No abstract

This study provides Class III evidence that patients with SE receiving IVADs have a higher proportion of infection and an increased risk of death as compared to patients not receiving IVADs.

Evidence for an association between antibiotic drugs and symptomatic seizures is low to very low (evidence Class III-IV). Despite this, numerous reports point to an increased risk for symptomatic seizures especially of unsubstituted penicillins, fourth-generation cephalosporins, imipenem, and ciprofloxacin in combination with renal dysfunction, brain lesions, and epilepsy. During administration of such antibiotics in patients with particular predispositions, close monitoring of serum levels is advocated. As most seizures associated with cephalosporins are nonconvulsive, continuous EEG should be considered in patients with altered levels of consciousness.

40-4.12; p = 0.001 and RR 2.81, 95%CI 1.59-4.96; p < 0.0001). The estimated hazard ratio of death was 3.1 (95% CI1.6-6.0; p = 0.001) for patients with HE and 1.1 (95% CI 0.5-2.3; p = 0.745) for patients with brain tumors. RSE duration and nonconvulsive status epilepticus in coma were independently associated with death (for every hour RR 1.001; 95%CI 1.00-1.002; p = 0.011 and RR 3.62; 95%CI 1.34-9.77; p = 0.005). Significance: Brain tumors and HE had high relative risks for death and were independently associated with mortality in our cohort of critically ill RSE patients. Other clinical characteristics, as well as the use of intravenous anesthetic drugs and mechanical ventilation, may not be strongly related to outcome and should therefore be used cautiously for informed decision making regarding treatment. KEY WORDS: Refractory status epilepticus, Mortality, Hypoxic encephalopathy, Brain tumor, Neurocritical care.Refractory status epilepticus (RSE) is one of the most life-threatening neurologic emergencies and is characterized by high morbidity and mortality. This severe condition heralds a worse prognosis than treatment-responsive status epilepticus (SE) (Holtkamp et al., 2005;Rossetti et al., 2005), and serious outcome is considered to be mainly related to its etiology. Most studies propose the definition of RSE as a persistent SE after failure of a first-line (intravenous benzodiazepines) and one second-line antiepileptic drug (AED) (mostly phenytoin, valproate, levetiracetam, or phenobarbital), whereas others suggest a SE duration of >60 min (Hanley and Kross, 1998;Mayer et al., 2002). Despite the clinical and socioeconomic impact of RSE, current knowledge relies almost exclusively on retrospective assessments, its management on small case series, and expert opinions (Mayer et al., 2002;Holtkamp et al., 2005;Leppert et al., 2005;Rossetti et al., 2005;Holtkamp, 2011;Rossetti & Lowenstein, 2011). These reports suggest a frequency of RSE of up to 43% of all SE episodes, with nearly all subjects needing critical care and pharmacologic coma induction. Beyond these series one recent prospective study assessed frequency and clinical predictors of RSE emergence, and reported a 40% mortality in a tertiary clinical setting. However, the small sample size of 29 RSE episodes hinders inferences regarding the individual impact of different comorbidities (Novy et al., 2010). In order to respond to the discrepancy of important clinical and socioeconomic impact on the one hand and lack of larger and quantifying studies on the other hand, the Innsbruck Colloquium on SE held in April 2009, underscored the urgent need for more investigations in this field.

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.

This study is the first independent external validation of the predictive accuracy of the Status Epilepticus Severity Score and its transportability to ICU patients with status epilepticus. Measures of discrimination and calibration indicated that Status Epilepticus Severity Score performed reasonably well on our cohort of ICU patients with status epilepticus. However, the specific optimal cutoff point for survival versus death in our cohort was different than proposed.

IMPORTANCE In critically ill patients with altered consciousness, continuous electroencephalogram (cEEG) improves seizure detection, but is resource-consuming compared with routine EEG (rEEG). It is also uncertain whether cEEG has an effect on outcome. OBJECTIVE To assess whether cEEG is associated with reduced mortality compared with rEEG. DESIGN, SETTING, AND PARTICIPANTS The pragmatic multicenter Continuous EEG Randomized Trial in Adults (CERTA) was conducted between 2017 and 2018, with follow-up of 6 months. Outcomes were assessed by interviewers blinded to interventions.The study took place at 4 tertiary hospitals in Switzerland (intensive and intermediate care units). Depending on investigators' availability, we pragmatically recruited critically ill adults having Glasgow Coma Scale scores of 11 or less or Full Outline of Responsiveness score of 12 or less, without recent seizures or status epilepticus. They had cerebral (eg, brain trauma, cardiac arrest, hemorrhage, or stroke) or noncerebral conditions (eg, toxic-metabolic or unknown etiology), and EEG was requested as part of standard care. An independent physician provided emergency informed consent. INTERVENTIONS Participants were randomized 1:1 to cEEG for 30 to 48 hours vs 2 rEEGs (20 minutes each), interpreted according to standardized American Clinical Neurophysiology Society guidelines. MAIN OUTCOMES AND MEASURES Mortality at 6 months represented the primary outcome. Secondary outcomes included interictal and ictal features detection and change in therapy. RESULTS We analyzed 364 patients (33% women; mean [SD] age, 63 [15] years). At 6 months, mortality was 89 of 182 in those with cEEG and 88 of 182 in those with rEEG (adjusted relative risk [RR], 1.02; 95% CI, 0.83-1.26; P = .85). Exploratory comparisons within subgroups stratifying patients according to age, premorbid disability, comorbidities on admission, deeper consciousness reduction, and underlying diagnoses revealed no significant effect modification. Continuous EEG was associated with increased detection of interictal features and seizures (adjusted RR, 1.26; 95% CI, 1.08-1.15; P = .004 and 3.37; 95% CI, 1.63-7.00; P = .001, respectively) and more frequent adaptations in antiseizure therapy (RR, 1.84; 95% CI, 1.12-3.00; P = .01). CONCLUSIONS AND RELEVANCE This pragmatic trial shows that in critically ill adults with impaired consciousness and no recent seizure, cEEG leads to increased seizure detection and modification of antiseizure treatment but is not related to improved outcome compared with repeated rEEG. Pending larger studies, rEEG may represent a valid alternative to cEEG in centers with limited resources.

Neurologic complications are reported frequently and with high occurrence rate, especially with venoarterial extracorporeal membrane oxygenation, and associated with high mortality calling for daily weaning from sedation and neuromuscular blockers for neurologic assessment and coagulation monitoring. The low quality of evidence indicates the need for higher quality studies in this context.