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Aim: EEG is considered in guidelines for poor outcome prognostication in comatose patients after cardiac arrest (CA), but elements related to favorable prognosis have also been increasingly described. While spindle EEG activity is known to herald good outcome in critically ill patients, its occurrence in CA has received limited attention, essentially in pediatric cohorts. We postulated that this feature is related to favorable outcome in adults., Methods: Retrospective assessment of comatose adults following CA in a prospective institutional registry (09.2021-09.2023). Spindle-like activity, noted prospectively on early (12-36 h) and late (36-72 h) routine EEGs, was tested using 2x2 tables and comparisons of proportions for the likelihood of favorable outcome (CPC 1-2 at 3 months), including combinations with existing benign EEG descriptions (Westhall: no malignant or highly malignant features; modified: also allowing background discontinuity, low voltage, inverse development). Spindles were correlated with peak serum neuron-specific enolase (NSE) at 24-48 h as a marker of neuronal damage., Results: Among 276 patients, spindle-like activity was observed in 66 (23.9 %) of them, more often in early EEGs. While, in isolation, this feature detected within 72 h showed high specificity for CPC 1-2 (82.2 %) and low sensitivity (36.8 %), its addition significantly enhanced sensitivity of modified benign EEG (from 90.5 % to 95.8 %; p < 0.001; specificity at 54.4 %). Patients with spindle-like activity had significantly lower NSE (median 25.7µg/l, interquartile range 16.1-24.4, vs. 39.4 µg/l, interquartile range 21.1-95.1; p < 0.001)., Conclusion: Spindle-like EEG activity may orient on prognostication of favorable outcome in adult post CA patients, and correlates with lower neuronal damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Electroencephalographic reactivity (EEG-R) is a promising early predictor of arousal in comatose patients after cardiac arrest. Despite recent guidelines advocating for the integration of EEG-R into the multimodal prognostication model, EEG-R testing methods remain heterogeneous across studies. While efforts towards standardization have been made to reduce interrater variability by the development of quantitative approaches and machine learning models, future validation studies are needed to increase clinical applicability. Furthermore, the specific neurophysiological mechanisms and neuroanatomical correlates underlying EEG-R are not fully understood. In this narrative review, we explore the value and possible mechanisms of EEG-R, focusing on post-cardiac arrest comatose patients. We aim to discuss the current standard of knowledge and future directions, as well as elucidate possible implications for patient care and research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Geocadin and Dr. Thakor are supported in part by cardiac arrest related grants from the National Institutes of Health (NIH) (UH3HL145269-04; RO1HL071568; RO1NS119825; RO1 NS 127959). Dr. Cho is funded by the NIH (K23HL157610). Dr. Habela is supported by the Doris Duke Foundation and the NIH Clinical Scientist Award (K08NS102526). Dr. Kaplan has been an expert witness on qEEG, a member of the ExCo of IFCN and receives royalties from publication from Wiley-Blackwell and Demos. Dr. Geocadin is a member of the Editorial Board of Resuscitation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Somatosensory evoked potentials (SEPs) are highly specific predictors of poor prognosis in hypoxic-ischemic coma when cortical responses (N20s) are absent. However, bilateral N20 presence is nonspecific for good outcomes. High-frequency oscillations (HFOs) in the SEP waveform predict neurologic recovery in animals, but clinical applications are poorly understood. We sought to develop a clinical measure of HFOs to potentially improve detection of good outcomes in coma., Materials and Methods: We collected SEP waveform data from all comatose inpatients (GCS<=8) who underwent neurologic prognostication from 2020 to 2022 at Johns Hopkins Hospital. We developed a novel measure - HFO evoked to spontaneous ratios (HFO-ESRs) - and applied this to those patients with bilaterally present N20s using both standard univariate classification and cubic kernal vector machine (SVM) models to predict the last documented in-hospital Glasgow Coma Scale (GCS) prior to discharge or death., Results: Of 58 total patients, 34 (58.6%) had bilaterally present N20s. Of these, 14 had final GCS>=9, and 20 had final GCS<=8. Mean age was 52 (+/- 17) years, 20.1% female. Etiologies of coma were primarily global hypoxic-ischemic brain injury (79.4%), intracranial hemorrhage (11.8%), and traumatic brain injury (2.9%). In univariate classification, the addition of averaged HFO-ESRs to bilaterally present N20s predicted final GCS>=9 with 68% specificity. The SVM model further improved specificity to 85%., Conclusions: In this pilot investigation, we developed a novel clinical measure of SEP HFOs. Incorporation of this measure may improve the specificity of the SEP to predict in-hospital GCS outcomes in coma, but requires further validation in specific neurologic injuries and with longitudinal outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: Assess the prognostic ability of a non-highly malignant and reactive EEG to predict good outcome after cardiac arrest (CA)., Methods: Prospective observational multicentre substudy of the "Targeted Hypothermia versus Targeted Normothermia after Out-of-hospital Cardiac Arrest Trial", also known as the TTM2-trial. Presence or absence of highly malignant EEG patterns and EEG reactivity to external stimuli were prospectively assessed and reported by the trial sites. Highly malignant patterns were defined as burst-suppression or suppression with or without superimposed periodic discharges. Multimodal prognostication was performed 96 h after CA. Good outcome at 6 months was defined as a modified Rankin Scale score of 0-3., Results: 873 comatose patients at 59 sites had an EEG assessment during the hospital stay. Of these, 283 (32%) had good outcome. EEG was recorded at a median of 69 h (IQR 47-91) after CA. Absence of highly malignant EEG patterns was seen in 543 patients of whom 255 (29% of the cohort) had preserved EEG reactivity. A non-highly malignant and reactive EEG had 56% (CI 50-61) sensitivity and 83% (CI 80-86) specificity to predict good outcome. Presence of EEG reactivity contributed (p < 0.001) to the specificity of EEG to predict good outcome compared to only assessing background pattern without taking reactivity into account., Conclusion: Nearly one-third of comatose patients resuscitated after CA had a non-highly malignant and reactive EEG that was associated with a good long-term outcome. Reactivity testing should be routinely performed since preserved EEG reactivity contributed to prognostic performance., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate whether rhythmic/periodic EEG patterns (RPP) appearing after propofol discontinuation are more likely to be related to the elimination phase of propofol, or are an expression of severe brain damage., Methods: In a retrospective cohort of comatose postanoxic patients, EEG was assessed one hour before (baseline) and on hour after discontinuation of propofol. Presence and duration of RPP were related to (changes in) EEG background pattern and duration of sedation., Results: In eleven (of 36 eligible) patients RPP appeared after propofol discontinuation and disappeared in seven of these patients within one hour. A continuous background pattern at baseline and shorter duration of propofol infusion seemed associated with (earlier) spontaneous disappearance of RPP. In ten patients with RPP at baseline, the EEG did not change, and in one patient it changed into burst-suppression., Conclusion: Our findings suggest that RPP after propofol discontinuation could be propofol-related., Discussion: RPP might be related to propofol discontinuation rather than an expression of severe brain damage, especially in case of, and congruent with, a continuous pattern at the time of propofol discontinuation. This opens a new insight in this phenomenon and its transient nature. In clinical practice, we suggest to consider the timing of propofol discontinuation when assessing the EEG signal in postanoxic patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To systematically review the effectiveness and safety of intravascular temperature management (IVTM) vs. surface cooling methods (SCM) for induced hypothermia (IH)., Methods: Systematic review and meta-analysis. English-language PubMed, Embase and the Cochrane Database of Systematic Reviews were searched on May 27, 2019. The quality of included observational studies was graded using the Newcastle-Ottawa Quality Assessment tool. The quality of included randomized trials was evaluated using the Cochrane Collaboration's risk of bias tool. Random effects modeling was used to calculate risk differences for each outcome. Statistical heterogeneity and publication bias were assessed using standard methods., Eligibility: Observational or randomized studies comparing survival and/or neurologic outcomes in adults aged 18 years or greater resuscitated from out-of-hospital cardiac arrest receiving IH via IVTM vs. SCM were eligible for inclusion., Results: In total, 12 studies met inclusion criteria. These enrolled 1573 patients who received IVTM; and 4008 who received SCM. Survival was 55.0% in the IVTM group and 51.2% in the SCM group [pooled risk difference 2% (95% CI -1%, 5%)]. Good neurological outcome was achieved in 40.9% in the IVTM and 29.5% in the surface group [pooled risk difference 5% (95% CI 2%, 8%)]. There was a 6% (95% CI 11%, 2%) lower risk of arrhythmia with use of IVTM and 15% (95% CI 22%, 7%) decreased risk of overcooling with use of IVTM vs. SCM. There was no significant difference in other evaluated adverse events between groups., Conclusions: IVTM was associated with improved neurological outcomes vs. SCM among survivors resuscitated following cardiac arrest. These results may have implications for care of patients in the emergency department and intensive care settings after resuscitation from cardiac arrest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Multimodal neurological prognostication is recommended for comatose patients after cardiac arrest. The absence of cortical N20-potentials in a somatosensory evoked potential (SSEP) examination reliably predicts poor outcome, but presence of N20-potentials have limited prognostic value. A benign routine electroencephalogram (EEG) may identify patients with a favourable prognosis who are likely to have present N20-potentials., Objective: To investigate whether a routine EEG can identify patients where SSEP is unnecessary to perform., Methods: In a multi-centre trial, comatose patients after cardiac arrest were randomised to a controlled temperature of 33 °C or 36 °C. A routine EEG was protocolised and SSEP performed at the clinicians' discretion, both during normothermic conditions. EEGs were categorised into benign, malignant or highly malignant based on standardised terminology. A benign EEG was defined as a continuous normal-voltage background without abundant discharges. The N20-potentials were reported as absent (bilaterally) or present (bilaterally or unilaterally)., Results: Both EEG and SSEP were performed in 161 patients. EEG was performed before SSEP in 60%. A benign EEG was seen in 29 patients and 100% (CI 88-100%) had present N20-potentials. For the 69 patients with a malignant EEG and the 63 patients with a highly malignant EEG, 67% (CI 55-77%) and 44% (CI 33-57%) had present N20-potentials, respectively., Conclusions: All patients with a benign EEG had present N20-potentials, suggesting that SSEP may be omitted in these patients to save resources. SSEP is useful in patients with a malignant or highly malignant EEG since these patterns are associated with both present and absent N20-potentials., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: We tested the impact of antiepileptic drug (AED) administration on post-cardiac arrest epileptiform electroencephalographic (EEG) activity., Methods: We studied an observational cohort of comatose subjects treated at a single academic medical center after cardiac arrest from September 2010 to January 2018. We aggregated the observed EEG patterns into 5 categories: suppressed; discontinuous background with superimposed epileptiform activity; discontinuous background without epileptiform features; continuous background with epileptiform activity; and continuous background without epileptiform activity. We calculated overall probabilities of transitions between EEG states in a multistate model, then used Aalen's additive regression to test if AEDs or hypothermia are associated with a change in these probabilities., Results: Overall, 828 subjects had EEG-monitoring for 42,840 h with a median of 40 [IQR 23-64] h per subject. Among patients with epileptiform findings on initial monitoring, 50% transitioned at least once to a non-epileptiform, non-suppressed state. By contrast, 19% with non-epileptiform initial activity transitioned to an epileptiform state at least once. Overall, 568 (78%) patients received at least one AED. Among patients with continuous EEG background activity, valproate, levetiracetam and lower body temperature were each associated with an increased probability of transition from epileptiform states to non-epileptiform states, where patients with discontinuous EEG background activity no agent linked to an increased probability of transitioning from epileptiform states., Conclusion: After cardiac arrest, the impact of AEDs may depend on the presence of continuous cortical background activity. These data serve to inform experimental work to better define the opportunities to improve neurologic care post-cardiac arrest., (Copyright © 2019. Published by Elsevier B.V.)

Aim: Predicting recovery in comatose post-cardiac arrest patients requires multiple modalities of prognostic assessment. In isolation, absent N20 cortical responses in somatosensory evoked potentials (SSEPs) are a specific predictor of poor outcome. It is unknown whether SSEP results, when assessed in the context of prior knowledge (demographic and clinical information), change the pretest predicted probability of recovery., Methods: In a single center retrospective study, a cohort of 323 patients admitted to post-cardiac arrest service at a tertiary care center were classified into a group based on SSEP testing. We built adjusted logistic regression models including clinical examination findings on the day SSEPs were recorded to generate a pre-test outcome probability for awakening, withdrawal of life-sustaining therapy (WLST) and survival to discharge. We then added the upper extremity N20 cortical response results to the model to obtain updated outcome probabilities. ROC curve was used to determine the additive effect of using SSEPs to the model. Survival to discharge, awakening, and WLST due to neurological reasons were designated as primary, secondary and tertiary outcomes, respectively., Results: Analyses showed that evoked potentials are ordered in sicker patients. Adding SSEP to the model increased the proportion of patients with less than 1% and 5% chance of survival, as well as the proportion of patients with over 95% chance of WLST. AUC for survival increased from 0.85 to 0.93 when SSEP was included (p = 0.006)., Conclusion: Adding the N20 SSEP response results to prior knowledge changed the predicted probability of WLST and survival to discharge in comatose post-arrest patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: To assess whether stimulus-induced modifications of electromyographic activity observed on scalp EEG have a prognostic value in comatose patients after cardiac arrest., Methods: 184 adult patients from a multi-centric prospective register who underwent an early EEG after cardiac arrest were included. Auditory and somatosensory stimulation was performed during EEG-recording. EEG reactivity (EEG-R) and EMG reactivity (EMG-R) were retrospectively assessed visually by board-certified electroencephalographers, and compared with clinical outcome (cerebral performance category, CPC) at three months. A favorable functional outcome was defined as CPC 1-2, an unfavorable outcome as CPC 3-5., Results: Both EEG-R and EMG-R were predictors for good outcome (EEG-R accuracy 72% (95%-CI 66-79), sensitivity 86% (78-93), specificity 60% (50-69); EMG-R accuracy 65% (58-72), sensitivity 61% (51-75), specificity 69% (60-78)). When reactivity was defined as EEG-R and/or EMG-R, the accuracy was 73% (67-70), the sensitivity 94% (90-99), and the specificity 53% (43-63)., Conclusion: Taking EMG into account when assessing reactivity of EEG seems to reduce false negative predictions for identifying patients with favorable outcome after cardiac arrest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Prognostic tools typically combine several time-invariant clinical predictors using regression models that yield a single, time-invariant outcome prediction. This results in considerable information loss as repeatedly or continuously sampled data are aggregated into single summary measures. We describe a method for real-time multivariate outcome prediction that accommodates both longitudinal data and time-invariant clinical characteristics., Methods: We included comatose patients treated after resuscitation from cardiac arrest who underwent ≥6 h of electroencephalographic (EEG) monitoring. We used Persyst v13 (Persyst Development Corp, Prescott AZ) to generate quantitative EEG (qEEG) features and calculated hourly summaries of whole brain suppression ratio and amplitude-integrated EEG. We randomly selected half of subjects as a training sample and used the other half as a test sample. We applied group-based trajectory modeling (GBTM) to the training sample to group patients based on qEEG evolution, then estimated the relationship of group membership and clinical covariates with awakening from coma and surviving to hospital discharge using logistic regression. We used these parameters to calculate posterior probabilities of group membership (PPGMs) in the test sample, and built three prognostic models: adjusted logistic regression (no GBTM), unadjusted GBTM (no clinical covariates) and adjusted GBTM (all data). We compared these models performance characteristics., Results: We included 723 patients. Group-specific outcome estimates from a 7-group GBTM ranged from 0 to 75%. Compared to unadjusted GBTM, adjusted GBTM calibration was significantly improved at 6 and 12 h, and time to an outcome estimate <10% and <5% were significantly shortened. Compared to simple logistic regression, adjusted GBTM identified a substantially larger proportion of subjects with outcome probability <1%., Conclusions: We describe a novel methodology for combining GBTM output and clinical covariates to estimate patient-specific prognosis over time. Refinement of such methods should form the basis for new avenues of prognostication research that minimize loss of clinically important information., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To test if prognostic performance is affected by prolonged targeted temperature management (TTM) in comatose out-of-hospital cardiac arrest patients using two recently proposed EEG pattern classification models., Methods: In this sub-study of the "Target Temperature Management for 48 vs. 24 hand Neurologic Outcome after Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial", EEGs of 20-30 min duration were collected 24 h and 48 h after reaching the target temperature of 33 ± 1 °C. We classified EEGs according to two EEG classification models by Westhall et al. ("highly malignant", "malignant" and "benign") and Hofmeijer et al. ("unfavorable", "intermediate" and "favorable"). We tested prognostic ability against 6 months functional outcome using the Cerebral Performance Category score., Results: We recorded EEGs in 120 patients at 24 h and in 44 patients at 48 h. We found no difference in specificities or sensitivities of the two models between the two TTM groups (all p-values >0.19) or in prognostication at 24 h compared to 48 h (all p-values >0.13), except for the presence of EEG reactivity favoring prognostication at 24 h (p < 0.001). Being classified in the "benign" or "favorable" category was strongly associated with good outcome with specificities of 100% (90-100) and 97% (85-100) for the Westhall and Hofmeijer models respectively., Conclusions: We found no difference in the prognostic performance of the two studied EEG classification models during prolonged TTM for 48 h compared to standard duration, nor between EEG classification performed at 24 h versus 48 h after reaching target temperature. The two models performed best in good outcome prediction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Early EEG patterns and SSEP responses are associated with neurological recovery of comatose patients with postanoxic encephalopathy after cardiac arrest. However, the nature and distribution of brain damage underlying the characteristic EEG and SSEP patterns are unknown. We relate EEG and SSEP findings with results from histological analyses of the brains of eleven non-survivors. With restoration towards continuous rhythms within 24 h after cardiac arrest, no signs of structural neuronal damage were observed. Absent SSEP responses were always accompanied by thalamic damage. Pathological burst suppression patterns were associated with a variable degree of neuronal damage to cortex, cerebellum and hippocampus. In patients with additional thalamic involvement, burst-suppression with identical bursts was observed, a characteristic EEG pattern presumably reflecting residual activity from a relatively isolated and severely compromised cortex., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The targets for vital parameters following return of spontaneous circulation (ROSC) from an out-of-hospital cardiac arrest (OHCA) are based on studies carried out predominantly in intensive care units. Therefore, we studied the pre-hospital phase., Method: We included all adult OHCA from the French OHCA Registry. Vital parameters [peripheral oxygen saturation level (SpO 2 ), end-tidal carbon dioxide (ETCO 2 ) and systolic blood pressure (SBP)] documented during the pre-hospital phase by mobile medical team, were evaluated with regard to the neurological outcome on day 30 (classified as good for Cerebral Performance Category (CPC) 1 - 2, and poor for CPC 3 - 5 or death)., Results: When compared with a reference range of 94-98%, SpO 2 values less than 94% were associated with a worse outcome on univariate analysis [relative risk (RR) = 1.108(1.069 - 1.147)]. An SpO 2 of 99 - 100% did not appear to be harmful [RR = 0.9851(0.956-1.015)]. ETCO 2 values that deviated from the reference of 30 - 40 mmHg were associated with a worse outcome on univariate analysis [<20, RR = 1.191(1.143 - 1.229); 20 - 29, RR = 1.092(1.061 - 1.123); 41 - 50, RR = 1.075(1.039 - 1.110); >50, RR = 1.136(1.085 - 1.179)]. When compared with a reference range of 100 - 130, higher or lower values of SBP were associated with a worse outcome on univariate analysis [<80, RR = 1.203(1.158 - 1.243); 80 - 99, RR = 1.069(1.033 - 1.105); 131 - 160, RR = 1.076(1.043 - 1.110); >160, RR = 1.168(1.126 - 1.208)]. The multivariate analysis yielded similar results., Conclusion: In comatose patients who have achieved ROSC after OHCA, vital parameters in the pre-hospital phase appear to have a real impact on the 30-day neurological outcome. We found that an SpO 2 ≥ 94%, an ETCO 2 of 30 - 40 mmHg, and an SBP of 100 - 130 mmHg were associated with a better prognosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Hypoxic-ischemic brain injury is the main cause of death and disability of comatose patients after cardiac arrest. Early and reliable prognostication is challenging. Common prognostic tools include clinical neurological examination and electrophysiological measures. Brain imaging is well established for diagnosis of focal cerebral ischemia but has so far not found worldwide application in this patient group., Objective: To review the value of Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) for early prediction of neurological outcome of comatose survivors of cardiac arrest., Methods: A literature search was performed to identify publications on CT, MRI or PET in comatose patients after cardiac arrest., Results: We included evidence from 51 articles, 21 on CT, 27 on MRI, 1 on CT and MRI, and 2 on PET imaging. Studies varied regarding timing of measurements, choice of determinants, and cut-off values predicting poor outcome. Most studies were small (n = 6-398) and retrospective (60%). In general, cytotoxic oedema, defined by a grey-white matter ratio <1.10, derived from CT, or MRI-diffusion weighted imaging <650 × 10 -6  mm 2 /s in >10% of the brain could differentiate between patients with favourable and unfavourable outcomes on a group level within 1-3 days after cardiac arrest. Advanced imaging techniques such as functional MRI or diffusion tensor imaging show promising results, but need further evaluation., Conclusion: CT derived grey-white matter ratio and MRI based measures of diffusivity and connectivity hold promise to improve outcome prediction after cardiac arrest. Prospective validation studies in a multivariable approach are needed to determine the additional value for the individual patient., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Electroencephalography (EEG) is a key modality for assessment of prognosis following cardiac arrest (CA); however, whether continuous EEG (cEEG) is superior to routine intermittent EEG (rEEG) remains debated. We examined the impact of cEEG (>18 h) vs. rEEG (<30 min) on outcome in comatose CA patients as part of multimodal prognostication., Methods: We analysed a large prospective registry of comatose post-CA adults (n = 497; 2009-2018), stratified based on whether they received cEEG (n = 62) or rEEG (n = 435), including standardized reactivity testing at two time-points. The primary endpoint was the impact of cEEG vs. rEEG on Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at three months; we also assessed impact on time to death., Results: Main patients' baseline clinical characteristics and CPC scores were comparable between the EEG groups. By multivariable analysis age, non-shockable rhythm, presence of early myoclonus, absent EEG background reactivity, absent somato-sensory evoked potentials, and serum NSE were independently associated with poor neurological outcome (CPC 3-5), while the EEG approach had no impact on patient prognosis and time to death., Conclusions: Our data suggest that cEEG does not confer any advantage over intermittent rEEG regarding outcome in patients with CA, and does not influence the time to death., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinical course and early prognostic markers in cardiac arrest (CA) patients discharged from the intensive care unit (ICU) in an unresponsive wakefulness syndrome (UWS) or coma., Methods: 89 patients were identified from a prospective CA database. Follow-up was conducted by telephone interviews with legal guardians, evaluation of re-admission and rehabilitation reports assessing core elements of the coma recovery scale-revised (CRS-R). Somatosensory evoked potential (SSEP) and electroencephalography (EEG) original recordings were re-analyzed, the gray-white-matter ratio (GWR) was determined from brain computed tomography (CT) and neuron-specific enolase (NSE) serum concentrations were retrieved., Results: Follow-up was successful for 32/50 (64%) patients admitted between 2001-2009 and 31/39 (79%) between 2009-2015. Median ICU stay was 27 days (IQR 20-36). Neurological improvement beyond UWS was found in 2 of 63 patients. Among 61 patients with successful follow-up and no improvement, NSE serum concentrations within the reference range, SSEP amplitudes above 2.5 μV or continuous reactive EEG were found in 5%, 3% and 2% of those tested. NSE > 90 μg/L, SSEP ≤ 0.3 μV, highly malignant EEG or GWR < 1.10 were found in 44%, 49%, 35% and 22% of those tested., Conclusions: Neurological recovery was rare in CA patients discharged in UWS after prolonged ICU treatment. Status epilepticus requiring prolonged deep sedation is one potential reason for delayed awakening. Sensitivity for established poor outcome parameters to predict persistent UWS early after CA was moderate. SSEP, EEG and NSE may indicate absence of severe HIE early after CA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Routine EEG is widely used and accessible for post arrest neuroprognostication. Recent studies, using standardised EEG terminology, have proposed highly malignant EEG patterns with promising predictive ability., Objectives: To validate the performance of standardised routine EEG patterns to predict neurological outcome after cardiac arrest., Methods: In the prospective multicenter Target Temperature Management trial, comatose cardiac arrest patients were randomised to different temperature levels (950 patients, 36 sites). According to the prospective protocol a routine EEG was performed in patients who remained comatose after the 36 h temperature control intervention. EEGs were retrospectively reviewed blinded to outcome using the standardised American Clinical Neurophysiology Society terminology. Highly malignant, malignant and benign EEG patterns were correlated to poor and good outcome, defined by best achieved Cerebral Performance Category up to 180 days., Results: At 20 sites 207 patients had a routine EEG performed at median 76 h after cardiac arrest. Highly malignant patterns (suppression or burst-suppression with or without discharges) had a high specificity for poor outcome (98%, CI 92-100), but with limited sensitivity (31%, CI 24-39). Our false positive patient had a burst-suppression pattern during ongoing sedation. A benign EEG, i.e. continuous normal-voltage background without malignant features, identified patients with good outcome with 77% (CI 66-86) sensitivity and 80% (CI 73-86) specificity., Conclusion: Highly malignant routine EEG after targeted temperature management is a strong predictor of poor outcome. A benign EEG is an important indicator of a good outcome for patients remaining in coma., (Published by Elsevier B.V.)

Aim: Which haemodynamic variable is the best predictor of neurological outcome remains unclear. We investigated the association of several haemodynamic variables with neurological outcome in CA patients., Methods: Retrospective analysis of adult comatose survivors of CA admitted to the intensive care unit (ICU) of a University Hospital. Exclusion criteria were early death due to withdrawal of care, missing haemodynamic data and use of intra-aortic balloon pump or extracorporeal membrane oxygenation. We retrieved CA characteristics; lactate concentration and cardiovascular sequential organ failure assessment (cSOFA) score on admission; systolic (SAP), diastolic (DAP), mean arterial pressure (MAP), and the use of vasopressors and inotropic agents during the first 6 h of ICU stay. Unfavourable neurological outcome (UO) was defined as a 3-month cerebral performance category score of 3-5., Results: Among the 170 patients (median age 63 years, 67% male, 60% out-of-hospital CA), 106 (63%) had UO. Admission lactate was higher in patients with UO than in those with favourable neurological outcome (4.0[2.4-7.3] vs. 2.5[1.4-6.0] mEq/L; p = 0.003) as was the cSOFA (3 [1-4] vs. 2[0-3]; p = 0.007). The lowest DAP during the first 6 h after ICU admission was significantly lower in patients with unfavourable neurological outcome, notably in patients with high cSOFA scores. In multivariable analysis, high adrenaline doses and the lowest value of DAP during the first 6 h after ICU admission was significantly associated with unfavourable neurological outcome., Conclusions: In CA patients admitted to the ICU, low DAP during the first 6 h is an independent predictor of unfavourable neurological outcome at 3 months., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim of the Study: Brain swelling after cardiac arrest may affect the ventricles. We aimed to investigate the prognostic performance of ventricular characteristics on brain computed tomography (CT) in cardiac arrest survivors who underwent targeted temperature management (TTM)., Methods: This retrospective cohort study included adult comatose cardiac arrest survivors who underwent brain CT scan within 24 h after resuscitation and underwent TTM from 2014 to 2016. The ventricular areas (lateral, third, and fourth ventricle), distances between the anterior horns of the lateral ventricle (LV) and the posterior horns of the LV, and maximal internal diameter of the skull were measured. Grey-to-white matter ratio (GWR), Evans' index, and relative LV area were calculated. The primary outcome was a 6-month neurologic outcome., Results: Of 258 patients, 176 (68.2%) had an unfavourable neurologic outcome. GWR, LV area, third ventricle area, distance between the anterior horns of the LV, distance between the posterior horns of the LV, Evans' index, and relative LV area were different between neurologic outcome groups. Evans' index (0.683; 95% confidence interval [CI], 0.623-0.739) and relative LV area (0.670; 95% CI, 0.609-0.727) had higher value of area under the curve than the other ventricular characteristics and showed prognostic performance comparable with GWR (0.600; 95% CI, 0.538-0.661). All ventricular characteristics and GWR were not independently associated with neurologic outcome after adjusting for covariates., Conclusion: Ventricular characteristics on brain CT were associated with 6 months neurologic outcome in cardiac arrest survivors. Ventricular characteristics were objective measures that had comparable prognostic performance with GWR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim of the Study: To determine the optimal mean arterial pressure (MAP) during the early-to-intermediate phase care of comatose survivors of out-of-hospital cardiac arrest (OHCA)., Methods: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm. Using blood pressure-over-time plots, we calculated the area below pre-specified MAP thresholds (ABT; mmHg*hours) during the first 96 h of admission. We used incremental MAP thresholds ranging between 65 and 85 mmHg. Logistic regression analyses were used to examine the association between ABT and clinical outcomes for each MAP threshold and to adjust for age, duration of cardiac arrest, and bystander CPR. The primary outcome was severe neurological dysfunction as defined by a cerebral performance category (CPC) ≥3., Results: We identified 122 consecutive OHCA patients meeting inclusion criteria. The rate of the primary outcome was 33%. There was a significant association between ABT and the rate of the primary outcome when MAP thresholds of 60 (p = 0.01), 65 (p < 0.01), 70 (p < 0.01), 75 (p < 0.01), and 80 mmHg (p < 0.01) were used. This association was lost once a MAP threshold of 85 mmHg was reached (p = 0.63). In the adjusted analysis, the association between ABT and the primary outcome was no longer present when the MAP threshold reached 75 mmHg., Conclusions: In comatose survivors of OHCA with an initial shockable rhythm, higher ABT is associated with increased rates of severe neurological dysfunction when MAP thresholds <75 mmHg are used. The current findings support the hypothesis that higher MAP targets (≥75 mmHg) may be indicated in this patient population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: The aim of this study was to determine the prognosis of 26 consecutive adults with alpha coma (AC), theta coma (TC) or alpha-theta coma (ATC) following CRA and to describe the clinical setting and EEG features of these patients., Methods: We retrospective analyzed a prospectively collected cohort of adult patients diagnosed as having AC, TC or ATC after CRA between January 2008 and June 2016. None of patients included in this analysis underwent therapeutic hypothermia (TH). Neurological outcome was expressed as the best score 6 months after CRA using the five-point Glasgow-Pisttsburgh Cerebral Performance Categories (CPC) RESULTS: Twenty-six patients were identified with a diagnosis of postanoxic AC, TC or ATC coma. There were 20 (77%) men and 6 (23%) women. The mean age was 63 ± 16 years. The most frequent EEG pattern was TC (21 patients, 80%), followed by AC (3 patients, 12%) and ATC (2 patients, 8%). The cardiac rhythm as primary origin of the CRA was ventricular fibrillation (VF) in 16 patients (61.5%), asystole in 8 patients (34.6%) and ventricular tachycardia (VT) in one patient (3.8%). The presence of EEG reactivity was present in 8 patients (30%). The mortality rate was 85%. Of the 4 surviving patients, two (3.8%) had moderate disability (CPC 2), one (3.8%) had severe disability (CPC 3) and one (3.8%) reached a good recovery. The age was significantly lower in survivors 46.2 ± 10.8 versus nonsurvivors 63.3 ± 15.5 (p = 0.04). There was increased association of EEG reactivity with survival (p = 0.07)., Conclusion: Hypoxic-ischemic AC, TC and ATC are associated with a poor prognosis and a high rate of mortality. In younger patients with AC, TC and ATC and incomplete forms showing reactivity on the EEG, there is a greater probability of clinical recovery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim of the Study: Estimation of cerebral anaerobic metabolism in survivors and non-survivors after cardiac arrest., Methods: We performed an observational study in twenty comatose patients after cardiac arrest and 19 healthy control subjects. We measured mean flow velocity in the middle cerebral artery (MFV MCA ) by transcranial Doppler. Arterial and jugular blood samples were used for calculation of the jugular venous-to-arterial CO 2 /arterial to-jugular venous O 2 content difference ratio., Results: After cardiac arrest, MFV MCA increased from 26.0[18.6-40.4]cm/sec on admission to 63.9[48.3-73.1]cm/sec after 72h (p<0.0001), with no significant differences between survivors and non-survivors (p=0.4853). The MFV MCA in controls was 59.1[52.8-69.0]cm/sec. The oxygen extraction fraction (O 2 EF) was 38.9[24.4-47.7]% on admission and decreased significantly to 17.3[12.1-26.2]% at 72h (p<0.0001). The decrease in O 2 EF was more pronounced in non-survivors (p=0.0173). O 2 EF in the control group was 35.4[32.4-38.7]%. The jugular bulb-arterial CO 2 to arterial-jugular bulb O 2 content difference ratio was >1 at all time points after cardiac arrest and did not change during admission, with no differences between survivors and non-survivors. Values in cardiac arrest patients were similar to those in normal subjects., Conclusions: In this study, low CBF after cardiac arrest is not associated with anaerobic metabolism. Hypoperfusion appears to be the consequence of a decrease of neuronal functioning and metabolic needs. Alternatively, hypoperfusion may decrease cerebral metabolism. Subsequently, metabolism increases in survivors, consistent with resumption of neuronal activity, whereas in non-survivors lasting low metabolism reflects irreversible neuronal damage., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: Few data are available on the use of brainstem auditory evoked potentials (BAEPs) in combination with other electrophysiological tools to assess prognosis of comatose survivors from cardiac arrest (CA)., Methods: Retrospective analysis of data from all adult patients (>18years of age) admitted to our Dept of Intensive Care after CA over a 6-year period who were comatose (Glasgow Coma Scale <9) on admission, had been treated with targeted temperature management and had BAEP testing. We collected variables related to CA, as well as electroencephalography (EEG) findings, N20 somatosensory evoked potentials, and the presence of I, III and/or V waves on BAEP testing. Outcome was assessed at 3 months using the Cerebral Performance Categories (3-5=poor outcome)., Results: We studied 65 patients; 48 (74%) had a poor neurological outcome. BAEP assessment was performed day 3 [3,4] after the CA. At least one of the three waves was absent bilaterally in 34 patients (52%); of these patients, 29 (85%) had a poor neurological outcome (sensitivity 60%, specificity 71%, positive predictive value [PPV] 85% and negative predictive value [NPV] 39%). Three patients (5%) had bilateral absence of all three waves, all of whom had a poor neurological outcome., Conclusions: In this series of patients after CA, at least one of the BAEP waves was absent bilaterally in half the survivors; however, their use for prediction of poor neurological outcome remains limited., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Despite decades of research into the prognostic significance of post anoxic myoclonic status (MS), no consistent definition has been used to describe its clinical appearance. We set out to characterize the clinical features of MS and hypothesized that there are distinct clinical subtypes that may have prognostic implications., Methods: Video EEG reports from 2008 to 2016 were searched to identify adult patients with post anoxic MS defined as persistent myoclonus for >30min beginning within 3days of cardiac arrest in a comatose patient. Forty-three patients met inclusion and exclusion criteria. To generate definitions of the clinical features of MS, we reviewed videos of 23 cases and characterized 3 distinct clinical semiologies. An additional 20 cases were independently reviewed and categorized by 3 raters to evaluate inter-rater agreement (IRA). All 43 patients were assigned to a group based on consensus review for the first 23 patients and majority agreement for IRA patients. We also examined the relationship between semiology and outcome., Results: Three distinct clinical semiologies of MS were identified: Type 1: distal, asynchronous, variable; type 2: axial or axial and distal, asynchronous, variable; and type 3: axial, synchronous, stereotyped. For IRA, Gwet's kappa was 0.64 indicating substantial agreement. Two of 3 type 1 patients (66.6%) and 7.4% of type 2 followed commands whereas none of type 3 followed commands (p=0.03)., Conclusion: We defined and validated a classification system of post anoxic MS based on clinical semiology. This classification may be a useful bedside prognostication tool., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: In-hospital cardiac arrest (IHCA) strikes over 200,000 people in the United States annually. Targeted temperature management (TTM) is considered beneficial in other settings, but there is no prospective data for IHCA. Recent work on TTM and IHCA found an association between TTM and worse outcome. However, the authors used intubation as a marker for coma to determine eligibility for TTM. The validity of this approach is unexplored., Methods: Retrospective, single center study of adult patients with IHCA occurring in an intensive care unit, intubated prior to or during the event, or immediately after ROSC. We evaluated the percentage of patients documented as comatose after arrest, defined as Glasgow Comas Score (GCS) <8 for the primary analysis. We also evaluated the difference in hospital survival in patients with GCS <8 versus ≥8. Two sensitivity analyses using different methods for defining coma using post-ROSC GCS were conducted., Results: 29/102 (28%) intubated patients had a post-ROSC GCS≥8, and 22 (22%) were documented as following commands. Survival in patients with GCS≥8 vs.<8 was 62% (18/29) vs. 37% (27/73) in unadjusted analysis (p=0.02). The adjusted odds ratio for survival to hospital discharge was 3.81 (95%CI: 1.37-10.61, p=0.01). Results were similar in both sensitivity analyses., Conclusions: Intubation prior to or during IHCA was not a valid marker of coma after ROSC. Post-ROSC mental status was associated with hospital survival, and thus could be an important confounder when conducting observational studies on the association of TTM with outcomes in this patient population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: The majority of comatose patients after cardiac arrest do not regain consciousness due to severe postanoxic encephalopathy. Early and accurate outcome prediction is therefore essential in determining further therapeutic interventions. The electroencephalogram is a standardized and commonly available tool used to estimate prognosis in postanoxic patients. The identification of pathological EEG patterns with poor prognosis relies however primarily on visual EEG scoring by experts. We introduced a model-based approach of EEG analysis (state space model) that allows for an objective and quantitative description of spectral EEG variability., Methods: We retrospectively analyzed standard EEG recordings in 83 comatose patients after cardiac arrest between 2005 and 2013 in the intensive care unit of the University Hospital Zürich. Neurological outcome was assessed one month after cardiac arrest using the Cerebral Performance Category. For a dynamic and quantitative EEG analysis, we implemented a model-based approach (state space analysis) to quantify EEG background variability independent from visual scoring of EEG epochs. Spectral variability was compared between groups and correlated with clinical outcome parameters and visual EEG patterns., Results: Quantitative assessment of spectral EEG variability (state space velocity) revealed significant differences between patients with poor and good outcome after cardiac arrest: Lower mean velocity in temporal electrodes (T4 and T5) was significantly associated with poor prognostic outcome (p<0.005) and correlated with independently identified visual EEG patterns such as generalized periodic discharges (p<0.02). Receiver operating characteristic (ROC) analysis confirmed the predictive value of lower state space velocity for poor clinical outcome after cardiac arrest (AUC 80.8, 70% sensitivity, 15% false positive rate)., Conclusion: Model-based quantitative EEG analysis (state space analysis) provides a novel, complementary marker for prognosis in postanoxic encephalopathy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Outcome prognostication in postanoxic comatose patients is more accurate in predicting poor than good recovery. Using electroencephalography recordings in patients treated with targeted temperature management at 33°C (TTM 33), we have previously shown that improvement in auditory discrimination over the first days of coma predicted awakening. Given the increased application of a 36°C temperature target (TTM 36), here we aimed at validating the predictive value of auditory discrimination in the TTM 36 setting., Methods: In this prospective multicenter study, we analyzed the EEG responses to auditory stimuli from 60 consecutive patients from the first and second coma day. A semiautomatic decoding analysis was applied to single patient data to quantify discrimination performance between frequently repeated and deviant sounds. The decoding change from the first to second day was used for predicting patient outcome., Results: We observed an increase in auditory discrimination in 25 out of 60 patients. Among them, 17 awoke from coma (68% positive predictive value; 95% confidence interval: 0.46-0.85). By excluding patients with electroencephalographic epileptiform features, 15 of 18 exhibited improvement in auditory discrimination (83% positive predictive value; 95% confidence interval: 0.59-0.96). Specificity of good outcome prediction increased after adding auditory discrimination to EEG reactivity., Conclusion: These results suggest that tracking of auditory discrimination over time is informative of good recovery independent of the temperature target. This quantitative test provides complementary information to existing clinical tools by identifying patients with high chances of recovery and encouraging the maintenance of life support., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: To evaluate post-cardiac arrest myocardial dysfunction during prolonged targeted temperature management (TTM) compared with standard TTM in comatose out-of-hospital cardiac arrest (OHCA) survivors., Methods: A randomised, controlled trial comparing myocardial function after TTM at 33 ±1°C for 48h compared with 24h. A total of 105 OHCA patients were computer-randomised to 24h (n=50) or 48h (n=55) of TTM. Transthoracic echocardiography was performed after 24h, 48h and 72h. Echocardiographic parameters were evaluated by an investigator who was blinded to randomisation. The primary endpoint was peak systolic mitral annular velocity (Ś) measured as the difference in the period from 24h to 72h. The model was adjusted for age, primary rhythm and heart rate. The secondary outcomes were global peak longitudinal strain, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and the diastolic measures e' and E/e'., Results: The mean difference of S' was significantly increased in the 48h group compared with the 24h group: -1.14cm/s (-1.83; -0.45), p=0.001. This difference was consistent after adjusting the data (p=0.008). However, there were no significant changes between the study groups with respect to the adjusted secondary outcomes of global peak longitudinal strain (p=0.07), LVEF (p=0.31), TAPSE (p=0.91), e' (p=0.26) and E/e' (p=0.18)., Conclusion: Prolonged TTM at 33°C of 48h compared with 24h in comatose OHCA survivors may improve the recovery of post-cardiac arrest left myocardial dysfunction demonstrated by the echocardiographic outcome, S'. ClinicalTrials.gov identifier: NCT02066753., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim of the Study: We sought to assess the relationship between mean arterial pressure (MAP) and clinical outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA)., Methods: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm treated with targeted temperature management. We examined clinical outcomes in relation to mean MAP (measured hourly) during the first 96h of hospitalization. Co-primary outcomes were the rates of death and severe neurological dysfunction at discharge., Results: In 122 patients meeting inclusion criteria, death occurred in 29 (24%) and severe neurological dysfunction in 39 (32%). Higher mean MAPs were associated with lower odds of death (OR 0.55 per 5mmHg increase; 95%CI 0.38-0.79; p=0.002) and severe neurological dysfunction (OR 0.66 per 5mmHg increase; 95%CI 0.48-0.90; p=0.01). After adjustment for differences in patient, index event, and treatment characteristics, higher mean MAPs remained associated with lower odds of death (OR 0.60 per 5mmHg increase; 95%CI 0.40-0.89; p=0.01) but not severe neurological dysfunction (OR 0.73 per 5mmHg increase; 95%CI 0.51-1.03; p=0.07). The relationship between mean MAP and the odds of death (p-interaction=0.03) and severe neurological dysfunction (p-interaction=0.03) was attenuated by increased patient age., Conclusion: In comatose survivors of OHCA treated with target temperature management, a higher mean MAP during the first 96h of admission is associated with increased survival. The association between mean MAP and clinical outcomes appears to be attenuated by increased age., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate spontaneous variability in the time and frequency domain in mean flow velocity (MFV) and mean arterial pressure (MAP) in comatose patients after cardiac arrest, and determine possible differences between survivors and non-survivors., Methods: A prospective observational study was performed at the ICU of a tertiary care university hospital in the Netherlands. We studied 11 comatose patients and 10 controls. MFV in the middle cerebral artery was measured with simultaneously recording of MAP. Coefficient of variation (CV) was used as a standardized measure of dispersion in the time domain. In the frequency domain, the average spectral power of MAP and MFV were calculated in the very low, low and high frequency bands., Results: In survivors CV of MFV increased from 4.66 [3.92-6.28] to 7.52 [5.52-15.23] % at T=72h. In non-survivors CV of MFV decreased from 9.02 [1.70-9.36] to 1.97 [1.97-1.97] %. CV of MAP was low immediately after admission (1.46 [1.09-2.25] %) and remained low at 72h (3.05 [1.87-3.63] %) (p=0.13). There were no differences in CV of MAP between survivors and non-survivors (p=0.30). We noticed significant differences between survivors and non-survivors in the VLF band for average spectral power of MAP (p=0.03) and MFV (p=0.003), whereby the power of both MAP and MFV increased in survivors during admission, while remaining low in non-survivors., Conclusions: Cerebral blood flow is altered after cardiac arrest, with decreased spontaneous fluctuations in non-survivors. Most likely, these changes are the consequence of impaired intrinsic myogenic vascular function and autonomic dysregulation., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

Aim: This study estimated the critical closing pressure (CrCP) of the cerebrovascular circulation during the post-cardiac arrest syndrome and determined if CrCP differs between survivors and non-survivors. We also compared patients after cardiac arrest to normal controls., Methods: A prospective observational study was performed at the ICU of a tertiary university hospital in Nijmegen, the Netherlands. We studied 11 comatose patients successfully resuscitated from a cardiac arrest and treated with mild therapeutic hypothermia and 10 normal control subjects. Mean flow velocity (MFV) in the middle cerebral artery was measured by transcranial Doppler at several time points after admission to the ICU. CrCP was determined by a cerebrovascular impedance model., Results: MFV was similar in survivors and non-survivors upon admission to the ICU, but increased stronger in non-survivors compared to survivors throughout the observation period (P<0.001). MFV was significantly lower in survivors immediately after cardiac arrest compared to normal controls (P<0.001), with a gradual restoration toward normal values. CrCP decreased significantly from 61.4[51.0-77.1]mmHg to 41.7[39.9-51.0]mmHg in the first 48h, after which it remained stable (P<0.001). CrCP was significantly higher in survivors compared to non-survivors (P=0.002). CrCP immediately after cardiac arrest was significantly higher compared to the control group (P=0.02)., Conclusions: CrCP is high after cardiac arrest with high cerebrovascular resistance and low MFV. This suggests that cerebral perfusion pressure should be maintained at a sufficient high level to avoid secondary brain injury. Failure to normalize the cerebrovascular profile may be a parameter of poor outcome., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Post-cardiac arrest syndrome (PCAS) is characterized by whole-body ischemia triggering systemic inflammation and damage of the endothelium. This study investigated the relationship between systemic inflammation, endothelial damage and severity of PCAS and the association between endothelial damage and outcome after out-of-hospital cardiac arrest (OHCA)., Methods: In this post hoc study, we analyzed 163 comatose patients included at a single center in the target temperature management (TTM) trial, randomly assigned to TTM at 33°C or 36°C for 24h. Endothelial biomarkers (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin) and the inflammatory biomarker interleukin-6 (IL-6) were measured at admission (baseline) and 24, 48 and 72h after OHCA. Severity of PCAS was assessed by Sequential Organ Failure Assessment score. Mortality at 30-days was evaluated by Cox regression analysis., Results: By linear regression, baseline IL-6 levels (two-fold) was independently associated with glycocalyx damage (syndecan-1 (10.3ng/ml (p=0.01))), endothelial activation (sE-selectin (2.0ng/ml (p=0.03))) and endothelial damage (thrombomodulin 0.7ng/ml (p=0.0005)) at 24h after OHCA. Adjusted for baseline IL-6, a two-fold increase in thrombomodulin from baseline to 48h (1.7 (0.9-2.4), p<0.0001) and 72h (1.5 (0.6-2.3), p<0.0007) was more closely associated with severity of PCAS than IL-6. Levels of syndecan-1, thrombomodulin and sVE-cadherin was not influenced by level of target temperature but levels of sE-selectin was significantly lower in the 36°C group (-55ng/ml (95%CI: -53 to -58ng/ml), p=0.005) compared to the 33°C group. High levels of thrombomodulin at 24h (HR=2.1 (1.3-3.3), p=0.001) and 48h (HR=1.75 (1.0-2.8), p=0.02) were associated with increased 30-day mortality in univariate analysis, but not in multivariable analyses., Conclusion: In comatose survivors after OHCA treated with TTM, systemic inflammation was associated with endothelial activation and endothelial damage. Sustained endothelial damage was independently associated with severity of PCAS, adjusted for level of systemic inflammation. TTM at 36°C compared to 33°C after OHCA was associated with lower endothelial activation, but not endothelial damage., Clinical Trial Registration: URL: clinicaltrials.gov/ct2/show/NCT01020916. Unique identifier: NCT01020916., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: Besides supportive care, the only recommended treatment for comatose patients after cardiac arrest is target temperature management. Helium reduces ischaemic injury in animal models, and might ameliorate neurological injury in patients after cardiac arrest. As no studies exist on the use of helium in patients after cardiac arrest we investigated whether this is safe and feasible., Methods: The study was an open-label single arm intervention study in a mixed-bed academic intensive care unit. We included 25 patients admitted after circulatory arrest, with a presenting rhythm of ventricular fibrillation or pulseless tachycardia, return of spontaneous circulation within 30min and who were treated with hypothermia. Helium was administrated in a 1:1 mix with oxygen for 3h. A safety committee reviewed all ventilation problems, complications and causes of mortality., Results: Helium ventilation was started 4:59±0:52 (mean±SD)h after circulatory arrest. In one patient, helium ventilation was discontinued prematurely due to oxygenation problems. This was caused by pre-existing pulmonary oedema, and imposed limitations to PEEP and FiO2 by the study protocol, rather than the use of helium ventilation. Sixteen (64%) patients had a favourable neurological outcome., Conclusions: We found that helium ventilation is feasible and can be used safely in patients treated with hypothermia after cardiac arrest. No adverse events related to the use of helium occurred during the three hours of administration., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

Aim: To date, no clinical test is able to predict cognitive and functional outcome of cardiac arrest survivors. Improvement of auditory discrimination in acute coma indicates survival with high specificity. Whether the degree of this improvement is indicative of recovery remains unknown. Here we investigated if progression of auditory discrimination can predict cognitive and functional outcome., Methods: We prospectively recorded electroencephalography responses to auditory stimuli of post-anoxic comatose patients on the first and second day after admission. For each recording, auditory discrimination was quantified and its evolution over the two recordings was used to classify survivors as "predicted" when it increased vs. "other" if not. Cognitive functions were tested on awakening and functional outcome was assessed at 3 months using the Cerebral Performance Categories (CPC) scale., Results: Thirty-two patients were included, 14 "predicted survivors" and 18 "other survivors". "Predicted survivors" were more likely to recover basic cognitive functions shortly after awakening (ability to follow a standardized neuropsychological battery: 86% vs. 44%; p=0.03 (Fisher)) and to show a very good functional outcome at 3 months (CPC 1: 86% vs. 33%; p=0.004 (Fisher)). Moreover, progression of auditory discrimination during coma was strongly correlated with cognitive performance on awakening (phonemic verbal fluency: rs=0.48; p=0.009 (Spearman))., Conclusions: Progression of auditory discrimination during coma provides early indication of future recovery of cognitive functions. The degree of improvement is informative of the degree of functional impairment. If confirmed in a larger cohort, this test would be the first to predict detailed outcome at the single-patient level., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Life threatening arrhythmias are increasingly frequent with lower body temperature. While targeted temperature management (TTM) with mild hypothermia following out-of-hospital cardiac arrest (OHCA) is generally considered safe and has been suggested as a potential antiarrhythmic add-on therapy, it is unknown whether the level of TTM affects the burden of ventricular ectopic activity. We sought to assess the ventricular ectopic burden between patients treated with TTM at 33°C or 36°C for 24h., Methods: Continuous 12-lead digital Holter electrocardiograms performed during the intervention were analyzed blinded to treatment allocation in 115 comatose OHCA-survivors from a single center of the TTM-trial. The main study showed no difference with regards to mortality., Results: Fifty-eight patients were randomized to 33°C and 57 to 36°C. Cardiac arrest characteristics were similar between the groups. The number of isolated ventricular ectopic beats (VEB) per hour was similar at the beginning of the maintenance phase of TTM and decreased over time in both groups (both ptime<0.001). The reduction in VEB per hour was significantly affected by target temperature (pinteraction<0.0001), with fewer VEB in the 36°C-group. The total number of isolated, couplets and number of runs of VEB per hour showed similar results, with less ventricular ectopic activity in the 36°C-group (pinteraction<0.0001). Increasing numbers of pre-hospital defibrillations (log2) were associated with a 46% increase in ventricular ectopic activity (p<0.01), adjusted for potential confounders., Conclusions: Ventricular ectopic activity was reduced in comatose OHCA-survivors treated with TTM at 36°C compared to 33°C. Higher numbers of pre-hospital defibrillations were associated with higher incidence of ventricular ectopic activity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims: To investigate patterns of neurologic "awakening" in out-of-hospital cardiac arrest (OHCA) patients using different criteria for prognostication post-arrest., Methods: Data was collected on 194 OHCA survivors to hospital admission. Patients were assigned to one of two groups based on whether they received therapeutic hypothermia (TH). Three separate criteria were used to assess neurologic "awakening": motor-GCS=6, total-GCS ≥ 9, and CPC=1 or 2. Demographics, arrest characteristics and intensive care events were compared using unpaired t-test, Chi-square or nonparametric Wilcoxon rank-sum test as appropriate. Primary outcome was the time from arrest to neurologic awakening., Results: Of 194 OHCA survivors, TH was implemented in 94 patients (48%). Compared to conventional care patients, hypothermia treated patients were more likely to be younger (58 vs. 69 years, p<0.01),), and have a shockable arrest rhythm (27% vs. 10%, p<0.01). Using the three criteria (m-GCS=6, t-GCS ≥ 9 & CPC=1 or 2), median time to awakening for patients in the hypothermia group versus the conventional therapy group were 6 [4,9] vs. 3 [2,5] days, 3 [3,5] vs. 2 [2,3] days, and 3 [3,6] vs. 2 [2,4] days respectively (all p<0.01) and prognostication using these criteria on day 3 yielded discordant results about which patients achieved awakening., Conclusions: Patients undergoing therapeutic hypothermia achieve meaningful neurologic "awakening" beyond 72 h post-arrest. Use of different criteria for the assessment of neurologic "awakening" can yield different prognostication predictions which calls for standardization and validation of a single definition of "awakening" by the resuscitation community., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Electroencephalogram (EEG) background reactivity is a potentially interesting outcome predictor in comatose patients, especially after cardiac arrest, but recent studies report only fair interrater reliability. Furthermore, there are no definite guidelines for its testing. We therefore investigated the EEG effect of standardized noxious stimuli in comatose patients not reactive to auditory stimuli., Methods: In this prospective study we applied a protocol using three different painful stimuli (bilateral nipple pinching, pinprick at the nose base, finger-nail compression on each side), grouped in three distinct clusters with an alternated sequence, during EEG recordings in comatose patients. We only analyzed recordings showing any reactivity to pain. Fisher and χ2 tests were used as needed to assess contingency tables., Results: Of 42 studies, 12 did not show any background reactivity, 2 presented SIRPIDs, and 2 had massive artefacts; we thus analyzed 26 EEGs recorded in 17 patients (4 women, 24%). Nipple pinching more frequently induced a change in EEG background activity (p<0.001), with a sensitivity of 97.4% for reactivity. Neither the order of the stimuli in the cluster (p=0.723), nor the cluster order (p=0.901) influenced the results., Conclusion: In this pilot study, bilateral, synchronous nipple pinching seems to be the most efficient method to test nociceptive EEG reactivity in comatose patients. This approach may enhance interrater reliability, but deserves confirmation in larger cohorts., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC., Methods: In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days., Results: Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM., Conclusion: Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate the association between impaired cerebrovascular autoregulation (CVAR) and outcome in comatose survivors of cardiac arrest., Methods: The correlation in the time domain between cerebral tissue oxygenation (cStO2) using near infrared spectroscopy (NIRS) and mean arterial pressure was used to determine the tissue oxygenation index (TOx) as a reflection of normal (TOx<0) or impaired (TOx>0) CVAR. Daily measurements (>1h recording time) were performed in the first three days post cardiac arrest. Survival and neurological outcome was assessed at three months following cardiac arrest. A control group of healthy volunteers was also investigated., Results: 23 patients and 28 volunteers were studied. All survivors (n=8) of cardiac arrest had a good neurological outcome. The TOx (median [interquartile range] for days 1-3) was higher (Mann Whitney test, p<0.001) in non-survivors (0.04 [-0.02 to -0.16]) compared to survivors (-0.11 [-0.19 to -0.02]) and healthy volunteers (-0.15 [-0.27 to -0.04]) on every day and for days 1-3 following cardiac arrest. The TOx was not significantly different between survivors and healthy volunteers. The cStO2 did not discriminate survivors (67 [62-72]%) from non-survivors (71 [65-75]%). Logistic regression analysis demonstrated TOx to be independently associated with survival at three months post cardiac arrest (odds ratio [95% confidence interval] 0.01 [0.01-0.50], p=0.04)., Conclusions: Early impairment of CVAR following cardiac arrest is independently associated with mortality at three months follow-up. Assessments of CVAR could add to the management and prognostication during post-resuscitation care and should be further investigated as a guide to optimise cerebral perfusion pressure., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Time to awakening after out-of-hospital cardiac arrest (OHCA) and post-resuscitation therapeutic hypothermia (TH) varies widely. We examined the time interval from when comatose OHCA patients were rewarmed to 37°C to when they showed definitive signs of neurological recovery and tried to identify potential predictors of awakening., Methods: With IRB approval, a retrospective case study was performed in OHCA patients who were comatose upon presentation to a community hospital during 2006-2010. They were treated with TH (target of 33°C) for 24h, rewarmed, and discharged alive. Comatose patients were generally treated medically after TH for at least 48h before any decision to withdraw supportive care was made. Pre-hospital TH was not used. Data are expressed as medians and interquartile range., Results: The 89 patients treated with TH in this analysis were divided into three groups based upon the time between rewarming to 37°C and regaining consciousness. The 69 patients that regained consciousness in ≤48h after rewarming were termed "early-awakeners". Ten patients regained consciousness 48-72h after rewarming and were termed "intermediate-awakeners". Ten patients remained comatose and apneic >72h after rewarming but eventually regained consciousness; they were termed "late-awakeners". The ages for the early, intermediate and late awakeners were 56 [49,65], 62 [48,74], and 58 [55,65] years, respectively. Nearly 67% were male. Following rewarming, the time required to regain consciousness for the early, intermediate and late awakeners was 9 [2,18] (range 0-47), 60.5 [56,64.5] (range 49-71), and 126 [104,151]h (range 73-259), respectively. Within 90 days of hospital admission, favorable neurological function based on a Cerebral Performance Category (CPC) score of 1 or 2 was reported in 67/69 early, 10/10 intermediate, and 8/10 late awakeners., Conclusion: Following OHCA and TH, arbitrary withdrawal of life support <48h after rewarming may prematurely terminate life in many patients with the potential for full neurological recovery. Additional clinical markers that correlate with late awakening are needed to better determine when withdrawal of support is appropriate in OHCA patients who remain comatose >48h after rewarming., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To build new algorithms for prognostication of comatose cardiac arrest patients using clinical examination, and investigate whether therapeutic hypothermia influences the value of the clinical examination., Methods: From 2000 to 2007, 500 consecutive patients in non-traumatic coma were prospectively enrolled, 200 of whom were post-cardiac arrest. Outcome was determined by modified Rankin Scale (mRS) score at 6 months, with mRS≤3 indicating good outcome. The clinical examination was performed on days 0, 1, 3 and 7 post-arrest, and clinical variables analyzed for importance in prognostication of outcome. A classification and regression tree analysis (CART) was used to develop a predictive algorithm., Results: Good outcome was achieved in 9.9% of patients. In CART analysis, motor response was often chosen as a root node, and spontaneous eye movements, pupillary reflexes, eye opening and corneal reflexes were often chosen as splitting nodes. Over 8% of patients with absent or extensor motor response on day 3 achieved a good outcome, as did 2 patients with myoclonic status epilepticus. The odds of achieving a good outcome were lower in patients who suffered asystole (OR 0.187, 95% CI: 0.039-0.875, p=0.033) compared with ventricular fibrillation or non-perfusing ventricular tachycardia, but some still achieved good outcome. The absence of pupillary and corneal reflexes on day 3 remained highly reliable for predicting poor outcome, regardless of therapeutic hypothermia utilization., Conclusion: The clinical examination remains central to prognostication in comatose cardiac arrest patients in the modern area. Future studies should incorporate the clinical examination along with modern technology for accurate prognostication., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aim of the Study: This observational study was performed to assess the cerebral tissue oxygen saturation during and after therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest., Methods: We performed a prospective observational study on the cerebral tissue oxygen saturation (SctO(2)) in post-cardiac arrest patients treated with therapeutic hypothermia (TH) between March 2011 and April 2012. SctO(2) (measured by near-infrared spectroscopy) was non-invasively and continuously measured in 28 post-cardiac arrest patients during hypothermia and active rewarming., Results: At the start of mechanically induced TH, SctO(2) was 68% (65-72) and PaCO(2) was 47.2 mmHg (36.9-51.4). SctO(2) and PaCO(2) significantly decreased to 59% (57-64; p=0.006) and 36.6 mmHg (33.9-44.7; p=0.002), respectively, within the first 3h of mechanically induced TH. Cerebral tissue oxygen saturation was significantly lower in non-survivors (n=10) compared with survivors (n=18) at 3h after induction of hypothermia (p=0.02) while the decrease in PaCO(2) was similar in both groups. During TH maintenance, SctO(2) gradually returned to baseline values (69% (63-72)) at 24h, with no differences between survivors and non-survivors (p=0.65). Carbon dioxide remained within the range of mild hypocapnia (32-38 mmHg) throughout the hypothermic period. During rewarming, SctO(2) further increased to 71% (67-78)., Conclusions: Induction of TH in comatose post-CA patients changes the balance between oxygen delivery and supply. The decrease in SctO(2) was less pronounced in patients surviving to hospital discharge., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aim of the Study: To evaluate the association between haemodynamic variables during the first 24h after intensive care unit (ICU) admission and neurological outcome in out-of-hospital cardiac arrest (OHCA) victims undergoing therapeutic hypothermia., Methods: In a multi-disciplinary ICU, records were reviewed for comatose OHCA patients undergoing therapeutic hypothermia. The hourly variable time integral of haemodynamic variables during the first 24h after admission was calculated. Neurologic outcome was assessed at day 28 and graded as favourable or adverse based on the Cerebral Performance Category of 1-2 and 3-5. Bi- and multivariate regression models adjusted for confounding variables were used to evaluate the association between haemodynamic variables and functional outcome., Results: 67/134 patients (50%) were classified as having favourable outcome. Patients with adverse outcome had a higher mean heart rate (73 [62-86] vs. 66 [60-78]bpm; p=0.04) and received noradrenaline more frequently (n=17 [25.4%] vs. n=9 [6%]; p=0.02) and at a higher dosage (128 [56-1004] vs. 13 [2-162] μgh(-1); p=0.03) than patients with favourable outcome. The mean perfusion pressure (mean arterial blood pressure minus central venous blood pressure) (OR=1.001, 95% CI =1-1.003; p=0.04) and cardiac index time integral (OR=1.055, 95% CI=1.003-1.109; p=0.04) were independently associated with adverse outcome at day 28., Conclusion: Mean perfusion pressure and cardiac index during the first 24h after ICU admission were weakly associated with neurological outcome in an OHCA population undergoing therapeutic hypothermia. Further studies need to elucidate whether norepinephrine-induced increases in perfusion pressure and cardiac index may contribute to adverse neurologic outcome following OHCA., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Brain injury is considered the main cause of death in patients who are hospitalized after cardiac arrest (CA). Induced hypothermia is recommended as neuroprotective treatment after (CA) but may affect prognostic parameters. We evaluated the effect of delayed neurological prognostication on the mode of death in hypothermia-treated CA-survivors., Study Design: Retrospective study at a Swedish university hospital, analyzing all in-hospital and out-of-hospital CA-patients treated with hypothermia during a 5-year period. Cause of death was categorized as brain injury, cardiac disorder or other. Multimodal neurological prognostication and decision on level of care was performed in comatose patients 72 h after rewarming. Neurological function was evaluated by Cerebral Performance Categories scale (CPC)., Results: Among 162 patients, 76 survived to hospital discharge, 65 of whom had a good neurological outcome (CPC 1-2), and 11 were severely disabled (CPC 3). No patient was in vegetative state. The cause of death was classified as brain injury in 61 patients, cardiac disorder in 14 and other in 11. Four patients were declared brain dead and became organ donors. They were significantly younger (median 40 years) and with long time to ROSC. Active intensive care was withdrawn in 50 patients based on a statement of poor neurological prognosis at least 72 h after rewarming. These patients died, mainly from respiratory complications, at a median 7 days after CA., Conclusion: Following induced hypothermia and delayed neurological prognostication, brain injury remains the main cause of death after CA. Most patients with a poor prognosis statement died within 2 weeks., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: The independent prognostic significance of postanoxic status epilepticus (PSE) has not been evaluated prospectively since the introduction of therapeutic hypothermia. We studied 1-year functional outcomes and their determinants in comatose survivors of cardiac arrest (CA), with special attention to PSE., Methods: 106 comatose CA survivors admitted to the intensive care unit in 2005-2010 were included in a prospective observational study. The main outcome measure was a Cerebral Performance Category scale (CPC) of 1 or 2 (favorable outcome) 1 year after CA., Results: CA occurred out-of-hospital in 89 (84%) patients and was witnessed from onset in 94 (89%). Median times were 6 min (IQR, 0-11) from CA to first-responder arrival and 23 min (14-40) from collapse to return of spontaneous circulation. PSE was diagnosed in 33 (31%) patients at a median of 39 h (4-49) after CA. PSE was refractory in 24 (22%) cases and malignant in 19 (20%). After 1 year, 31 (29.3%) patients had favorable outcomes including 2 (6.44%) with PSE. Factors independently associated with poor outcome (CPC ≥ 3) were PSE (odds ratio [OR], 14.28; 95% confidence interval [95% CI], 2.77-50.0; P=0.001), time to restoration of spontaneous circulation (OR, 1.04/min; 95% CI, 1-1.07; P=0.035), and LOD score on day 1 (OR, 1.28/point; 95% CI, 1.08-1.54; P=0.003)., Conclusion: PSE strongly and independently predicts a poor outcome in comatose CA survivors receiving therapeutic hypothermia, but some patients with PSE survive with good functional outcomes. PSE alone is not sufficient to predict failure to awaken after CA in the era of therapeutic hypothermia., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Therapeutic hypothermia (TH) has revolutionized the management of comatose post-cardiac arrest syndrome (PCAS) patients. The 2008 ILCOR/AHA Consensus Statement for the treatment of PCAS suggests that goal-directed therapy, targeting mean arterial pressure (MAP), central venous pressure (CVP), and central venous oxygen saturation (ScvO(2)), should be employed to normalize oxygen delivery. However, the optimal PCAS haemodynamic management strategy has not been defined and few objective data exist to guide clinicians., Objective: To describe the haemodynamic strategies used in TH implementation studies., Methods: A Medline search (time period, 3/2002 to 3/2010) was performed using the terms cardiac arrest and hypothermia, induced, then limited post-search to implementation studies of TH in comatose adults. The identified studies were examined for explicit definitions of the following terms: MAP; systolic blood pressure (SBP), CVP, ScvO(2), pulmonary artery catheter (PAC), echocardiogram (ECHO), lactate, and volume status., Results: Forty-four implementation studies were identified and 43% (19/44) of them mentioned haemodynamics in any fashion. At least one haemodynamic goal was specifically defined in 16/44 (36%). The median number defined was 4 (range 1-6); individual goals as follows: MAP, 13/44 (30%); SBP, 3/44 (7%); CVP, 5/44 (11%); ScvO(2), 4/44 (9%); PAC, 7/44 (16%); ECHO, 7/44 (16%); lactate, 5/44 (11%); and volume status, 8/44 (18%)., Conclusions: Specific haemodynamic goals are defined in a minority of published TH implementation studies. Given the volatile haemodynamics of the PCAS and lack of consensus on an optimal resuscitation strategy, explicit description of haemodynamic goals should be provided in future studies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Troponin is a major diagnostic criterion of acute myocardial infarction (AMI) but in out-of-hospital cardiac arrest (OHCA) patients, its diagnostic value may be altered by cardiopulmonary resuscitation., Methods: Single-centre study assessing the diagnostic characteristics of troponin for AMI diagnosis in consecutive patients resuscitated from OHCA between 2002 and 2008 with coronary angiogram (CA) performed on admission. Patients with obvious non-cardiac cause of OHCA, unsustained or absent return of spontaneous circulation were excluded. AMI was defined on CA by the presence of acute occlusion or critical stenosis with intracoronary fresh thrombus easily crossed by an angioplasty wire. Troponin concentration was recorded once on admission and once 6-12h after the OHCA., Results: A total of 163 patients aged 56 (median) years (interquartile range (IQR) 48-65) was included, all comatose. Most prevalent initial OHCA rhythms were ventricular fibrillation (49%) and asystole (41%). AMI was diagnosed on coronary angiogram in 37% of the patients. Median troponin concentration on admission was 1.7 (0.3-10)ngml(-1) and sensitivity for AMI diagnosis was 72% and specificity 75% for a 2.5ngml(-1) cut-off. A combined criterion comprising ST elevation and troponin >2.5ngml(-1) had a sensitivity of 93% and specificity of 64%. Six to twelve hours after the OHCA, median troponin concentration was 7.6ngml(-1) (1.4-47.5), sensitivity was 84% and specificity 84% for a 14.5ngml(-1) cut-off., Conclusion: Troponin I has a good diagnostic value for AMI diagnosis in OHCA patients. In combination with ST elevation, troponin I on admission achieves a very high sensitivity., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Therapeutic hypothermia improves neurologic outcomes in patients resuscitated from cardiac arrest due to ventricular fibrillation. However, its role in patients with cardiac arrest due to non-shockable rhythms (pulseless electrical activity (PEA) and asystole) is unclear. We hypothesized that therapeutic hypothermia favorably impacts neurologic outcome and survival in patients resuscitated from cardiac arrest due to non-shockable rhythms., Methods: Retrospectively collected data on consecutive adult patients admitted to Hartford Hospital from 1/1/2004 to 11/1/2010 who survived a cardiac arrest due to PEA or asystole were analyzed. Patients who underwent therapeutic hypothermia (1/1/2007-11/1/2010) formed the hypothermia group while patients admitted prior to the institution of therapeutic hypothermia (1/1/2004-1/1/2007) at Hartford Hospital formed the control group. The primary end-point was measured using the Pittsburgh cerebral performance category (CPC) scale and patients were assessed for a good (CPC 1 and 2) or poor (CPC 3-5) neurological outcome prior to discharge from hospital. A secondary end-point was measured as survival at discharge from hospital., Results: Of 100 post-cardiac arrest patients included in the study, 15/52 (29%) patients in the hypothermia group had a good neurologic outcome as compared to 5/43 (10%) patients in the control group (P=0.021). On multivariate analysis, the odds ratio for good neurologic outcome and survival at discharge from the hospital with therapeutic hypothermia as compared to control were 4.35 (95% CI 1.10-17.24, P=0.04) and 5.65 (CI 1.66-19.23, P=0.006) respectively., Conclusion: Therapeutic hypothermia is associated with favorable neurologic outcome and survival in patients resuscitated after cardiac arrest due to non-shockable rhythms., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)