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Departments of Neurology and Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
Time to treatment of pediatric status epilepticus remains delayed.
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Multiple barriers to timely management exist in the pre- and in-hospital settings.
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Proposed interventions to improve time to treatment are reviewed.
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Status epilepticus should be recognized as a time-sensitive emergency.
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Acute intervention teams can be developed to improve status epilepticus management.
Abstract
Purpose
To identify areas of treatment delay and barriers to care in pediatric status epilepticus, review ongoing quality improvement initiatives, and provide suggestions for further innovations to improve and standardize these patient care processes.
Methods
Narrative review of current status epilepticus management algorithms, anti-seizure medication administration and outcomes associated with delays, and initiatives to improve time to treatment. Articles reviewing or reporting quality improvement initiatives were identified through a PubMed search with keywords “status epilepticus,” “quality improvement,” “guideline adherence,” and/or “protocol;” references of included articles were also reviewed.
Results
Rapid initiation and escalation of status epilepticus treatment has been associated with shortened seizure duration and more favorable outcomes. Current evidence-based guidelines for management of status epilepticus propose medication algorithms with suggested times for each management step. However, time to antiseizure medication administration for pediatric status epilepticus remains delayed in both the pre- and in-hospital settings. Barriers to timely treatment include suboptimal preventive care, inaccurate seizure detection, infrequent or restricted use of home rescue medications by caregivers and pre-hospital emergency personnel, delayed summoning and arrival of emergency personnel, and use of inappropriately dosed medications. Ongoing quality improvement initiatives in the pre- and in-hospital settings targeting these barriers are reviewed.
Conclusion
Improved preventive care, seizure detection, and rescue medication education may advance pre-hospital management, and we propose the use of acute status epilepticus intervention teams to initiate and incorporate in-hospital interventions as time-sensitive “Seizure Code” emergencies.
Status epilepticus (SE) is one of the most common pediatric neurologic emergencies, affecting between 17 and 23/100,000 children per year and 10–20% of pediatric epilepsy patients [
]. While etiology and age are the main predictors of outcome after SE, seizure duration may additionally affect outcome. Importantly, seizure duration is the only modifiable risk factor [
]. Studies have yielded mixed results regarding the impact of seizure duration and adherence to management guidelines. Some studies have identified no impact on outcome related to adherence to treatment guidelines [
]. Conversely, other studies have shown that rapid administration of antiseizure medications (ASMs) is associated with shorter seizure duration and more favorable outcomes including mortality [
]. The Neurocritical Care and American Epilepsy Societies have published evidence-based and consensus guidelines with SE management algorithms and suggested treatment timelines [
Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society.
Barriers to timely management may occur at any step of the care process, from preventive care and education to acute, in-hospital management. Even prior to SE occurrence, lack of regular epilepsy clinic appointments are associated with a higher risk of emergency department (ED) visits or hospital admissions [
With the identification of these barriers to timely SE management, multiple centers have taken on initiatives to improve management and time to ASM administration [
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
] invites means for improvement. Gaps remain and provide opportunities for ongoing innovation and improvement. This review summarizes current guidelines on pediatric SE management, outcomes associated with delayed treatment and prolonged seizures, and barriers to rapid management, highlighting approaches which might lead to optimized care.
2. Evidence guiding ASM choice and administration
Prompt administration of benzodiazepines is recommended as first-line treatment. In a double-blind trial, 273 children with convulsive SE were randomized to receive either intravenous (IV) lorazepam or diazepam. Seizure cessation occurred in 72% of subjects in each group without differences in need for assisted ventilation. The authors concluded that IV lorazepam has similar safety and efficacy when compared to diazepam [
]. Considering other benzodiazepine formulations when IV access is not available, a meta-analysis indicated that the most effective non-IV rescue medication for stopping seizures within 10 min of drug administration is intranasal midazolam, with rectal diazepam being less efficacious than both intranasal and buccal midazolam [
]. Additionally, in a cost-effectiveness analysis comparing non-IV first-line rescue medications, intranasal and buccal midazolam were the most cost-effective options while rectal diazepam was not cost-effective at any willingness to pay in the United States [
The cost effectiveness of licensed oromucosal midazolam (Buccolam((R))) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited.
Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society.
], and when IV access is not available then midazolam (intranasal, buccal or intramuscular) is potentially more effective than diazepam (IV or rectal) [
Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society.
Few studies have compared the effectiveness of second-line therapies. The ongoing Established Status Epilepticus Treatment Trial (ESETT) is evaluating levetiracetam, valproic acid, and fosphenytoin [
]. Other international pediatric trials comparing levetiracetam and phenytoin in benzodiazepine-resistant SE are additionally underway and may offer further evidence [
A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive status epilepticus paediatric trial (consept) - a predict study.
A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): convulsive Status Epilepticus Paediatric Trial (ConSEPT) – a PREDICT study.
Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: study protocol for a randomised controlled trial.
], fosphenytoin is chosen as the second-line ASM for the majority of children. A combined adult and pediatric meta-analysis comparing second-line ASM therapy reported that seizure cessation rates were 76%, 74%, 69%, and 50% with valproic acid, phenobarbital, levetiracetam, and phenytoin, respectively. This analysis concluded that there is insufficient evidence to support phenytoin as the preferred ASM in benzodiazepine-resistant SE [
The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies.
]. A recent comparison of IV levetiracetam to IV valproic acid in children found them to be equally effective, though valproic acid was associated with more adverse effects including liver dysfunction in 13% of cases [
]. Given these data, SE guidelines state that phenytoin, valproic acid, levetiracetam, and phenobarbital are appropriate second-line or urgent control therapy options, though there is currently insufficient evidence to suggest one ASM is preferred [
Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society.
]. Continuous infusions, including midazolam, pentobarbital, propofol, and ketamine, are considered appropriate management options for refractory SE treatments [
]. However, there are even fewer data available to guide selections between these options.
3. Time to treatment recommendations & outcomes associated with delays
The recommendation for rapid administration of first-line benzodiazepines in SE stems from in vitro and animal models demonstrating the pathophysiology of neuronal excitation, increasing medication pharmacoresistance with longer seizures, and brain injury with prolonged seizures. In in vitro models, ongoing seizure activity promotes internalization of synaptic gamma-aminobutyric acid (GABA)-receptors and thus decreases neuronal inhibition [
]. In a prospective study in children experiencing prolonged seizures, seizures lasting longer than 5–7 min were less likely to terminate spontaneously than shorter seizures [
Seizures induced by allylglycine, 3-mercaptopropionic acid and 4-deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase.
Epileptic brain damage in rats induced by sustained electrical stimulation of the perforant path: I. Acute electrophysiological and light microscopic studies.
]. One prospective, population-based United Kingdom study demonstrated that for each minute delay from onset of SE to arrival at the ED, there was a 5% cumulative increase in the risk of the episode lasting more than 60 min [
]. In another retrospective analysis, 73% of children with aggressive ASM treatment within 60 min after initial treatment returned to neurological baseline during long-term follow-up (mean duration of 3.9 years), while all children not aggressively treated experienced new neurologic deficits and continued to deteriorate at follow-up [
]. In a study of pediatric refractory SE, patients receiving an initial benzodiazepine after 10 min had higher odds of death (adjusted odds ratio (OR) 11.0), longer seizure duration (adjusted OR 2.6), higher rates of hypotension (adjusted OR 2.3), and higher likelihood of requiring continuous infusions (adjusted OR 1.8) than patients who received timely treatment [
In keeping with the management goal of rapid initiation and escalation of treatment, the 2012 Neurocritical Care Society consensus guideline recommends emergent initial ASM therapy (i.e. first-line treatment) within 5 min of seizure onset, urgent control ASM therapy (i.e. second-line treatment) within 5–10 min, and refractory SE therapy (i.e. third and fourth-line treatment) within 20–60 min [
]. The 2016 American Epilepsy Society evidence-based guideline suggests initiation of treatment with a benzodiazepine at 5 min of ongoing seizure, second-line therapy at 20–40 min, and either repeating second-line therapy or moving directly to a continuous infusion by 40 min [
Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society.
]. Fig. 1 summarizes a pediatric SE medication algorithm with a suggested timeline.
Fig 1Medication Algorithm and Suggested Time to Treatment A pediatric SE medication algorithm with a suggested timeline for medication administration is outlined. To follow this timeline, providers may order the next medication as the prior medication is administered. Optimal medication selections and doses may depend on efficacy data, patient and seizure characteristics, but also on institutional factors impacting which can be administered most rapidly. This is adapted from our institutional management plan in addition to those from the Neurocritical Care Society [
Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society.
Despite these adverse outcomes and proposed management guidelines, time to treatment is often delayed in pediatric SE. In a pediatric and adult cohort presenting with SE from 1989 to 1994, only 42% of patients received an ASM within 30 min of seizure onset.[
] Comparatively, two decades later, in a multicenter observational prospective pediatric refractory SE cohort from 2011 to 2013, only 38% of patients received an ASM before hospital arrival. Further, first, second, and third ASMs were administered at a median (interquartile range) time of 28 (6–67) minutes, 40 (20–85) minutes, and 59 (30–120) minutes after SE onset [
4. Barriers to timely management and methods of improving time to treatment
Barriers to timely SE management may occur at any step of the care process spanning suboptimal preventive care, pre-hospital seizure detection and management initiation, and in-hospital advanced treatment. Table 1 summarizes these areas of delay and proposed interventions.
Table 1Areas of Delay in Anti-Seizure Medication Administration and Proposed Interventions.
Area of Delay
Proposed Interventions
Lack of Preventive Care
–
Epilepsy urgent care clinics focusing on patient education and understanding [
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
4.1 Missed clinic visits and lack of preventive care and education
Problems accessing care may lead to higher ED use and subsequent hospitalization due to seizures in patients with epilepsy. A case-control single center study found that patients with a higher number of missed epilepsy clinic visits were more likely to have an unplanned ED visit or admission (OR = 5.7) [
]. A pediatric hospital employed multiple quality improvement initiatives aiming to reduce ED and hospital utilization. Patients with multiple missed clinic visits and high ED utilization were identified for an intervention that included an urgent care epilepsy clinic that was easily accessible to patients, social work involvement, and longer than standard appointments to ensure the caregiver(s) received epilepsy education and services. Initiating an urgent care epilepsy clinic had the largest impact on ED and hospital utilization, resulting in a 28% and 43% reduction in ED visits and hospitalizations, respectively. These modifications were estimated to have saved over $2 million in healthcare costs [
]. Another institution employed an epilepsy nurse navigator, a nurse dedicated to meeting with families for support and education. Those who met with the navigator experienced lower ED utilization (more than one ED visit in 4% with the navigator versus 52% without the navigator), hospital admissions, 30-day readmissions, and episodes of SE (0% with the navigator versus 9% without the navigator) [
]. These findings highlight that interventions aimed at improving access and adherence to clinic care and patient/caregiver education, targeting patients with multiple missed clinic visits and higher ED utilization/admission rates, may result in meaningful healthcare utilization and clinical improvements.
4.2 Seizure detection by caregivers/patients
In the pre-hospital setting, seizure detection may be delayed or missed entirely by patients and caregivers. Studies have shown that even healthcare professionals may not identify many clinical seizures [
]. Seizure detection devices may offer a way to quantify seizures, and algorithms may detect impending seizures prior to onset through the monitoring of movement and physiologic parameters [
]. The increasing sensitivity and specificity of seizure detection devices may improve care for patients with epilepsy in the near future, though currently their use remains limited in routine care [
]. In general, multimodal devices are felt to be most promising with a focus on pairing a device able to identify an individual patient’s specific seizure type(s) [
]. Newer devices include a portable EEG headset that can be set up within minutes and translates the electrical signal into sound for seizure detection and quantification [
]. Many caregivers report interest in this type of technology, though the accuracy and affordability and insurance coverage of the device were perceived as important [
]. Further review of seizure detection devices is discussed in another article in this edition.
4.3 Rescue medication use by caregivers and schools
Non-IV rescue medications available at home and school probably improve SE outcomes. In the United States, rectal diazepam is currently available in a ready-to-use, dialed dosage delivery system for out-of-hospital treatment of SE by nonmedical caregivers. Rectal diazepam has shown better efficacy [
]. In a retrospective review of pediatric patients, pre-hospital treatment with IV and rectal diazepam was associated with shorter seizure duration (32 versus 60 min in diazepam treatment versus no treatment groups, respectively) and fewer recurrent seizures after arrival to the ED (58% versus 85%) [
The cost effectiveness of licensed oromucosal midazolam (Buccolam((R))) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited.
]. Despite these readily available forms, a multicenter prospective observational study found that only 33% of patients with prior SE were administered a rescue medication by caregivers for a subsequent prolonged seizure [
A survey of caregivers of patients with epilepsy in the United States provided insight into the low usage of pre-hospital rescue medications. In this study, 29% of families reported not receiving training on how to use a recue medication [
]. Having a seizure action plan was a predictor of knowing the name of the rescue medication, knowing when to give the rescue medication, knowing what to do if a seizure continues despite the rescue medication, and having the medication available at school [
]. A study found that caregivers reported a high level of confidence administering buccal and rectal rescue medications, but clinically relevant drug-handling errors were identified in the majority of caregivers when observed giving medication to a mannequin, including 97% of caregivers administering rectal medication and 58% of caregivers administering buccal medication [
]. Therefore, simply prescribing the rescue medication may be insufficient. Rather, improved rescue medication education/training and use of a seizure action plan may improve caregiver comfort and appropriate use of rescue medications in the out-of-hospital setting. Of note, a pediatric cohort study found no decrease in healthcare utilization (ED visits, hospitalizations, or phone calls) before and after use of a seizure action plan [
], though the outcome measures of this study may not have been optimal to determine if the plan made a difference in other patient outcomes.
For school-aged children, the use of a seizure action plan and communication with the school is of particular importance since different school districts may have variable resources and legal requirements [
]. Another United States survey revealed school nurses feel less confident managing seizures than other pediatric emergencies, such as respiratory distress or anaphylaxis [
]. To intervene, a German study undertook a training program for preschool teachers and found that the training improved both level of confidence and competence with administering rectal and buccal seizure medications, improving rectal administration without error from 0.5% to 60% and buccal administration from 8% to 55% before and after training [
Time from seizure onset to arrival of emergency personnel and hospital transport is often delayed and without pre-hospital ASM administration. There are multiple potential time points for delay including caregivers calling/summoning EMS, activation and arrival of EMS, and seizure recognition by EMS providers. A review of pediatric and adult SE found that the median time to paramedic arrival was 13–30 min, time to ED arrival was 30–105 min, and that pre-hospital ASMs were administered to 34–51% of patients [
A study in adults analyzed components of delay in the pre-hospital setting and identified the most substantial sources of delay as delays calling paramedics, difficulty with administering a rectal medication, and inability of paramedics to administer a second-line ASM [
]. A recent study analyzing outcomes in pediatric SE patients treated by paramedics with or without completion of a pediatric simulation-based training course found pediatric trained paramedics were slightly more likely to administer a correct midazolam dose, though other outcomes did not differ between the two groups [
]. Thus, another management optimization approach is to improve knowledge and comfort with the management of pediatric emergencies by emergency personnel.
4.5 Medication use by pre-hospital emergency personnel
Thirty-six percent of children in a refractory SE cohort [
]. The FEBSTAT study showed time from EMS arrival to first ASM administration was a median of 10 min, suggesting that even after EMS arrival there is further delay in medication administration [
]. In the minority of patients who receive pre-hospital medication, management is most often limited to benzodiazepines and not second-line ASMs if benzodiazepines are ineffective. This was seen in the FEBSTAT study where only diazepam, lorazepam and midazolam were administered by EMS [
Pre-hospital medication algorithms for pediatric and adult SE from a single state in the United States provide highly varied recommendations regarding timeline, dosing, route and medications, often proposing low weight-based benzodiazepine dosing without mention of therapy beyond benzodiazepines [
There are currently no completed pediatric trials evaluating pre-hospital use of second-line therapy. In the adult literature, a randomized, double-blind, placebo-controlled superiority trial of pre-hospital use of clonazepam plus levetiracetam versus clonazepam plus placebo was conducted. The study ended early after finding no significant differences between groups (seizure cessation at 15 min in 84% versus 74% in the levetiracetam versus placebo groups) [
Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial.
] or use of levetiracetam as opposed to alternative potential second-line ASMs, and this remains a future target for further study and intervention.
While evidence for the most effective second-line ASM therapy is lacking, options for such therapies could be outlined in EMS algorithms and emergency personnel appropriately equipped with the ability to provide these medications in the pre-hospital setting. Additionally, standardization of algorithms to use appropriate weight-based dosing is of importance as existing algorithms are often under-dosing medications (see below) [
]. Issues with medication degradation in extreme heat settings experienced in ambulances should be considered when creating algorithms, and studies suggest midazolam may be most stable in these conditions [
]. Checking a blood glucose may certainly be helpful when indicated, but testing may be completed in conjunction with standard seizure management so as to not substantially delay seizure treatment. Adherence to a standardized algorithm approach may also potentially improve emergency personnel comfort in treating critically ill pediatric patients with or without IV access [
4.6 Use of inappropriately dosed medications pre- and in-hospital
ASM dosing, particularly of benzodiazepines, is found to be inaccurate in a large proportion of pediatric SE cases. In one retrospective pediatric cohort, only 32% of patients received the recommended weight-based dose of a benzodiazepine, and most patients were under-dosed [
]. In another prospective observational study of 100 consecutively treated cases of SE requiring intensive care unit admission, 23% were administered a benzodiazepine dose outside of the suggested range [
]. High or repeat benzodiazepine dosing may lead to respiratory depression. Receiving more than two doses of benzodiazepines has been associated with an increased risk of intubation (relative risk (RR) 2.4) and intensive care unit admission (RR 1.7) [
]. A similar association with receiving more than two doses of benzodiazepines and subsequent respiratory insufficiency was observed in another cross-sectional retrospective study [
]. Patients with an incorrect dose or absence of a seizure rescue medication were more likely to have an unplanned admission or ED evaluation (OR = 11.3) in a retrospective case-control study, and 80% of patients who utilized emergency care had an incorrect seizure rescue medication dose compared to 19% in patients who utilized care less frequently [
Establishing appropriate, weight-based dosing of benzodiazepines is another target for intervention. The use of seizure action plans, standardized EMS and in-hospital medication algorithms, or weight-based order sets may improve correct dosing.
4.7 In-hospital ASM use
Management of SE in-hospital is also often delayed. In a multicenter refractory SE cohort, among patients with SE onset in the hospital, first and second ASMs were administered at a median (interquartile range) of 8 (5–15) minutes and 16 (10–40) minutes [
]. In a quality improvement initiative to evaluate the safety and efficiency of a midazolam medication protocol for treatment of pediatric SE in an ED setting, 93% had adherence to midazolam as first-line therapy, with a median seizure duration of 6 min for those treated [
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
]. Another intervention analyzed time to treatment of inpatient pediatric seizure management before and after employment of an activated order set for ASMs; after use of this intervention, time to first-line ASM administration significantly decreased from 7.7 to 3.7 min and time to second-line ASM administration decreased from 50 to 25 min [
]. The use of a management pathway has also been shown to improve time to treatment in non-convulsive electrographic seizures during continuous EEG monitoring in critically ill children. In a study evaluating treatment before and after pathway initiation, the time from seizure onset to ASM administration decreased from a median (interquartile range) of 129 (71–189) minutes to 64 (50–101) minutes, and this was associated with a higher likelihood of seizure abortion with the initial ASM (67% versus 27%) [
]. Mastery of following such hospital-proposed guidelines was demonstrated and achieved via high-fidelity simulation with pediatrics interns in one institution [
], initiation of a SE alert team has been shown to decrease time to treatment in adults. In a single center study, a “status epilepticus alert” was created when a patient in SE was identified to summon a neurology resident, neuro-intensivist, house officer, rapid response team, and pharmacist for urgent evaluation. The time to treatment with the second ASM improved from 71 to 82 min before to 19 min after the intervention [
Several pediatric studies have identified benefits associated with use of management algorithms. A study analyzed the effect of a SE treatment algorithm in neonates and reported that with 80% adherence to the protocol there was a reduction in the number of seizures that progressed to SE after implementation and also a decreased length of hospital stay (19 versus 26 days) [
]. In another study evaluating care processes of patients admitted to a tertiary care hospital after presenting with SE, patients admitted to the intensive care unit were more likely to have deviated from a proposed medication algorithm than those admitted to the floor (66% versus 26%) and patients admitted to the intensive care unit were more likely to have received greater than two doses of a benzodiazepine than those admitted to the floor (65% versus 33%) [
]. In a retrospective study of children treated at community hospitals, 61% did not receive medications per protocol, most often receiving more than two doses of a benzodiazepine which yielded an increased risk of intubation (RR 2.4) and intensive care unit admission (RR 1.7) [
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
]. Despite the demonstration of improved outcomes with rapid administration of appropriately dosed ASMs in both the out-of-hospital and in-hospital settings [
]. As reviewed, there are encouraging ongoing quality improvement initiatives and targets for future interventions. Identifying patients with high ED utilization and missed preventive clinic visits for the use of urgent epilepsy clinics or nurse navigators has shown to have a large impact on healthcare utilization and costs [
]. In the pre-hospital setting, advances in affordable, insurance-covered seizure detection devices may improve seizure recognition and subsequently more rapid initiation and escalation of treatment [
]. Training programs for school nurses/teachers and caregivers may be employed to increase confidence and competency with seizure rescue medication use [
], the understanding of SE as a time-sensitive emergency with rapid summoning, dispatch, and medication administration by emergency personnel is critical; further training of such personnel with pediatric patients and optimization of out-of-hospital management pathways may be beneficial [
]. Standardization and use of pre-hospital medication algorithms that extend beyond weight-based benzodiazepine dosing for more extensive pre-hospital treatment are future aims for improvement [
]. In both the pre- and in-hospital settings, use of appropriately dosed ASMs is needed as inappropriate benzodiazepine doses are associated with higher rates of intensive care unit admissions [
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
Overall, data suggest that improving time to treatment is crucial in improving management and outcomes in pediatric SE. Increased awareness and knowledge regarding the time-critical nature of SE is key. Improvements in preventive care, seizure detection, and rescue medication education may serve as initial targets for further innovation in the pre-hospital setting. Implementation of “Seizure Code Teams” may be one strategy to address these in-hospital issues. Ideally these teams would be interdisciplinary with representatives from EMS, ED, critical care, neurology, nursing, pharmacy, information technology, and quality improvement groups. Some members of the team might guide acute care of a seizing child, and the overall group would help develop broader pathways and management systems to optimize care throughout a healthcare system or region. Thus, this type of team may serve as a means of initiating and integrating improvement interventions.
Conflicts of interest/disclosures
Coral Stredny has no conflicts of interest or disclosures to report.
Nicholas Abend receives primary investigator funding from NIH (NINDS)K02NS096058 and site investigator funding from EFA, PCORI, and UCB Pharma.
Tobias Loddenkemper serves on the Council (and as Vice President and President Elect) of the American Clinical Neurophysiology Society, on the American Board of Clinical Neurophysiology, as committee chair at the American Epilepsy Society (Special Interest Group and Investigator Workshop Committees), as founder and consortium PI of the pediatric status epilepticus research group, as an Associate Editor for Seizure, and as an Associate Editor for Wyllie’s Treatment of Epilepsy 6th edition and 7th editions. He is part of pending patent applications to detect and predict seizures and to diagnose epilepsy. He receives research support from the NIH, PCORI, Epilepsy Research Fund, the American Epilepsy Society, the Epilepsy Foundation of America, the Epilepsy Therapy Project, the Pediatric Epilepsy Research Foundation, CURE, and received research grants from Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Sage, and Pfizer. He serves as a consultant for Zogenix, Engage, Amzell, Upsher Smith, Eisai, and Sunovion. He performs video electroencephalogram long-term and ICU monitoring, electroencephalograms, and other electrophysiological studies at Boston Children's Hospital and affiliated hospitals and bills for these procedures and he evaluates pediatric neurology patients and bills for clinical care. He has received speaker honorariums from national societies including the AAN, AES and ACNS, and for grand rounds at various academic centers. His wife, Dr. Karen Stannard, is a pediatric neurologist and she performs video electroencephalogram long-term and ICU monitoring, electroencephalograms, and other electrophysiological studies and bills for these procedures and she evaluates pediatric neurology patients and bills for clinical care.
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Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study.
Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society.
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation.
The cost effectiveness of licensed oromucosal midazolam (Buccolam((R))) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited.
A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive status epilepticus paediatric trial (consept) - a predict study.
A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): convulsive Status Epilepticus Paediatric Trial (ConSEPT) – a PREDICT study.
Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: study protocol for a randomised controlled trial.
The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies.
Seizures induced by allylglycine, 3-mercaptopropionic acid and 4-deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase.
Epileptic brain damage in rats induced by sustained electrical stimulation of the perforant path: I. Acute electrophysiological and light microscopic studies.
Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial.
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