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. (Crit Care Med 2018; 46:138–145) Key Words: convulsive status epilepticus; neurocritical care; neurointensive care treatment; systemic complication

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

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

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

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.; 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.; 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).; 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.; Clinicaltrials.gov (No. NCT03860467)

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

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

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.; Retrospective observational study.; Medical ICUs at a tertiary academic medical care center.; Consecutive patients with status epilepticus treated at the ICUs from 2012 to 2016 were included.; None.; 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).; 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

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 &lt; 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

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

To explore 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.; 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, ICU and hospital stay.; 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 non-anesthetic 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 with 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, ICU and hospital stay.; 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, ICU and hospital stays.; 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, ICU and hospital stays compared to the use of a second-line non-anesthetic antiseizure drug instead or prior to anesthetics, without an associated increase in complications

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

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.; 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.; 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.; 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).; 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

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

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