Electroencephalography for neurological prognostication after cardiac arrest

This thesis focuses on the prognostic value of electroencephalography(EEG) in comatose patients resuscitated after cardiac arrest (CA), using both simplified continuous EEG monitoring (cEEG) and routine EEG. Background: Comatose survivors are admitted to an intensive care unit (ICU) to support vital functions. Postresuscitation care includes target temperature management (TTM) for 24 hours. The degree of brain injury after CA varies among patients. Withdrawal of life-sustaining therapy due to presumed extensive brain injury is the most common cause of death during the hospital stay. Multiple prognostic tools are used to identify patients with a potential for recovery. Next to the neurological examination, EEG is the most commonly used tool to assess prognosis. However, the value of EEG has been limited by varying classification systems, interrater variability and influence of sedation. Methods: In the “coma project” (2004-2008) consecutive patients at the general ICU in Lund were monitored with simplified cEEG from arrival until 120 hours after CA. Pre-defined cEEG patterns at different time points were correlated to outcome. In the TTM trial (2010-2013) where patients were randomized to 33ºC versus 36ºC, a routine EEG was performed in patients still comatose after rewarming. The EEGs were classified into highly malignant, malignant and benign patterns by four EEG specialists from different countries according to the standardized EEG terminology proposed by the American Clinical Neurophysiology Society. The rationale and study design for this EEG evaluation was published. Results: 95 patients in the “coma project” were monitored with simplified cEEG. A continuous background at start of registration or at normothermia strongly predicted a good outcome. All patients with electrographic status epilepticus (ESE) evolving from a burst-suppression background died without regaining consciousness whereas ESE evolving late from an established continuous background was compatible with good outcome. At 8 selected TTM trial sites, routine EEGs were recorded after rewarming in 103 comatose patients. A highly malignant EEG was identified with substantial interrater agreement and had a specificity of 100% to predict poor outcome for all four EEG specialists. Any malignant EEG feature was identified with moderate interrater agreement but had a low specificity to predict a poor outcome (48%). A benign EEG was found in 1% of the patients with a poor outcome. Conclusions: Simplified cEEG provides early positive and negative prognostic information in comatose patients after cardiac arrest. A highly malignant routine EEG after rewarming reliably predicted a poor outcome. An isolated malignant routine EEG feature was not a reliable predictor whereas a benign routine EEG was highly predictive of good outcome

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

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)

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

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). 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. 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. 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)

Postanoxic alpha, theta or alpha-theta coma: Clinical setting and neurological outcome

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

Standardized EEG interpretation accurately predicts prognosis after cardiac arrest.

OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3-5 until 180 days. RESULTS: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p &lt; 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. CONCLUSIONS: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome

EEG for good outcome prediction after cardiac arrest: a multicentre cohort study.

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 hours 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 hours (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

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