First-Response ABCDE Management of Status Epilepticus: A Prospective High-Fidelity Simulation Study

Respiratory infections following status epilepticus (SE) are frequent, and associated with higher mortality, prolonged ICU stay, and higher rates of refractory SE. Lack of airway protection may contribute to respiratory infectious complications. This study investigates the order and frequency of physicians treating a simulated SE following a systematic Airways-Breathing-Circulation-Disability-Exposure (ABCDE) approach, identifies risk factors for non-adherence, and analyzes the compliance of an ABCDE guided approach to SE with current guidelines. We conducted a prospective single-blinded high-fidelity trial at a Swiss academic simulator training center. Physicians of different affiliations were confronted with a simulated SE. Physicians (; n; = 74) recognized SE and performed a median of four of the five ABCDE checks (interquartile range 3-4). Thereof, 5% performed a complete assessment. Airways were checked within the recommended timeframe in 46%, breathing in 66%, circulation in 92%, and disability in 96%. Head-to-toe (exposure) examination was performed in 15%. Airways were protected in a timely manner in 14%, oxygen supplied in 69%, and antiseizure drugs (ASDs) administered in 99%. Participants' neurologic affiliation was associated with performance of fewer checks (regression coefficient -0.49;; p; = 0.015). We conclude that adherence to the ABCDE approach in a simulated SE was infrequent, but, if followed, resulted in adherence to treatment steps and more frequent protection of airways

Estrogenic regulation of skeletal muscle proteome : a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy

Female middle age is characterized by a decline in skeletal muscle mass and performance, predisposing women to sarcopenia, functional limitations, and metabolic dysfunction as they age. Menopausal loss of ovarian function leading to low circulating level of 17-estradiol has been suggested as a contributing factor to aging-related muscle deterioration. However, the underlying molecular mechanisms remain largely unknown and thus far androgens have been considered as a major anabolic hormone for skeletal muscle. We utilized muscle samples from 24 pre- and postmenopausal women to establish proteome-wide profiles, associated with the difference in age (30-34 years old vs. 54-62 years old), menopausal status (premenopausal vs. postmenopausal), and use of hormone replacement therapy (HRT; user vs. nonuser). None of the premenopausal women used hormonal medication while the postmenopausal women were monozygotic (MZ) cotwin pairs of whom the other sister was current HRT user or the other had never used HRT. Label-free proteomic analyses resulted in the quantification of 797 muscle proteins of which 145 proteins were for the first time associated with female aging using proteomics. Furthermore, we identified 17-estradiol as a potential upstream regulator of the observed differences in muscle energy pathways. These findings pinpoint the underlying molecular mechanisms of the metabolic dysfunction accruing upon menopause, thus having implications for understanding the complex functional interactions between female reproductive hormones and health.Peer reviewe

Advance Directives in the Neurocritically Ill: A Systematic Review

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.; PubMed, Embase, and Cochrane databases.; 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 [PROSPERO]-Identification number 149185).; Data were collected using standardized forms. Primary outcomes were the frequency of directives and associated withholding/withdrawal of life-sustaining care.; 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%).; 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

Accuracy of Calculated Free Valproate Levels in Adult Patients With Status Epilepticus

To test the accuracy of an equation in adult patients with status epilepticus (SE) that calculates the free concentration of serum valproic acid (fVPA) from the total concentration of serum VPA (tVPA) and serum albumin.; All adult SE patients that were treated at a Swiss academic medical center between 2005 and 2018 with concurrent measurements of tVPA, fVPA and serum albumin were included. fVPA was categorized as subtherapeutic, therapeutic (5-10 mg/L), or supratherapeutic. Agreement was defined as the proportion of measured and calculated fVPA falling within the same category.; Of 676 SE patients, 104 had 506 measurements with a median of 3 (interquartile-range [IQR] 1.5-6.5) per patient). The median tVPA was 43.5 mg/L (27.4-63.6), with measured fVPA 9.1 mg/L (4.5-14.7) and calculated fVPA 10.1 mg/L (7.0-13.0), respectively. The median deviation of calculated from measured fVPA was -0.8 mg/L (-3.2 to 2.5) with 336 measurements >1 mg/L. While the association between measured and calculated fVPA was linear (regr. coeff. = 1.1, 95% CI 0.9-1.2,; p; < 0.0001), the agreement on effective drug levels did not match in 39.8% of measurements regardless of serum albumin levels, with calculated fVPA overestimating measured fVPA in 30.4%. tVPA and serum albumin independently influenced the accuracy of the calculated fVPA in the multivariable model.; Calculated fVPA is inaccurate when using the proposed equation in adult patients with SE, calling for drug monitoring based on measured fVPA in this context

Procedures of brain death diagnosis and organ explantation in a tertiary medical centre – a retrospective eight-year cohort study

AIMS OF THE STUDY: To assess the frequency and variables associated with the need for ancillary tests to confirm suspected brain death in adult patients, and to assess the time from brain death to organ explantation in donors. We further sought to identify modifiable factors influencing the time between brain death and start of surgery. METHODS: Medical records and the Swiss organ allocation system registry were screened for all consecutive adult patients diagnosed with brain death at an intensive care unit of a Swiss tertiary medical centre from 2013 to 2020. The frequency and variables associated with the performance of ancillary tests (i.e., transcranial doppler, digital subtraction angiography, and computed tomography angiography) to confirm brain death were primary outcomes; the time from death to organ explantation as well as modifying factors were defined as secondary outcomes. RESULTS: Among 91 patients with a diagnosis of brain death, 15 were not explanted and did not undergo further ancillary tests. Of the remaining 76 patients, who became organ donors after brain death, ancillary tests were performed in 24%, most frequently in patients with hypoxic-ischaemic encephalopathy. The leading presumed causes of death (not mutually exclusive) were haemorrhagic strokes (49%), hypoxic-ischaemic encephalopathies (33%) and severe traumatic brain injuries (22%). Surgery for organ explantation was started within a median of 16 hours (interquartile range [IQR] 13–18) after death with delay increasing over time (nonparametric test for trend p = 0.05), mainly due to organ allocation procedures. Patients with brain death confirmed during night shifts were explanted earlier (during night shifts 14.3 hours, IQR 11.8–16.8 vs 16.3 hours, IQR 13.5–18.5 during day shifts; p = 0.05). CONCLUSIONS: Ancillary tests to confirm brain death are frequently performed, mainly in resuscitated patients. The delay to surgery for organ explantation after confirmed brain death was longer during day shifts, increased over time and was mainly determined by organ allocation procedures. The trial was registered on clinical trials.gov (identifier: NCT03984981

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

To identify early predictors of postictal delirium in adult patients after termination of status epilepticus.; Retrospective study.; ICUs at a Swiss tertiary academic medical center.; Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018.; None.; 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).; 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).; 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

Diagnostic yield of cerebrospinal fluid analysis in status epilepticus: an 8-year cohort study

We investigate the frequency and diagnostic yield of cerebrospinal fluid (CSF) analysis in adult patients with status epilepticus (SE) and its impact on the outcome.; From 2011 to 2018, adult patients treated at the University Hospital Basel were included. Primary outcomes were defined as the frequency of lumbar puncture and results from chemical, cellular, and microbiologic CSF analyses. Secondary outcomes were differences between patients receiving and not receiving lumbar puncture in the context of SE.; In 18% of 408 patients, a lumbar puncture was performed. Of those, infectious pathogens were identified in 21% with 15% detected ± 24 h around SE diagnosis. 74% of CSF analyses revealed abnormal chemical or cellular components without infectious pathogens. Screening for autoimmune diseases was only performed in 22%. In 8%, no or late (i.e., > 24 after SE diagnosis) lumbar puncture was performed despite persistent unknown SE etiology in all, transformation into refractory SE in 78%, and no recovery to premorbid neurologic function in 66%. Withholding lumbar puncture was associated with no return to premorbid neurologic function during hospital stay independent of potential confounders. Not receiving a lumbar puncture was associated with presumed known etiology and signs of systemic infectious complications.; Withholding lumbar puncture in SE patients is associated with increased odds for no return to premorbid neurologic function, and CSF analyses in SE detect infectious pathogens frequently. These results and pathologic chemical and cellular CSF findings in the absence of infections call for rigorous screening to confirm or exclude infectious or autoimmune encephalitis in this context which should not be withheld

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

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.; 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.; 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.; 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

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 &gt; 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.</p