Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE).

BACKGROUND: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. METHODS: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. DISCUSSION: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. TRIAL REGISTRATION: NCT number: NCT05839418.

Violence against healthcare professionals in intensive care units: a systematic review and meta-analysis of frequency, risk factors, interventions, and preventive measures.

BACKGROUND: To assess the frequency, risk factors, consequences, and prevention of violence against healthcare workers in intensive care units. METHODS: PubMed, Scopus, Google Scholar, EMBASE, Cochrane, and Web of Science were searched for studies on violence against healthcare workers in adult intensive care units. Risk factors, patient characteristics, and implications for healthcare workers were collected. Study quality, bias, and level of evidence were assessed using established tools. RESULTS: Seventy-five studies with 139,533 healthcare workers from 32 countries were included. The overall median frequency of violence was 51% (IQR 37-75%). Up to 97% of healthcare workers experienced verbal violence, and up to 82% were victims of physical violence. Meta-analysis of frequency revealed an average frequency of 31% (95% CI 22-41%) for physical violence, 57% for verbal violence (95% CI 48-66%), and 12% for sexual violence (95% CI 4-23%). Heterogeneity was high according to the I2 statistics. Patients were the most common perpetrators (median 56%), followed by visitors (median 22%). Twenty-two studies reported increased risk ratios of up to 2.3 or odds ratios of up to 22.9 for healthcare workers in the ICU compared to other healthcare workers. Risk factors for experiencing violence included young age, less work experience, and being a nurse. Patients who exhibited violent behavior were often male, older, and physically impaired by drugs. Violence was underreported in up to 80% of cases and associated with higher burnout rates, increased anxiety, and higher turnover intentions. Overall the level of evidence was low. CONCLUSIONS: Workplace violence is frequent and underreported in intensive care units, with potential serious consequences for healthcare workers, calling for heightened awareness, screening, and preventive measures. The potential risk factors for violence should be further investigated. SYSTEMATIC REVIEW REGISTRATION: The protocol for this review was registered with Prospero on January 15, 2023 (ID CRD42023388449).

Sex differences in the SOFA score of ICU patients with sepsis or septic shock: a nationwide analysis.

BACKGROUND: The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations. METHODS: Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022. RESULTS: Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3-5.3) vs men 2.7 days (IQR 1.2-6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17). CONCLUSION: Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications.

Efficacy and Tolerability of Intranasal Midazolam Administration for Antiseizure Treatment in Adults: A Systematic Review.

OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of intranasal midazolam (in-MDZ) administration for antiseizure treatment in adults. METHODS: Embase and Medline literature databases were searched. We included randomized trials and cohort studies (excluding case series) of adult patients (≥ 18 years of age) examining in-MDZ administration for epilepsy, epileptic seizures, or status epilepticus published in English between 1985 and 2022. Studies were screened for eligibility based on predefined criteria. The primary outcome was the efficacy of in-MDZ administration, and the secondary outcome was its tolerability. Extracted data included study design, patient characteristics, intervention details, and outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: A total of 12 studies with 929 individuals treated with in-MDZ were included. Most studies were retrospective, with their number increasing over time. Administered in-MDZ doses ranged from 2.5 to 20 mg per single dose. The mean proportion of successful seizure termination after first in-MDZ administration was 72.7% (standard deviation [SD] 18%), and the proportion of seizure recurrence or persistent seizures ranged from 61 to 75%. Most frequent adverse reactions to in-MDZ were dizziness (mean 23.5% [SD 38.6%]), confusion (one study; 17.4%), local irritation (mean 16.6% [SD 9.6%]), and sedation (mean 12.7% [SD 9.7%]). CONCLUSIONS: Administration of in-MDZ seems promising for the treatment of prolonged epileptic seizures and seizure clusters in adults. Limited evidence suggests that intranasal administration is safe. Further research is warranted because of the heterogeneity of cohorts, the variation in dosages, and the lack of uniformity in defining successful seizure termination.

Mechanical Thrombectomy Versus Best Medical Treatment in the Late Time Window in Non-DEFUSE-Non-DAWN Patients: A Multicenter Cohort Study.

BACKGROUND: We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. METHODS: Cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by computer tomography or magnetic resonance imaging perfusion with automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days. RESULTS: Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46 [1.02-2.10]; P=0.04) and lower odds of all-cause mortality within 90 days (aOR, 0.59 [0.37-0.93]; P=0.02). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P=0.63). CONCLUSIONS: Two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Early timing of anesthesia in status epilepticus is associated with complete recovery: A 7-year retrospective two-center study.

OBJECTIVE: This study was undertaken to investigate the efficacy, tolerability, and outcome of different timing of anesthesia in adult patients with status epilepticus (SE). METHODS: Patients with anesthesia for SE from 2015 to 2021 at two Swiss academic medical centers were categorized as anesthetized as recommended third-line treatment, earlier (as first- or second-line treatment), and delayed (later as third-line treatment). Associations between timing of anesthesia and in-hospital outcomes were estimated by logistic regression. RESULTS: Of 762 patients, 246 received anesthesia; 21% were anesthetized as recommended, 55% earlier, and 24% delayed. Propofol was preferably used for earlier (86% vs. 55.5% for recommended/delayed anesthesia) and midazolam for later anesthesia (17.2% vs. 15.9% for earlier anesthesia). Earlier anesthesia was statistically significantly associated with fewer infections (17% vs. 32.7%), shorter median SE duration (.5 vs. 1.5 days), and more returns to premorbid neurologic function (52.9% vs. 35.5%). Multivariable analyses revealed decreasing odds for return to premorbid function with every additional nonanesthetic antiseizure medication given prior to anesthesia (odds ratio [OR] = .71, 95% confidence interval [CI] = .53-.94) independent of confounders. Subgroup analyses revealed decreased odds for return to premorbid function with increasing delay of anesthesia independent of the Status Epilepticus Severity Score (STESS; STESS = 1-2: OR = .45, 95% CI = .27-.74; STESS > 2: OR = .53, 95% CI = .34-.85), especially in patients without potentially fatal etiology (OR = .5, 95% CI = .35-.73) and in patients experiencing motor symptoms (OR = .67, 95% CI = .48-.93). SIGNIFICANCE: In this SE cohort, anesthetics were administered as recommended third-line therapy in only every fifth patient and earlier in every second. Increasing delay of anesthesia was associated with decreased odds for return to premorbid function, especially in patients with motor symptoms and no potentially fatal etiology.

Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation.

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

Balancing the risks and benefits of anesthetics in status epilepticus.

PURPOSE: According to international guidelines, status epilepticus refractory to first- and second-line antiseizure medication should be treated with anesthetics. Therefore, continuously delivered intravenous midazolam, propofol, or barbiturates are recommended as third-line therapy. While electroencephalographically (EEG)-controlled titration of anesthetics to seizure termination or to the emergence of an EEG burst-suppression pattern makes sense, evidence of the efficacy and tolerability of such third-line treatment is limited and concerns regarding the risks of anesthesia remain. The lack of treatment alternatives and persistent international discord reflecting contradictory results from some studies leave clinicians on their own when deciding to escalate treatment. In this conference-accompanying narrative review, we highlight the challenges of EEG-monitored third-line treatment and discuss recent studies that examined earlier administration of anesthetics. RESULTS: Based on the literature, maintaining continuous burst suppression is difficult despite the constant administration of anesthetics, and the evidence for burst suppression as an adequate surrogate target is limited by methodological shortcomings as acknowledged by international guidelines. In our Swiss cohort including 102 patients with refractory status epilepticus, burst suppression as defined by the American Clinical Neurophysiology Society's Critical Care EEG Terminology 2021 was established in only 21%. Besides case reports suggesting that rapid but short-termed anesthesia can be sufficient to permanently stop seizures, a study including 205 patients revealed that anesthesia as second-line treatment was associated with a shorter median duration of status epilepticus (0.5 versus 12.5 days, p < 0.001), median ICU (2 versus 5.5 days, p < 0.001) and hospital stay (8 versus 17 days, p < 0.001) with equal rates of complications when compared to anesthesia as third-line treatment. CONCLUSIONS: Recent investigations have led to important findings and new insights regarding the use of anesthetics in refractory status epilepticus. However, numerous methodological limitations and remaining questions need to be considered when it comes to the translation into clinical practice, and, in consequence, call for prospective randomized studies. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Serum Neurofilament Light Chain Levels in the Intensive Care Unit: Comparison between Severely Ill Patients with and without Coronavirus Disease 2019.

There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID-19), but little is known regarding whether they reflect structural damage to the nervous system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID-19 patients, 10 critically ill non-COVID-19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID-19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short-term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610-616.

Predicting neurological outcome in adult patients with cardiac arrest: systematic review and meta-analysis of prediction model performance.

This work aims to assess the performance of two post-arrest (out-of-hospital cardiac arrest, OHCA, and cardiac arrest hospital prognosis, CAHP) and one pre-arrest (good outcome following attempted resuscitation, GO-FAR) prediction model for the prognostication of neurological outcome after cardiac arrest in a systematic review and meta-analysis. A systematic search was conducted in Embase, Medline, and Web of Science Core Collection from November 2006 to December 2021, and by forward citation tracking of key score publications. The search identified 1'021 records, of which 25 studies with a total of 124'168 patients were included in the review. A random-effects meta-analysis of C-statistics and overall calibration (total observed vs. expected [O:E] ratio) was conducted. Discriminatory performance was good for the OHCA (summary C-statistic: 0.83 [95% CI 0.81-0.85], 16 cohorts) and CAHP score (summary C-statistic: 0.84 [95% CI 0.82-0.87], 14 cohorts) and acceptable for the GO-FAR score (summary C-statistic: 0.78 [95% CI 0.72-0.84], five cohorts). Overall calibration was good for the OHCA (total O:E ratio: 0.78 [95% CI 0.67-0.92], nine cohorts) and the CAHP score (total O:E ratio: 0.78 [95% CI 0.72-0.84], nine cohorts) with an overestimation of poor outcome. Overall calibration of the GO-FAR score was poor with an underestimation of good outcome (total O:E ratio: 1.62 [95% CI 1.28-2.04], five cohorts). Two post-arrest scores showed good prognostic accuracy for predicting neurological outcome after cardiac arrest and may support early discussions about goals-of-care and therapeutic planning on the intensive care unit. A pre-arrest score showed acceptable prognostic accuracy and may support code status discussions.

Prediction of Postictal Delirium Following Status Epilepticus in the ICU: First Insights of an Observational Cohort Study.

OBJECTIVES: To identify early predictors of postictal delirium in adult patients after termination of status epilepticus. DESIGN: Retrospective study. SETTING: ICUs at a Swiss tertiary academic medical center. PATIENTS: Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018. INTERVENTIONS: None. METHODS: Primary outcome was postictal delirium during post-status epilepticus treatment defined as an Intensive Care Delirium Screening Checklist greater than or equal to 4. Associations with postictal delirium were secondary outcomes. A time-dependent multivariable Cox proportional hazards model was used to identify risks of postictal delirium. It included variables that differed between patients with and without delirium and established risk factors for delirium (age, sex, number of inserted catheters, illness severity [quantified by the Sequential Organ Failure Assessment and Status Epilepticus Severity Score], neurodegenerative disease, dementia, alcohol/drug consumption, infections, coma during status epilepticus, dose of benzodiazepines, anesthetics, and mechanical ventilation). MEASUREMENTS AND MAIN RESULTS: Among 224 patients, post-status epilepticus Intensive Care Delirium Screening Checklist was increased in 83% with delirium emerging in 55% with a median duration of 2 days (interquartile range 1-3 d). Among all variables, only the history of alcohol and/or drug consumption was associated with increased hazards for delirium in multivariable analyses (hazard ratio = 3.35; 95% CI, 1.53-7.33). CONCLUSIONS: Our study provides first exploratory insights into the risks of postictal delirium in adult status epilepticus patients treated in the ICU. Delirium following status epilepticus is frequent, lasting mostly 2-3 days. Our findings that with the exception of a history of alcohol and/or drug consumption, other risk factors of delirium were not found to be associated with a risk of postictal delirium may be related to the limited sample size and the exploratory nature of our study. Further investigations are needed to investigate the role of established risk factors in other status epilepticus cohorts. In the meantime, our results indicate that the risk of delirium should be especially considered in patients with a history of alcohol and/or drug consumption.

Prolonged mechanical ventilation in patients with terminated status epilepticus and outcome: An observational cohort study.

OBJECTIVE: Classical clinical characteristics associated with successful or unsuccessful extubation are unreliable in neurocritically ill patients, and attempts to predict successful extubation in this context have failed. We aimed to investigate the frequency of mechanical ventilation (MV) in adult patients in status epilepticus (SE) and its clinical associations, to identify predictors at SE onset of prolonged postictal MV, and to determine the associated outcomes with prolonged MV. METHODS: From 2012 to 2018, SE patients treated in intensive care units at a Swiss academic care center were included. Multivariable Poisson regression adjusting for potential confounders, such as continuously administered anesthetics, was performed to identify risks for postictal MV for >24 h after SE and its association with no return to neurologic function and death. Linear regression was performed to identify correlations between the durations of administered specific anesthetics and postictal MV. RESULTS: Of 262 patients, 42% were ventilated, with 24% being on ventilators for >24 h after SE. Patients with prolonged postictal MV were extubated at a median of 7 days, with 56% not being extubated on the day of successful weaning from MV because of altered consciousness and/or lack of airway-protective reflexes. After extubation, noninvasive ventilation and reintubation were rarely needed. Prolonged postictal MV was associated with increased risk for death independent of potential confounders, including fatal etiology of SE, age, SE severity, and use of anesthetics (relative risk for every additional day = 2.7, p = .024). At SE onset, decreased consciousness and presumed fatal etiology predicted prolonged postictal MV. Anesthetics were associated with prolonged MV, but linear regression could not identify significant correlations. SIGNIFICANCE: Our data reveal that prolonged postictal MV is frequent and an independent risk factor for death. Extubation is often delayed for days despite sufficient weaning from the ventilator and altered airway-protective reflexes in only few patients. Studies need to investigate whether more rigorous extubation strategies improve outcome.

Bilateral acute renal cortical necrosis after a dog bite: case report.

BACKGROUND: Capnocytophaga canimorsus is a Gram-negative capnophilic rod and part of dogs/cats' normal oral flora. It can be transmitted by bites, scratches, or even by contact of saliva with injured skin. Asplenic patients and patients with alcohol abuse are at particular risk for fulminant C. canimorsus sepsis. However, also immunocompetent patients can have a severe or even fatal infection. This is the first case of a severe C. canimorsus infection in an immunocompromised host complicated by acute renal cortical necrosis with a "reverse rim sign" in contrast-enhanced computed tomography on hospital admission. CASE PRESENTATION: We report the case of a 44-year functionally asplenic patient after an allogeneic stem cell transplantation, who presented with septic shock after a minor dog bite injury 4 days prior. Because of abdominal complaints, epigastric pain with local peritonism, and radiological gallbladder wall thickening, an abdominal focus was suspected after the initial work-up. The patient underwent emergent open cholecystectomy, but the clinical suspicion of abdominal infection was not confirmed. Septic shock was further complicated by cardiomyopathy and disseminated intravascular coagulation. As a causative pathogen, C. canimorsus could be isolated. The clinical course was complicated by permanent hemodialysis and extensive acral necrosis requiring amputation of several fingers and both thighs. CONCLUSION: We present a severe case of a C. canimorsus infection in a functionally asplenic patient after a minor dog bite. The clinical course was complicated by septic shock, disseminated intravascular coagulation, and the need for multiple amputations. In addition, the rare form of acute renal failure - bilateral acute renal cortical necrosis - was visible as "reverse rim sign" on computed tomography scan. This case is an example of the potential disastrous consequences when omitting pre-emptive antibiotic therapy in wounds inflicted by cats and dogs, particularly in asplenic patients.

Delirium in Meningitis and Encephalitis: Emergence and Prediction in a 6-Year Cohort.

BACKGROUND/OBJECTIVE: Data regarding delirium in patients presenting with infections of the central nervous system, such as meningitis and/or encephalitis (ME), are scarce. We aimed to determine the frequency and early predictors of delirium in the acute phase of ME. METHODS: We assessed clinical, radiologic, and laboratory data of patients with ME at a Swiss academic medical center from 2011 to 2017. The highest Intensive Care Delirium Screening Checklist (ICDSC) score was assessed within 24 hours around lumbar puncture. Multivariable logistic regression was performed to identify predictors of delirium (ICDSC ≥4). RESULTS: Among 330 patients with ME, infectious pathogens were identified in 41%. An ICDSC >1 was found in 28% with and 19% without identified infectious pathogens. Delirium was diagnosed in 18% with and 14% without infectious pathogens and significantly associated with prolonged in-hospital treatment and mechanical ventilation, more frequent administration of neuroleptics and anesthetics (in 96% with delirium vs 35% without), complications, and less recovery to premorbid functional baseline. Low serum albumin at presentation was the only independent predictor of delirium (area under the receiver-operating curve [AUROC] = 0.792) in patients with pathogens. In patients with infections, the AUROC was smallest for encephalitis (AUROC = 0.641) and larger for patients with meningeal infections (meningitis AUROC = 0.807; meningoencephalitis AUROC = 0.896). CONCLUSIONS: Delirium in the context of ME is seen in almost every fifth patient and linked to prolonged treatment, complications, and incomplete recovery. Among clinical, radiologic, and laboratory parameters, the good calibration and discrimination of low albumin serum concentrations for the prediction of delirium in patients with ME seem promising, especially if meninges are affected.

Association of medical futility with do-not-resuscitate (DNR) code status in hospitalised patients.

Guidelines recommend a 'do-not-resuscitate' (DNR) code status for inpatients in which cardiopulmonary resuscitation (CPR) attempts are considered futile because of low probability of survival with good neurological outcome. We retrospectively assessed the prevalence of DNR code status and its association with presumed CPR futility defined by the Good Outcome Following Attempted Resuscitation score and the Clinical Frailty Scale in patients hospitalised in the Divisions of Internal Medicine and Traumatology/Orthopedics at the University Hospital of Basel between September 2018 and June 2019. The definition of presumed CPR futility was met in 467 (16.2%) of 2889 patients. 866 (30.0%) patients had a DNR code status. In a regression model adjusted for age, gender, main diagnosis, nationality, language and religion, presumed CPR futility was associated with a higher likelihood of a DNR code status (37.3% vs 7.1%, adjusted OR 2.99, 95% CI 2.31 to 3.88, p<0.001). In the subgroup of patients with presumed futile CPR, 144 of 467 (30.8%) had a full code status, which was independently associated with younger age, male gender, non-Christian religion and non-Swiss citizenship. We found a significant proportion of hospitalised patients to have a full code status despite the fact that CPR had to be considered futile according to an established definition. Whether these decisions were based on patient preferences or whether there was a lack of patient involvement in decision-making needs further investigation.

Advance Directives in the Neurocritically Ill: A Systematic Review.

OBJECTIVES: To determine the frequency of advance directives or directives disclosed by healthcare agents and their influence on decisions to withdraw/withhold life-sustaining care in neurocritically ill adults. DATA SOURCES: PubMed, Embase, and Cochrane databases. STUDY SELECTION: Screening was performed using predefined search terms to identify studies describing directives of neurocritically ill patients from 2000 to 2019. The review was registered prior to the screening process (International Prospective Register of Systematic Reviews identification number 149185). DATA EXTRACTION: Data were collected using standardized forms. Primary outcomes were the frequency of directives and associated withholding/withdrawal of life-sustaining care. DATA SYNTHESIS: Out of 721 articles, 25 studies were included representing 35,717 patients. The number of studies and cohort sizes increased over time. A median of 39% (interquartile range, 14-72%) of patients had directives and/or healthcare agents. The presence of directives was described in patients with stroke, status epilepticus, neurodegenerative disorders, neurotrauma, and neoplasms, with stroke patients representing the largest subgroup. Directives were more frequent among patients with neurodegenerative disorders compared with patients with other illnesses (p = 0.043). In reference to directives, care was adapted in 71% of European, 50% of Asian, and 42% of American studies, and was withheld or withdrawn more frequently over time with a median of 58% (interquartile range, 39-89%). Physicians withheld resuscitation in reference to directives in a median of 24% (interquartile range, 22-70%). CONCLUSIONS: Studies regarding the use and translation of directives in neurocritically ill patients are increasing. In reference to directives, care was adapted in up to 71%, withheld or withdrawn in 58%, and resuscitation was withheld in every fourth patient, but the quality of evidence regarding their effects on critical care remains weak and the risk of bias high. The limited number of patients having directives is worrisome and studies aiming to increase the use and translation of directives are scarce. Efforts need to be made to increase the perception, use, and translation of directives of the neurocritically ill.

Frequency and Implications of Complications in the ICU After Status Epilepticus: No Calm After the Storm.

OBJECTIVES: To investigate the frequency, types, and implications of complications during intensive care in patients after status epilepticus has been successfully terminated. DESIGN: Retrospective study. SETTING: ICUs at a Swiss tertiary academic medical care center. PATIENTS: Data were collected from the digital patient records of all adult patients with status epilepticus from 2012 to 2018. INTERVENTIONS: None. METHODS: Primary outcomes were defined as frequency of complications following status epilepticus termination and return to premorbid functional baseline. Univariable analyses regarding the relative risks of complications occurring after status epilepticus termination for no return to premorbid neurologic function were estimated by Poisson regression with robust error variance. RESULTS: Of 311 patients with status epilepticus, 224 patients (72%) were treated on the ICU for more than 24 hours following status epilepticus termination. Ninety-six percent of patients remained in a prolonged state of altered consciousness for a median of 2 days (interquartile range, 1-3 d) and 80% had complications during their ICU treatment. Fifty-five percent had new-onset delirium with a median duration of 2 days (interquartile range, 1-3 d). Forty-two percent had mechanical ventilation for a median of 4 days (interquartile range, 2-11 d) and 21% had nosocomial infections diagnosed after status epilepticus. Multivariable analyses revealed that mechanical ventilation for more than 24 hours after status epilepticus, and arterial hypotension requiring vasopressors were independently associated with increased risk of no return to premorbid function (RRfor each additional day = 1.01; 95% CI, 1.02-1.03 and RRfor each additional day = 1.03; 95% CI, 1.01-1.05) and death (RRfor each additional day = 1.11; 95% CI, 1.04-1.19 and RRfor each additional day = 1.15; 95% CI, 1.03-1.28). Delirium was independently associated with a decreased relative risk of death (RRfor each additional day = 0.55; 95% CI, 0.37-0.80), but prolonged ICU- and hospital stays. CONCLUSIONS: Complications after status epilepticus termination are frequent and associated with no return to premorbid function, death, and prolonged ICU- and hospital stays. These results call for heightened awareness and further studies mainly regarding prediction and preventive strategies in this context.

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

OBJECTIVE: To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. METHODS: Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. RESULTS: Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. INTERPRETATION: In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432.

Predictors of infectious meningitis or encephalitis: the yield of cerebrospinal fluid in a cross-sectional study.

BACKGROUND: Cerebrospinal fluid (CSF) analyses are recommended in patients with meningitis and/or encephalitis, but evidence regarding its diagnostic yield is low. We aimed to determine predictors of infectious pathogens in the CSF of adult patients presenting with meningitis, and/or encephalitis. METHODS: Consecutive patients with meningitis and/or encephalitis form 2011-17 at a Swiss academic medical care center were included in this cross-sectional study. Clinical, neuroradiologic, and laboratory data were collected as exposure variables. Infectious meningitis and/or encephalitis were defined as the composite outcome. For diagnosis of bacterial meningitis the recommendations of the European Society of Clinical Microbiology and Infectious Diseases were followed. Viral meningitis was diagnosed by detection of viral ribonucleic or deoxyribonucleic acid in the CSF. Infectious encephalitis was defined according to the International Encephalitis Consortium (IEC). Meningoencephalitis was diagnosed if the criteria for meningitis and encephalitis were fulfilled. Multinomial logistic regression was performed to identify predictors of the composite outcome. To quantify discriminative power, the c statistic analogous the area under the receiver-operating curve (AUROC) was calculated. An AUROC between 0.7-0.8 was defined as "good", 08-0.9 as "excellent", and > 0.9 as "outstanding". Calibration was defined as "good" if the goodness of fit tests revealed insignificant p-values. RESULTS: Among 372 patients, infections were diagnosed in 42.7% presenting as meningitis (51%), encephalitis (32%), and meningoencephalitis (17%). Most frequent infectious pathogens were Streptococcus pneumoniae, Varicella zoster, and Herpes simplex 1&2. While in multivariable analysis lactate concentrations and decreased glucose ratios were the only independent predictors of bacterial infection (AUROCs 0.780, 0.870, and 0.834 respectively), increased CSF mononuclear cells were the only predictors of viral infections (AUROC 0.669). All predictors revealed good calibration. CONCLUSIONS: Prior to microbiologic workup, CSF data may guide clinicians when infection is suspected while other laboratory and neuroradiologic characteristics seem less useful. While increased CSF lactate and decreased glucose ratio are is the most reliable predictors of bacterial infections in patients with meningitis and/or encephalitis, only mononuclear cell counts predicted viral infections. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03856528. Registered on February 26th 2019.