The role of the electroencephalogram and evoked potentials after cardiac arrest.

PURPOSE OF REVIEW: In comatose cardiac arrest survivors, the electroencephalogram (EEG) is the most widely used test to assess the severity of hypoxic-ischemic brain injury (HIBI) and guide antiseizure treatment. However, a wide variety of EEG patterns are described in literature. Moreover, the value of postarrest seizure treatment is uncertain. Absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) are a specific predictor of irreversible HIBI. However, the prognostic significance of the N20 amplitude is less known. RECENT FINDINGS: The increasing adoption of standardized EEG pattern classification identified suppression and burst-suppression as 'highly-malignant' EEG patterns, accurately predicting irreversible HIBI. Conversely, continuous normal-voltage EEG is a reliable predictor of recovery from postarrest coma. A recent trial on EEG-guided antiseizure treatment in HIBI was neutral but suggested potential benefits in specific subgroups. A prognostic approach based on the amplitude rather than on the presence/absence of the N20 SSEP wave recently showed greater sensitivity for poor outcome prediction and added potential for predicting recovery. SUMMARY: Standardized EEG terminology and quantitative approach to SSEP are promising for improving the neuroprognostic accuracy of these tests. Further research is needed to identify the potential benefits of antiseizure treatment after cardiac arrest.

Bedside interpretation of simplified continuous EEG after cardiac arrest.

BACKGROUND: Continuous EEG-monitoring (cEEG) in the ICU is recommended to assess prognosis and detect seizures after cardiac arrest but implementation is often limited by the lack of EEG-technicians and experts. The aim of the study was to assess ICU physicians ability to perform preliminary interpretations of a simplified cEEG in the post cardiac arrest setting. METHODS: Five ICU physicians received training in interpretation of simplified cEEG - total training duration 1 day. The ICU physicians then interpreted 71 simplified cEEG recordings from 37 comatose survivors of cardiac arrest. The cEEG included amplitude-integrated EEG trends and two channels with original EEG-signals. Basic EEG background patterns and presence of epileptiform discharges or seizure activity were assessed on 5-grade rank-ordered scales based on standardized EEG terminology. An EEG-expert was used as reference. RESULTS: There was substantial agreement (κ 0.69) for EEG background patterns and moderate agreement (κ 0.43) for epileptiform discharges between ICU physicians and the EEG-expert. Sensitivity for detecting seizure activity by ICU physicians was limited (50%), but with high specificity (87%). CONCLUSIONS: After cardiac arrest, preliminary bedside interpretations of simplified cEEGs by trained ICU physicians may allow earlier detection of clinically relevant cEEG changes, prompting changes in patient management as well as additional evaluation by an EEG-expert. This strategy requires awareness of limitations of both the simplified electrode montage and the cEEG interpretations performed by ICU physicians. cEEG evaluation by an expert should not be delayed.

Electroencephalography as a Prognostic Tool after Cardiac Arrest.

Multiple prognostic tools are used to evaluate prognosis for comatose survivors resuscitated after cardiac arrest (CA). Next to the clinical neurologic examination, electroencephalography (EEG) is the most commonly used method to assess prognosis. However, the reliability of EEG has been limited by varying classification systems, interrater variability, and the influence of sedation. Another important purpose of EEG is to evaluate clinical and subclinical seizures. The American Clinical Neurophysiology Society (ACNS) recently proposed a standardized EEG terminology for critically ill patients suitable for use after CA. Standardization is essential for reproducibility, meta-analyses, and clinical application of study results. Electrophysiological recovery or failure of recovery can be monitored with EEG during the first few days after CA. Electroencephalographic patterns highly predictive of poor outcome, such as generalized suppression and burst suppression, will be discussed in relation to the ACNS terminology and the time point after CA. The author focuses on the prognostic value of EEG after CA, using both continuous EEG monitoring and routine EEG. The evidence for predicting poor as well as good prognosis will be reviewed and practical suggestions are provided.

Outcome following postanoxic status epilepticus in patients with targeted temperature management after cardiac arrest.

BACKGROUND: Postanoxic electrographic status epilepticus (ESE) is considered a predictor of poor outcome in resuscitated patients after cardiac arrest (CA). Observational data suggest that a subgroup of patients may have a good outcome. This study aimed to describe the prevalence of ESE and potential clinical and electrographic prognostic markers. METHODS: In this retrospective single study, we analyzed consecutive patients who suffered from CA, and who received temperature management and were monitored with simplified continuous EEG (cEEG) during a five-year period. The patients' charts and cEEG data were initially screened to identify patients with clinical seizures or ESE. The cEEG diagnosis of ESE was retrospectively reanalyzed according to strict criteria by a neurophysiologist blinded to patient outcome. The EEG background patterns prior to the onset of ESE, duration of ESE, presence of clinical seizures, and use of antiepileptic drugs were analyzed. The results of somatosensory-evoked potentials (SSEPs) and neuron-specific enolase (NSE) at 48 h after CA were described in all patients with ESE. Antiepileptic treatment strategies were not protocolized. Outcome was evaluated using the Cerebral Performance Category (CPC) scale at 6 months, and good outcome was defined as CPC 1-2. RESULTS: Of 127 patients, 41 (32%) developed ESE. Twenty-five patients had a discontinuous EEG background prior to ESE, and all died without regaining consciousness. Sixteen patients developed a continuous EEG background prior to the start of ESE, four of whom survived, three with CPC 1-2 and one with CPC 3 at 6 months. Among survivors, ESE developed at a median of 46 h after CA. All had preserved N20 peaks on SSEP and NSE values of 18-37 µg/l. CONCLUSION: Electrographic status epilepticus is common among comatose patients after cardiac arrest, with few survivors. A combination of a continuous EEG background prior to ESE, preserved N20 peaks on SSEPs, and low or moderately elevated NSE levels may indicate a good outcome. This article is part of a Special Issue entitled "Status Epilepticus".

Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design.

BACKGROUND: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. METHODS/DESIGN: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. DISCUSSION: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. TRIAL REGISTRATION: The TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

The predictive value of highly malignant EEG patterns after cardiac arrest: evaluation of the ERC-ESICM recommendations.

PURPOSE: The 2021 guidelines endorsed by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) recommend using highly malignant electroencephalogram (EEG) patterns (HMEP; suppression or burst-suppression) at > 24 h after cardiac arrest (CA) in combination with at least one other concordant predictor to prognosticate poor neurological outcome. We evaluated the prognostic accuracy of HMEP in a large multicentre cohort and investigated the added value of absent EEG reactivity. METHODS: This is a pre-planned prognostic substudy of the Targeted Temperature Management trial 2. The presence of HMEP and background reactivity to external stimuli on EEG recorded > 24 h after CA was prospectively reported. Poor outcome was measured at 6 months and defined as a modified Rankin Scale score of 4-6. Prognostication was multimodal, and withdrawal of life-sustaining therapy (WLST) was not allowed before 96 h after CA. RESULTS: 845 patients at 59 sites were included. Of these, 579 (69%) had poor outcome, including 304 (36%) with WLST due to poor neurological prognosis. EEG was recorded at a median of 71 h (interquartile range [IQR] 52-93) after CA. HMEP at > 24 h from CA had 50% [95% confidence interval [CI] 46-54] sensitivity and 93% [90-96] specificity to predict poor outcome. Specificity was similar (93%) in 541 patients without WLST. When HMEP were unreactive, specificity improved to 97% [94-99] (p = 0.008). CONCLUSION: The specificity of the ERC-ESICM-recommended EEG patterns for predicting poor outcome after CA exceeds 90% but is lower than in previous studies, suggesting that large-scale implementation may reduce their accuracy. Combining HMEP with an unreactive EEG background significantly improved specificity. As in other prognostication studies, a self-fulfilling prophecy bias may have contributed to observed results.

Clinical review: Continuous and simplified electroencephalography to monitor brain recovery after cardiac arrest.

There has been a dramatic change in hospital care of cardiac arrest survivors in recent years, including the use of target temperature management (hypothermia). Clinical signs of recovery or deterioration, which previously could be observed, are now concealed by sedation, analgesia, and muscle paralysis. Seizures are common after cardiac arrest, but few centers can offer high-quality electroencephalography (EEG) monitoring around the clock. This is due primarily to its complexity and lack of resources but also to uncertainty regarding the clinical value of monitoring EEG and of treating post-ischemic electrographic seizures. Thanks to technical advances in recent years, EEG monitoring has become more available. Large amounts of EEG data can be linked within a hospital or between neighboring hospitals for expert opinion. Continuous EEG (cEEG) monitoring provides dynamic information and can be used to assess the evolution of EEG patterns and to detect seizures. cEEG can be made more simple by reducing the number of electrodes and by adding trend analysis to the original EEG curves. In our version of simplified cEEG, we combine a reduced montage, displaying two channels of the original EEG, with amplitude-integrated EEG trend curves (aEEG). This is a convenient method to monitor cerebral function in comatose patients after cardiac arrest but has yet to be validated against the gold standard, a multichannel cEEG. We recently proposed a simplified system for interpreting EEG rhythms after cardiac arrest, defining four major EEG patterns. In this topical review, we will discuss cEEG to monitor brain function after cardiac arrest in general and how a simplified cEEG, with a reduced number of electrodes and trend analysis, may facilitate and improve care.

Cortical somatosensory evoked potential amplitudes and clinical outcome after cardiac arrest: a retrospective multicenter study.

OBJECTIVE: Bilaterally absent cortical somatosensory evoked potentials (SSEPs) reliably predict poor outcome in comatose cardiac arrest (CA) patients. Cortical SSEP amplitudes are a recent prognostic extension; however, amplitude thresholds, inter-recording, and inter-rater agreement remain uncertain. METHODS: In a retrospective multicenter cohort study, we determined cortical SSEP amplitudes of comatose CA patients using a standardized evaluation pathway. We studied inter-recording agreement in repeated SSEPs and inter-rater agreement by four raters independently determining 100 cortical SSEP amplitudes. Primary outcome was assessed using the cerebral performance category (CPC) upon intensive care unit discharge dichotomized into good (CPC 1-3) and poor outcome (CPC 4-5). RESULTS: Of 706 patients with SSEPs with median 3 days after CA, 277 (39.2%) had good and 429 (60.8%) poor outcome. Of patients with bilaterally absent cortical SSEPs, one (0.8%) survived with CPC 3 and 130 (99.2%) had poor outcome. Otherwise, the lowest cortical SSEP amplitude in good outcome patients was 0.5 µV. 184 (42.9%) of 429 poor outcome patients had lower cortical SSEP amplitudes. In 106 repeated SSEPs, there were 6 (5.7%) with prognostication-relevant changes in SSEP categories. Following a standardized evaluation pathway, inter-rater agreement was almost perfect with a Fleiss' kappa of 0.88. INTERPRETATION: Bilaterally absent and cortical SSEP amplitudes below 0.5 µV predicted poor outcome with high specificity. A standardized evaluation pathway provided high inter-rater and inter-recording agreement. Regain of consciousness in patients with bilaterally absent cortical SSEPs rarely occurs. High-amplitude cortical SSEP amplitudes likely indicate the absence of severe brain injury.

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.

Prediction of good neurological outcome in comatose survivors of cardiac arrest: a systematic review.

PURPOSE: To assess the ability of clinical examination, blood biomarkers, electrophysiology or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict good neurological outcome, defined as no, mild, or moderate disability (CPC 1-2 or mRS 0-3) at discharge from intensive care unit or later, in comatose adult survivors from cardiac arrest (CA). METHODS: PubMed, EMBASE, Web of Science and the Cochrane Database of Systematic Reviews were searched. Sensitivity and specificity for good outcome were calculated for each predictor. The risk of bias was assessed using the QUIPS tool. RESULTS: A total of 37 studies were included. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. A withdrawal or localisation motor response to pain immediately or at 72-96 h after ROSC, normal blood values of neuron-specific enolase (NSE) at 24 h-72 h after ROSC, a short-latency somatosensory evoked potentials (SSEPs) N20 wave amplitude > 4 µV or a continuous background without discharges on electroencephalogram (EEG) within 72 h from ROSC, and absent diffusion restriction in the cortex or deep grey matter on MRI on days 2-7 after ROSC predicted good neurological outcome with more than 80% specificity and a sensitivity above 40% in most studies. Most studies had moderate or high risk of bias. CONCLUSIONS: In comatose cardiac arrest survivors, clinical, biomarker, electrophysiology, and imaging studies identified patients destined to a good neurological outcome with high specificity within the first week after cardiac arrest (CA).

Postanoxic electrographic status epilepticus and serum biomarkers of brain injury.

AIM: To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells. METHODS: Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome. RESULTS: 128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p < 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest. CONCLUSION: ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE.

Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest.

PURPOSE: The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. METHODS: Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1-2) at 6 months. RESULTS: Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2-98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87-95% of patients). Normal S100B and NSE predicted good outcome with NPV 76-82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. CONCLUSION: Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.

Continuous amplitude-integrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients.

OBJECTIVE: To assess the prognostic value of continuous amplitude-integrated electroencephalogram in comatose survivors after cardiac arrest and treated with hypothermia. DESIGN: Prospective observational study. SETTING: General intensive care unit at a university hospital. PATIENTS: Comatose patients after cardiac arrest and treated with hypothermia. INTERVENTIONS: Patients were sedated and continuously monitored using an amplitude-integrated electroencephalogram. Monitoring was commenced on arrival in the intensive care unit and continued until recovery of consciousness, death, or 120 hrs after cardiac arrest. The amplitude-integrated electroencephalogram was interpreted together with the original electroencephalogram and analyzed without knowledge of the patient's clinical status. The amplitude-integrated electroencephalogram patterns at start of registration and at normothermia and the transitions of the amplitude-integrated electroencephalogram patterns over time were correlated to outcome. MEASUREMENTS AND MAIN RESULTS: A total of 111 consecutive patients were assessed; 11 patients were not included because of technical reasons and five were excluded because of death before normothermia. Ninety-five patients remained; 57 (60%) eventually regained consciousness, of whom 49 (52%) lived an independent life at 6 months. Thirty-one patients (33%) at start of registration and 62 patients (65%) at normothermia had a continuous electroencephalogram pattern, and this was strongly associated with recovery of consciousness (29/31 [90%] and 54/62 [87%]). A suppression-burst pattern was always transient and patients with suppression-burst at any time remained in coma until death. An initial flat pattern was registered in 47 patients, but this had no prognostic value. Electrographic status epilepticus was a common finding (26/95 patients [27%]) and two types of electrographic status epilepticus were identified: one developed from suppression-burst and one developed from a continuous background. Two patients from the latter group regained consciousness. CONCLUSIONS: Continuous amplitude-integrated electroencephalogram adds valuable early positive and negative prognostic information in comatose survivors after cardiac arrest. We identified two types of postanoxic electrographic status epilepticus, which is a novel finding with possible therapeutic implications.

Reduced EEG montage has a high accuracy in the post cardiac arrest setting.

OBJECTIVE: To study if comatose cardiac arrest patients can be assessed with a reduced number of EEG electrodes. METHODS: 110 routine EEGs from 67 consecutive patients, including both hypothermic and normothermic EEGs were retrospectively assessed by three blinded EEG-experts using two different electrode montages. A standard 19-electrode-montage was compared to the reduced version of the same EEGs, down-sampled to six electrodes (F3, T3, P3, F4, T4, P4). We used intra-rater and inter-observer statistics to assess the reliability of the reduced montage for background features and discharges. RESULTS: The reduced montage had almost perfect performance for background continuity (κ 0.80-0.88), including identification of highly malignant backgrounds (burst-suppression/suppression) (κ 0.85-0.94) and benign backgrounds (continuous/nearly continuous) (κ 0.85-0.91). We found substantial performance for identifying rhythmic/periodic discharges (κ 0.79-0.86). The reduced montage had high accuracy for assessment of both highly malignant (sensitivity 91-95%, specificity 94-99%) and benign (sensitivity 89-98%, specificity 91-96%) backgrounds, and periodic/rhythmic patterns (sensitivity 79-100%, specificity 89-99%), compared to the full montage. The inter-observer variability was not increased by the reduced montage. CONCLUSION: Reduced EEG had high performance for classifying important background and discharge patterns in this post cardiac arrest cohort. SIGNIFICANCE: Our results support the use of reduced EEG-montage for monitoring comatose cardiac arrest patients.

Hypoxic-Ischemic Encephalopathy Evaluated by Brain Autopsy and Neuroprognostication After Cardiac Arrest.

Importance: Neuroprognostication studies are potentially susceptible to a self-fulfilling prophecy as investigated prognostic parameters may affect withdrawal of life-sustaining therapy. Objective: To compare the results of prognostic parameters after cardiac arrest (CA) with the histopathologically determined severity of hypoxic-ischemic encephalopathy (HIE) obtained from autopsy results. Design, Setting, and Participants: In a retrospective, 3-center cohort study of all patients who died following cardiac arrest during their intensive care unit stay and underwent autopsy between 2003 and 2015, postmortem brain histopathologic findings were compared with post-CA brain computed tomographic imaging, electroencephalographic (EEG) findings, somatosensory-evoked potentials, and serum neuron-specific enolase levels obtained during the intensive care unit stay. Data analysis was conducted from 2015 to 2020. Main Outcomes and Measures: The severity of HIE was evaluated according to the selective eosinophilic neuronal death (SEND) classification and patients were dichotomized into categories of histopathologically severe and no/mild HIE. Results: Of 187 included patients, 117 were men (63%) and median age was 65 (interquartile range, 58-74) years. Severe HIE was found in 114 patients (61%) and no/mild HIE was identified in 73 patients (39%). Severe HIE was found in all 21 patients with bilaterally absent somatosensory-evoked potentials, all 15 patients with gray-white matter ratio less than 1.10 on brain computed tomographic imaging, all 9 patients with suppressed EEG, 15 of 16 patients with burst-suppression EEG, and all 29 patients with neuron-specific enolase levels greater than 67 µg/L more than 48 hours after CA without confounders. Three of 7 patients with generalized periodic discharges on suppressed background and 1 patient with burst-suppression EEG had a SEND 1 score (<30% dead neurons) in the cerebral cortex, but higher SEND scores (>30% dead neurons) in other oxygen-sensitive brain regions. Conclusions and Relevance: In this study, histopathologic findings suggested severe HIE after cardiac arrest in patients with bilaterally absent cortical somatosensory-evoked potentials, gray-white matter ratio less than 1.10, highly malignant EEG, and serum neuron-specific enolase concentration greater than 67 µg/L.

Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review.

PURPOSE: To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. RESULTS: Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors. CONCLUSION: In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169).

Performance of a guideline-recommended algorithm for prognostication of poor neurological outcome after cardiac arrest.

PURPOSE: To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). METHODS: Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72-96 h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3-5. Variations of the ERC/ESICM algorithm were explored within the same cohort. RESULTS: The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1-44.7) and 100% specificity (95% CI 98.8-100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7-48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8-100) remaining. CONCLUSION: The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6-42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies.

Serum Neurofilament Light Chain for Prognosis of Outcome After Cardiac Arrest.

Importance: Prognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units. Objective: To determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest. Design, Setting and Participants: Prospective clinical biobank study of data from the randomized Target Temperature Management After Cardiac Arrest trial, an international, multicenter study with 29 participating sites. Patients were included between November 11, 2010, and January 10, 2013. Serum NFL levels were analyzed between August 1 and August 23, 2017, after trial completion. A total of 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac origin were eligible. Exposures: Serum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrest with an ultrasensitive immunoassay. Main Outcomes and Measures: Poor neurologic outcome at 6-month follow-up, defined according to the Cerebral Performance Category Scale as cerebral performance category 3 (severe cerebral disability), 4 (coma), or 5 (brain death). Results: Of 782 eligible patients, 65 patients (8.3%) were excluded because of issues with aliquoting, missing sampling, missing outcome, or transport problems of samples. Of the 717 patients included (91.7%), 580 were men (80.9%) and median (interquartile range [IQR]) age was 65 (56-73) years. A total of 360 patients (50.2%) had poor neurologic outcome at 6 months. Median (IQR) serum NFL level was significantly increased in the patients with poor outcome vs good outcome at 24 hours (1426 [299-3577] vs 37 [20-70] pg/mL), 48 hours (3240 [623-8271] vs 46 [26-101] pg/mL), and 72 hours (3344 [845-7838] vs 54 [30-122] pg/mL) (P < .001 at all time points), with high overall performance (area under the curve, 0.94-0.95) and high sensitivities at high specificities (eg, 69% sensitivity with 98% specificity at 24 hours). Serum NFL levels had significantly greater performance than the other biochemical serum markers (ie, tau, neuron-specific enolase, and S100). At comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes (ranging from 29.2% to 49.0% greater for serum NFL level). Conclusions and Relevance: Findings from this study suggest that the serum NFL level is a highly predictive marker of long-term poor neurologic outcome at 24 hours after cardiac arrest and may be a useful complement to currently available neurologic prognostication methods.

Electroencephalographic characteristics of status epilepticus after cardiac arrest.

OBJECTIVE: To describe the electrophysiological characteristics and pathophysiological significance of electrographic status epilepticus (ESE) after cardiac arrest and specifically compare patients with unequivocal ESE to patients with rhythmic or periodic borderline patterns defined as possible ESE. METHODS: Retrospective cohort study of consecutive patients treated with targeted temperature management and monitored with simplified continuous EEG. Patients with ESE were identified and electrographically characterised until 72h after ESE start using the standardised terminology of the American Clinical Neurophysiology Society. RESULTS: ESE occurred in 41 of 127 patients and 22 fulfilled the criteria for unequivocal ESE, which typically appeared early and transiently. Three of the four survivors had unequivocal ESE, starting after rewarming from a continuous background. There were no differences between the groups of unequivocal ESE and possible ESE regarding outcome, neuron-specific enolase levels or prevalence of reported clinical convulsions. CONCLUSION: ESE is common after cardiac arrest. The distinction between unequivocal and possible ESE patterns was not reflected by differences in clinical features or survival. SIGNIFICANCE: A favourable outcome is seen infrequently in patients with ESE, regardless of using strict or liberal ESE definitions.

Prognostic significance of clinical seizures after cardiac arrest and target temperature management.

AIM: Clinical seizures are common after cardiac arrest and predictive of a poor neurological outcome. Seizures may be myoclonic, tonic-clonic or a combination of seizure types. This study reports the incidence and prognostic significance of clinical seizures in the target temperature management (TTM) after cardiac arrest trial. Our hypotheses were that seizures are associated with a poor prognosis and that the incidence of seizures is not affected by the target temperature. METHODS: Post-hoc analysis of reported clinical seizures during day 1-7 in the TTM-trial including their treatment, EEG-findings, and long-term neurological outcome. The trial randomised 939 comatose survivors to TTM at 33°C or 36°C with strict criteria for withdrawal of life-sustaining therapies. Sensitivity, specificity and false positive rate for poor outcome were reported for different types of seizures. RESULTS: Clinical seizures were registered in 268 patients (29%), similarly distributed in both intervention arms. Early and late seizures were equally predictive of poor outcome. Myoclonic seizures were the most common (240 patients, 26%) and the most predictive of a poor outcome (sensitivity 36.1%, false positive rate 4.3%). Two patients with status myoclonus regained consciousness, one with a good neurological outcome, generating a false positive rate of poor outcome of 0.2% (95%CI 0.0-1.0). CONCLUSION: Clinical seizures are common after cardiac arrest and indicate poor outcome with limited specificity. Prolonged seizures are a very grave sign but occasional patients may have a good outcome. The level of the target temperature does not affect the prevalence or prognostic significance of seizures.