Quantitative Characterization of Rhythmic and Periodic EEG Patterns in Patients in a Coma After Cardiac Arrest and Association With Outcome.

OBJECTIVES: Rhythmic and periodic patterns (RPPs) on EEG in patients in a coma after cardiac arrest are associated with a poor neurologic outcome. We characterize RPPs using qEEG in relation to outcomes. METHODS: Post hoc analysis was conducted on 172 patients in a coma after cardiac arrest from the TELSTAR trial, all with RPPs. Quantitative EEG included corrected background continuity index (BCI*), relative discharge power (RDP), discharge frequency, and shape similarity. Neurologic outcomes at 3 months after arrest were categorized as poor (CPC = 3-5) or good (CPC = 1-2). RESULTS: A total of 16 patients (9.3%) had a good outcome. Patients with good outcomes showed later RPP onset (28.5 vs 20.1 hours after arrest, p < 0.05) and higher background continuity at RPP onset (BCI* = 0.83 vs BCI* = 0.59, p < 0.05). BCI* <0.45 at RPP onset, maximum BCI* <0.76, RDP >0.47, or shape similarity >0.75 were consistently associated with poor outcomes, identifying 36%, 22%, 40%, or 24% of patients with poor outcomes, respectively. In patients meeting both BCI* >0.44 at RPP onset and BCI* >0.75 within 72 hours, the probability of good outcomes doubled to 18%. DISCUSSION: Sufficient EEG background continuity before and during RPPs is crucial for meaningful recovery. Background continuity, discharge power, and shape similarity can help select patients with relevant chances of recovery and may guide treatment. TRIAL REGISTRATION INFORMATION: February 4, 2014, ClinicalTrial.gov, NCT02056236.

Plasma Neurofilament Light Chain as a Biomarker for Poor Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Neurofilament light chain (NfL), a biomarker reflecting neuro-axonal damage, may be useful in improving clinical outcome prediction after aneurysmal subarachnoid hemorrhage (aSAH). We explore the robust and additional value of NfL to neurologic and radiologic grading scales in predicting poor outcome after aSAH. METHODS: In this prospective cohort study conducted in a single tertiary center, blood samples were collected of aSAH patients within 24 hours after ictus and before endovascular/surgical intervention. The primary endpoint was poor outcome at 6 months' follow-up. Receiver operating curves (ROC), area under the curve (AUC, 95% CI) and model-fit (Nagelkerke R2) were calculated for NfL, neurologic grading scale (WFNS), modified Fisher, age ,and sex. A combined ROC and AUC were calculated for variables with an AUC ≥ 0.70. RESULTS: A total of 66 (42%) had poor outcome. The AUC of NfL for poor outcome was 0.70 (0.62-0.78). Combining NfL and WFNS resulted in a slightly higher model fit and not-significantly higher AUC for predicting poor outcome (R2 0.51; AUC 0.86, 0.80-0.92) compared with WFNS alone. When patients were stratified according to hemorrhage severity, median NfL [IQR] levels were significantly higher in poor grade (14 [7-32] pg/mL) than good grade patients (7 [5-14] pg/mL). Within poor grade patients, median NfL [IQR] levels were significantly higher in non-survivors (19 [11-36] pg/mL) than survivors (7 [6-13] pg/mL). CONCLUSION: In the entire aSAH cohort, plasma NfL has an acceptable predictive performance but does not improve clinical outcome prediction. However, NfL may have potential value in subgroups based on hemorrhage severity.

Clinical observation: Rhythmic and periodic EEG patterns in postanoxic coma can possibly be related to propofol discontinuation.

OBJECTIVES: To investigate whether rhythmic/periodic EEG patterns (RPP) appearing after propofol discontinuation are more likely to be related to the elimination phase of propofol, or are an expression of severe brain damage. METHODS: In a retrospective cohort of comatose postanoxic patients, EEG was assessed one hour before (baseline) and on hour after discontinuation of propofol. Presence and duration of RPP were related to (changes in) EEG background pattern and duration of sedation. RESULTS: In eleven (of 36 eligible) patients RPP appeared after propofol discontinuation and disappeared in seven of these patients within one hour. A continuous background pattern at baseline and shorter duration of propofol infusion seemed associated with (earlier) spontaneous disappearance of RPP. In ten patients with RPP at baseline, the EEG did not change, and in one patient it changed into burst-suppression. CONCLUSION: Our findings suggest that RPP after propofol discontinuation could be propofol-related. DISCUSSION: RPP might be related to propofol discontinuation rather than an expression of severe brain damage, especially in case of, and congruent with, a continuous pattern at the time of propofol discontinuation. This opens a new insight in this phenomenon and its transient nature. In clinical practice, we suggest to consider the timing of propofol discontinuation when assessing the EEG signal in postanoxic patients.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Prevalence and trajectories of neuropsychological post-COVID-19 symptoms in initially hospitalized patients.

OBJECTIVE: To investigate the prevalence and trajectories of post-COVID-19 neuropsychological symptoms. DESIGN: Prospective longitudinal multicentre cohort study. SUBJECTS: A total of 205 patients initially hospitalized with SARS-CoV-2 (COVID-19). METHODS: Validated questionnaires were administered at 9 months (T1) and 15 months (T2) post-hospital discharge to assess fatigue, cognitive complaints, insomnia, anxiety, depression, and post-traumatic stress symptoms. RESULTS: Analyses included 184 out of 205 patients. Approximately 50% experienced high cognitive complaints at T1 and T2, while severe fatigue affected 52.5% at T1 and 55.6% at T2. Clinically relevant insomnia scores were observed in 25% of patients at both time-points. Clinically relevant anxiety scores were present in 18.3% at T1 and 16.7% at T2, depression in 15.0% at T1 and 18.9% at T2, and PTSD in 12.4% at T1 and 11.8% at T2. Most symptoms remained stable, with 59.2% of patients experiencing at least 1 persistent symptom. In addition, 31.5% of patients developed delayed-onset symptoms. CONCLUSION: Post-COVID-19 cognitive complaints and fatigue are highly prevalent and often persist. A subgroup develops delayed symptoms. Emotional distress is limited. Screening can help identify most patients experiencing long-term problems. Future research should determine risk factors for persistent and delayed onset symptoms.

A Biopsychosocial Approach to Persistent Post-COVID-19 Fatigue and Cognitive Complaints: Results of the Prospective Multicenter NeNeSCo Study.

OBJECTIVE: To evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints. DESIGN: Prospective, multicenter cohort study. SETTING: Six Dutch hospitals. PARTICIPANTS: 205 initially hospitalized (March-June 2020), confirmed patients with SARS-CoV-2, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, magnetic resonance imaging (MRI) contraindication, or severe neurologic damage post-hospital discharge (N=205). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Nine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from medical dossiers. Hierarchical regression analyses were performed on fatigue severity (Fatigue Severity Scale; FSS) and cognitive complaints (Cognitive Consequences after Intensive Care Admission; CLC-IC; dichotomized into CLC-high/low). Variable blocks: (1) Demographic and premorbid factors (sex, age, education, comorbidities), (2) Illness severity (ICU/general ward, PROMIS physical functioning [PROMIS-PF]), (3) Neuro-cognitive factors (self-reported neurological symptoms, MRI abnormalities, cognitive performance), (4) Psychological and social factors (Hospital Anxiety and Depression Scale [HADS], Utrecht Coping List, Social Support List), and (5) Fatigue or cognitive complaints. RESULTS: The final models explained 60% (FSS) and 48% (CLC-IC) variance, with most blocks (except neuro-cognitive factors for FSS) significantly contributing. Psychological and social factors accounted for 5% (FSS) and 11% (CLC-IC) unique variance. Higher FSS scores were associated with younger age (P=.01), lower PROMIS-PF (P<.001), higher HADS-Depression (P=.03), and CLC-high (P=.04). Greater odds of CLC-high were observed in individuals perceiving more social support (OR=1.07, P<.05). CONCLUSIONS: Results show that psychological and social factors add to biomedical factors in explaining persistent post-COVID-19 fatigue and cognitive complaints. Objective neuro-cognitive factors were not associated with symptoms. Findings highlight the importance of multidomain treatment, including psychosocial care, which may not target biologically-rooted symptoms directly but may reduce associated distress.

Optimal Design of Clinical Trials Involving Persons with Disorders of Consciousness.

BACKGROUND: Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC. METHODS: The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC. RESULTS: There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC. CONCLUSIONS: Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care.

Predicting 30-day mortality in intensive care unit patients with ischaemic stroke or intracerebral haemorrhage.

BACKGROUND: Stroke patients admitted to an intensive care unit (ICU) follow a particular survival pattern with a high short-term mortality, but if they survive the first 30 days, a relatively favourable subsequent survival is observed. OBJECTIVES: The development and validation of two prognostic models predicting 30-day mortality for ICU patients with ischaemic stroke and for ICU patients with intracerebral haemorrhage (ICH), analysed separately, based on parameters readily available within 24 h after ICU admission, and with comparison with the existing Acute Physiology and Chronic Health Evaluation IV (APACHE-IV) model. DESIGN: Observational cohort study. SETTING: All 85 ICUs participating in the Dutch National Intensive Care Evaluation database. PATIENTS: All adult patients with ischaemic stroke or ICH admitted to these ICUs between 2010 and 2019. MAIN OUTCOME MEASURES: Models were developed using logistic regressions and compared with the existing APACHE-IV model. Predictive performance was assessed using ROC curves, calibration plots and Brier scores. RESULTS: We enrolled 14 303 patients with stroke admitted to ICU: 8422 with ischaemic stroke and 5881 with ICH. Thirty-day mortality was 27% in patients with ischaemic stroke and 41% in patients with ICH. Important factors predicting 30-day mortality in both ischaemic stroke and ICH were age, lowest Glasgow Coma Scale (GCS) score in the first 24 h, acute physiological disturbance (measured using the Acute Physiology Score) and the application of mechanical ventilation. Both prognostic models showed high discrimination with an AUC 0.85 [95% confidence interval (CI), 0.84 to 0.87] for patients with ischaemic stroke and 0.85 (0.83 to 0.86) in ICH. Calibration plots and Brier scores indicated an overall good fit and good predictive performance. The APACHE-IV model predicting 30-day mortality showed similar performance with an AUC of 0.86 (95% CI, 0.85 to 0.87) in ischaemic stroke and 0.87 (0.86 to 0.89) in ICH. CONCLUSION: We developed and validated two prognostic models for patients with ischaemic stroke and ICH separately with a high discrimination and good calibration to predict 30-day mortality within 24 h after ICU admission. TRIAL REGISTRATION: Trial registration: Dutch Trial Registry ( https://www.trialregister.nl/ ); identifier: NTR7438.

Neurobiological basis and risk factors of persistent fatigue and concentration problems after COVID-19: study protocol for a prospective case-control study (VeCosCO).

INTRODUCTION: The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation, could be the underlying pathophysiological mechanism for persisting complaints.To unravel factors associated with persisting complaints, VeCosCO will compare individuals with and without persistent fatigue and cognitive complaints >3 months after infection with SARS-CoV-2. The study consists of two work packages. The first work package aims to (1) investigate the relation between persisting complaints and neuropsychological functioning; (2) determine risk factors and at-risk phenotypes for the development of persistent fatigue and cognitive complaints, including the presence of postexertional malaise and (3) describe consequences of persistent complaints on quality of life, healthcare consumption and physical functioning. The second work package aims to (1) determine the presence of neuroinflammation with [18F]DPA-714 whole-body positron emission tomography (PET) scans in patients with persisting complaints and (2) explore the relationship between (neuro)inflammation and brain structure and functioning measured with MRI. METHODS AND ANALYSIS: This is a prospective case-control study in participants with and without persistent fatigue and cognitive complaints, >3 months after laboratory-confirmed SARS-CoV-2 infection. Participants will be mainly included from existing COVID-19 cohorts in the Netherlands covering the full spectrum of COVID-19 acute disease severity. Primary outcomes are neuropsychological functioning, postexertional malaise, neuroinflammation measured using [18F]DPA-714 PET, and brain functioning and structure using (f)MRI. ETHICS AND DISSEMINATION: Work package 1 (NL79575.018.21) and 2 (NL77033.029.21) were approved by the medical ethical review board of the Amsterdam University Medical Centers (The Netherlands). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in peer-reviewed journals and shared with the key population.

Value of EEG in outcome prediction of hypoxic-ischemic brain injury in the ICU: A narrative review.

Prognostication of comatose patients after cardiac arrest aims to identify patients with a large probability of favourable or unfavouble outcome, usually within the first week after the event. Electroencephalography (EEG) is a technique that is increasingly used for this purpose and has many advantages, such as its non-invasive nature and the possibility to monitor the evolution of brain function over time. At the same time, use of EEG in a critical care environment faces a number of challenges. This narrative review describes the current role and future applications of EEG for outcome prediction of comatose patients with postanoxic encephalopathy.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Randomized Controlled Trials in ICU in the Four Highest-Impact General Medicine Journals.

OBJECTIVE: To study ICU trials published in the four highest-impact general medicine journals by comparing them with concurrently published non-ICU trials in the same journals. DATA SOURCES: PubMed was searched for randomized controlled trials (RCTs) published between January 2014 and October 2021 in the New England Journal of Medicine , The Lancet , the Journal of the American Medical Association , and the British Medical Journal. STUDY SELECTION: Original RCT publications investigating any type of intervention in any patient population. DATA EXTRACTION: ICU RCTs were defined as RCTs exclusively including patients admitted to the ICU. Year and journal of publication, sample size, study design, funding source, study outcome, type of intervention, Fragility Index (FI), and Fragility Quotient were collected. DATA SYNTHESIS: A total of 2,770 publications were screened. Of 2,431 original RCTs, 132 (5.4%) were ICU RCTs, gradually rising from 4% in 2014 to 7.5% in 2021. ICU RCTs and non-ICU RCTs included a comparable number of patients (634 vs 584, p = 0.528). Notable differences for ICU RCTs were the low occurrence of commercial funding (5% vs 36%, p < 0.001), the low number of RCTs that reached statistical significance (29% vs 65%, p < 0.001), and the low FI when they did reach significance (3 vs 12, p = 0.008). CONCLUSIONS: In the last 8 years, RCTs in ICU medicine made up a meaningful, and growing, portion of RCTs published in high-impact general medicine journals. In comparison with concurrently published RCTs in non-ICU disciplines, statistical significance was rare and often hinged on the outcome events of just a few patients. Increased attention should be paid to realistic expectations of treatment effects when designing ICU RCTs to detect differences in treatment effects that are reliable and clinically relevant.

A Survey on Monitoring and Management of Cerebral Vasospasm and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: The Mantra Study.

INTRODUCTION: Cerebral infarction from delayed cerebral ischemia (DCI) is a leading cause of poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). We performed an international clinical practice survey to identify monitoring and management strategies for cerebral vasospasm associated with DCI in aSAH patients requiring intensive care unit admission. METHODS: The survey questionnaire was available on the European Society of Intensive Care Medicine (May 2021-June 2022) and Neurocritical Care Society (April - June 2022) websites following endorsement by these societies. RESULTS: There were 292 respondents from 240 centers in 38 countries. In conscious aSAH patients or those able to tolerate an interruption of sedation, neurological examination was the most frequently used diagnostic modality to detect delayed neurological deficits related to DCI caused by cerebral vasospasm (278 respondents, 95.2%), while in unconscious patients transcranial Doppler/cerebral ultrasound was most frequently used modality (200, 68.5%). Computed tomography angiography was mostly used to confirm the presence of vasospasm as a cause of DCI. Nimodipine was administered for DCI prophylaxis by the majority of the respondents (257, 88%), mostly by an enteral route (206, 71.3%). If there was a significant reduction in arterial blood pressure after nimodipine administration, a vasopressor was added and nimodipine dosage unchanged (131, 45.6%) or reduced (122, 42.5%). Induced hypertension was used by 244 (85%) respondents as first-line management of DCI related to vasospasm; 168 (59.6%) respondents used an intra-arterial procedure as second-line therapy. CONCLUSIONS: This survey demonstrated variability in monitoring and management strategies for DCI related to vasospasm after aSAH. These findings may be helpful in promoting educational programs and future research.

EEG in a four-electrode frontotemporal montage reliably predicts outcome after cardiac arrest.

AIM: To increase efficiency of continuous EEG monitoring for prognostication of neurological outcome in patients after cardiac arrest, we investigated the reliability of EEG in a four-electrode frontotemporal (4-FT) montage, compared to our standard nine-electrode (9-EL) montage. METHODS: EEG recorded with Ag/AgCl cup-electrodes at 12 and/or 24 h after cardiac arrest of 153 patients was available from a previous study. 220 EEG epochs of 5 minutes were reexamined in a 4-FT montage according to the ACNS criteria. Background classification was compared to the available 9-EL classification using Cohens kappa. Reliability for prognostication was assessed in 151 EEG epochs at 24 h after CA using sensitivity and specificity for prediction of poor (cerebral performance categories (CPC) 3-5) and good (CPC 1-2) neurological outcome. RESULTS: Agreement for EEG background classification between the two montages was substantial with a kappa of 0.85 (95%-CI 0.81-0.90). Specificity for prediction of poor outcome was 100% (95%-CI 95-100) for both montages, sensitivity was 31% (95%-CI 21-43) for the 4-FT montage and 35% (95%-CI 24-47) for the 9-EL montage. Good outcome was predicted with 65% specificity (95%-CI 53-76) and 81% sensitivity (95%-CI 71-89) for the 4-FT montage, similar to the 9-EL montage. CONCLUSION: In this cohort, EEG background patterns determined in a four-electrode frontotemporal montage predict both poor and good outcome after CA with similar reliability. Our results may contribute to decreasing the workload of EEG monitoring in patients after CA without compromising reliability of outcome prediction. However, validation in a larger cohort is necessary, as is a multimodal approach.

Neurological and (neuro)psychological sequelae in intensive care and general ward COVID-19 survivors.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) affects the brain, leading to long-term complaints. Studies combining brain abnormalities with objective and subjective consequences are lacking. Long-term structural brain abnormalities, neurological and (neuro)psychological consequences in COVID-19 patients admitted to the intensive care unit (ICU) or general ward were investigated. The aim was to create a multidisciplinary view on the impact of severe COVID-19 on functioning and to compare long-term consequences between ICU and general ward patients. METHODS: This multicentre prospective cohort study assessed brain abnormalities (3 T magnetic resonance imaging), cognitive dysfunction (neuropsychological test battery), neurological symptoms, cognitive complaints, emotional distress and wellbeing (self-report questionnaires) in ICU and general ward (non-ICU) survivors. RESULTS: In al, 101 ICU and 104 non-ICU patients participated 8-10 months post-hospital discharge. Significantly more ICU patients exhibited cerebral microbleeds (61% vs. 32%, p < 0.001) and had higher numbers of microbleeds (p < 0.001). No group differences were found in cognitive dysfunction, neurological symptoms, cognitive complaints, emotional distress or wellbeing. The number of microbleeds did not predict cognitive dysfunction. In the complete sample, cognitive screening suggested cognitive dysfunction in 41%, and standard neuropsychological testing showed cognitive dysfunction in 12%; 62% reported ≥3 cognitive complaints. Clinically relevant scores of depression, anxiety and post-traumatic stress were found in 15%, 19% and 12%, respectively; 28% experienced insomnia and 51% severe fatigue. CONCLUSION: Coronavirus disease 2019 ICU survivors had a higher prevalence for microbleeds but not for cognitive dysfunction compared to general ward survivors. Self-reported symptoms exceeded cognitive dysfunction. Cognitive complaints, neurological symptoms and severe fatigue were frequently reported in both groups, fitting the post-COVID-19 syndrome.

A Systematic Review of Viscoelastic Testing in Patients with Subarachnoid Hemorrhage.

OBJECTIVE: Bleeding and thromboembolic complications frequently occur after subarachnoid hemorrhage (SAH) and substantially contribute to poor outcome. Viscoelastic testing could be used for detection of coagulopathies after SAH. This review summarizes literature on the usefulness of viscoelastic testing to detect coagulopathy in patients with SAH and explores whether viscoelastic parameters are associated with SAH-related complications and clinical outcome. METHODS: PubMed, Embase, and Google Scholar were systematically searched on August 18, 2022. Two authors independently selected studies that reported viscoelastic testing in patients with SAH and assessed the quality of studies using the Newcastle-Ottawa Scale or a previously reported framework for quality assessment. Data were meta-analyzed if methodologically possible. RESULTS: The search yielded 19 studies (1160 patients with SAH). Pooling of data including all relevant studies was not possible for any of the outcome measurements because of methodological differences. Thirteen of 19 studies evaluated the association of coagulation profiles and SAH, of which 11 studies showed a hypercoagulable profile. Rebleeding was associated with platelet dysfunction, deep venous thrombosis was associated with faster clot initiation, and both delayed cerebral ischemia and poor outcome were associated with increased clot strength. CONCLUSIONS: This explorative review shows that patients with SAH frequently have a hypercoagulable profile. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) parameters are associated with rebleeding, delayed cerebral ischemia, deep venous thrombosis, and poor clinical outcome after SAH; however, more research on the subject is needed. Future studies should focus on determining the optimal time frame and cutoff values for TEG or ROTEM to predict these complications.

Clinical features, etiologies, and outcomes in adult patients with meningoencephalitis requiring intensive care (EURECA): an international prospective multicenter cohort study.

PURPOSE: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. METHODS: We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint. RESULTS: Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78) and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective. CONCLUSION: Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission.

Oxygen Consumption with High-Flow Nasal Oxygen versus Mechanical Ventilation- An International Multicenter Observational Study in COVID-19 Patients (PROXY-COVID).

The COVID-19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4-18.4] versus 2.9 [1.8-4.1] L/minute; mean difference = 11.3 [95% CI 11.0-11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen.

Myoclonus in comatose patients with electrographic status epilepticus after cardiac arrest: Corresponding EEG patterns, effects of treatment and outcomes.

OBJECTIVE: To clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome. DESIGN: Post hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation (TELSTAR) trial. SETTING: Eleven ICUs in the Netherlands and Belgium. PATIENTS: One hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring. INTERVENTIONS: Anti-seizure medication vs no anti-seizure medication in addition to standard care. MEASUREMENTS AND MAIN RESULTS: Of 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16-0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64-9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03-3.32). CONCLUSIONS: Myoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives.