort analysis of a prospective, observational, multicenter study "FINNRESUSCI," we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models. RESULTS: Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68-0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65-0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome. CONCLUSIONS: Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.

Serum neutrophil gelatinase-associated lipocalin levels predict the neurological outcomes of out-of-hospital cardiac arrest victims.

BACKGROUND: Serum neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. Serum NGAL was recently proposed as a potential predictor of mortality in post cardiac arrest syndrome (PCAS) patients following out-of-hospital cardiac arrest (OHCA). However, the potential predictive value of NGAL for neurological outcomes is unknown. Therefore, we assessed the potential predictive value of NGAL for neurological outcomes after OHCA. We also compared its predictive value with that of neuron-specific enolase (NSE) as an established biomarker. METHODS: Blood samples were prospectively collected from 43 PCAS patients following OHCA. Serum NGAL was measured on days 1 and 2, and NSE was measured on day 2. These biomarkers were compared between patients with favourable (cerebral performance category [CPC] 1-2) and unfavourable (CPC 3-5) outcomes. Receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Serum NGAL and NSE on day 2 (both P < 0.001), but not NGAL on day 1 (P = 0.609), were significantly different between the favourable and unfavourable groups. In ROC curve analysis, the sensitivity and specificity were 83% and 85%, respectively, for NGAL (day 2) at a cutoff value of 204 ng/mL and were 84% and 100% for NSE (day 2) at a cutoff value of 28.8 ng/mL. The area under the ROC curve of NGAL (day 2) was equivalent to that of NSE (day 2) (0.830 vs. 0.918). Additionally, the area under the ROC curve in subgroup of estimated glomerular filtration rate (eGFR) > 20 mL/min/1.73 m2 (n = 38, 0.978 vs. 0.923) showed the potential of NGAL predictability. CONCLUSIONS: Serum NGAL might predict the neurological outcomes of PCAS patients, and its predictive value was equivalent to that of NSE.

Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management: A Multicenter Study on 1,053 Patients.

OBJECTIVE: Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management. DESIGN, SETTING, AND PATIENTS: We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 µg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 µg/L (upper limit of normal). MEASUREMENTS AND MAIN RESULTS: A neuron-specific enolase serum concentration greater than 90 µg/L predicted Cerebral Performance Category 4-5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 µg/L and Cerebral Performance Category 1-2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 µg/L excluded Cerebral Performance Category 4-5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 µg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. CONCLUSION: High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our "in-the-field" data indicate 90 µg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively considered: neuron-specific enolase-producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 µg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.

Decreased a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 activity and neurologic outcome in patients with successful resuscitation of out-of-hospital cardiac arrest: A prospective observational study.

PURPOSE: The purpose of this study is to investigate the association between a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and neurologic outcome in patients with resuscitation of out-of-hospital cardiac arrest (R-OHCA). MATERIALS AND METHODS: A prospective observational study of adult patients with R-OHCA was conducted. Plasma activity of ADAMTS13 and inflammatory markers, an immunologic marker, and a marker of endothelial damage were measured on admission and day 2. Neurologic outcome was evaluated using the Cerebral Performance Categories on day 90. RESULTS: Plasma activity of ADAMTS13 on day 2 was lower in patients with poor neurologic outcome (n = 18) than that in those with good neurologic outcome (n = 16; P = .008). It was also lower in 28-day nonsurvivors (n = 12) than in survivors (n = 21; P = .019). Soluble thrombomodulin showed a strong correlation with ADAMTS13 (P = .021). Furthermore, ADAMTS13 activity was negatively correlated with the Sequential Organ Failure Assessment score (P < .001), levels of high-mobility group box 1 (P = .028), and levels of interleukin 6 (P = .047) but positively correlated with the monocyte expression of human leukocyte antigen DR (P = .023). CONCLUSION: Decreased ADAMTS13 activity was associated with poor neurologic outcome, high mortality, and worsened immune-inflammatory status in patients with R-OHCA. These results suggest that ADAMTS13 may have pathophysiologic relevance in postcardiac arrest syndrome.