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.

Translation of patients' advance directives in intensive care units: are we there yet?

OBJECTIVES: This review examined studies regarding the implementation and translation of patients' advance directives (AD) in intensive care units (ICUs), focusing on practical difficulties and obstacles. METHODS: The digital PubMed and Medline databases were screened using predefined keywords to identify relevant prospective and retrospective studies published until 2022. RESULTS: Seventeen studies from the United States, Europe, and South Africa (including 149,413 patients and 1210 healthcare professionals) were identified. The highest prevalence of ADs was described in a prospective study in North America (49%), followed by Central Europe (13%), Asia (4%), Australia and New Zealand (4%), Latin America (3%), and Northern and Southern Europe (2.6%). While four retrospective studies reported limited effects of ADs, four retrospective studies, one survey and one systematic review indicated significant effects on provision of intensive care, higher rates of do-not-resuscitate orders, and care withholding in patients with ADs. Four of these studies showed shorter ICU stays, and lower treatment costs in patients with ADs. One prospective and two retrospective studies reported issues with loss, delayed or no transmission of ADs. One survey revealed that 91% of healthcare workers did not regularly check for ADs. Two retrospective studies and two survey revealed that the implementation of directives is further challenged by issues with their applicability, phrasing, and compliance by the critical care team and family members. CONCLUSIONS: Although ADs may improve intensive- and end-of-life care, insufficient knowledge, lack of awareness, poor communication between healthcare providers and patients or surrogates, lack of standardization of directives, as well as ethical and legal concerns challenge their implementation.

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.

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.

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.