Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

Communication trends over time in new-onset refractory status epilepticus (NORSE): Interim analysis from the NORSE/FIRES Family Registry.

The new-onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) Family Registry contributes to a systematic effort to collect clinical and epidemiological information on individuals affected by NORSE/FIRES. We explore diagnostic and prognostic information provided to patients and their families, their satisfaction with the communication, and utilisation of palliative care services during acute hospitalization. Communication about the diagnosis of NORSE/FIRES to families has improved since the publication of consensus definitions in 2018, with families being more likely to be told about NORSE/FIRES after 2018. Families rate the quality of prognostic information as being moderate. Palliative care services were involved in a minority of patients. Understanding and characterizing the prevalence and satisfaction of diagnostic and prognostic conversations is important for improving overall care, the quality of physician-patient-family relationships, and the recovery process for those affected by NORSE/FIRES.

Guidelines for Neuroprognostication in Critically Ill Adults with Intracerebral Hemorrhage.

BACKGROUND: The objective of this document is to provide recommendations on the formal reliability of major clinical predictors often associated with intracerebral hemorrhage (ICH) neuroprognostication. METHODS: A narrative systematic review was completed using the Grading of Recommendations Assessment, Development, and Evaluation methodology and the Population, Intervention, Comparator, Outcome, Timing, Setting questions. Predictors, which included both individual clinical variables and prediction models, were selected based on clinical relevance and attention in the literature. Following construction of the evidence profile and summary of findings, recommendations were based on Grading of Recommendations Assessment, Development, and Evaluation criteria. Good practice statements addressed essential principles of neuroprognostication that could not be framed in the Population, Intervention, Comparator, Outcome, Timing, Setting format. RESULTS: Six candidate clinical variables and two clinical grading scales (the original ICH score and maximally treated ICH score) were selected for recommendation creation. A total of 347 articles out of 10,751 articles screened met our eligibility criteria. Consensus statements of good practice included deferring neuroprognostication-aside from the most clinically devastated patients-for at least the first 48-72 h of intensive care unit admission; understanding what outcomes would have been most valued by the patient; and counseling of patients and surrogates whose ultimate neurological recovery may occur over a variable period of time. Although many clinical variables and grading scales are associated with ICH poor outcome, no clinical variable alone or sole clinical grading scale was suggested by the panel as currently being reliable by itself for use in counseling patients with ICH and their surrogates, regarding functional outcome at 3 months and beyond or 30-day mortality. CONCLUSIONS: These guidelines provide recommendations on the formal reliability of predictors of poor outcome in the context of counseling patients with ICH and surrogates and suggest broad principles of neuroprognostication. Clinicians formulating their judgments of prognosis for patients with ICH should avoid anchoring bias based solely on any one clinical variable or published clinical grading scale.

Guidelines for neuroprognostication in adults with traumatic spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (tSCI) impacts patients and their families acutely and often for the long term. The ability of clinicians to share prognostic information about mortality and functional outcomes allows patients and their surrogates to engage in decision-making and plan for the future. These guidelines provide recommendations on the reliability of acute-phase clinical predictors to inform neuroprognostication and guide clinicians in counseling adult patients with tSCI or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of an appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Timing/Setting question was framed as "When counseling patients or surrogates of critically ill patients with traumatic spinal cord injury, should < predictor, with time of assessment if appropriate > be considered a reliable predictor of < outcome, with time frame of assessment >?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four Grading of Recommendations Assessment, Development, and Evaluation criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. Good practice recommendations addressed essential principles of neuroprognostication that could not be framed in the Population/Intervention/Comparator/Outcome/Timing/Setting format. Throughout the guideline development process, an individual living with tSCI provided perspective on patient-centered priorities. RESULTS: Six candidate clinical variables and one prediction model were selected. Out of 11,132 articles screened, 369 met inclusion criteria for full-text review and 35 articles met eligibility criteria to guide recommendations. We recommend pathologic findings on magnetic resonance imaging, neurological level of injury, and severity of injury as moderately reliable predictors of American Spinal Cord Injury Impairment Scale improvement and the Dutch Clinical Prediction Rule as a moderately reliable prediction model of independent ambulation at 1 year after injury. No other reliable or moderately reliable predictors of mortality or functional outcome were identified. Good practice recommendations include considering the complete clinical condition as opposed to a single variable and communicating the challenges of likely functional deficits as well as potential for improvement and for long-term quality of life with SCI-related deficits to patients and surrogates. CONCLUSIONS: These guidelines provide recommendations about the reliability of acute-phase predictors of mortality, functional outcome, American Spinal Injury Association Impairment Scale grade conversion, and recovery of independent ambulation for consideration when counseling patients with tSCI or their surrogates and suggest broad principles of neuroprognostication in this context.

Guidelines for Neuroprognostication in Critically Ill Adults with Moderate-Severe Traumatic Brain Injury.

BACKGROUND: Moderate-severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted. RESULTS: After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining "poor" functional outcomes. For consistency, we treated "poor" as "unfavorable". Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using "moderately reliable" predictors or prediction models, the clinician must acknowledge "substantial" uncertainty in the prognosis. CONCLUSIONS: These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication.

Short-Acting Neuromuscular Blockade Improves Inter-rater Reliability of Median Somatosensory Evoked Potentials in Post-cardiac arrest Prognostication.

BACKGROUND: Although median nerve somatosensory evoked potentials are routinely used for prognostication in comatose cardiac arrest survivors, myogenic artifact can reduce inter-rater reliability, leading to unreliable or inaccurate results. To minimize this risk, we determined the benefit of neuromuscular blockade agents in improving the inter-rater reliability and signal-to-noise ratio of SSEPs in the context of prognostication. METHODS: Thirty comatose survivors of cardiac arrest were enrolled in the study, following the request from an intensivist to complete an SSEP for prognostication. Right and left median nerve SSEPs were obtained from each patient, before and after administration of an NMB agent. Clinical histories and outcomes were retrospectively reviewed. The SSEP recordings before and after NMB were randomized and reviewed by five blinded raters, who assessed the latency and amplitude of cortical and noncortical potentials (vs. absence of response) as well as the diagnostic quality of cortical recordings. The inter-rater reliability of SSEP interpretation before and after NMB was compared via Fleiss' κ score. RESULTS: Following NMB administration, Fleiss' κ score for cortical SSEP interpretation significantly improved from 0.37 to 0.60, corresponding to greater agreement among raters. The raters were also less likely to report the cortical recordings as nondiagnostic following NMB (40.7% nondiagnostic SSEPs pre-NMB; 17% post-NMB). The SNR significantly improved following NMB, especially when the pre-NMB SNR was low (< 10 dB). Across the raters, there were three patients whose SSEP interpretation changed from bilaterally absent to bilaterally present after NMB was administered (potential false positives without NMB). CONCLUSIONS: NMB significantly improves the inter-rater reliability and SNR of median SSEPs for prognostication among comatose cardiac arrest survivors. To ensure the most reliable prognostic information in comatose post-cardiac arrest survivors, pharmacologic paralysis should be consistently used before recording SSEPs.

Guidelines for Neuroprognostication in Comatose Adult Survivors of Cardiac Arrest.

BACKGROUND: Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: "When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?" Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence.

Guidelines for Neuroprognostication in Adults with Guillain-Barré Syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10-30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: "When counseling patients or surrogates of critically ill patients with Guillain-Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed.

Hospital to Hospital Transfers of Cerebral Hemorrhage: Characteristics of Early Withdrawal of Life-Sustaining Treatment.

BACKGROUND: Large intracerebral hemorrhages (ICHs) are associated with significant morbidity and mortality. Patient transfer to higher level centers is common, but care in these centers rarely demonstrably improves morbidity or reduces mortality. Patients may rapidly progress to brain death, but a large number die shortly after transferring because of withdrawal of life-sustaining treatment (WOLST). This outcome may result in poor resource use and unnecessary cost to patients, families, and institutions. We sought to determine clinical and radiographic predictors of early death or WOLST that may alter potential transfer. METHODS: We performed a retrospective review of patients admitted from outside medical centers to the neurosciences intensive care unit at Saint Marys Mayo Clinic Hospital in Rochester, MN, from January 2014 to December 2019. Patients ≥ 18 years old with a spontaneous ICH were included. Exclusion criteria included trauma, subarachnoid hemorrhage, and subdural hematoma. We identified patients who died or underwent WOLST within 24 h of transfer. Descriptive characteristics of patients and ICH were collected. Data were analyzed with univariable, multivariable, and logistic regression. Predictive modeling was performed. An additional case-matched study was completed to evaluate for characteristics further. RESULTS: A total of 317 consecutive patients were identified. Forty-two patients were found with early death or WOLST within 24 h of transfer. Do not resuscitate/do not intubate (DNR/DNI) code status (odds ratio [OR] 5.23, confidence interval [CI] 3.31-8.28), anticoagulation use (OR 2.11, CI 1.09-4.09), and lower level of consciousness at presentation based on Glasgow Coma Score (OR 1.41, CI 1.29-1.54) and Full Outline of Unresponsiveness (FOUR) score (OR 1.34, CI 1.26-1.46) were associated with WOLST. Associated characteristics on the computed tomography scan included midline shift (OR 4.64, CI 2.32-9.29), hydrocephalus (OR 9.30, CI 4.56-18.96), and intraventricular extension (OR 5.27, CI 2.60-10.68). Case matching restricted to midline shift demonstrated similarity between patients with aggressive care and WOLST. DNR/DNI code status, warfarin use, ICH score, and composite FOUR score were the best predictive characteristics (area under the curve 0.942). CONCLUSIONS: Early death or WOLST after ICH within 24 h of presentation was most associated with DNR/DNI code status, warfarin use, ICH score, and lower level of consciousness at presentation. These characteristics may be used by clinicians to guide conversations prior to transfer to tertiary care centers.

Incidence and Predictive Factors Associated with Beta-Lactam Neurotoxicity in the Critically Ill: A Retrospective Cohort Study.

BACKGROUND: Beta-lactam neurotoxicity is a relatively uncommon yet clinically significant adverse effect in critically ill patients. This study sought to define the incidence of neurotoxicity, derive a prediction model for beta-lactam neurotoxicity, and then validate the model in an independent cohort of critically ill adults. METHODS: This retrospective cohort study evaluated critically ill patients treated with ≥ 48 h of cefepime, piperacillin/tazobactam, or meropenem. Two separate cohorts were created: a derivation cohort and a validation cohort. Patients were screened for beta-lactam neurotoxicity by using search terms and diagnosis codes, followed by clinical adjudication using a standardized adverse event scoring tool. Multivariable regression models and least absolute shrinkage and selection operator were used to identify surrogates for neurotoxicity and develop a multivariable prediction model. RESULTS: The overall incidence of beta-lactam neurotoxicity was 2.6% (n/N = 34/1323) in the derivation cohort and 2.1% in the validation cohort (n/N = 16/767). The final multivariable neurotoxicity assessment tool included weight, Charlson comorbidity score, age, and estimated creatinine clearance as predictors of neurotoxicity. Incidence of neurotoxicity reached 4% in those with a body mass index more than 30 kg/m2. Use of the candidate variables in the neurotoxicity assessment tool suggested that a score more than 35 would identify a patient at high risk for neurotoxicity with 75% sensitivity and 54% specificity. CONCLUSIONS: In this single center cohort of critically ill patients, beta-lactam neurotoxicity was demonstrated less frequently than previously reported. We identified obesity as a novel risk factor for the development of neurotoxicity. The prediction model needs to be further refined before it can be used in clinical practice as a tool to avoid drug-related harm.

CT-Negative Subarachnoid Hemorrhage in the First Six Hours.

BACKGROUND: There are no reported cases of negative CT head in the first six hours after a thunderclap headache in a patient found to have an aneurysmal subarachnoid hemorrhage (SAH). METHODS: We present a case of an anemic patient who experienced aneurysmal SAH with a negative head CT within the first 6 h following thunderclap headache. RESULTS: A 47-year-old woman presented with a thunderclap headache and examination showed somnolence and marked meningismus. After a negative CT head was obtained within the first 6 hours of symptom onset, a non-traumatic lumbar puncture (LP) showed consistently bloody collection tubes, prompting repeat imaging that demonstrated a tiny amount of intraventricular hemorrhage. CT angiography revealed an intradural carotid artery aneurysm, and pipeline embolization was successfully performed. CONCLUSION: Non-contrast head CT may be falsely negative within the first 6 hours of aneurysmal SAH in the setting of anemia. In our case, the cause may not have been determined if an LP had not been performed. LP still has a role in diagnosing SAH, particularly in the setting of significant anemia, despite the high sensitivity of non-contrast head CT.

The Clinical Spectrum of New-Onset Status Epilepticus.

OBJECTIVES: There is a paucity of data on patients with new-onset status epilepticus in patients without a prior history of epilepsy; we aimed to describe clinical characteristics and assess variables predictive of outcomes. DESIGN: Retrospective cohort. SETTING: Quaternary academic medical center. PATIENTS: Adult patients with new-onset status epilepticus. METHODS: Retrospective review of adults with new-onset status epilepticus admitted to Mayo Clinic, Rochester MN between January 1, 1990, and December 31, 2015, was performed. Patient demographics, status epilepticus etiology, Status Epilepticus Severity Score, and status epilepticus classification per the Status Epilepticus Severity Score were recorded. Six-month mortality and functional outcomes defined as modified Rankin scale (≥3 at last follow-up was considered poor) were primary outcomes. Refractory status epilepticus was a secondary outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred seventy-seven patients were included. Status epilepticus was convulsive in 124 (70.1%) and nonconvulsive in 53 (29.9%); 96 cases (54.2%) were refractory status epilepticus. Mean age at onset was 63 ± 18 years; 52.5% were greater than or equal to 65 years. Etiologies were acute in 50.8%, progressive in 18.1%, remote in 19.2%, and unknown in 11.9% patients. Six-month mortality was 32.2%, and 70.1% had poor modified Rankin scale at mean follow-up 3.1 ± 3.5 years. Age greater than or equal to 65 was a significant predictor of poor functional outcome and 6-month mortality. Loss of consciousness, status epilepticus classification, or age greater than or equal to 65 did not predict progression to refractory status epilepticus. Progression to refractory status epilepticus did not impact functional outcome or mortality at last follow-up. CONCLUSIONS: Poor outcomes in new-onset status epilepticus were associated with older age as well as predominantly progressive or remote symptomatic disease. Further prospective investigations assessing the course and outcomes of these patients would be useful in management and prognostication.

Causes of Death in Status Epilepticus.

OBJECTIVES: To determine the causes of death in patients with status epilepticus. To analyze the relative contributions of seizure etiology, seizure refractoriness, use of mechanical ventilation, anesthetic drugs for seizure control, and medical complications to in-hospital and 90-day mortality, hospital length of stay, and discharge disposition. DESIGN: Retrospective cohort. SETTING: Single-center neuroscience ICU. PARTICIPANTS: Patients with status epilepticus were identified by retrospective search of electronic database from January 1, 2011, to December 31, 2016. INTERVENTIONS: Review of electronic medical records. MEASUREMENTS AND MAIN RESULTS: Demographics, clinical characteristics, treatments, and outcomes were collected. Univariable and multivariable logistic regression analysis were used to determine whether the use of anesthetic drugs, mechanical ventilation, Status Epilepticus Severity Score, refractoriness of seizures, etiology of seizures, or medical complications were associated with in-hospital, 90-day mortality or discharge disposition. Among 244 patients with status epilepticus (mean age was 64 yr [interquartile range, 42-76], 55% male, median Status Epilepticus Severity Score 3 [interquartile range, 2-4]), 24 received anesthetic drug infusions for seizure control. In-hospital and 90-day mortality rates were 9.2% and 19.2%, respectively. Death was preceded by withdrawal of life-sustaining treatment in 19 patients (86.3%) and cardiac arrest in three (13.7%). Only Status Epilepticus Severity Score was associated with in-hospital and 90-day mortality, whereas the use of anesthetic drugs for seizure control, mechanical ventilation, medical complications, etiology, and refractoriness of seizures were not. Hospital length of stay was longer in patients with medical complications (p = 0.0091), refractory seizures (p = 0.0077), and in those who required anesthetic drugs for seizure control (p = 0.0035). Patients who had refractory seizures were less likely to be discharged home (odds ratio, 0.295; CI, 0.143-0.608; p = 0.0009). CONCLUSIONS: In this cohort, death primarily resulted from the underlying neurologic disease and withdrawal of life-sustaining treatment and not from our treatment choices. Use of anesthetic drugs, medical complications, and mechanical ventilation were not associated with in-hospital and 90-day mortality.

Weaning from antiseizure drugs after new onset status epilepticus.

OBJECTIVE: In patients with status epilepticus (SE) without prior epilepsy, there are limited data on the safety of discontinuing antiseizure drugs (ASDs) after seizure control. We aimed to describe seizure recurrence when weaning from ASDs following new onset SE (NOSE). METHODS: Retrospective review of adult patients with NOSE admitted to Mayo Clinic, Rochester, Minnesota between January 1, 1990 and December 31, 2015 was performed. Weaning was defined as a discontinuation of ASDs following discharge. Patient demographics, SE characteristics, timing of ASD withdrawal, and seizure recurrence were collected. RESULTS: One hundred seventy-seven patients with mean age 63 ± 18 years were identified; 96 (54.2%) patients had refractory SE (RSE), and 81 (45.8%) had nonrefractory SE. Mean follow-up was 3.8 ± 3.2 years for those successfully weaned off ASDs. One hundred thirty (73.4%) with outpatient follow-up were included in the analysis; 128 (98.5%) patients were discharged on an ASD; 44 of 128 (34.4%) patients underwent weaning from at least 1 ASD following discharge, including 27 of 128 (21.1%) who were completely weaned off of all ASDs. Younger patients (P = 0.009) and those with RSE (P = 0.048, odds ratio = 2.12, 95% confidence interval = 1.00-4.48) tended to undergo weaning. Six of 44 (13.6%) patients had seizure recurrence when weaned off of any ASD, and two of 27 (7.4%) patients completely weaned off all ASDs had seizure recurrence. Two of seven (28.6%) patients who underwent attempted barbiturate weaning experienced seizure recurrence. SIGNIFICANCE: We found a rate of 13.6% for late seizure recurrence after weaning from at least one ASD in patients with NOSE; seizure recurrence was more likely in patients with RSE treated with barbiturates. Systematic collection of longitudinal data in patients requiring multiple ASDs for NOSE control will provide more conclusive guidance on weaning from ASDs.

Why do patients die after status epilepticus?

The epidemiology of status epilepticus (SE) and predictors of outcome in particular have been well described with consistent findings around the world. Understanding of the actual causes of death in patients hospitalized with SE is limited. The following is a summary of published information about causes of death in patients hospitalized with SE and a reconciling of conflicting studies examining the influence of continuous intravenous anesthetic drugs on the mortality of SE. A recently published paper was presented at the Colloquium and is summarized here, along with new data addressing an audience question about withdrawal of care in SE. In the spirit of the conference, we end with a call to arms and invitation for collaborators. Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

The anesthetic drug treatment of refractory and super-refractory status epilepticus around the world: Results from a global audit.

Multinational and multicenter registries collecting cases of refractory and super-refractory status epilepticus help to understand what the current practice in the treatment of such conditions is and can improve the rational therapy. We prospectively collected 776 cases of refractory status epilepticus requiring continuous intravenous anesthetic drugs in an intensive care unit setting, through online questionnaires compiled by the treating physicians in 50 countries. Initiation of an intravenous anaesthetic drug was relatively delayed in middle-income compared with high-income countries. There were marked regional differences in the choice of initial intravenous anaesthetic drug. Generally, midazolam was the most commonly used initial anesthetic drug (56%), followed by propofol (35%), in Europe, propofol was preferred over midazolam. In addition to anesthesia, 26% of cases received some form of immunosuppression (with corticosteroids and/or intravenous immunoglobulin). In this observational study, outcome was not affected by choice or sequence of anesthetic drugs, and nor was the use of barbiturate anesthetics associated with poorer outcome. The proportion of patients responding to cycles of different anaesthetic drugs was high even after failure of the earlier anesthetics, but the neurological outcome progressively worsened the longer anaesthetic drugs were needed and the longer the status epilepticus continued. However, even in the 158 patients who required three or more different anaesthetic trials, 49% had seizure control on tapering the third anesthetic, and 20% had a good neurological outcome anywhere. For these reasons we believe that it is important to persist with therapy in patients who are intractable initially, especially as etiology, not the number of duration of anesthesia, is the primary determinant of prognosis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Anesthetic drugs for the treatment of status epilepticus.

Worsening pharmacoresistance to antiseizure drugs is common with ongoing excitotoxic neuronal and systemic injury. Early initiation of anesthetic drugs in refractory status epilepticus (RSE) may halt these processes while allowing time for treatment targeting the cause of the seizures. Current guidelines support the use of anesthetic drugs as the third line pharmacologic therapy in generalized convulsive status epilepticus but do not clearly define the indications for these drugs in other types of status epilepticus. There is wide practice variation in choice of third line therapy for RSE, but there is overall consensus that anesthetics should be initiated earlier in generalized convulsive status epilepticus than in nonconvulsive forms. More recently, doubt has been cast on the appropriateness of anesthetic treatment of RSE following a series of studies associating their use with higher mortality and morbidity. This suggests that efforts should focus on determination of who benefits most, optimal use, and prevention of refractoriness. The risk-benefit ratio of anesthetic use is discussed, with specific indications proposed. In addition, anesthetic dosing, supportive neurocritical care, electroencephalogram suppression target, and weaning of anesthesia are reviewed.

Parenteral phenobarbital in status epilepticus revisited: Mayo Clinic experience.

Despite phenobarbital (PB) being a key component in status epilepticus (SE) treatment algorithms for decades, it has fallen out of favor compared to newer nonsedating medications due to potential for respiratory suppression and prolonged sedation. We retrospectively analyzed all nonintubated patients with refractory SE treated with parenteral PB. Forty patients were identified as having received PB in the neurologic intensive care unit at Mayo Clinic over a 7-year period through our pharmacy dispensing database. Patients who received PB for maintenance therapy, those replenishing subtherapeutic levels, those who were already intubated, and those receiving PB for a non-SE indication were excluded. Clinical data, prior treatments, therapeutic response, and outcome were reviewed. Eight patients were identified. Ages ranged from 24 to 77 years (median = 64 years); all had focal SE, and none was comatose. Seizure activity improved acutely following PB administration in seven and stopped in six. Dosages ranged from 5 to 19.8 mg/kg (median = 10.1 mg/kg); none required intubation, and one received supplemental oxygen. Patients received a median of four antiepileptic drugs prior to PB. Median interval between first drug and PB was 23.5 hours. Glasgow Coma Scale score did not change following PB administration. One patient required intervention for hypotension. Moderate-dose parenteral PB was effective in attaining seizure control in a significant proportion of noncomatose refractory SE patients. None required ventilatory support. PB dosages below those in recent guidelines may be sufficient to stop SE without clinically significant cardiopulmonary complications.

Etiologies and characteristics of refractory status epilepticus cases in different areas of the world: Results from a global audit.

To describe the demographics, etiologies, types of status epilepticus (SE), and outcomes in people with refractory and super-refractory SE from around the world, we prospectively collected cases of refractory SE (RSE) treated with continuous intravenous anesthetic drugs in an intensive care unit setting through online questionnaires using "active surveillance." We collected information about 776 cases of RSE in 50 countries over 4 years. Control of SE was achieved in 74% of the cases. Neurologic outcomes were poor in 41% of patients, and 24% died. Good outcome was associated with younger age and a history of epilepsy. Etiology strongly influenced the outcome. Patients from Asia were younger, more frequently presented with convulsive SE, and were more frequently affected by infectious etiologies when compared with patients from Europe and the Americas. Despite these differences, outcomes were similar in all countries. Demographics of patients with RSE in a global audit are similar to those in prior single center series, providing evidence of generalizability of those studies. Important differences exist among patients with RSE from different regions of the world, but these do not seem to significantly influence patient outcomes.