Lactate and lactate clearance as predictors of one-year survival in extracorporeal cardiopulmonary resuscitation - An international, multicentre cohort study.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) can be considered in selected patients with refractory cardiac arrest. Given the risk of patient futility and high resource utilisation, identifying ECPR candidates, who would benefit from this therapy, is crucial. Previous ECPR studies investigating lactate as a potential prognostic marker have been small and inconclusive. In this study, it was hypothesised that the lactate level (immediately prior to initiation of ECPR) and lactate clearance (within 24 hours after ECPR initiation) are predictors of one-year survival in a large, multicentre study cohort of ECPR patients. METHODS: Adult patients with refractory cardiac arrest at three German and four Danish tertiary cardiac care centres between 2011 and 2021 were included. Pre-ECPR lactate and 24-hour lactate clearance were divided into three equally sized tertiles. Multivariable logistic regression analyses and Kaplan-Meier analyses were used to analyse survival outcomes. RESULTS: 297 adult patients with refractory cardiac arrest were included in this study, of which 65 (22%) survived within one year. The pre-ECPR lactate level and 24-hour lactate clearance were level-dependently associated with one-year survival: OR 5.40 [95% CI 2.30-13.60] for lowest versus highest pre-ECPR lactate level and OR 0.25 [95% CI 0.09-0.68] for lowest versus highest 24-hour lactate clearance. Results were confirmed in Kaplan-Meier analyses (each p log rank < 0.001) and subgroup analyses. CONCLUSION: Pre-ECPR lactate levels and 24 hour-lactate clearance after ECPR initiation in patients with refractory cardiac arrest were level-dependently associated with one-year survival. Lactate is an easily accessible and quickly available point-of-care measurement which might be considered as an early prognostic marker when considering initiation or continuation of ECPR treatment.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

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.

Blood-brain barrier disruption as a cause of various serum neuron-specific enolase cut-off values for neurological prognosis in cardiac arrest patients.

We compared the cut-off and prognostic value of serum neuron-specific enolase (NSE) between groups with and without severe blood-brain barrier (BBB) disruption to reveal that a cause of various serum NSE cut-off value for neurological prognosis is severe BBB disruption in out-of-hospital cardiac arrest (OHCA) patients underwent target temperature management (TTM). This was a prospective, single-centre study conducted from January 2019 to June 2021. Severe BBB disruption was indicated using cerebrospinal fluid-serum albumin quotient values > 0.02. The area under the receiver operating characteristic curve of serum NSE obtained on day 3 of hospitalisation to predict poor outcomes was used. In patients with poor neurologic outcomes, serum NSE in those with severe BBB disruption was higher than in those without (P = 0.006). A serum NSE cut-off value of 40.4 µg/L for poor outcomes in patients without severe BBB disruption had a sensitivity of 41.7% and a specificity of 96.0%, whereas a cut-off value of 34.6 µg/L in those with severe BBB disruption had a sensitivity of 86.4% and a specificity of 100.0%. We demonstrated that the cut-off and prognostic value of serum NSE were heterogeneous, depending on severe BBB disruption in OHCA patients treated with TTM.

The role of the lactate/albumin ratio in predicting survival outcomes in patients resuscitated after out-of-hospital cardiac arrest: A preliminary report.

OBJECTIVE: To investigate the effect of lactate/albumin (L/A) ratio on survival to discharge in patients who have had out-of-hospital cardiac arrest (OHCA). METHODS: We analyzed adult patients (aged ≥18 years) who were admitted to our hospital's emergency department (ED) due to OHCA between January 2018 and June 2020 and who achieved return of spontaneous circulation after successful resuscitation. Blood lactate and albumin concentrations were obtained within the first 10 min after admission to the ED. Patients were grouped according to clinical outcomes. The primary outcome was survival until hospital discharge. The groups were then statistically compared. RESULTS: In this study, 235 OHCA patients were analyzed, 42 (17.9%) of whom had survived until discharge. The L/A ratio was higher in the non-survivor group than in the survivor group (2.0 (interquartile range: 1.4-2.8) vs 1.4 (0.9-1.9); P < 0.001). A low L/A ratio was significantly associated with survival at discharge (odds ratio: 2.55; 95% confidence interval (CI): 3.24-11.08; P < 0.001). In the prediction of survival to discharge, the area under the curve (AUC) for the L/A ratio (AUC: 0.823) was higher than that for lactate (AUC: 0.762) or albumin (AUC: 0.722) alone. Moreover, the predictive value of L/A ratio for survival to discharge might significantly improve when the cutoff value is higher than 1.62. CONCLUSION: The L/A ratio is more valuable than the lactate or albumin levels alone in predicting survival to discharge. Our findings indicate that a combination of these parameters might increase the predictability of survival to discharge in OHCA patients.

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.

Plasma Exosome Profile in ST-Elevation Myocardial Infarction Patients with and without Out-of-Hospital Cardiac Arrest.

The identification of new biomarkers allowing an early and more accurate characterization of patients with ST-segment elevation myocardial infarction (STEMI) is still needed, and exosomes represent an attractive diagnostic tool in this context. However, the characterization of their protein cargo in relation to cardiovascular clinical manifestation is still lacking. To this end, 35 STEMI patients (17 experiencing resuscitated out-of-hospital cardiac arrest (OHCA-STEMI) and 18 uncomplicated) and 32 patients with chronic coronary syndrome (CCS) were enrolled. Plasma exosomes were characterized by the nanoparticle tracking analysis and Western blotting. Exosomes from STEMI patients displayed a higher concentration and size and a greater expression of platelet (GPIIb) and vascular endothelial (VE-cadherin) markers, but a similar amount of cardiac troponin compared to CCS. In addition, a difference in exosome expression of acute-phase proteins (ceruloplasmin, transthyretin and fibronectin) between STEMI and CCS patients was found. GPIIb and brain-associated marker PLP1 accurately discriminated between OHCA and uncomplicated STEMI. In conclusion, the exosome profile of STEMI patients has peculiar features that differentiate it from that of CCS patients, reflecting the pathophysiological mechanisms involved in STEMI. Additionally, the exosome expression of brain- and platelet-specific markers might allow the identification of patients experiencing ischemic brain injury in STEMI.

Bedside microdialysis for detection of early brain injury after out-of-hospital cardiac arrest.

Bedside detection and early treatment of lasting cerebral ischemia may improve outcome after out-of-hospital cardiac arrest (OHCA). This feasibility study explores the possibilities to use microdialysis (MD) for continuous monitoring of cerebral energy metabolism by analyzing the draining cerebral venous blood. Eighteen comatose patients were continuously monitored with jugular bulb and radial artery (reference) MD following resuscitation. Median time from cardiac arrest to MD was 300 min (IQR 230-390) with median monitoring time 60 h (IQR 40-81). The lactate/pyruvate ratio in cerebral venous blood was increased during the first 20 h after OHCA, and significant differences in time-averaged mean MD metabolites between jugular venous and artery measurements, were documented (p < 0.02). In patients with unfavorable outcome (72%), cerebral venous lactate and pyruvate levels remained elevated during the study period. In conclusion, the study indicates that jugular bulb microdialysis (JBM) is feasible and safe. Biochemical signs of lasting ischemia and mitochondrial dysfunction are frequent and associated with unfavorable outcome. The technique may be used in comatose OHCA patients to monitor biochemical variables reflecting ongoing brain damage and support individualized treatment early after resuscitation.

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.

Relationships between serum levels of lactate dehydrogenase and neurological outcomes of patients who underwent targeted temperature management after out-of-hospital cardiac arrest.

ABSTRACT: This study aimed to evaluate times for measuring serum lactate dehydrogenase levels (SLLs) to predict neurological prognosis among out-of-hospital cardiac arrest (OHCA) survivors.This retrospective study examined patients who experienced OHCA treated with targeted temperature management (TTM). The SLLs were evaluated at the return of spontaneous circulation (ROSC) and at 24, 48, and 72 hours later. Neurological outcomes after 3 months were evaluated for relationships with the SLL measurement times.A total of 95 comatose patients with OHCA were treated using TTM. Seventy three patients were considered eligible, including 31 patients (42%) who experienced good neurological outcomes. There were significant differences between the good and poor outcome groups at most time points (P < .001), except for ROSC (P = .06). The ROSC measurement had a lower area under the receiver operating characteristic curve (AUC: 0.631, 95% confidence interval [CI]: 0.502-0.761) than at 48 hours (AUC: 0.830, 95% CI: 0.736-0.924), at 24 hours (AUC: 0.786, 95% CI: 0.681-0.892), and at 72 hours (AUC: 0.821, 95% CI: 0.724-0.919).A higher SLL seemingly predicted poor neurological outcomes, with good prognostic values at 48 hours and 72 hours. Prospective studies should be conducted to confirm these results.

Admission C-reactive protein concentrations are associated with unfavourable neurological outcome after out-of-hospital cardiac arrest.

Whether admission C-reactive protein (aCRP) concentrations are associated with neurological outcome after out-of-hospital cardiac arrest (OHCA) is controversial. Based on established kinetics of CRP, we hypothesized that aCRP may reflect the pre-arrest state of health and investigated associations with neurological outcome. Prospectively collected data from the Vienna Clinical Cardiac Arrest Registry of the Department of Emergency Medicine were analysed. Adults (≥ 18 years) who suffered a non-traumatic OHCA between January 2013 and December 2018, without return of spontaneous circulation or extracorporeal cardiopulmonary resuscitation therapy were eligible. The primary endpoint was a composite of unfavourable neurologic function or death (defined as Cerebral Performance Category 3-5) at 30 days. Associations of CRP levels drawn within 30 min of hospital admission were assessed using binary logistic regression. ACRP concentrations were overall low in our population (n = 832), but higher in the unfavourable outcome group [median: 0.44 (quartiles 0.15-1.44) mg/dL vs. 0.26 (0.11-0.62) mg/dL, p < 0.001]. The crude odds ratio for higher aCRP concentrations was 1.19 (95% CI 1.10-1.28, p < 0.001, per mg/dL) to have unfavourable neurological outcome. After multivariate adjustment for traditional prognostication markers the odds ratio of higher aCRP concentrations was 1.13 (95% CI 1.04-1.22, p = 0.002). Sensitivity of aCRP was low, but specificity for unfavourable neurological outcome was 90% for the cut-off at 1.5 mg/dL and 97.5% for 5 mg/dL CRP. In conclusion, high aCRP levels are associated with unfavourable neurological outcome at day 30 after OHCA.

Early blood pH as an independent predictor of neurological outcome in patients with out-of-hospital cardiac arrest: A retrospective observational study.

ABSTRACT: Metabolic acidosis is observed in 98% of patients with out-of-hospital cardiac arrest (OHCA). The longer the no-flow or low-flow duration, the more severe is the acidosis in these patients. This study explored whether blood pH in early stages of advanced life support (ALS) was an independent predictor of neurological prognosis in patients with OHCA.We retrospectively enrolled patients with OHCA from January 2012 to June 2018 in a single-medical tertiary hospital in Taiwan. Patients with OHCA whose blood gas analyses within 5 minutes after receiving ALS at the emergency department (ED) were enrolled. Patients younger than 20 years old, with cardiac arrest resulting from traumatic or circumstantial causes, with return of spontaneous circulation (ROSC) before ED arrival, lacking record of initial blood gas analysis, and with do-not-resuscitate orders were excluded. The primary outcome of this study was neurological status at hospital discharge.In total, 2034 patients with OHCA were enrolled. The majority were male (61.89%), and the average age was 67.8 ±â€Š17.0 years. Witnessed OHCA was noted in 571 cases, cardiopulmonary resuscitation was performed before paramedic arrival in 512 (25.2%) cases, and a shockable rhythm was observed in 269 (13.2%). Blood pH from initial blood gas analysis remained an independent predictor of neurological outcome after multivariate regression.Blood pH at early stages of ALS was an independent prognostic factor of post-OHCA neurological outcome. Blood gas analysis on arrival at the ED may provide additional information about the prognosis of patients with OHCA.

The prognostic value of early lactate clearance for survival after out-of-hospital cardiac arrest.

BACKGROUND: Prognostication of survival after out-of-hospital cardiac arrest (OHCA) remains challenging with current guidelines recommending the prognostication no earlier than 72 h after return of spontaneous circulation (ROSC). Prognostic factors that could be used earlier after ROSC, like lactate clearance, are still being studied. OBJECTIVES: This paper aims to investigate the prognostic strength of early lactate clearance for survival after OHCA. METHODS: This retrospective observational single-center study focuses on patients for whom ROSC was achieved after OHCA. Patients ≥18 years admitted between September 2012 and January 2019, for which arterial serum lactate measurements were available immediately at and 3 h after hospital admission (T0 and T3), were included. RESULTS: 192 patients were included. Lactate clearance at T3 (p < 0.001) was identified as an independent predictor for 24 h, 48 h and 72 h survival. Witnessed arrest, bystander CPR and initial shockable rhythm were independent significant predictors for long term survival after ROSC (1 month, 3 months and 1 year; p < 0.05), but not for 24 h survival. Age (above or below 65 years) was not significant for predicting survival. Upon combination of witnessed arrest, bystander CPR and initial shockable rhythm in a multivariate logistic regression model for long term survival, the initial rhythm was the dominant factor in the combined model, making witnessed arrest and bystander CPR redundant. CONCLUSION: Lactate clearance at T3 after ROSC is associated with 24 h, 48 h and 72 h survival. Further research is needed to determine how to incorporate lactate clearance as part of a clinically useful tool to predict long term survival.

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.

Neuron-specific enolase level as a predictor of neurological outcome in near-hanging patients: A retrospective multicenter study.

OBJECTIVES: Neuron-specific enolase (NSE) is frequently used to predict neurological outcomes in patients with hypoxic brain injury. Hanging can cause hypoxic brain damage, and survivors can suffer from neurological deficits that may impair daily activities. Here, we investigated the utility of the initial serum NSE level as a predictor of neurological outcomes in near-hanging patients with decreased consciousness. METHODS: This retrospective multicenter study was conducted in patients who visited the emergency department due to near-hanging injury from October 2013 to February 2019 at three university hospitals in Korea. They were divided into two groups according to the presence of out-of-hospital cardiac arrest. The neurological outcome was determined using the Cerebral Performance Category (CPC) measured at the time of discharge. Multivariate analysis was performed to determine whether initial serum NSE is an independent predictor of neurological outcome. RESULTS: Of the 70 patients included in the study, 44 showed a poor neurological outcome (CPC score = 3-5). Among the 52 patients with cardiac arrest, only 10 (19.2%) were discharged with good neurological outcome (CPC score = 1-2). In the whole cohort, a high serum NSE level was a significant predictor of poor neurological outcome (odds ratio [OR], 1.343; 95% confidence interval [CI], 1.003-1.800, p = 0.048). Among the patients with cardiac arrest, a high serum NSE level was a significant predictor of poor neurological outcome (OR, 1.138; 95% CI, 1.009-1.284, p = 0.036). CONCLUSIONS: In near-hanging patients, a high initial serum NSE level is an independent predictor of poor neurological outcome.

Relationship between D-dimer level upon emergency room arrival and the duration of cardiac arrest in patients with witnessed out-of-hospital cardiac arrest.

In patients with out-of-hospital cardiac arrest (OHCA), the probability of resuscitation is strongly influenced by the duration of cardiac arrest, which activates the blood coagulation-fibrinolysis system. Because plasma D-dimer levels reflect activity of blood coagulation and fibrinolysis, they should increase with the duration of cardiac arrest. We evaluated 222 consecutive non-traumatic witnessed OHCA patients who underwent measurement of plasma D-dimer levels on arrival in the emergency room. Return of spontaneous circulation was achieved in 138 patients (62%), but only 42 (19%) were alive 30 days post-OHCA. D-dimer levels were elevated in 217 patients (97.7%). There was a positive correlation between plasma D-dimer levels and duration of cardiac arrest in the 222 patients (r = 0.623, p < 0.001). When the cause of OHCA was limited to cardiovascular disease, the positive correlation between level of D-dimer and the duration of cardiac arrest (r = 0.776, p < 0.001) increased.D-dimer levels were significantly lower in survivors than in non-survivors [9.5 (1.4-17.5) vs 54.2 (34.2-74.3) µg/mL, p = 0.024]. Receiver operating characteristic curve analysis showed that a cutoff value of D-dimer ≤ 10 µg/L led to sensitivity (69.0%) and specificity (72.8%) for 30 day survival (area under curve 0.75). Multivariate logistic regression analysis showed that D-dimer ≤ 10 µg/ml was an independent predictor for 30 day survival (odds ratio 4.39, 95% confidence interval 1.41-13.70; p = 0.01). D-dimer level correlates with duration of cardiac arrest, especially in OHCA patients due to cardiovascular causes, and may help physicians assess the probability of survival in OHCA patients.

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.

Novel biomarkers of oxidative stress as predictive indicators of neurological outcome after out-of-hospital cardiopulmonary arrest.

AIM: Among patients of out-of-hospital cardiopulmonary arrest (OHCPA), only 6% resume their pre-OHCPA social life. The prediction of neurological outcome immediately after the return of spontaneous circulation (ROSC) is urgently needed in OHCPA patients. Novel biomarkers, biological antioxidant potential (BAP), and diacron-reactive oxygen metabolites (d-ROM) are potential predictors of neurological outcome after OHCPA. This study was conducted to evaluate the utility of BAP and d-ROM in the prediction of patient outcomes after OHCPA. METHODS: Blood samples were collected immediately after OHCPA patients were admitted to our hospital between May 2011 and June 2013. BAP and d-ROM concentrations were measured with the simple equipment FRAS4 ™ (Wismerll, Italy). Their association with favorable (cerebral performance category [CPC], 1 and 2) and unfavorable (CPC 3-5) clinical outcomes was compared. BAP and d-ROM values from 23 normal healthy volunteers (HV) were used as controls. RESULTS: Overall, 152 OHCPA patients were included, and 26 patients achieved ROSC. Eleven died during hospitalization were allocated a CPC of 5 and remaining patients were discharged or transported (CPC 1: n = 4; CPC 2: n = 6; CPC 3: n = 3; CPC 4: n = 2; CPC 5: n = 11). The receiver operating characteristics curve of d-ROM and BAP for predicting survival 28 days after OHCPA was 0.596 and 0.834, respectively. Patients without ROSC had significantly higher BAP than HV and patients with ROSC (p < 0.001). A significant correlation was evident between BAP and the time to ROSC (r = 0.641, p < 0.01). CONCLUSION: Oxidative stress, indicated by BAP on admission, strongly correlated with the neurological outcome after OHCPA.