Post-cardiac arrest myoclonus and in ICU mortality: insights from the Parisian Registry of Cardiac Arrest (PROCAT).

BACKGROUND: Post-cardiac arrest myoclonus (PCAM) is a frequent finding in resuscitated patients after cardiac arrest (CA), with rather poor prognostic significance. In this study, we evaluated the association of PCAM within intensive care unit (ICU) mortality from a university hospital CA patients' registry. METHODS: Clinical data of consecutive CA survivors admitted in the intensive care unit (ICU) between January and December 2016 at the Paris Cochin University Hospital were assessed from the Parisian registry of cardiac arrest (PROCAT) and analyzed. Neurologic outcome was assessed using the Cerebral Performance Categories (CPC) scale at ICU discharge. Prevalence of PCAM and their association with mortality at ICU discharge were computed. RESULTS: One hundred thirty-two (132) patients were included (73.5% males), median age of 66 years. Among them, 37 (28%) developed PCAM during their ICU stay. Only two patients with PCAM survived (5.4%). PCAM was strongly associated with mortality at ICU discharge (odds ratio 17.5 [4.2-123.2]). Sensitivity, specificity, PPV, and NPV of PCAM for prediction of death were 41%, 96%, 95%, and 46%, respectively. CONCLUSION: PCAM was observed in nearly one-third of CA patients admitted in ICU. Patients with PCAM had a significantly higher likelihood of ICU mortality and a low likelihood of a good outcome. The prognostic value of PCAM seems rather bleak but remains nuanced and merits study in larger-scale prospective studies taking into account confounding factors.

Past Life Experiences and Neurological Recovery: The Role of Cognitive Reserve in the Rehabilitation of Severe Post-Anoxic Encephalopathy and Traumatic Brain Injury.

OBJECTIVE: Patients with an equivalent clinical background may show unexpected interindividual differences in their outcome. The cognitive reserve (CR) model has been proposed to account for such discrepancies, but its role after acquired severe injuries is still being debated. We hypothesize that inappropriate investigative methods might have been used when dealing with severe patients, which have very likely reduced the possibility of observing meaningful influences in recovery from severe traumas. METHODS: To overcome this issue, the potential neuroprotective role of CR was investigated, considering a wider spectrum of clinical symptoms ranging from low-level brain stem functions necessary for life to more complex motor and cognitive skills. In the present study, data from 50 severe patients, 20 suffering from post-anoxic encephalopathy (PAE) and 30 with traumatic brain injury (TBI), were collected and retrospectively analyzed. RESULTS: We found that CR, diagnosis, time of hospitalization, and their interaction had an effect on the clinical indexes. When the predictive power of CR was investigated by means of two machine learning classifier algorithms, CR, together with age, emerged as the strongest factor in discriminating between patients who reached or did not reach successful recovery. CONCLUSIONS: Overall, the present study highlights a possible role of CR in shaping the recovery of severe patients suffering from either PAE or TBI. The practical implications underlying the need to routinely considered CR in the clinical practice are discussed.

EEG patterns associated with present cortical SSEP after cardiac arrest.

BACKGROUND: After cardiac arrest (CA), present cortical somatosensory evoked potentials (N20 response of SSEPs) have low predictive value for good outcome and might be redundant with EEG. AIMS: To determine whether specific features, or rather global, standardized EEG assessments, are reliably associated with cortical SSEP occurrence after cardiac arrest (CA). METHODS: In a prospective CA registry, EEGs recorded within 72 hours were scored according to the ACNS nomenclature, and also categorized into "benign," "malignant," and "highly malignant." Correlations between EEGs and SSEPs (bilaterally absent vs present), and between EEGs/SSEPs and outcome (good: CPC 1-2) were assessed. RESULTS: Among 709 CA episodes, 532 had present N20 and 366 "benign EEGs." While EEG categories as well as background, epileptiform features, and reactivity differed significantly between patients with and without N20 (each P < .001), only "benign EEG" was almost universally associated with present N20: 99.5% (95%CI: 97.9%-99.9%) PPV. The combination of "benign EEG" and present N20 showed similar PPV for good outcome as "benign" EEG alone: 69.0% (95% CI: 65.2-72.4) vs 68.6% (95% CI: 64.9-72.0). CONCLUSION: Global EEG ("benign") assessment, rather than single EEG features, can reliably predict cortical SSEP occurrence. SSEP adjunction does not increase EEG prognostic performance toward good outcome. SSEP could therefore be omitted in patients with "benign EEG."

Comparison of extracorporeal and conventional cardiopulmonary resuscitation: a retrospective propensity score matched study.

BACKGROUND: The potential benefit of extracorporeal cardiopulmonary resuscitation (ECPR) compared to conventional CPR (CCPR) for patients with refractory cardiac arrest (CA) remains unclear. METHODS: This study is a retrospective analysis of a prospective database of CA patients, which includes all consecutive adult patients admitted to the Department of Intensive Care after CA between January 2012 and December 2017. The decision to initiate ECPR was made by the attending physician and ECPR performed by the ECPR team, which is composed of ICU physicians. A propensity score was derived using a logistic regression model, including characteristics that varied between groups with a p <  0.10 and were potentially related to outcome. Primary outcomes were survival to ICU discharge and favorable 3-month neurologic outcome, assessed by a Cerebral Performance Category (CPC) score of 1-2. RESULTS: From a total of 635 patients with CA during the study period (ECPR, n = 112), 80 ECPR patients were matched to 80 CCPR patients. The time from arrest to termination of CPR (i.e., return of spontaneous circulation [ROSC], extracorporeal membrane oxygenation [ECMO] initiation, or death) was 54 ± 22 and 54 ± 19 min in the ECPR and CCPR groups, respectively. ROSC rates were 77/80 (96%) for ECPR and 30/80 (38%) for CCPR (p <  0.001). Survival to ICU discharge was 18/80 (23%) vs. 14/80 (18%) in the ECPR and CCPR groups, respectively (p = 0.42). At 3 months, 17/80 (21%) ECPR patients and 9/80 (11%) CCPR patients had a favorable outcome (p = 0.11). Cox regression analysis stratified by matched pairs showed a significantly higher neurologic outcome rate in the ECPR group than in the CCPR group (log-rank test p = 0.003). CONCLUSIONS: ECPR after CA may be associated with improved long-term neurological outcome.

Retrospective study of perampanel efficacy and tolerability in myoclonic seizures.

OBJECTIVES: Perampanel is an antiepileptic drug (AED) approved for add-on treatment of focal seizures (with or without generalization) and primary generalized tonic-clonic (GTC) seizures. Our objective was to explore the effectiveness and tolerability of adjunctive perampanel in patients with drug-resistant myoclonic seizures, after failure of other AEDs. MATERIALS AND METHODS: Retrospective, multicenter, observational study. Data were collected from individual patient clinical files and analysed using appropriate descriptive statistics and inferential analyses. RESULTS: Data are reported for 31 patients with mean age 36.4 years, who had an average epilepsy duration of 18 years, previously taken an average of 5.03 AEDs, and were taking an average of 2.4 AEDs on perampanel initiation. Patients exhibited myoclonic, GTC, absence, tonic and focal seizures, and most had associated cognitive decline and/or ataxia. Median time on perampanel was 6 months, most common dose was 6 mg, and overall retention rate was 84%. The responder rate for myoclonic seizures was defined via reduction of days with myoclonic seizures per month. At 6 months, 15 (48.4%) of the 31 patients were classed as myoclonic seizure responders, 10 (32.3%) were myoclonic seizure free, and 39% saw improvements in functional ability. Of 17 patients with GTC seizures at baseline, 9 (53%) were responders at 6 months, and 8 (47.1%) were seizure free. The most frequent side effects were psychiatric disorders, instability, dizziness and irritability, and mostly resolved with dose reduction. Five patients discontinued perampanel due to side effects. CONCLUSIONS: Perampanel caused clinically meaningful improvements in patients with drug-resistant myoclonic seizures. It was generally well tolerated, but psychiatric and neurological side effects sometimes required follow-up and dose reduction.

Quantitative EEG Metrics Differ Between Outcome Groups and Change Over the First 72 h in Comatose Cardiac Arrest Patients.

BACKGROUND: Forty to sixty-six percent of patients resuscitated from cardiac arrest remain comatose, and historic outcome predictors are unreliable. Quantitative spectral analysis of continuous electroencephalography (cEEG) may differ between patients with good and poor outcomes. METHODS: Consecutive patients with post-cardiac arrest hypoxic-ischemic coma undergoing cEEG were enrolled. Spectral analysis was conducted on artifact-free contiguous 5-min cEEG epochs from each hour. Whole band (1-30 Hz), delta (δ, 1-4 Hz), theta (θ, 4-8 Hz), alpha (α, 8-13 Hz), beta (ß, 13-30 Hz), α/δ power ratio, percent suppression, and variability were calculated and correlated with outcome. Graphical patterns of quantitative EEG (qEEG) were described and categorized as correlating with outcome. Clinical outcome was dichotomized, with good neurologic outcome being consciousness recovery. RESULTS: Ten subjects with a mean age = 50 yrs (range = 18-65) were analyzed. There were significant differences in total power (3.50 [3.30-4.06] vs. 0.68 [0.52-1.02], p = 0.01), alpha power (1.39 [0.66-1.79] vs 0.27 [0.17-0.48], p < 0.05), delta power (2.78 [2.21-3.01] vs 0.55 [0.38-0.83], p = 0.01), percent suppression (0.66 [0.02-2.42] vs 73.4 [48.0-97.5], p = 0.01), and multiple measures of variability between good and poor outcome patients (all values median [IQR], good vs. poor). qEEG patterns with high or increasing power or large power variability were associated with good outcome (n = 6). Patterns with consistently low or decreasing power or minimal power variability were associated with poor outcome (n = 4). CONCLUSIONS: These preliminary results suggest qEEG metrics correlate with outcome. In some patients, qEEG patterns change over the first three days post-arrest.

[Post anoxia impairment of autobiographical memory and time estimation]. / Déficit de mémoire autobiographique et d'estimation du temps après une anoxie cérébrale.

A case of episodic amnesia with impairment of time perception is described; it illustrates the link between time perception and autobiographical memory. This woman suffered from a Sheehan syndrome with anoxia at the age of 36 and since that date has had a strong and isolated difficulty to estimate the date and duration of events in a range of weeks, months or years. Conversely, short duration time spans are correctly evaluated. The patient's complaints also involve episodic memory. She reports many events from her biography very imprecisely while the semantic autobiographical data are preserved. The patient has difficulty in recalling the date of public events and the period of celebrity of well-known people. That observation confirms the specificity of time organization for long periods and the link with the episodic memory where the context of the dating task is crucial. The results are discussed in reference to autobiographical memory that involves mental wandering in time-space and the constitution of self over a time continuum.

Impact of inhaled sedation on delirium incidence and neurological outcome after cardiac arrest - A propensity-matched control study (Isocare).

RATIONALE: Poor neurological outcome is common following a cardiac arrest. The use of volatile anesthetic agents has been proposed during post-resuscitation to improve outcome. OBJECTIVES: To determine the effects of inhaled isoflurane on neurological outcome, delirium incidence, ICU length-of-stay, ventilation duration, mortality during post-resuscitation care of ICU patients. PATIENTS: 510 patients were admitted within our medical ICU following a cardiac arrest during the study period, 401 of them being sedated using intravenous sedation prior to 2017 and 109 of them using inhaled isoflurane according to a standardized protocol following 2017. RESULTS: Matched-pair analysis depicted a delirium incidence decrease, without improved neurologic outcome on ICU discharge (CPC ≤ 2) for isoflurane patients (16.1% vs 32.2%, p 0.03 and 29% vs 23%, p 0.47, respectively). Ventilation duration and ICU length of stay were shorter for isoflurane patients (78 vs 167 h, p 0.01 and 7.9 vs 8.5 days, p 0.01 respectively). Isoflurane had no impact on mortality. CONCLUSION: In this propensity-matched control study, isoflurane sedation during the post-resuscitation care of ICU patients was associated with a lower incidence of delirium, a shorter duration of mechanical ventilation and a reduced ICU length of stay. Prospective data are needed before its widespread use.

Interrogating the performance and microbial ecology of an enhanced biological phosphorus removal/post-anoxic denitrification process at bench and pilot scales.

Research focused on interrogating post-anoxic enhanced biological phosphorus removal (EBPR) at bench and pilot scales. Average bench-scale effluent ranged from 0.33 to 1.4 mgP/L, 0.35 to 3.7 mgNH3 -N/L, and 1.1 to 3.9 mgNOx -N/L. Comparatively, the pilot achieved effluent (50th percentile/average) of 0.13/0.2 mgP/L, 9.7/8.2 mgNH3 -N/L, and 0.38/3.3 mgNOx -N/L under dynamic influent and environmental conditions. For EBPR process monitoring, P:C ratio data indicated that 0.2-0.4 molP/molC will result in stable EBPR; relatedly, a target design influent volatile fatty acid (VFA):P ratio would exceed 15 mgCOD/mgP. Post-anoxic EBPR was enriched for Nitrobacter spp. at 1.70%-20.27%, with Parcubacteria also dominating; the former is putatively associated with nitritation and the latter is a putative fermenting heterotrophic organism. Post-anoxic specific denitrification rates (SDNRs) (20°C) ranged from 0.70 to 3.10 mgN/gVSS/h; there was a strong correlation (R2 = 0.94) between the SDNR and %Parcubacteria for systems operated at a 20-day solids residence time (SRT). These results suggest that carbon substrate potentially generated by this putative fermenter may enhance post-anoxic EBPR. PRACTITIONER POINTS: Post-anoxic EBPR can achieve effluent of <0.2 mgP/L and <12 mgN/L. The P:C and VFA:P ratios can be predictive for EBPR process monitoring. Post-anoxic EBPR was enriched for Nitrobacter spp. over Nitrospira spp. and also for Parcubacteria, which is a putative fermenting heterotrophic organism. Post-anoxic specific denitrification rates (20°C) ranged from 0.70 to 3.10 mgN/gVSS/h. BLASTn analysis of 16S rDNA PAO primer set was shown to be improved to 93.8% for Ca. Accumulibacter phosphatis and 73.2%-94.0% for all potential PAOs.

Epileptiform patterns predicting unfavorable outcome in postanoxic patients: A matter of time?

OBJECTIVE: Historically, epileptiform malignant EEG patterns (EMPs) have been considered to anticipate an unfavorable outcome, but an increasing amount of evidence suggests that they are not always or invariably associated with poor prognosis. We evaluated the prognostic significance of an EMP onset in two different timeframes in comatose patients after cardiac arrest (CA): early-EMPs and late-EMPs, respectively. METHODS: We included all comatose post-CA survivors admitted to our intensive care unit (ICU) between 2016 and 2018 who underwent at least two 30-minute EEGs, collected at T0 (12-36 h after CA) and T1 (36-72 h after CA). All EEGs recordings were re-analyzed following the 2021 ACNS terminology by two senior EEG specialists, blinded to outcome. Malignant EEGs with abundant sporadic spikes/sharp waves, rhythmic and periodic patterns, or electrographic seizure/status epilepticus, were included in the EMP definition. The primary outcome was the cerebral performance category (CPC) score at 6 months, dichotomized as good (CPC 1-2) or poor (CPC 3-5) outcome. RESULTS: A total of 58 patients and 116 EEG recording were included in the study. Poor outcome was seen in 28 (48%) patients. In contrast to late-EMPs, early-EMPs were associated with a poor outcome (p = 0.037), persisting after multiple regression analysis. Moreover, a multivariate binomial model coupling the timing of EMP onset with other EEG predictors such as T1 reactivity and T1 normal voltage background can predict outcome in the presence of an otherwise non-specific malignant EEG pattern with quite high specificity (82%) and moderate sensitivity (77%). CONCLUSIONS: The prognostic significance of EMPs seems strongly time-dependent and only their early-onset may be associated with an unfavorable outcome. The time of onset of EMP combined with other EEG features could aid in defining prognosis in patients with intermediate EEG patterns.

Prognostic value of electroencephalographic paroxysms in post-anoxic coma: A new regularity EEG-based score.

OBJECTIVES: Several electroencephalographic (EEG) features -mainly the reactivity of background activity-have been suggested as reliable predictors of outcome for patients with post-anoxic coma (PAC). However, EEG in PAC often contains abundant EEG paroxysms (EP) that may hinder the detection of background EEG activity. We aimed to identify the features, among the different paroxysmal and non-paroxysmal EEG patterns, that may predict the outcome of patients with PAC. METHODS: We retrospectively reviewed the clinical and EEG characteristics of 67 patients with PAC and selected those with abundant EP. We classified EP according to several features and assessed their prognostic value for survival at 15 days. We calculated a global regularity score, as the sum of the value (1 if regular, 0 if not) attributed to each of 4 features of EP (duration, morphology, amplitude, and frequency). RESULTS: The 35 patient-group with abundant EP showed a higher mortality than the group without abundant EP. Among 12 features of EP, four regularity features (regularity of EP duration, morphology, amplitude, and global regularity score) had a poor prognostic value. A global regularity score ≥ 3 showed a positive predictive value of 100 % for a poor outcome and a negative predictive value of 54 %, with good interrater consistency (Cohen's kappa = .63). CONCLUSIONS: The presence of EP and their regularity features in PAC patients are strongly associated with poor outcome. We propose a global regularity score, easily derived from visual EEG inspection, that may be a reliable prognostic tool for these patients. Prospective and larger studies are needed to confirm these findings.

Investigating the use of anaerobically stored carbon in post-anoxic denitrification.

Significant methanol savings are hypothesized to result from anaerobic storage of internal carbon that is used for post-anoxic denitrification. An investigation into this internal carbon-driven denitrification was performed via a series of batch tests using biomass from Hampton Roads Sanitation District's (HRSD's) water resource recovery facilities (WRRFs): the Virginia Initiative Plant (VIP), Nansemond Plant (NP), and Army Base (AB) Treatment Plant. Internal carbon specific denitrification rates (SDNRs) increased during winter, by as much as 1 mg N/g MLVSS/h for VIP. Increasing the aeration time by 2-4 h lowered the SDNR by an average of 0.21-0.35 mg N/g MLVSS/h. No internal carbon denitrification was observed for biomass from non-nitrifying/denitrifying, biological phosphorus removal (bio-P) WRRFs. The increase in internal carbon SDNRs when the anaerobic acetate dose increased from 20 to 100 mg COD/L ranged from 0.06 to 0.28 mg N/g MLVSS/h. Higher phosphorus uptake rates were found to correlate to higher internal carbon SDNRs, but no significant post-anoxic P uptake was observed. The first steps are taken towards developing a strategy for full-scale implementation of this relatively novel type of denitrification by evaluating how some factors affect its occurrence. PRACTITIONER POINTS: Significant methanol savings at a full-scale facility may result from use of internally stored carbon for post-anoxic denitrification. Short aerobic HRTs and high anaerobic zone VFA loading increase the post-anoxic internal carbon-driven denitrification. Non-nitrifying, bio-P biomass is not capable of internal carbon-driven denitrification. Internal carbon-driven denitrification is correlated with the activity of polyphosphate accumulating organisms.

Advancements of sequencing batch biofilm reactor for slaughterhouse wastewater assisted with response surface methodology.

Slaughterhouse wastewater (SWW) contains a significant volume of highly polluted organic wastes. These include blood, fat, soluble proteins, colloidal particles, suspended materials, meat particles, and intestinal undigested food that consists of higher concentrations of organics such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), nitrogen and phosphorus hence an efficient treatment is required before discharging into the water bodies. The effluent concentrations and performance of simultaneous sequential batch biofilm reactor (SBBR) with recycled plastic carrier media support are better than the local single-stage sequential batch reactor (SBR), which is lacking in the literature in terms of COD, NH3, NO3, and PO4 treatment efficiency. The present study reports a novel strategy to remove the above mentioned contaminants using an intermittently aerated SBBR with recycled plastic carrier media support along with simultaneous nitrification and denitrification. The central composite design was evaluated to optimize the treatment performance of seven different process variables including; different alternating conditions (Oxic/anoxic) for aeration cycles (3/2 h in a 6 h cycle, 6/5 h in a 12 h cycle and 9/8 h in an 18 h cycle) and hydraulic retention time (6, 12 and 18 h). The average removal efficiencies are 94.5% for NH3, 93% for NO3 and 90.1% for PO4, and 99% for COD. The study reveals that the denitrification in the post-anoxic phase was more efficient than the pre-anoxic phase for pollutant removal and maintaining higher quality effluent. The effluent concentrations and performance of simultaneous SBBR with recycled polyethylene carrier support media were better than local SBR system in terms of COD, NH3, NO3 and PO4 treatment efficiency. Results stipulated the suitability of SBBR for wastewater treatment and reusability as a sustainable approach for wastewater management under optimum conditions.

Strengthening anoxic glycogen consumption in SNEDPR-CW as a strategy to control PAO-GAO competition under carbon limited condition.

Cooperation between Phosphate and Glycogen Accumulating Organisms (PAOs and GAOs) plays a pivotal role in nutrients removal in simultaneous nitrification endogenous denitrification and phosphorous removal (SNEDPR) systems. Recent findings have expanded the application of SNEDPR from activated sludge system to constructed wetland (CW). However, how to regulate competition between PAOs and GAOs in SNEDPR-based CW is still unclear. Here we showed that, GAOs could easily gain dominance over PAOs in SNEDPR-CW under alternating anaerobic/aerobic (A/O) operational mode. Shortening aerobic hydraulic retention time (HRT) at low oxygen concentration was benefit for simultaneous nitrification endogenous denitrification (SNED) and denitrifying dephosphatation but would reduce the overall phosphorus uptake rate and lead to high phosphorus effluent concentrations. Extended aerobic HRT promoted the proliferation of aerobic GAOs over PAOs, decreasing both enhanced biological phosphorus removal (EBPR) and SNED performance. Surprisingly, by switching the operation of system to alternating anaerobic/aerobic/anoxic (A/O/A) mode, an extraordinary nutrients removal performance with mean nitrogen and phosphorus removal efficiency of 84.57% and 89.37% was achieved under carbon sources limited condition. Stoichiometric analysis demonstrated that adding anoxic stage strengthened the intracellular glycogen oxidization of GAOs for denitrification which compromised its subsequent anaerobic carbon sources uptake and PHA storage and provided sufficient carbon sources for PAOs. Microbial community analysis showed that numerical ratio of GAOs to PAOs decreased from 6.67 under A/O to 4.89 under A/O/A mode, which further indicated strengthening glycogen denitrification of GAOs should be an effective way to regulate microbial competition in order to obtain a desired nutrients removal performance in SNEDPR-CW.

Early vigabatrin augmenting GABA-ergic pathways in post-anoxic status epilepticus (VIGAB-STAT) phase IIa clinical trial study protocol.

BACKGROUND: Nearly one in three unconscious cardiac arrest survivors experience post-anoxic status epilepticus (PASE). Historically, PASE has been deemed untreatable resulting in its exclusion from status epilepticus clinical trials. However, emerging reports of survivors achieving functional independence following early and aggressive treatment of PASE challenged this widespread therapeutic nihilism. In the absence of proven therapies specific to PASE, standard of care treatment leans on general management strategies for status epilepticus. Vigabatrin-an approved therapy for refractory focal-onset seizures in adults-inhibits the enzyme responsible for GABA catabolism, increases brain GABA levels and may act synergistically with anesthetic agents to abort seizures. Our central hypothesis is that early inhibition of GABA breakdown is possible in the post-cardiac arrest period and may be an effective adjunctive treatment in PASE. METHODS: This is a phase IIa, single-center, open-label, pilot clinical trial with blinded outcome assessment, of a single dose of vigabatrin in 12 consecutive PASE subjects. Subjects will receive a single loading dose of 4500 mg of vigabatrin (or dose adjusted in moderate and severe renal impairment) via enteric tube within 48 h of PASE onset. Vigabatrin levels will be monitored at 0- (baseline), 0.5-, 1-, 2-, 3-, 6-, 12-, 24-, 48-, 72- and 168-h (7 days) post-vigabatrin. Serum biomarkers of neuronal injury will be measured at 0-, 24-, 48-, 72- and 96-h post-vigabatrin. The primary feasibility endpoint is the proportion of enrolled subjects among identified eligible subjects receiving vigabatrin within 48 h of PASE onset. The primary pharmacokinetic endpoint is the measured vigabatrin level at 3 h post-administration. Descriptive statistics with rates and proportions will be obtained regarding feasibility outcomes, along with the noncompartmental method for pharmacokinetic analyses. The area under the vigabatrin concentration-time curve in plasma from zero to the time of the last quantifiable concentration (AUC0-tlqc) will be calculated to estimate dose-linear pharmacokinetics. PERSPECTIVE: Vigabatrin demonstrates high potential for synergism with current standard of care therapies. Demonstration of the feasibility of vigabatrin administration and preliminary safety in PASE will pave the way for future efficacy and safety trials of this pharmacotherapeutic. Trial Registration NCT04772547.

Accuracy of EEG Biomarkers in the Detection of Clinical Outcome in Disorders of Consciousness after Severe Acquired Brain Injury: Preliminary Results of a Pilot Study Using a Machine Learning Approach.

Accurate outcome detection in neuro-rehabilitative settings is crucial for appropriate long-term rehabilitative decisions in patients with disorders of consciousness (DoC). EEG measures derived from high-density EEG can provide helpful information regarding diagnosis and recovery in DoC patients. However, the accuracy rate of EEG biomarkers to predict the clinical outcome in DoC patients is largely unknown. This study investigated the accuracy of psychophysiological biomarkers based on clinical EEG in predicting clinical outcomes in DoC patients. To this aim, we extracted a set of EEG biomarkers in 33 DoC patients with traumatic and nontraumatic etiologies and estimated their accuracy to discriminate patients' etiologies and predict clinical outcomes 6 months after the injury. Machine learning reached an accuracy of 83.3% (sensitivity = 92.3%, specificity = 60%) with EEG-based functional connectivity predicting clinical outcome in nontraumatic patients. Furthermore, the combination of functional connectivity and dominant frequency in EEG activity best predicted clinical outcomes in traumatic patients with an accuracy of 80% (sensitivity = 85.7%, specificity = 71.4%). These results highlight the importance of functional connectivity in predicting recovery in DoC patients. Moreover, this study shows the high translational value of EEG biomarkers both in terms of feasibility and accuracy for the assessment of DoC.

Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management.

BACKGROUND: Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients' outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome. METHODS: Retrospective analysis of prospectively collected data. INCLUSION CRITERIA: adult cardiac arrest survivors treated by targeted temperature management (TTM). EXCLUSION CRITERIA: trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3-5 assessed 3 months after CA defined unfavorable neurological outcome (UO). RESULTS: We included 50 patients (Jan 2015-Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10-35] min. HT (core body temperature 33.7 [33.2-34] °C) lasted for 24 [23-28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6-37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11-0.58] vs. 0.58 [0.30-0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43-0.83] vs. 0.31 [- 0.01-0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO. CONCLUSIONS: CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.

Multimodal Approach to Predict Neurological Outcome after Cardiac Arrest: A Single-Center Experience.

Introduction: The aims of this study were to assess the concordance of different tools and to describe the accuracy of a multimodal approach to predict unfavorable neurological outcome (UO) in cardiac arrest patients. Methods: Retrospective study of adult (>18 years) cardiac arrest patients who underwent multimodal monitoring; UO was defined as cerebral performance category 3-5 at 3 months. Predictors of UO were neurological pupillary index (NPi) ≤ 2 at 24 h; highly malignant patterns on EEG (HMp) within 48 h; bilateral absence of N20 waves on somato-sensory evoked potentials; and neuron-specific enolase (NSE) > 75 µg/L. Time-dependent decisional tree (i.e., NPi on day 1; HMp on day 1-2; absent N20 on day 2-3; highest NSE) and classification and regression tree (CART) analysis were used to assess the prediction of UO. Results: Of 137 patients, 104 (73%) had UO. Abnormal NPi, HMp on day 1 or 2, the bilateral absence of N20 or NSE >75 mcg/L had a specificity of 100% to predict UO. The presence of abnormal NPi was highly concordant with HMp and high NSE, and absence of N20 or high NSE with HMp. However, HMp had weak to moderate concordance with other predictors. The time-dependent decisional tree approach identified 73/103 patients (70%) with UO, showing a sensitivity of 71% and a specificity of 100%. Using the CART approach, HMp on EEG was the only variable significantly associated with UO. Conclusions: This study suggests that patients with UO had often at least two predictors of UO, except for HMp. A multimodal time-dependent approach may be helpful in the prediction of UO after CA. EEG should be included in all multimodal prognostic models.

EEG patterns and their correlations with short- and long-term mortality in patients with hypoxic encephalopathy.

OBJECTIVE: To analyze the association between electroencephalographic (EEG) patterns and overall, short- and long-term mortality in patients with hypoxic encephalopathy (HE). METHODS: Retrospective, mono-center analysis of 199 patients using univariate log-rank tests (LR) and multivariate cox regression (MCR). RESULTS: Short-term mortality, defined as death within 30-days post-discharge was 54.8%. Long-term mortality rates were 69.8%, 71.9%, and 72.9%, at 12-, 24-, and 36-months post-HE, respectively. LR revealed a significant association between EEG suppression (SUP) and short-term mortality, and identified low voltage EEG (LV), burst suppression (BSP), periodic discharges (PD) and post-hypoxic status epilepticus (PSE) as well as missing (aBA) or non-reactive background activity (nrBA) as predictors for overall, short- and long-term mortality. MCR indicated SUP, LV, BSP, PD, aBA and nrBA as significantly associated with overall and short-term mortality to varying extents. LV and BSP were significant predictors for long-term mortality in short-term survivors. Rhythmic delta activity, stimulus induced rhythmic, periodic or ictal discharges and sharp waves were not significantly associated with a higher mortality. CONCLUSION: The presence of several specific EEG patterns can help to predict overall, short- and long-term mortality in HE patients. SIGNIFICANCE: The present findings may help to improve the challenging prognosis estimation in HE patients.

A multimodal sevoflurane-based sedation regimen in combination with targeted temperature management in post-cardiac arrest patients reduces the incidence of delirium: An observational propensity score-matched study.

BACKGROUND: Recent studies suggest that volatile anaesthetics are safe, efficient, and reliable alternatives to the use of intravenous anaesthetics for out-of-hospital cardiac arrest (OHCA) patients admitted to the intensive care unit (ICU). We hypothesised that volatile anaesthetics may reduce the incidence of delirium rather than intravenous sedatives. This retrospective study aimed to investigate whether sevoflurane combined with higher targeted temperature management could decrease the incidence of delirium when compared with intravenous anaesthetics with lower targeted temperature management. METHODS: Using a propensity score-matched analysis, we retrospectively compared a target temperature management (32-34 °C) method along with intravenous sedation (TTM-33/IV) and a modified target temperature management (34-36 °C) method along with sevoflurane sedation (mTTM-36/sevo). We used the confusion assessment method for the ICU to measure the incidence of delirium. We calculated the time-dependent risk on delirium using the multivariate Cox regression model. RESULTS: The incidence of delirium was significantly lower (p = 0.001) in OHCA patients of the mTTM-36/sevo group (9/56, 16.1%) than in those of the TTM-33/IV group (25/67, 37.3%). Mechanical ventilation and lengths of stay in the ICU (p < 0.001) and hospital stay (p = 0.04) were shorter in the mTTM-36/sevo group. Patients in the TTM-33/IV group required more midazolam, propofol, and fentanyl. We observed no significant difference in mortality. CONCLUSION: A multimodal sevoflurane-based sedation regimen together with targeted temperature management resulted in a lower incidence of delirium and a shorter duration for mechanical ventilation and ICU length of stay than did the treatment with intravenous sedation combined with the classical cooling protocol.