Treatment Of Refractory Status Epilepticus Research Articles

Hydrogen treatment reduces electroencephalographic activity and neuronal death in rats with refractory status epilepticus by inhibiting membrane NR2B phosphorylation and oxidative stress.

To investigate the effects of hydrogen therapy on epileptic seizures in rats with refractory status epilepticus and the underlying mechanisms. Status epilepticus was induced using pilocarpine. The effects of hydrogen treatment on epilepsy severity in model rats were then monitored using Racine scores and electroencephalography (EEG), followed by western blot of plasma membrane N-methyl-D-aspartate receptor subtype 2B (NR2B) and phosphorylated NR2B expression. We also generated a cellular epilepsy model using Mg2+-free medium and used polymerase chain reaction to investigate the neuroprotective effects of hydrogen. There were no significant differences in Racine scores between the hydrogen and control groups. EEG amplitudes were lower in the hydrogen treatment group than in the control group. In epilepsy model rats, hippocampal cell membrane NR2B expression and phosphorylation increased gradually over time. Although hippocampal cell membrane NR2B expression was not significantly different between the two groups, NR2B phosphorylation levels were significantly lower in the hydrogen group. Hydrogen treatment also increased superoxide dismutase, mitochondrial (SOD2) expression. Hydrogen treatment reduced EEG amplitudes and NR2B phosphorylation; it also decreased neuronal death by reducing oxidative stress. Hydrogen may thus be a potential treatment for refractory status epilepticus by inhibiting membrane NR2B phosphorylation and oxidative stress.

Provider Experience With the Use of Ketamine for Refractory Status Epilepticus.

Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE. A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated. There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use. Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.

Ketamine in the treatment of refractory and super-refractory status epilepticus: Experience from two centres

PurposeThere is insufficient evidence on the management of refractory status epilepticus (RSE) and super-RSE (SRSE). Ketamine is a N-methyl-d-aspartate receptor antagonist in the treatment of these entities. Our objectives were to study the effectiveness and safety of ketamine in the treatment of adult patients with RSE and SRSE, to determine the factors that can influence the response to ketamine, and to explore its use in patients without mechanical ventilation. MethodsAdult patients who had received intravenous ketamine for the treatment of RSE or SRSE at Hospital Universitario Clínico San Carlos (Madrid, Spain) or Hospital Universitari Vall d'Hebron (Barcelona, Spain) from 2017 to 2023 were retrospectively analysed. ResultsThis study included 58 adult patients, mean (standard deviation) age 60.2 (15.7) years, of whom 41 (70.7 %) were male; 33 (56.9 %) patients responded to ketamine without recurrence, with a low rate of adverse effects (8.6 %). The presence of SRSE at the time of ketamine initiation (OR 0.287, p = 0.028) and the time elapsed between status epilepticus onset and ketamine administration (OR 0.991, p = 0.034) were associated with worse response to ketamine. Patients treated without mechanical ventilation had similar rates of response without recurrence (62.5% vs 56.9 %) and lower mortality (37.5% vs 53.5 %) compared to the overall group. ConclusionKetamine is an effective drug with few adverse effects. Prompt administration should be considered in patients with RSE requiring anaesthesia, in patients with SRSE, and in patients with RSE who do not respond to standard antiseizure drugs and in whom mechanical ventilation is not advised.

Third-Generation Antiseizure Medication in the Treatment of Benzodiazepine-Refractory Status Epilepticus in Poststroke Epilepsy: A Retrospective Observational Register-Based Study.

Status epilepticus in poststroke epilepsy is a challenging condition because of multiple vascular comorbidities and the advanced age of patients. Data on third-generation antiseizure medication (ASM) in this condition are limited. The aim of this study was to evaluate the efficacy of third-generation ASMs in the second- or third-line therapy of benzodiazepine-refractory status epilepticus in poststroke epilepsy following acute ischemic stroke. Data on the effectiveness of third-generation ASMs in patients with status epilepticus in poststroke epilepsy were gathered from two German Stroke Registries and the Mainz Epilepsy Registry. We included only cases with epilepsy remote to the ischemic event. No patients with acute symptomatic seizures were included. The following third-generation ASMs were included: brivaracetam, lacosamide, eslicarbazepine, perampanel, topiramate, and zonisamide. The assessment of effectiveness was based on seizure freedom within 48 h since the start of therapy with the respective ASM. Seizure freedom was evaluated both clinically (clinical evaluation at least three times per day) and by daily electroencephalogram records. Of the 138 patients aged 70.8 ± 8.1 years with benzodiazepine-refractory status epilepticus in ischemic poststroke epilepsy, 33 (23.9%) were treated with lacosamide, 24 (17.4%) with brivaracetam, 23 (16.7%) with eslicarbazepine, 21 (15.2%) with perampanel, 20 (14.5%) with topiramate, and 17 (12.3%) with zonisamide. Seizure freedom within 48 h was achieved in 66.7% of patients with lacosamide, 65.2% with eslicarbazepine, 38.1% with perampanel, 37.5% with brivaracetam, 35.0% with topiramate, and 35.3% with zonisamide (p < 0.05 for comparison of lacosamide or eslicarbazepine to other ASMs). Based on these data, lacosamide and eslicarbazepine might be more favorable in the treatment of refractory status epilepticus in poststroke epilepsy, when administered as second- or third-line ASMs before anesthesia. Because of the fact that these ASMs share the same mechanism of action (slow inactivation of sodium channels), our findings could motivate further research on the role that this pharmaceutical mechanism of action has in the treatment of poststroke epilepsy. This study was registered at ClinicalTrials.gov (NCT05267405).

Epilepsiechirurgie beim therapierefraktären Status epilepticus des Kindesalters

AbstractThe mainstay of status epilepticus (SE) treatment is pharmacotherapy with anti-seizure medications (ASM). In refractory status epilepticus (RSE), when additional ASM are not effective, high-dose suppressive therapy with either benzodiazepines, thiopental, phenobarbitone, or propofol is used to suppress clinical and EEG seizure activity. However, in selected eligible cases of RSE or in super-refractory cases, epilepsy surgery may be the treatment of choice to terminate SE. Here, we review epilepsy surgery including deep brain stimulation (DBS) for treatment for RSE with emphasis on special aspects of presurgical evaluation, patient selection, and outcome. We focus on surgical treatment options for patients in the acute phase of RSE, who have received high-dose suppressive therapy prior to surgery in the majority of the cases.

Electroconvulsive therapy and seizure: a double-edged sword?

Electroconvulsive therapy (ECT) is a widely used therapeutic option of drug-refractory psychiatric disorders. ECT treats psychiatric symptoms by inducing brief controlled seizures through electrical stimulation, but ECT does not generally cause prolonged seizures or epilepsy. However, several studies have reported cases of prolonged seizures after ECT. This review aimed to determine the mechanism of epileptogenesis with neurobiological changes after ECT. Contrary to epileptogenesis by ECT, several cases have reported that ECT was successfully applied for treatment of refractory status epilepticus. In addition, ECT might be applied to hyperkinetic movement and psychiatric symptoms of encephalitis. We also investigated the anticonvulsant mechanism of ECT and how it controls encephalitis symptoms.

Comparison of three types of Epilepsy Surgery for the treatment of Refractory Status Epilepticus: A Single Center Experience (P9-1.005)

<h3>Objective:</h3> Comparing outcomes for three categories of epilepsy surgery in Refractory Status Epilepticus Patients (RSE). <h3>Background:</h3> Literature comparing morbidity and mortality outcomes between three types of epilepsy surgery for RSE patients is scarce. Previous case series have focused on one type of surgery or does not directly compare outcomes between the modalities. <h3>Design/Methods:</h3> A retrospective analysis for RSE between 2010 and 2021 was done. Sociodemographic data, semiology and etiology were collected. The patients were deidentified using our institute’s software, and comparison data was extracted from the secure system. Data collected included lag time between diagnosis and surgery, number of anti-seizure medications (ASMs) tried, EEG and imaging data, type of surgery performed, level of post-operative care, number of post-operative days admitted, complications and seizure freedom outcomes. <h3>Results:</h3> The mean age was 35.6 ± 23.5 years, with 4/12 patients being female. Seizure types were primarily generalized tonic-clonic or focal seizures with impaired awareness. A plethora of etiologies were included. The mean number of ASMs tried was 2.3 ± 1.4. Every patient had EEG and MRI Brain with ancillary testing such as grid placement. Out of 12, 6 had resection, 5 disconnections and 2 neuromodulations. 11/12 patients required an ICU admission and mean post-operative days admitted was 12 ± 11.2. Minor to no complications occurred in 33 % of all resection patients, and minor complications occurred in 40 % and 50 % patients of the disconnection and modulation patients. 3/4 and 3/5 of patients that had undergone resections and disconnections respectively had Class 1 outcomes in. Patients that received modulation had a Class 4 outcome and 1 patient death. <h3>Conclusions:</h3> Our study reveals that while there is no substantial difference between resection and disconnection, resections have slightly better outcomes and fewer complications. Modulation had poorer seizure freedom and may only be considered as a temporizing measure. <b>Disclosure:</b> Dr. Khan has received personal compensation for serving as an employee of University of Kentucky. Dr. Mirza has nothing to disclose. Dr. Mathias has received research support from My Epilepsy Society Non Profit Organization.

Possible immuno-modulatory effects of tocilizumab in patients with refractory status epilepticus.

Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the United States, affecting people of all ages. This study aimed to investigate the possible immuno-modulatory effect of tocilizumab in RSE patients receiving conventional anti-epileptic drugs. 50 outpatients who fulfilled the inclusion requirements for RSE were recruited in this randomized, controlled, and prospective study. The patients were divided into two groups randomly (n=25); the control group received standard RSE treatment, consisting of propofol, pentobarbital, and midazolam, and the tocilizumab group received standard RSE treatment plus tocilizumab. A neurologist evaluated each patient at the beginning of the therapy and after 3 months. Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and serum electrolytes were assessed. The tocilizumab group showed a statistically significant reduction in the level of assessed parameters in comparison with the control group. Tocilizumab might be a novel adjuvant anti-inflammatory medication in managing RSE.

Management of convulsive status epilepticus: recent updates.

Convulsive status epilepticus (SE) is a medical emergency associated with high morbidity and mortality. Recently, clinical trials and meta-analyses investigating medical treatment of SE have been published. Benzodiazepine is well known as the first-line treatment for SE. Recent evidence suggests the equivalence of intravenous fosphenytoin, valproate, and levetiracetam for treatment of established SE. There is lack of evidence regarding treatment for refractory SE. Intravenous midazolam is commonly used, and recent evidence supports the use of ketamine. Additional studies are needed to improve the management of convulsive SE.

The efficacy and safety of ketamine in refractory and super-refractory status epilepticus: a systemic review

Background: In published animal studies, N-methyl-D-aspartate antagonists such as ketamine (KET) have been reported to reduce Status epilepticus (SE) even after benzodiazepines had failed. In addition, there are studies on the human population that have reported on the use of KET to manage SE seizures. However, despite its history of use as an anesthetic, there are few published review studies on using KET in the treatment of refractory SE (RSE). Objective: This research aims to determine whether KET is an effective treatment for RSE and super-refractory (SRSE) in both children and adult patients. Methods: A systematic search was done on PubMed, EMBASE, Google Scholar, and Cochrane databases from inception until September 12, 2022. In addition, a search was also done for gray literature (ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform). Results: The initial search identified 164 articles and only 21 were included in this systematic review; 10 case reports, 9 case series, and 2 cohort studies. In total, the study population is 408. Regarding individual case reports, there were 56 cases, of which 52 were adults. In addition, there were 27 males, 26 females, and 3 unidentified (50). Conclusion: The admission of KET as management for RSE and SRSE has effectively controlled and terminated SE seizures. KET presented to generally be safe, as there are a few reported adverse events. The mortality rates appeared to be high, but none of the studies reported any direct link between these adverse outcomes and using KET to manage SE.

555: IMPACT OF A PROTOCOL FOR CONTINUOUS-INFUSION ANESTHETIC AGENTS IN REFRACTORY STATUS EPILEPTICUS

Introduction: When status epilepticus (SE) persists despite emergent and urgent treatment with antiepileptic drugs (AED), it is referred to as refractory SE (RSE). Guidelines recommend quickly escalating therapy by either repeating initial agents, choosing an alternative AED, or even initiating continuous intravenous (CIV) anesthetic agents. Adherence to a standardized treatment protocol for general treatment of SE has been associated with better seizure control and shorter intensive care unit and hospital length of stay, but no literature exists evaluating protocols aimed at treating patients for RSE with CIV anesthetic agents. Due to the lack of literature in this area, we aimed to determine the benefits of implementing a standard protocol for use of CIV anesthetic agents in the treatment of RSE. Methods: A retrospective analysis of adult patients admitted to the Methodist University Hospital (MUH) with a diagnosis of RSE was conducted from January 1, 2011 – July 31, 2021. In 2018, MUH began using a standard protocol for treatment for RSE. Therefore, patients were grouped based on whether they received treatment prior to or after implementation of the protocol. Discharge disposition, duration of hospitalization, time to seizure termination, and rates of adverse effects were evaluated. Results: A total of 64 patients were included, with 16 (20%) pre-implementation and 48 (80%) post-implementation. Patients included were predominantly female (61%), had a history of seizures (62.5%), and a mean age of 59 years. For the primary outcome, the percent of patients with in-hospital death or discharge to hospice was numerically lower in the post-implementation group (25% vs 16.7%, p=0.48). Patients who received treatment through the protocol also had a numerically shorter time to seizure termination (21 vs 26.7 hours, p=0.19). Duration of hospitalization (13.8 vs 14.4 hours, p=0.93) was similar between groups. Conclusions: Although there was no statistical difference in the primary outcome between groups, there was a nearly 10% improvement in survival, as well as reduced time to seizure termination, through implementation of an RSE protocol. Further research is needed to determine the overall impact of similar protocols amongst a larger cohort of patients.

Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus.

To model bolus dosing, infusion rate, and weaning rate on theoretical serum concentration of midazolam and pentobarbital used in the treatment of refractory status epilepticus (RSE). One- and two-compartment in silico pharmacokinetic models of midazolam and pentobarbital. Not applicable. Not applicable. We compared the model variables used in midazolam and pentobarbital protocols for standard RSE. Standard RSE treatment protocols result in steady-state serum concentrations that are 6.2-9.0-fold higher for the one-compartment model and 2.3-4.7-fold higher for the two-compartment model. In the model, not including bolus doses delays the achievement of serum steady-state concentration by 0.5 and 2.7 hours for midazolam and pentobarbital, respectively. Abrupt discontinuation of these medications reduces modeled medication exposure by 1.1 and 6.4 hours, respectively. Our in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies.

Ketamine: Is It Pro-Epileptic or Anti-Epileptic? The Debate Continues. A Narrative Review with a Case Discussion

Ketamine is one of the old anaesthetic agents which has regained popularity in analgesia, trauma, emergency medicine, neurology and psychiatry. Recently several cases were reported on ketamine induced seizures in otherwise healthy children despite its popularity in the treatment of refractory status epilepticus. We present an eight-year-old prematurely born healthy boy who developed two episodes of generalized tonic clonic seizures following administration of ketamine for a short ophthalmic procedure. This case and our comprehensive narrative review of literature on pro- and anti-epileptic effects of ketamine show that the debate continues and gaps on mechanism of action, etiology and risk factors for ketamine’s epileptic activity remains. Due to the recent increase in its use further evaluation on ketamine’s epileptic effects is warranted to ensure safe and effective use of ketamine.

Ketamine for Management of Neonatal and Pediatric Refractory Status Epilepticus.

Few data are available regarding the use of anesthetic infusions for refractory status epilepticus (RSE) in children and neonates, and ketamine use is increasing despite limited data. We aimed to describe the impact of ketamine for RSE in children and neonates. Retrospective single-center cohort study of consecutive patients admitted to the intensive care units of a quaternary care children's hospital treated with ketamine infusion for RSE. Sixty-nine patients were treated with a ketamine infusion for RSE. The median age at onset of RSE was 0.7 years (interquartile range 0.15-7.2), and the cohort included 13 (19%) neonates. Three patients (4%) had adverse events requiring intervention during or within 12 hours of ketamine administration, including hypertension in 2 patients and delirium in 1 patient. Ketamine infusion was followed by seizure termination in 32 patients (46%), seizure reduction in 19 patients (28%), and no change in 18 patients (26%). Ketamine administration was associated with few adverse events, and seizures often terminated or improved after ketamine administration. Further data are needed comparing first-line and subsequent anesthetic medications for treatment of pediatric and neonatal RSE. This study provides Class IV evidence on the therapeutic utility of ketamine for treatment of RSE in children and neonates.

The role of ketamine-induced beta activity in the treatment of refractory status epilepticus. Is the EEG useful to determine responder’s rate? A retrospective study

IntroductionMultiple investigations have been done to evaluate the possible effect of ketamine in the treatment of status epilepticus (SE). ObjectivesTo evaluate the electrographic effect of ketamine on EEG, and its clinical utility following-up refractory and super refractory status epilepticus (SRSE). MethodsRetrospective review of 24 patients with SE. Clinical record and Video-electroencephalogram (video-EEG) of all included patients were reviewed. The patients’ EEGs were then monitored for any immediate changes after administration of the first dose of ketamine as well as at the time patients would be predicted to have peak serum concentration of ketamine. Patients with cessation of electrographic seizures and no SE recurrence within the same admissions were categorized as “Responders”. Statistical differences between qualitative variables were analyzed using chi square test. Differences between median were analyzed by Mann–Whitney U test. Difference between groups were considered significant when p < 0.05. ResultsWe identified 24 patients with SE. Twelve out of 24 (50%) had SRSE and 12 out of 24 (50%) had refractory status epilepticus (RSE). The appearance of superimposed beta activity after ketamine was initiated was associated with a higher responder rate (100% versus 33.3% in the responder group versus the non-responder group respectively). Notably, the presence of a burst suppression pattern had no significant association with one group compared to the other (41.6% versus 33.3%, in the responder group vs the non-responder group respectively). ConclusionsBackground superimposed beta activity induced by ketamine is an early and reliable EEG finding associated with status epilepticus termination.

P.019 A machine learning approach to asymmetric burst suppression and refractory status epilepticus outcome

Background: Treatment of refractory status epilepticus (RSE) is often titrated to achieve EEG burst suppression. However, optimal burst suppression characteristics are largely unknown. We used an unsupervised machine learning algorithm to predict RSE outcome based on the quantitative burst suppression ratio (QBSR). Methods: We conducted principal component analysis (PCA) as a linear combination of 22 QBSR features from non-anoxic adult RSE patients at the Winnipeg Health Sciences Centre. We also determined the most predictive components that significantly differed between survivors and non-survivors. Results: Using 135,765 QBSRs from 7 survivors and 10 non-survivors, PCA identified a predominantly non-survivor cluster of 8 patients (75% non-survivors). The first 2 PCA components comprised 75% data variance. The most important first component feature was skewness of QBSR distribution in the right or left hemisphere (0.52 each). The most important second component feature was third QBSR quantile of the left hemisphere (0.49). Only right hemispheric QBSR features significantly differed between groups: QBSR skewness for the first component (Benjamini-Hochberg adjusted p=0.038) and average QBSR for the second component (0.32, Benjamini-Hochberg adjusted p=0.046). Conclusions: Our pilot study shows that RSE patient survival may be impacted by QBSR, with differential hemispheric EEG burst suppression characteristics predicting poor RSE outcome.

Isoflurane in (Super-) Refractory Status Epilepticus: A Multicenter Evaluation

BackgroundWe aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs).MethodsThis was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011–2018.ResultsWe identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy.ConclusionsIsoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge.

Advances in the management of generalized convulsive status epilepticus: what have we learned?

Convulsive status epilepticus is the most serious manifestation of an epileptic diathesis. In the early stages (5-30 min), there exists class A evidence to support the efficacy of benzodiazepines as first-line treatment. As status epilepticus progresses into the later stages, the evidence for treatment becomes less robust until we are depending upon short case series and case reports for the treatment of refractory status epilepticus. However, the past year saw the publication of three randomized controlled trials in the setting of benzodiazepine-resistant established convulsive status epilepticus: the EcLiPSE and ConSEPT studies, compared levetiracetam to phenytoin in children; and the ESETT study compared fosphenytoin, levetiracetam and sodium valproate in adults and children. In addition, the emergence of data from the SENSE study, a multicentre multinational prospective cohort study and the publication of a systematic review and meta-analysis of the mortality of status epilepticus over the past 30 years, has brought the treatment of status epilepticus into sharp focus. In this update we provide a detailed analysis of these studies and their impact on clinical practice. We review contentious areas of management in status epilepticus where a consensus is lacking and advance the case for more research on existing and alternative treatment strategies.

Editors' Note: Association of Guideline Publication and Delays to Treatment in Pediatric Status Epilepticus

In “Association of guideline publication and delays to treatment in pediatric status epilepticus,” Fernandez et al. reported that despite publication of evidence of delays in treatment of refractory status epilepticus (SE) in the Pediatric Status Epilepticus Research Group (pSERG) at the end of 2014, there was no difference in time to initiation of benzodiazepines, nonbenzodiazepine antiepileptic drugs (AEDs), and continuous infusions to patients with refractory SE in pSERG in the hospital between 2011–2014 and 2015–2019. The authors identified a number of proposed actions to overcome potential barriers to the timely initiation of AEDs. Albuja et al. commented that they improved the time to administration of second-line AEDs at their institution by creating a SE alert system to contact neurology, pharmacy, the rapid response team, and the bed manager simultaneously when an inpatient is suspected to be in SE. Amengual-Gual et al. applauded them for implementing this initiative. It is imperative to continue to identify quality improvement measures to identify SE and ensure that AEDs are given in a timely fashion to patients with SE because it becomes more resistant over time, which may lead to increased morbidity and mortality.[1][1],[2][2] In “Association of guideline publication and delays to treatment in pediatric status epilepticus,” Fernandez et al. reported that despite publication of evidence of delays in treatment of refractory status epilepticus (SE) in the Pediatric Status Epilepticus Research Group (pSERG) at the end of 2014, there was no difference in time to initiation of benzodiazepines, nonbenzodiazepine antiepileptic drugs (AEDs), and continuous infusions to patients with refractory SE in pSERG in the hospital between 2011–2014 and 2015–2019. The authors identified a number of proposed actions to overcome potential barriers to the timely initiation of AEDs. Albuja et al. commented that they improved the time to administration of second-line AEDs at their institution by creating a SE alert system to contact neurology, pharmacy, the rapid response team, and the bed manager simultaneously when an inpatient is suspected to be in SE. Amengual-Gual et al. applauded them for implementing this initiative. It is imperative to continue to identify quality improvement measures to identify SE and ensure that AEDs are given in a timely fashion to patients with SE because it becomes more resistant over time, which may lead to increased morbidity and mortality.1,2 [1]: #ref-1 [2]: #ref-2

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs.

Status epilepticus (SE) and cluster seizures (CS) are common occurrences in veterinary neurology and frequent reasons of admission to veterinary hospitals. With prolonged seizure activity, gamma amino-butyric acid (GABA) receptors (GABAa receptors) become inactive, leading to a state of pharmacoresistance to benzodiazepines and other GABAergic medications, which is called refractory status epilepticus (RSE). Prolonged seizure activity is also associated with overexpression of N-methyl-D-aspartic (NMDA) receptors. Rodent models have shown the efficacy of ketamine (KET) in treating RSE, and its use has been reported in one canine case of RSE. Boluses of KET 5 mg/kg IV have become the preferred treatment for RSE in our hospital. A retrospective study was performed to evaluate and report our experience with KET IV bolus to treat prolonged and/or repeated seizure activity in cases of canine CS, SE, and RSE. A total of 15 dogs were retrieved, for 20 hospitalizations and 28 KET IV injections over 3 years. KET IV boluses were used 12 times for RSE (9 generalized seizures, 3 focal seizures) and KET terminated the episode of RSE 12/12 times (100%); however, seizures recurred 4/12 times (33%) within ≤6 h of KET IV bolus. When used for CS apart from episodes of RSE, KET IV bolus was associated with termination of the CS episode only 4/14 times (29%). Only 4/28 (14%) KET IV boluses were associated with adverse effects imputable only to the use of KET. One dog experienced a short, self-limited seizure activity during administration of KET IV, which was most likely related to a pre-mature use of KET IV (i.e., before GABAergic resistance and NMDA receptor overexpression had taken place). This study indicates that KET 5 mg/kg IV bolus may be successful for the treatment of RSE in dogs.