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.

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.

Can carotid artery Doppler variations induced by the end-expiratory occlusion maneuver predict fluid responsiveness in septic shock patients?

BACKGROUND: An increase in cardiac index (CI) during an end-expiratory occlusion test (EEOt) predicts fluid responsiveness in ventilated patients. However, if CI monitoring is unavailable or the echocardiographic window is difficult, using the carotid Doppler (CD) could be a feasible alternative to track CI changes. This study investigates whether changes in CD peak velocity (CDPV) and corrected flow time (cFT) during an EEOt were correlated with CI changes and if CDPV and cFT changes predicted fluid responsiveness in patients with septic shock. METHODS: Prospective, single-center study in adults with hemodynamic instability. The CDPV and cFT on carotid artery Doppler and hemodynamic variables from the pulse contour analysis EV1000™ were recorded at baseline, during a 20-s EEOt, and after fluid challenge (500 mL). We defined responders as those who increased CI ≥ 15% after a fluid challenge. RESULTS: We performed 44 measurements in 18 mechanically ventilated patients with septic shock and without arrhythmias. The fluid responsiveness rate was 43.2%. The changes in CDPV were significantly correlated with changes in CI during EEOt (r = 0.51 [0.26-0.71]). A significant, albeit lower correlation, was found for cFT (r = 0.35 [0.1-0.58]). An increase in CI ≥ 5.35% during EEOt predicted fluid responsiveness with 78.9% sensitivity and 91.7% specificity, with an area under the ROC curve (AUROC) of 0.85. An increase in CDPV ≥ 10.5% during an EEOt predicted fluid responsiveness with 96.2% specificity and 53.0% sensitivity with an AUROC of 0.74. Sixty-one percent of CDPV measurements (from - 13.5 to 9.5 cm/s) fell within the gray zone. The cFT changes during EEOt did not accurately predict fluid responsiveness. CONCLUSIONS: In septic shock patients without arrhythmias, an increase in CDPV greater than 10.5% during a 20-s EEOt predicted fluid responsiveness with > 95% specificity. Carotid Doppler combined with EEOt may help optimize preload when invasive hemodynamic monitoring is unavailable. However, the 61% gray zone is a major limitation (retrospectively registered on Clinicaltrials.gov NCT04470856 on July 14, 2020).

SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study.

AIM: To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome. SETTING: Multicentre study in 13 Italian intensive care units. METHODS: The N20amp in microvolts (µV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology. Sensitivity and false positive rate (FPR) of N20amp alone or in combination were calculated. RESULTS: 403 patients (age 69[58-68] years) were included. At 12 h, an N20amp >3 µV predicted good neurological outcome (Cerebral Performance Categories [CPC] 1-2) with 61[50-72]% sensitivity and 11[6-18]% FPR. Combining it with a benign (continuous or nearly continuous) EEG increased sensitivity to 91[82-96]%. For poor outcome (CPC 3-5), an N20Amp ≤0.38 µV, ≤0.73 µV and ≤1.01 µV at 12 h, 24 h, and 72 h, respectively, had 0% FPR with sensitivity ranging from 61[51-69]% and 82[76-88]%. Sensitivity was higher than that of a bilaterally absent N20 at all time points. At 12 h and 24 h, a highly malignant (suppression or burst-suppression) EEG and bilaterally absent PLR achieved 0% FPR only when combined with SSEP. A combination of all three predictors yielded a 0[0-4]% FPR, with maximum sensitivity of 44[36-53]%. CONCLUSION: At 12 h from arrest, a high N20Amp predicts good outcome with high sensitivity, especially when combined with benign EEG. At 12 h and 24 h from arrest a low-voltage N20amp has a high sensitivity and is more specific than EEG or PLR for predicting poor outcome.

Does a combination of ≥2 abnormal tests vs. the ERC-ESICM stepwise algorithm improve prediction of poor neurological outcome after cardiac arrest? A post-hoc analysis of the ProNeCA multicentre study.

BACKGROUND: Bilaterally absent pupillary light reflexes (PLR) or N20 waves of short-latency evoked potentials (SSEPs) are recommended by the 2015 ERC-ESICM guidelines as robust, first-line predictors of poor neurological outcome after cardiac arrest. However, recent evidence shows that the false positive rates (FPRs) of these tests may be higher than previously reported. We investigated if testing accuracy is improved when combining PLR/SSEPs with malignant electroencephalogram (EEG), oedema on brain computed tomography (CT), or early status myoclonus (SM). METHODS: Post-hoc analysis of ProNeCA multicentre prognostication study. We compared the prognostic accuracy of the ERC-ESICM prognostication strategy vs. that of a new strategy combining ≥2 abnormal results from any of PLR, SSEPs, EEG, CT and SM. We also investigated if using alternative classifications for abnormal SSEPs (absent-pathological vs. bilaterally-absent N20) or malignant EEG (ACNS-defined suppression or burst-suppression vs. unreactive burst-suppression or status epilepticus) improved test sensitivity. RESULTS: We assessed 210 adult comatose resuscitated patients of whom 164 (78%) had poor neurological outcome (CPC 3-5) at six months. FPRs and sensitivities of the ≥2 abnormal test strategy vs. the ERC-ESICM algorithm were 0[0-8]% vs. 7 [1-18]% and 49[41-57]% vs. 63[56-71]%, respectively (p < .0001). Using alternative SSEP/EEG definitions increased the number of patients with ≥2 concordant test results and the sensitivity of both strategies (67[59-74]% and 54[46-61]% respectively), with no loss of specificity. CONCLUSIONS: In comatose resuscitated patients, a prognostication strategy combining ≥2 among PLR, SSEPs, EEG, CT and SM was more specific than the 2015 ERC-ESICM prognostication algorithm for predicting 6-month poor neurological outcome.

Standardized EEG analysis to reduce the uncertainty of outcome prognostication after cardiac arrest.

PURPOSE: Post-resuscitation guidelines recommend a multimodal algorithm for outcome prediction after cardiac arrest (CA). We aimed at evaluating the prevalence of indeterminate prognosis after application of this algorithm and providing a strategy for improving prognostication in this population. METHODS: We examined a prospective cohort of comatose CA patients (n = 485) in whom the ERC/ESICM algorithm was applied. In patients with an indeterminate outcome, prognostication was investigated using standardized EEG classification (benign, malignant, highly malignant) and serum neuron-specific enolase (NSE). Neurological recovery at 3 months was dichotomized as good (Cerebral Performance Categories [CPC] 1-2) vs. poor (CPC 3-5). RESULTS: Using the ERC/ESICM algorithm, 155 (32%) patients were prognosticated with poor outcome; all died at 3 months. Among the remaining 330 (68%) patients with an indeterminate outcome, the majority (212/330; 64%) showed good recovery. In this patient subgroup, absence of a highly malignant EEG by day 3 had 99.5 [97.4-99.9] % sensitivity for good recovery, which was superior to NSE < 33 µg/L (84.9 [79.3-89.4] % when used alone; 84.4 [78.8-89] % when combined with EEG, both p < 0.001). Highly malignant EEG had equal specificity (99.5 [97.4-99.9] %) but higher sensitivity than NSE for poor recovery. Further analysis of the discriminative power of outcome predictors revealed limited value of NSE over EEG. CONCLUSIONS: In the majority of comatose CA patients, the outcome remains indeterminate after application of ERC/ESICM prognostication algorithm. Standardized EEG background analysis enables accurate prediction of both good and poor recovery, thereby greatly reducing uncertainty about coma prognostication in this patient population.

Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

OBJECTIVES: To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS: GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS: Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron specific enolase at 48 72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

OBJECTIVES: To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS: GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS: Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥ 72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron-specific enolase at 48-72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival.

DESIGN: Review. OBJECTIVE: Medical literature on in-hospital cardiac arrest (IHCA) was reviewed to summarise: (a) the incidence of and survival after IHCA, (b) major prognostic factors, (c) possible interventions to improve survival. RESULTS AND CONCLUSIONS: The incidence of IHCA is rarely reported in the literature. Values range between 1 and 5 events per 1,000 hospital admissions, or 0.175 events/bed annually. Reported survival to hospital discharge varies from 0% to 42%, the most common range being between 15% and 20%. Pre-arrest prognostic factors: the prognostic value of age is controversial. Among comorbidities, sepsis, cancer, renal failure and homebound lifestyle are significantly associated with poor survival. However, pre-arrest morbidity scores have not yet been prospectively validated as instruments to predict failure to survive after IHCA. Intra-arrest factors: ventricular fibrillation/ventricular tachycardia (VF/VT) as the first recorded rhythm and a shorter interval between IHCA and cardiopulmonary resuscitation or defibrillation are associated with higher survival. However, VF/VT is present in only 25-35% of IHCAs. Short-term survival is also higher in patients resuscitated with chest compression rates above 80/min. Interventions likely to improve survival include: early recognition and stabilisation of patients at risk of IHCA to enable prevention, faster and better in-hospital resuscitation and early defibrillation. Mild therapeutic hypothermia is effective as post-arrest treatment of out-of-hospital cardiac arrest due to VF/VT, but its benefit after IHCA and after cardiac arrest with non-VF/VT rhythms has not been clearly demonstrated.