Seizure Detection by Critical Care Providers Using Amplitude-Integrated Electroencephalography and Color Density Spectral Array in Pediatric Cardiac Arrest Patients.

OBJECTIVES: Determine the accuracy and confidence of critical care medicine providers to identify seizures using amplitude-integrated electroencephalography versus amplitude-integrated electroencephalography combined with color density spectral array electroencephalography (aEEG + CDSA). DESIGN: Tutorial and questionnaire. SETTING: PICU. SUBJECTS: Pediatric critical care providers (attendings, fellows, and nurses). INTERVENTIONS: A standardized powerpoint tutorial on amplitude-integrated electroencephalography and color density spectral array followed by classification of 100 amplitude-integrated electroencephalography images and 100 amplitude-integrated electroencephalography combined with color density spectral array as displaying seizures or not displaying seizures. MEASUREMENTS AND MAIN RESULTS: Electroencephalography tracings were obtained from children monitored with continuous electroencephalography after cardiac arrest. The gold standard for seizure identification was continuous electroencephalography interpretation by a pediatric electroencephalographer. The same electroencephalography tracings were used to generate images containing only amplitude-integrated electroencephalography or aEEG + CDSA. Twenty-three critical care medicine providers underwent a 30-minute tutorial on amplitude-integrated electroencephalography and color density spectral array interpretation. They were then asked to determine if there were seizures on 100 amplitude-integrated electroencephalography images and 100 aEEG + CDSA. Amplitude-integrated electroencephalography seizure detection sensitivity was 77% (95% CI, 73%-80%), specificity of 65% (95% CI, 62%-67%), negative predictive value of 88% (95% CI, 86%-90%), and positive predictive value of 46% (95% CI, 43%-49%). For aEEG + CDSA, sensitivity was 77% (95% CI, 74%-81%), specificity of 68% (95% CI, 66%-71%), negative predictive value of 89% (95% CI, 87%-90%), and positive predictive value of 49% (95% CI, 46%-52%). Sensitivity for status epilepticus detection was 77% (95% CI, 71%-82%) with amplitude-integrated electroencephalography and 75% (95% CI, 69%-81%) with aEEG + CDSA. The addition of color density spectral array to amplitude-integrated electroencephalography did not improve seizure detection. However, 87% of critical care medicine providers qualitatively felt that combining both modalities increased their ability to detect seizures. CONCLUSIONS: Amplitude-integrated electroencephalography and aEEG + CDSA offer reasonable sensitivity and negative predictive value for seizure detection by critical care medicine providers. aEEG + CDSA did not improve seizure detection over amplitude-integrated electroencephalography alone although critical care medicine providers felt more confident using both tools combined. Amplitude-integrated electroencephalography and color density spectral array require further evaluation as a tool for screening for seizures and should only be used in conjunction with professional continuous electroencephalography review.

Early Electroencephalographic Background Features Predict Outcomes in Children Resuscitated From Cardiac Arrest.

OBJECTIVES: To determine 1) whether early electroencephalographic background features were associated with survival and neurologic outcomes among children resuscitated from cardiac arrest and not treated with therapeutic hypothermia and 2) if addition of electroencephalographic background to commonly used clinical criteria is more predictive of outcome than clinical criteria alone. DESIGN: Retrospective study. SETTING: PICU and Cardiac ICUs of a tertiary children's hospital. PATIENTS: Patients resuscitated from in-hospital or out-of-hospital cardiac arrest who underwent clinically indicated electroencephalographic monitoring and were not treated with therapeutic hypothermia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred twenty-eight patients underwent electroencephalographic monitoring within 1 day of return of spontaneous circulation. Background category was normal in four subjects (3%), slow-disorganized in 58 subjects (45%), discontinuous-burst suppression in 24 subjects (19%) and attenuated-flat in 42 subjects (33%). Forty-six subjects (36%) had a reactive electroencephalography. Twenty subjects (15%) had a seizure during electroencephalographic monitoring. Absence of reactivity (p < 0.001) and seizures (p = 0.04) were associated with worse electroencephalographic background category. After controlling for covariates, for each incrementally worse background score, the odds of death was 3.63 (95% CI, 2.18-6.0; p < 0.001) and the odds of unfavorable neurologic outcome was 4.38 (95% CI, 2.51-7.17; p = 0.001). CONCLUSIONS: Worse electroencephalographic background early after resuscitation from both in-hospital and out-of-hospital cardiac arrest is associated with increased odds of death and unfavorable neurologic outcomes at hospital discharge. These electroencephalographic background patterns may be used in addition to clinical criteria to support prognostic decision making.

Strategies to Maximize Enrollment in a Prospective Study of Comatose Children in the PICU.

OBJECTIVES: To analyze barriers to recruitment encountered during a prospective study in the PICU and evaluate strategies implemented to improve recruitment. DESIGN: Prospective observational study of continuous electroencephalogram monitoring in comatose children. SETTING: PICUs at four North American institutions. PATIENTS: Patients with a Glasgow Coma Scale score of less than or equal to 8 for at least an hour. INTERVENTIONS: Four strategies to increase recruitment were sequentially implemented. MEASUREMENTS AND MAIN RESULTS: The baseline enrollment rate was 2.1 subjects/mo, which increased following the single-site introduction of real-time patient screening using an online dashboard (4.5 subjects/mo), deferred consenting (5.2 subjects/mo), and weekend screening (6.1 subjects/mo). However, the subsequent addition of three new study sites was the greatest accelerator of enrollment (21 subjects/mo), representing a 10-fold increase from baseline (p < 0.0001). CONCLUSIONS: Identifying barriers to recruitment and implementing creative strategies to increase recruitment can successfully increase enrollment rates in the challenging ICU environment.

Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study.

OBJECTIVE: To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). STUDY DESIGN: This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. RESULTS: Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. CONCLUSIONS: After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures.

Electrographic status epilepticus is associated with mortality and worse short-term outcome in critically ill children.

OBJECTIVES: Electrographic seizures and electrographic status epilepticus are common in critically ill children. We aimed to determine whether electrographic seizures and electrographic status epilepticus are associated with higher mortality or worse short-term neurologic outcome. DESIGN: Prospective observational study. SETTING: PICU of a tertiary children's hospital. PATIENTS: Non-neonatal children admitted to a PICU with acute encephalopathy underwent continuous electroencephalographic monitoring. Electroencephalographs were scored as 1) no seizures, 2) electrographic seizures, or 3) electrographic status epilepticus. Covariates included age, acute neurologic disorder category, prior neurodevelopmental status, sex, and electroencephalographic background category. Outcomes were mortality and worsening of pediatric cerebral performance category from preadmission to PICU discharge. Chi-square analysis, Fisher's exact test, and multivariable logistic regression were used to evaluate the associations between electrographic seizures or electrographic status epilepticus and mortality or short-term neurologic outcome, using odds ratios and 95% confidence intervals. INTERVENTIONS: None. MAIN RESULTS: Two hundred children underwent continuous electroencephalographic monitoring. Eighty-four (42%) had seizures, which were categorized as electrographic seizures in 41 (20.5%) and electrographic status epilepticus in 43 (21.5%). Thirty-six subjects (18%) died, and 88 subjects (44%) had pediatric cerebral performance category worsening. In multivariable analysis, electrographic status epilepticus was associated with an increased risk of mortality (odds ratio 5.1; 95% confidence interval 1.4, 18; p = 0.01) and pediatric cerebral performance category worsening (odds ratio 17.3; 95% confidence interval 3.7, 80; p < 0.001), whereas electrographic seizures were not associated with an increased risk of mortality (odds ratio 1.3; 95% confidence interval 0.3, 5.1; p = 0.74) or pediatric cerebral performance category worsening (odds ratio 1.2; 95% confidence interval 0.4, 3.9; p = 0.77). CONCLUSIONS: Electrographic status epilepticus, but not electrographic seizures, is associated with mortality and worse short-term neurologic outcome in critically ill children with acute encephalopathy.

Electroencephalography monitoring in critically ill children: current practice and implications for future study design.

PURPOSE: Survey data indicate that continuous electroencephalography (EEG) (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multicenter studies evaluating the impact of electrographic seizures on outcome. METHODS: Eleven North American centers retrospectively enrolled 550 consecutive critically ill children who underwent CEEG. We collected data regarding subject characteristics, CEEG indications, and CEEG findings. KEY FINDINGS: CEEG indications were encephalopathy with possible seizures in 67% of subjects, event characterization in 38% of subjects, and management of refractory status epilepticus in 11% of subjects. CEEG was initiated outside routine work hours in 47% of subjects. CEEG duration was <12 h in 16%, 12-24 h in 34%, and >24 h in 48%. Substantial variability existed among sites in CEEG indications and neurologic diagnoses, yet within each acute neurologic diagnosis category a similar proportion of subjects at each site had electrographic seizures. Electrographic seizure characteristics including distribution and duration varied across sites and neurologic diagnoses. SIGNIFICANCE: These data provide a systematic assessment of recent CEEG use in critically ill children and indicate variability in practice. The results suggest that multicenter studies are feasible if CEEG monitoring pathways can be standardized. However, the data also indicate that electrographic seizure variability must be considered when designing studies that address the impact of electrographic seizures on outcome.

Electrographic status epilepticus and long-term outcome in critically ill children.

OBJECTIVE: Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in children in the pediatric intensive care unit (PICU) with acute neurologic conditions. We aimed to determine whether ES or ESE was associated with worse long-term outcomes. METHODS: Three hundred children with an acute neurologic condition and encephalopathy underwent clinically indicated EEG monitoring and were enrolled in a prospective observational study. We aimed to obtain follow-up data from 137 subjects who were neurodevelopmentally normal before PICU admission. RESULTS: Follow-up data were collected for 60 of 137 subjects (44%) at a median of 2.7 years. Subjects with and without follow-up data were similar in clinical characteristics during the PICU admission. Among subjects with follow-up data, ES occurred in 12 subjects (20%) and ESE occurred in 14 subjects (23%). Multivariable analysis indicated that ESE was associated with an increased risk of unfavorable Glasgow Outcome Scale (Extended Pediatric Version) category (odds ratio 6.36, p = 0.01) and lower Pediatric Quality of Life Inventory scores (23 points lower, p = 0.001). Among subjects without prior epilepsy diagnoses ESE was associated with an increased risk of subsequently diagnosed epilepsy (odds ratio 13.3, p = 0.002). ES were not associated with worse outcomes. CONCLUSIONS: Among children with acute neurologic disorders who were reported to be neurodevelopmentally normal before PICU admission, ESE but not ES was associated with an increased risk of unfavorable global outcome, lower health-related quality of life scores, and an increased risk of subsequently diagnosed epilepsy even after adjusting for neurologic disorder category, EEG background category, and age.

Treatment of electrographic seizures and status epilepticus in critically ill children: a single center experience.

PURPOSE: Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in encephalopathic children in the pediatric intensive care unit (PICU) and associated with worse short-term outcome. Survey data indicate most physicians treat ES and ESE with antiepileptic drugs (AEDs), but few data are available regarding AED usage patterns. We aimed to describe AED usage for ES and ESE in critically ill children. METHODS: We performed an observational study of patients who underwent continuous electroencephalographic (cEEG) monitoring in the PICU of a single quaternary care children's hospital. We collected data regarding age, clinical diagnoses, ES and ESE occurrence, and AEDs utilized. RESULTS: 200 subjects underwent cEEG. ES occurred in 21% (41/200) and ESE occurred in 22% (43/200). Of the 84 patients with ES or ESE, 80 received non-benzodiazepine AEDs including 48% (38 of 80) with ES and 52% (42 of 80) with ESE. The most commonly administered first AEDs were levetiracetam in 38% (30/80), phenobarbital in 31% (25/80), phenytoin-fosphenytoin in 28% (22/80), and valproate in 4% (3/80). Seizures terminated after administration of the first AED in 74% (28/38) with ES and 22% (9/41) with ESE. CONCLUSIONS: Levetiracetam, phenobarbital, and phenytoin-fosphenytoin are commonly used to manage ES and ESE at our center. Over half of subjects received multiple AEDs.

Density spectral array for seizure identification in critically ill children.

PURPOSE: We evaluated the validity and interrater reliability of encephalographer interpretation of color density spectral array EEG for seizure identification was evaluated in critically ill children and explored predictors of accurate seizure identification. METHODS: Conventional EEG tracings from 21 consecutive critically ill children were scored for electrographic seizures. Four 2-hour long segments from each subject were converted to 8-channel color density spectral array displays, yielding 84 images. Eight encephalographers received color density spectral array training and circled elements thought to represent seizures. Images were reviewed in random order (Group A) or with information regarding seizure presence in the initial 30 minutes and with subject images in order (Group B). Sensitivity, specificity, and interrater reliability were calculated. Factors associated with color density spectral array seizure identification were assessed. RESULTS: Seizure prevalence was 43% on conventional EEG. Specificity was significantly higher for Group A than Group B (92.3% vs. 78.2%, P < 0.00). Sensitivity was not significantly different between Groups A and B (64.8% vs. 75%, P = 0.22). Interrater reliability was moderate in both groups. Ten percent of images were falsely classified as containing a seizure. Seizure duration ≥2 minutes predicted identification (P < 0.001). CONCLUSIONS: Color density spectral array may be a useful screening tool for seizure identification by encephalographers, but it does not identify all seizures and false positives occur.

Pediatric ICU EEG monitoring: current resources and practice in the United States and Canada.

PURPOSE: To describe current continuous EEG monitoring (cEEG) utilization in critically ill children. METHODS: An online survey of pediatric neurologists from 50 US and 11 Canadian institutions was conducted in August 2011. RESULTS: Responses were received from 58 of 61 (95%) surveyed institutions. Common cEEG indications are altered mental status after a seizure or status epilepticus (97%), altered mental status of unknown etiology (88%), or altered mental status with an acute primary neurologic condition (88%). The median number of patients undergoing cEEG per month per center increased from August 2010 to August 2011 (6 to 10 per month in the United States; 2 to 3 per month in Canada). Few institutions have clinical pathways addressing cEEG use (31%). Physicians most commonly review cEEG twice per day (37%). There is variability regarding which services can order cEEG, the degree of neurology involvement, technologist availability, and whether technologists perform cEEG screening. CONCLUSIONS: Among the surveyed institutions, which included primarily large academic centers, cEEG use in pediatric intensive care units is increasing and is often considered indicated for children with altered mental status at risk for nonconvulsive seizures. However, there remains substantial variability in cEEG access and utilization among institutions.

Electrographic seizures in pediatric ICU patients: cohort study of risk factors and mortality.

OBJECTIVES: We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality. METHODS: Eleven sites in North America retrospectively reviewed a total of 550 consecutive children in pediatric intensive care units who underwent EEG monitoring. We collected data on demographics, diagnoses, clinical seizures, mental status at EEG onset, EEG background, interictal epileptiform discharges, electrographic seizures, intensive care unit length of stay, and in-hospital mortality. RESULTS: Electrographic seizures occurred in 162 of 550 subjects (30%), of which 61 subjects (38%) had electrographic status epilepticus. Electrographic seizures were exclusively subclinical in 59 of 162 subjects (36%). A multivariable logistic regression model showed that independent risk factors for electrographic seizures included younger age, clinical seizures prior to EEG monitoring, an abnormal initial EEG background, interictal epileptiform discharges, and a diagnosis of epilepsy. Subjects with electrographic status epilepticus had greater odds of in-hospital death, even after adjusting for EEG background and neurologic diagnosis category. CONCLUSIONS: Electrographic seizures are common among children in the pediatric intensive care unit, particularly those with specific risk factors. Electrographic status epilepticus occurs in more than one-third of children with electrographic seizures and is associated with higher in-hospital mortality.