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.

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.

Calorie Intake During Status Epilepticus and Outcome: A 5-Year Cohort Study.

OBJECTIVES: Recommendations regarding nutrition during status epilepticus are lacking, and it is unclear whether restriction of calorie intake would result in beneficial effects or potential harm. We thus aimed to investigate associations between daily calorie intake and outcome in adult status epilepticus patients deriving from a 5-year cohort with a systematic and prospective collection of nutritional data. DESIGN: Retrospective observational study. SETTING: Medical ICUs at a tertiary academic medical care center. PATIENTS: Consecutive patients with status epilepticus treated at the ICUs from 2012 to 2016 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients with status epilepticus were monitored regarding nutrition support provided according to the guidelines. Relative risks of no return to baseline were estimated by Poisson regression with robust error variance and adjusted for potential confounders. Of 203 patients, 86 (42%) had return to baseline. Metabolic characteristics of patients with and without return to baseline did not differ. Patients without return to baseline received more calories and proteins per status epilepticus day, and increasing nutritional support was associated with ventilator-associated pneumonia (relative risk, 1.19; 95% CI, 1.09-1.28). Multivariable regression analysis revealed significant increases in relative risks for no return to baseline with every percent of days with nutrition (relative risk, 1.35; 95% CI, 1.05-1.74), with every 100 kcal (relative risk, 1.01; 95% CI, 1.002-1.01), and gram of protein intake (relative risk, 1.01; 95% CI, 1.001-1.01) per status epilepticus day, independent of potential confounders (including fatal etiology, duration and severity of status epilepticus, Charlson comorbidity index, and treatment with anesthetics). CONCLUSIONS: Our results indicate that increased calorie intake during status epilepticus is independently associated with unfavorable outcome. These findings require further validation and investigations into potential mediators, such as induction of ketogenesis, immunomodulating effects, and/or reduction of ICU-associated complications, such as infections.

Prolonged status epilepticus: Early recognition and prediction of full recovery in a 12-year cohort.

OBJECTIVES: Early identification of patients who are at risk of prolonged status epilepticus (SE) and patients with high chances of full recovery despite prolonged SE may urge clinicians to intensify treatment rather than to withdraw care. We aimed to develop prediction models based on readily available clinical parameters to predict prolonged SE at seizure onset and to identify patients with high chances for full recovery. METHODS: From 2005 to 2016, all adult SE patients treated at the University Hospital Basel, a Swiss medical care center, were included. Multivariable Poisson regression was performed to identify predictors of prolonged SE (defined as SE for >12, >24, and >48 hours) and return to baseline from prolonged SE. The area under the receiver-operating characteristic curves (AUROC) for prediction models was calculated. RESULTS: Of 467 patients, the median age was 66.7 years and mortality was 12%. Relative risk (RR) for death was 1.06 (P < 0.0001) with every SE day. In multivariable analysis, nonconvulsive SE with coma, SE severity score ≥3, and acute brain lesions at SE onset independently predicted prolonged SE with an AUROC of 0.68 for >12, 0.67 for >24, and 0.72 for >48 hours of SE. Absence of nonconvulsive SE with coma and a decreasing Charlson comorbidity index were independent predictors for return to baseline in prolonged SE with an AUROC of 0.82 and 0.76 following cross-validation. Both associations remained significant despite adjustments for determinants of adverse outcome, such as anesthetics and vasopressors (nonconvulsive SE with coma RR = 0.24, 95% confidence interval [CI] 0.07-0.86; comorbidity index RR = 0.87, 95% CI 0.76-0.99). SIGNIFICANCE: Although our data indicate that identification of prolonged SE at seizure onset is unreliable, timely recognition of patients with high chances of good outcome despite prolonged SE is promising on the basis of comorbidities, type of SE, and level of consciousness. Further external validation of this prediction model is needed.

Illness severity scoring in status epilepticus-When STESS meets APACHE II, SAPS II, and SOFA.

OBJECTIVE: To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction. METHODS: The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed. RESULTS: Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.77-0.93 and OR = 1.34, 95% CI = 1.05-1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06-1.25). SIGNIFICANCE: Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.

Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review.

OBJECTIVES: Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. DATA SOURCES: We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. STUDY SELECTION: All identified studies were screened for eligibility by two independent reviewers. DATA EXTRACTION: Key data were extracted using standardized data collection forms. DATA SYNTHESIS: Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. CONCLUSIONS: Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.

Associations between periodic social events and status epilepticus-An 11-year cohort study.

OBJECTIVES: Periodic social events may influence the incidence and course of status epilepticus (SE), likely explained by patients' behavioral changes regarding alcohol intake, sleep, and compliance with antiseizure medication. However, data regarding the association between such events and SE are lacking. The aim of this study was to identify and quantify associations between periodic social events and the incidence, etiology, and outcome of SE. METHODS: Adult patients who were admitted to a tertiary academic medical care center with SE from 2005 to 2015 were included. Associations between periodic social events (including birthday, Christmas, New Year's Eve, carnival, national holiday) and the number and etiologies of SE over time were calculated using linear and Poisson regression. Logistic regression was applied to identify associations between time from social events and outcome. RESULTS: Four hundred nine patients with a median age of 66 years (interquartile range 52-76) were analyzed. The number of total SE events and SE in patients with known epilepsy peaked within 2 weeks following social events and then decreased with each additional day (incidence rate ratio [IRR]per day 0.99, 95% confidence interval [CI] 0.98-0.99; P < .001 and IRRper day 0.99, 95% CI 0.98-0.99; P < .001, respectively) and week (IRRper week 0.94, 95% CI 0.93-0.95; P < .001 and IRRper week 0.94, 95% CI 0.92-0.96; P < .001, respectively). The highest proportion of epilepsy patients not taking antiseizure medication was seen closest to social events and decreased thereafter (IRRper day 0.99, 95% CI 0.98-0.99; P = .003). There was no association between time from social events and outcome. SIGNIFICANCE: Our findings support the hypothesis that periodic social events in adults may be associated with an increase in SE and should heighten awareness for SE in this context. Clinicians are urged to inform epilepsy patients regarding this association and to instruct them on preventive measures around such events.

Association Between Dose Escalation of Anesthetics and Outcomes in Patients With Refractory Status Epilepticus.

BACKGROUND AND OBJECTIVES: To investigate the association between dose escalation of continuously administered IV anesthetics and its duration with short-term outcomes in adult patients treated for refractory status epilepticus (RSE). METHODS: Clinical and electroencephalographic data of patients with RSE without hypoxic-ischemic encephalopathy who were treated with anesthetics at a Swiss academic medical center from 2011 to 2019 were assessed. The frequency of anesthetic dose escalation (i.e., dose increase) and its associations with in-hospital death or return to premorbid neurologic function were primary endpoints. Multivariable logistic regression analysis was performed to identify associations with endpoints. RESULTS: Among 111 patients with RSE, doses of anesthetics were escalated in 57%. Despite patients with dose escalation having a higher morbidity (lower Glasgow Coma Scale [GCS] score at status epilepticus [SE] onset, more presumably fatal etiologies, longer duration of SE and intensive care, more infections, and arterial hypotension) as compared with patients without, the primary endpoints did not differ between these groups in univariable analyses. Multivariable analyses revealed decreased odds for death with dose escalation (odds ratio 0.09, 95% CI 0.01-0.86), independent of initial GCS score, presumably fatal etiology, SE severity score, SE duration, and nonconvulsive SE with coma, with similar functional outcome among survivors compared with patients without dose escalation. DISCUSSION: Our study reveals that anesthetic dose escalation in adult patients with RSE is associated with decreased odds for death without increasing the proportion of surviving patients with worse neurofunctional state than before RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anesthetic dose escalation decreases the odds of death in patients with RSE.

Comparing Patients With Isolated Seizures and Status Epilepticus in Intensive Care Units: An Observational Cohort Study.

BACKGROUND AND OBJECTIVES: To assess the frequency of status epilepticus (SE) among seizing critically ill adult patients and to determine clinical differences between patients with isolated seizures and patients with SE in the intensive care unit (ICU). METHODS: From 2015 to 2020, all consecutive adult ICU patients at a Swiss tertiary care center with isolated seizures or SE as reported by intensivists and/or consulting neurologists were identified by screening of all digital medical, ICU, and EEG records. Patients aged <18 years and patients with myoclonus due to hypoxic-ischemic encephalopathy but without seizures on EEG were excluded. The frequency of isolated seizures, SE, and clinical characteristics at seizure onset associated with SE were the primary outcomes. Uni- and multivariable logistic regression was performed to identify associations with the emergence of SE. RESULTS: Among 404 patients with seizures, 51% had SE. Compared with patients with isolated seizures, patients with SE had a lower median Charlson Comorbidity Index (CCI) (3 vs 5, p < 0.001), fewer fatal etiologies (43.6% vs 80.5%, p < 0.001), higher median Glasgow coma scores (7 vs 5, p < 0.001), fever more frequently (27.5% vs 7.5%, p < 0.001), shorter median ICU and hospital stay (ICU: 4 vs 5 days, p = 0.039; hospital stay: 13 vs 15 days, p = 0.045), and recovered to premorbid function more often (36.8% vs 17%, p < 0.001). Multivariable analyses revealed decreased odds ratios (ORs) for SE with increasing CCI (OR 0.91, 95% CI 0.83-0.99), fatal etiology (OR 0.15, 95% CI 0.08-0.29), and epilepsy (OR 0.32, 95% CI 0.16-0.63). Systemic inflammation was an additional association with SE after excluding patients with seizures as the reason for ICU admission (ORfor CRP 1.01, 95% CI 1.00-1.01; ORfor fever 7.35, 95% CI 2.84-19.0). Although fatal etiologies and increasing CCI remained associated with low odds for SE after excluding anesthetized patients and hypoxic-ischemic encephalopathy, inflammation remained associated in all subgroups except patients with epilepsy. DISCUSSION: Among all ICU patients with seizures, SE emerged frequently and seen in every second patient. Besides the unexpected low odds for SE with higher CCI, fatal etiology, and epilepsy, the association of inflammation with SE in the critically ill without epilepsy represents a potential treatment target and deserves further attention.

Association Between Induced Burst Suppression and Clinical Outcomes in Patients With Refractory Status Epilepticus: A 9-Year Cohort Study.

BACKGROUND AND OBJECTIVES: To investigate the frequency of induced EEG burst suppression pattern during continuous IV anesthesia (IVAD) and associated outcomes in adult patients treated for refractory status epilepticus (RSE). METHODS: Patients with RSE treated with anesthetics at a Swiss academic care center from 2011 to 2019 were included. Clinical data and semiquantitative EEG analyses were assessed. Burst suppression was categorized as incomplete burst suppression (with ≥20% and <50% suppression proportion) or complete burst suppression (with ≥50% suppression proportion). The frequency of induced burst suppression and association of burst suppression with outcomes (persistent seizure termination, in-hospital survival, and return to premorbid neurologic function) were the endpoints. RESULTS: We identified 147 patients with RSE treated with IVAD. Among 102 patients without cerebral anoxia, incomplete burst suppression was achieved in 14 (14%) with a median of 23 hours (interquartile range [IQR] 1-29) and complete burst suppression was achieved in 21 (21%) with a median of 51 hours (IQR 16-104). Age, Charlson comorbidity index, RSE with motor symptoms, the Status Epilepticus Severity Score and arterial hypotension requiring vasopressors were identified as potential confounders in univariable comparisons between patients with and without any burst suppression. Multivariable analyses revealed no associations between any burst suppression and the predefined endpoints. However, among 45 patients with cerebral anoxia, induced burst suppression was associated with persistent seizure termination (72% without vs 29% with burst suppression, p = 0.004) and survival (50% vs 14% p = 0.005). DISCUSSION: In adult patients with RSE treated with IVAD, burst suppression with ≥50% suppression proportion was achieved in every fifth patient and not associated with persistent seizure termination, in-hospital survival, or return to premorbid neurologic function.

Seizures and risks for recurrence in critically ill patients: an observational cohort study.

BACKGROUND: To assess the frequency and clinical characteristics of seizures in adult critically ill patients, to identify predictors of recurrent seizures not transforming into status epilepticus and to characterize their effects on course and outcome. METHODS: ICU patients at a Swiss academic medical center with seizures not transforming into status epilepticus from 2015 to 2020 were included. Recurrent seizures and associated clinical characteristics were primary, death, and return to premorbid neurologic function were secondary outcomes. RESULTS: Two hundred of 26,370 patients (0.8%) with a median age of 65 years had seizures during ICU stay. Seizure semiology was described in 82% (49% generalized; 33% focal) with impaired consciousness during seizures in 80% and motor symptoms in 62%. Recurrent seizures were reported in 71% (36% on EEG) and associated with longer mechanical ventilation (p = 0.031), higher consultation rate by neurologists (p < 0.001), and increased use of EEG (p < 0.001) when compared to single seizures. The use of EEG was not associated with secondary outcomes. Acidosis at seizure onset and prior emergency operations were associated with decreased odds for seizure recurrence (OR 0.43; 95% CI 0.20-0.94 and OR 0.48; 95% CI 0.24-0.97). Epilepsy had increased odds for seizure recurrence (OR 3.56; 95% CI 1.14-11.16). CONCLUSIONS: Seizures in ICU patients are infrequent, but mostly recurrent, and associated with higher resource utilization. Whenever seizures are observed, clinicians should be vigilant about the increased risk of seizures recurrence and the need for antiseizure treatment must be carefully discussed. While known epilepsy seems to promote recurrent seizures, our results suggest that both acidosis and previous emergency surgery seem to have protective/antiseizure effects. TRIAL REGISTRATION: Clinicaltrials.gov (No. NCT03860467).

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

OBJECTIVE: To test the accuracy of an equation in adult patients with status epilepticus that calculates the free concentration of serum valproic acid (fVPA) from the total concentration of serum valproic acid (tVPA) and serum albumin. METHODS: All adult patients with status epilepticus who 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. RESULTS: Of 676 patients with status epilepticus, 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 (regression coefficient 1.1, 95% confidence interval 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. CONCLUSIONS: Calculated fVPA is inaccurate when using the proposed equation in adult patients with status epilepticus, calling for drug monitoring based on measured fVPA in this context.

Safety and Efficacy of Coma Induction Following First-Line Treatment in Status Epilepticus: A 2-Center Study.

OBJECTIVE: To explore the safety and efficacy of artificial coma induction to treat status epilepticus (SE) immediately after first-line antiseizure treatment instead of following the recommended approach of first using second-line drugs. METHODS: Clinical and electrophysiologic data of all adult patients treated for SE from 2017 to 2018 in the Swiss academic medical care centers from Basel and Geneva were retrospectively assessed. Primary outcomes were return to premorbid neurologic function and in-hospital death. Secondary outcomes were the emergence of complications during SE, duration of SE, and intensive care unit (ICU) and hospital stays. RESULTS: Of 230 patients, 205 received treatment escalation after first-line medication. Of those, 27.3% were directly treated with artificial coma and 72.7% with second-line nonanesthetic antiseizure drugs. Of the latter, 16.6% were subsequently put on artificial coma after failure of second-line treatment. Multivariable analyses revealed increasing odds for coma induction after first-line treatment with younger age, the presence of convulsions, and an increased SE severity as quantified by the Status Epilepticus Severity Score (STESS). While outcomes and complications did not differ compared to patients with treatment escalation according to the guidelines, coma induction after first-line treatment was associated with shorter SE duration and ICU and hospital stays. CONCLUSIONS: Early induction of artificial coma is performed in more than every fourth patient and especially in younger patients presenting with convulsions and more severe SE. Our data demonstrate that this aggressive treatment escalation was not associated with an increase in complications but with shorter duration of SE and ICU and hospital stays. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that early induction of artificial coma after unsuccessful first-line treatment for SE is associated with shorter duration of SE and ICU and hospital stays compared to the use of a second-line nonanesthetic antiseizure drug instead of or before anesthetics, without an associated increase in complications.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Untangling operational failures of the Status Epilepticus Severity Score (STESS).

OBJECTIVE: To uncover clinical characteristics leading to false outcome prediction of the Status Epilepticus Severity Score (STESS), a validated and broadly used clinical scoring system for outcome prediction in status epilepticus (SE). METHODS: From 2005 to 2016, adult patients with SE treated at the University Hospital Basel, Switzerland, were included. To assess independent associations of variables differing between patients with false and correct prediction of death (STESS ≥ 3), multivariable logistic regression models were computed using automated selection. RESULTS: Among 467 patients, 12% died. The median STESS was 3 (interquartile range 2-4). Regarding prediction of death, the STESS was false-positive in 51% and false-negative in 1%. Patients surviving despite having a STESS ≥3 had less fatal etiologies, less nonconvulsive SE with coma, and lower Charlson Comorbidity Index, Simplified Acute Physiology Score II, and Acute Physiology and Chronic Health Evaluation II scores. In multivariable analyses, odds for survival were high with SE types other than nonconvulsive status with coma and low with an increasing Charlson Comorbidity Index in patients with a STESS ≥ 3 (odds ratio [OR]for survival 4.23, 95% confidence interval [CI] 2.33-9.60; and ORfor survival 0.86, 95% CI 0.75-0.98). In patients with SE types other than nonconvulsive with coma, the STESS was mainly increased because they were frequently older than 65 years and had no seizure history. CONCLUSIONS: The STESS frequently and inadequately predicts death especially in patients with SE other than nonconvulsive with coma and few comorbidities. Clinicians are urged to interpret a STESS ≥3 with caution in such patients.

Emergency response to out-of-hospital status epilepticus: A 10-year observational cohort study.

OBJECTIVE: To determine the implications of first responses of emergency medical services (EMS) to out-of-hospital status epilepticus (SE) on outcome. METHODS: From 2005 to 2014, prehospital and in-hospital data were assessed in consecutive adults admitted to an academic medical center with out-of-hospital SE. Logistic regression was performed to identify variables with a robust association between missed epileptic events by the EMS and no recovery to functional baseline in survivors. RESULTS: Among 213 SE patients, 150 were admitted via EMS. While nonconvulsive SE (NCSE) was missed by the EMS in 63.7%, convulsive SE (CSE) was not missed except in 4 patients with transformation into subtle SE. Missed NCSE was more likely with older age (odds ratio [OR]per year 1.06, 95% confidence interval [CI] 1.02-1.10, p = 0.003) and no seizure history (OR 6.64, 95% CI 2.43-18.1, p < 0.001). The area under the receiver operating characteristic curve for prediction of missed NCSE by these variables was 0.839. Independent predictors for not receiving benzodiazepines were increasing age (ORper year 1.05, 95% CI 1.01-1.08, p = 0.008) and higher Glasgow Coma Scale score (ORper increasing unit 1.21, 95% CI 1.09-1.36, p = 0.001). Missed NCSE was independently associated with increased odds for no return to functional baseline in survivors (OR 3.83, 95% CI 1.22-11.98, p = 0.021). CONCLUSIONS: Among patients admitted with out-of-hospital SE, CSE is mostly recognized while NCSE is frequently missed especially in patients with increasing age and no seizure history. This calls for heightened awareness for out-of-hospital NCSE in such patients, as missed NCSE is associated with lack of treatment and less recovery to functional baseline in survivors independent of established outcome predictors.

Anesthetics and Outcome in Status Epilepticus: A Matched Two-Center Cohort Study.

BACKGROUND: The use of anesthetics has been linked to poor outcome in patients with status epilepticus (SE). This association, however, may be confounded, as anesthetics are mostly administered in patients with more severe SE and critical illnesses. OBJECTIVE: To minimize treatment-selection bias, we assessed the association between continuously administered intravenous anesthetic drugs (IVADs) and outcome in SE patients by a matched two-center study design. METHODS: This cohort study was performed at the Johns Hopkins Bayview Medical Center, Baltimore, MD, USA and the University Hospital Basel, Basel, Switzerland. All consecutive adult SE patients from 2005 to 2013 were included. Odds ratios (ORs) for death and unfavorable outcome (Glasgow Outcome Score [GOS] 1-3) associated with administration of IVADs were calculated. To account for confounding by known outcome determinants (age, level of consciousness, worst seizure type, acute/fatal etiology, mechanical ventilation, and SE duration), propensity score matching and coarsened exact matching were performed in addition to multivariable regression models. RESULTS: Among 406 consecutive patients, 139 (34.2%) were treated with IVADs. Logistic regression analyses of the unmatched and matched cohorts revealed increased odds for death and unfavorable outcome in survivors who had received IVADs (unmatched: ORdeath = 3.13, 95% confidence interval [CI] 1.47-6.60 and ORGOS1-3 = 2.51, 95% CI 1.37-4.60; propensity score matched: ORdeath = 3.29, 95% CI 1.35-8.05 and ORGOS1-3 = 2.27, 95% CI 1.02-5.06; coarsened exact matched: ORdeath = 2.19, 95% CI 1.27-3.78 and ORGOS1-3 = 3.94, 95% CI 2.12-7.32). CONCLUSION: The use of IVADs in SE is associated with death and unfavorable outcome in survivors independent of known confounders and using different statistical approaches. Randomized trials are needed to determine if these associations are biased by outcome predictors not yet identified and hence not accounted for in this study.

Nonconvulsive status epilepticus in adults - insights into the invisible.

Nonconvulsive status epilepticus (NCSE) is a state of continuous or repetitive seizures without convulsions. Owing to the nonspecific symptoms and considerable morbidity and mortality associated with NCSE, clinical research has focused on early diagnosis, risk stratification and seizure termination. The subtle symptoms and the necessity for electroencephalographic confirmation of seizures result in under-diagnosis with deleterious consequences. The introduction of continuous EEG to clinical practice, and the characterization of electrographic criteria have delineated a number of NCSE types that are associated with different prognoses in several clinical settings. Epidemiological studies have uncovered risk factors for NCSE; knowledge of these factors, together with particular clinical characteristics and EEG observations, enables tailored treatment. Despite these advances, NCSE can be refractory to antiepileptic drugs, necessitating further escalation of treatment. The presumptive escalation to anaesthetics, however, has recently been questioned owing to an association with increased mortality. This Review compiles epidemiological, clinical and diagnostic aspects of NCSE, and considers current treatment options and prognosis.

Independent impact of infections on the course and outcome of status epilepticus: a 10-year cohort study.

Infections are frequent in patients with status epilepticus (SE). It remains unclear if infections merely reflect severity of the underlying illness or if they independently predict unfavourable course and outcome. We sought to determine if infections diagnosed within 48 h from SE onset are independent predictors of poor course and outcome and if their effect is modified by clinical characteristics. From 2005 to 2014, pertinent clinical data, microbiology, death, return to functional baseline, and unfavourable outcome in survivors were assessed in SE patients treated in the intensive care units (ICU) of an academic medical care center. Among 352 consecutive patients, 81 (23 %) were diagnosed with infections at SE onset. In-hospital mortality was higher in patients with infections (26 %) compared to 10 % in patients without infections (p < 0.001). Infections at SE onset increased the odds ratios (OR) for prolonged ICU (OR = 4.1, 95 %CI 1.87-6.74) and hospital stay (OR = 5.4, 95 %CI 1.24-9.63), refractory SE (OR = 3.1, 95 %CI 1.79-5.34), prolonged mechanical ventilation (OR = 3.8, 95 %CI 2.15-6.79), no return to functional baseline (OR = 2.1, 95 %CI 1.10-4.02), unfavourable outcome in survivors (OR = 2.0, 95 %CI 1.02-3.81), and death (OR = 2.5, 95 %CI 1.28-4.99). All associations were independent of confounders and without significant effect modification by age, level of consciousness, types and severity of SE, and etiologies. In addition, the number of infections increased the probability of unfavourable course and outcome. Infections at SE onset are frequent and associated with prolonged medical care, treatment refractory SE, higher morbidity and mortality independently of potential confounders calling for the evaluation of treatment strategies.