Intravenous Antiepileptic Drugs Research Articles

Management strategies for refractory status epilepticus

Refractory status epilepticus (RSE) is defined as the persistence of either clinical or electrographic seizures despite the administration of appropriate doses of an initial benzodiazepine and suitable second-line antiepileptic drugs (AEDs). The Neurocritical Care Society and the American Epilepsy Society have proposed a treatment paradigm for the management of convulsive status epilepticus (CSE). The third-line therapy in refractory CSE may involve general anesthesia using intravenous midazolam, propofol, or other agents, while recent evidence supports the use of ketamine to manage RSE in both adults and children. However, although these treatment strategies are frequently employed in nonconvulsive status epilepticus (NCSE), the efficacy of AEDs and anesthetics in NCSE has not been thoroughly investigated. Recent evidence has demonstrated the safety and efficacy of newer AEDs, including levetiracetam and lacosamide, in the treatment of status epilepticus (SE) and RSE, which also encompasses NCSE. Use of multiple combinations of various intravenous AEDs can also be considered in NCSE before the administration of general anesthesia. In addition, AEDs alone exhibit limited effectiveness in managing SE for new-onset RSE (NORSE) and its subset, febrile infection-related epilepsy syndrome. Therefore, in cases of refractory status, it is imperative to explore treatment options beyond AEDs, including immunotherapy and the incorporation of a ketogenic diet. The present review suggests treatment approaches for RSE based on subgroups, including CSE, NCSE, and NORSE. A discussion of recent clinical studies on AEDs and anesthetics in the management of RSE, as well as proposed treatment methods for NORSE, is also provided.

Perioperative Management in Pediatric Neurosurgery

Appropriate perioperative management can facilitate good outcomes in pediatric neurosurgical patients. This section discusses infusion therapy, prophylactic antibiotics, and antiepileptic drugs in the perioperative management of pediatric neurosurgical patients. Fluid requirements were calculated using the Holiday and Segar formula and the 4-2-1 rule for determining hourly infusion requirements based on metabolic rate and body weight. Recently, the risk of hyponatremia with the use of hypotonic solutions has been reported, and an isotonic electrolyte solution with 1-2.5% glucose is recommended for maintenance infusions in the perioperative period. Pediatric perioperative prophylactic antibiotics have been recommended as follows: application of cephazolin(30 mg/kg)with a redosing interval of 3 h intraoperatively and continuation for 48 h or less postoperatively. However, even for shunt surgery, there are currently no evidence-based protocols regarding specific antibiotic recommendations or the duration of prophylactic antibiotics. Early antiepileptic prophylaxis is recommended in cases of severe head trauma in children, especially infants. Available intravenous antiepileptic drugs should be used with an understanding of their indications, characteristics, and side effects.

The effectiveness of intravenous benzodiazepine for status epilepticus in Dravet syndrome

PurposeWe aimed to evaluate choice and efficacy of intravenous antiepileptic drugs (AEDs) for status epilepticus (SE) in Dravet syndrome and to find predictable clinical features demonstrating the effectiveness of benzodiazepine (BZD) for SE. MethodsWe retrospectively investigated the medical records in patients with Dravet syndrome and evaluated the effectiveness rate of intravenous AEDs and the rate of adverse effects. To find the clinical features of BZD-effective SE, we divided the SE episodes into the following two groups: BZD effective group and BZD non-effective group. The choice of treatment was dependent on physicians’ discretion according to the protocol for SE in our institution. ResultsSixty-eight SE episodes in 10 patients were assessed. The median age at SE was 31 months. Of 68 episodes, 42 episodes (61.8%) were in the BZD effective group and 26 (38.2%) in the BZD non-effective group. There were no significant differences in clinical features. In the BZD non-effective group, the effective rates of continuous midazolam, phenobarbital, phenytoin/fosphenytoin were 9/9 episodes (100%), 14/17 (82.4%), and 2/5 (40.0%), respectively. Adverse effects were identified in 19/68 episodes (27.9%), including 11/42 episodes in the BZD effective group and 8/26 in the BZD non-effective group, which was no statistical difference between the two groups. Respiratory suppression was found in all 19 episodes and the incidence of endotracheal intubation in the BZD non-effective group (15.4%) was higher than that in the BZD effective group (2.4%) (p = 0.046). ConclusionBZD may be used as first choice, and phenobarbital prior to continuous midazolam as second choice for SE with Dravet syndrome. There might be no predictable clinical features showing that BZD will be effective.

Clinical outcomes and treatments effectiveness in status epilepticus resolved by antiepileptic drugs: A five-year observational study.

ObjectiveTo evaluate clinical outcomes and treatment effectiveness of status epilepticus finally resolved by nonbenzodiazepine antiepileptic drugs (AEDs).MethodsAll consecutive SE episodes observed from September 1, 2013, to September 1, 2018, and resolved by AEDs were considered. Diagnosis and classification of SE followed the 2015 ILAE proposal. Nonconvulsive status (NCSE) diagnosis was confirmed according to the Salzburg EEG criteria. The modified Rankin Scale and deaths at 30 days from onset were used to evaluate outcomes.ResultsA total of 277 status episodes (mean age 71 years; 61% female) were treated and resolved by antiepileptic drugs after 382 treatment trials. 68% of the SE resolved after AED use as first/second treatment line, while subsequent trials with AEDs gave an additional 32% resolution. A return to baseline conditions was observed in 48% of the patients, while overall mortality was 19% without significant changes across the study years. Mortality was higher in NCSE than in convulsive SE (22.5% vs 12.9%; P < .05), while mortality did not differ in SE episodes resolved by a first/second AED trial (17.2%) versus SE resolved by successive treatment trials (18.9%). The resolution rate of intravenous AEDs was 82% for valproate, 77% for lacosamide, 71% for phenytoin, and 62% for levetiracetam. No significant differences were found in head‐to‐head comparison, but for the valproate‐levetiracetam one that was related to NCSE episodes in which valproate resulted to be effective in 86% of the trials while levetiracetam in 62% (P < .002).SignificanceA high short‐term mortality, stable over time, was observed in SE despite resolution of seizures, especially in SE with nonconvulsive semiology. Comparative AED efficacy showed no significant differences except for higher resolution rate for valproate versus levetiracetam in NCSE.

Benign Convulsions with Mild Gastroenteritis

Benign convulsions with mild gastroenteritis (CwG) are a well-known type of benign seizures that occur in infants and children aged between 6 months and 3 years and are associated with acute (viral) gastroenteritis. The pathogens found in the stool of CwG patients are mostly rotavirus or norovirus, which can result in mild dehydration. Short-lasting seizures (≤ 5 minutes) occur in clusters within 24 hours, without provoking features such as fever, abnormal laboratory findings in the blood (e.g., hypoglycemia, hyponatremia, or hypocalcemia), or abnormal results in the cerebrospinal fluid (e.g., central nervous system infection). Electroencephalography in CwG patients shows normal or mildly abnormal findings, and brain imaging findings are normal. Affected children develop normally before and after the seizures. The occurrence of seizures does not require the repeated use of first- or second-line intravenous antiepileptic drugs in the acute stage or daily antiepileptic drug medications, since they usually do not recur and have a good prognosis. Patients with CwG rarely have a family history of epilepsy. Although the mean interval between enteric symptom onset and seizure onset in CwG is roughly 2 days, some patients can experience seizures before enteric symptoms, meaning that clinicians should exercise caution during early winter and spring, when the prevalence of CwG is especially high. Additionally, reports of CwG in Korea are roughly as common as in Japan and other East Asian countries, and pediatricians should therefore be familiar with its clinical characteristics and take care not to overprescribe antiepileptic drugs in patients with CwG. Keywords: Seizures; Gastroenteritis; Norovirus; Rotavirus; Infant

Prevalence of Neurocysticercosis among Seizure patients: - Single Center Study

Background and purpose: The incidence of Epilepsy is high all over Nepal. This study was conducted to analyze the relationship between the incidence of seizure and neurocysticercosis (NCC) among patients admitted to our hospital in Far Eastern Nepal.&#x0D; Material and method: A descriptive cross-sectional study was done among patients diagnosed as NCC with a seizure disorder in B &amp; C Medical College Teaching, from September 2017 to August 2018. Neurocysticercosis was diagnosed based on Computer Tomography (CT), Magnetic Resonance Imaging (MRI), clinical features and laboratory investigations matching Del Brutto’s absolute and major criteria.&#x0D; Result: 103 patients were admitted to the hospital with clinical features of seizure disorder. Neurocysticercosis was diagnosed in 29(28%) patients. Among them, 21(72.41%) were males and 8(27.59%) were females. Patients presented with Generalized tonic-clonic seizure (GTCS) were 18(62%) and 3(10.35%) patients had focal seizures. Focal Seizure with secondary generalization (FSSG) was seen in 5(17%), 2(7%) had status epilepticus and 1(3.45%) patient had presented with absence seizure. Most of the patients 18(62%) had a calcified stage of NCC with perilesional edema in neuroimaging. Phenytoin was the most commonly used intravenous antiepileptic drug (AED) followed by Levetiracetam and Sodium Valproate. Carbamazepine was the most common oral AED used.&#x0D; Conclusion: NCC is the most common finding among seizure patients admitted to our hospital. The incidence of NCC is high in Eastern Nepal. Poor hygiene, insanitation, low socioeconomic status and lack of awareness were the key factors in spreading NCC.

A Study of Trends of Intravenous Antiepileptic Drugs in Patients with Status Epilepticus

Background and Objective: Status epilepticus (SE) called the neurological emergency. Currently, we have many kinds of intravenous antiepileptic drugs (AEDs) despite conventional antiepileptic drugs and new antiepileptic drugs. Therefore, objective of this study is acquiring for trends and cumulative cost of intravenous AEDs in patients with SE.

Management of refractory and super-refractory status epilepticus

If status epilepticus continues despite the use of intravenous antiepileptic drugs or narcotics, it is called "refractory" or "super-refractory" status epilepticus (RSE, SRSE). Prolonged seizure activity is associated with neuronal damage, systemic complications and mortality rates of up to 50%, especially in generalized tonic clonic seizure types. In order to terminate the status, several rescue interventions with drugs and other measures are available. However, their evidence base is low because the effectiveness of the measures was almost exclusively derived from case reports and case series. In individual cases, agood outcome is possible even after several months of ongoing SRSE.

Use of levetiracetam in pediatric refractory status epilepticus

Refractory status epilepticus, with persistence of seizures despite initial intravenous benzodiazepine and one secondline intravenous antiepileptic drug occurs in nine percent to 44% of the patients with status epilepticus. Aggressive treatment is needed to control such seizures with drug refractoriness. A case of a 2-year-old boy treated with intravenous levetiracetam with cessation of seizures, averting the need for general anesthesia is reported. Option of using levetiracetam in refractory status epilepticus is suggested.

Antiepileptic Drug Management in Hospitalized Epilepsy Patients With Nil Per Os Diets: A Retrospective Review.

Antiepileptic drug (AED) management in patients with epilepsy who cannot take their usual oral medications is a common neurologic dilemma in the hospital setting. Strategies to maintain seizure control in patients with nil per os (NPO, nothing by mouth) diet orders include continuation of oral AEDs despite NPO nutrition orders, administration of intravenous AED(s), or temporary administration of benzodiazepines. The frequency with which these strategies are used and their effectiveness in preventing in-hospital seizures is unknown. We conducted a retrospective cohort study to determine AED management strategies and seizure frequency in hospitalized epilepsy patients with NPO diet status admitted to an academic medical center between 2001 and 2016. Clinical documentation was reviewed. Antiepileptic drug selection (medication and route of administration) and presence or absence of seizures were recorded. We identified 199 admissions during which epilepsy patients had NPO diet orders. Antiepileptic drug management strategies included continuation of oral medications (50.3% of admissions), intravenous AED monotherapy (22.1%), intravenous AED polytherapy (12.6%), benzodiazepines (1.0%), holding AEDs (4.5%), or a combination (9.5%). Seizures occurred during 14 admissions. Treatment with AED polytherapy prior to admission and changing the patient's AED regimen during admission were associated with increased odds of seizures during admission (P = .0028; P = .0114). These results suggest that patients' home oral AED regimens should be continued when possible in order to minimize the frequency of seizures during hospitalizations.

Effectiveness and Adverse Effect of Intravenous Lacosamide in Nonconvulsive Status Epilepticus and Acute Repetitive Seizures in Children.

Nonconvulsive status epilepticus (NCSE) and acute repetitive seizures (ARS) are associated with significant morbidity and mortality. Due to the lack of randomized-controlled trials of intravenous antiepileptic drugs (AEDs) in these conditions, trials of a new generation of AEDs in this aspect are needed. A prospective interventional study was conducted in children under 18 years of age with NCSE or ARS who either had contraindication to or were refractory to first-line AEDs and received intravenous lacosamide. Demographic data, the efficacy of treatment, and adverse effects were recorded. Eleven patients with a median age of 11 years, predominantly female (72.7%), were enrolled. Average loading dose was 227 mg (8.3 mg/kg/dose) and average daily maintenance dose was 249 mg (4.6 mg/kg/dose). All patients (100%) experienced a reduction in seizure frequency within 24 hours. Eight of eleven patients (72.7%) experienced a reduction in seizure frequency of more than 50% by the end of the study, and one patient became seizure-free. In terms of adverse events, one patient had a bradycardia without prolongation of the PR interval. Interestingly, there was a case of neuronal ceroid lipofuscinosis in which a significant improvement in seizure control was achieved. The results indicate that intravenous lacosamide may be an alternative treatment for NCSE or ARS in children. To our knowledge, this is the first study on the use of intravenous lacosamide in Asian children. This study is registered to Thai Clinical Trials Registry (TCTR) and the trial registration number is TCTR20180508004.

Therapeutic burst-suppression coma in pediatric febrile refractory status epilepticus

BackgroundEvidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. MethodsWe retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. ResultsThirty-five patients (23 boys; age range: 1–18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. ConclusionsOur results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes.

What to do when patients with epilepsy cannot take their usual oral medications

When people with epilepsy are hospitalised for medical or surgical conditions, they may be unable to take their home antiepileptic drugs (AEDs). Such ‘nil by mouth’ people with epilepsy require...

Successful, Short-Term Drug Exchange Protocol in Epilepsy: Transient Addon of Intravenous Anti-Epileptic Drugs

Newer antiepileptic drugs (AEDs) are supposed to be more beneficial at controlling seizures than older AEDs. We substituted newer AEDs for older AEDs while conducting a transient add-on of an intravenous (IV) antiepileptic drug (AED) as a base therapy (AED adjustment), and in the present paper we evaluate the efficacy and safety of this method. The study participants were 40 consecutive referral patients with intractable epilepsy who had been treated with two or more AEDs but had epileptic seizure which spoiled their quality of life. Five of the patients were excluded because any IV AEDs exacerbated their clinical seizures and electro-encephalography (EEG). The mean age of the remaining 35 patients was 7.5 (range: 1.2 - 20.5). The patients had been on two to five AEDs (mean 3.3), and experienced seizures ranging from 0.2 to 100 times/day (mean 13.0). We kept the patients on one or two key oral AEDs and terminated the other oral AEDs simultaneously while they were treated with a base IV AED. After adjusting their dose, the patients were on two to four oral AEDs (mean 2.8) two years later, and the frequency of seizures was reduced to 0 to 10 times/day (mean 1.4). It took about one month of hospitalization to adjust the AEDs, and both seizure frequency and the number of drugs decreased significantly after AED adjustment (p<0.001). There were no serious side effects of clinical seizures or in their blood and chemistry tests. The adjusted AEDs included newer ones, and the older ones were still necessary. AED adjustment was possible and useful for epileptic patients once a transient add-on of intravenous antiepileptic drugs was done.

Status epilepticus: Refractory and super-refractory.

Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

Status Epilepticus in Adults: A Review of Diagnosis and Treatment.

Status epilepticus is a medical emergency that requires rapid diagnosis and treatment. Nonconvulsive status epilepticus is frequently underdiagnosed and therefore undertreated, which can lead to permanent neuronal damage resulting in disability or death. Despite the frequent occurrence and morbidity associated with status epilepticus, this topic has received little attention within the literature. A systematic approach to treatment should start with management of airway, breathing, and circulation, followed by administration of benzodiazepines and intravenous antiepileptic drugs, and rapid escalation of therapy to prevent morbidity and mortality. Armed with the information in this article, nurses will have a higher-level understanding of what to do when encountering a patient in status epilepticus.

Status epilepticus: Analysis of refractory cases

Objective: to analyze refractory status epilepticus (SE) cases. Patients and methods. Fifteen female patients aged 21 to 62 years with refractory SE were comprehensively examined using long-term electroencephalography monitoring. The investigators evaluated the efficiency of treatment regimens with intravenous antiepileptic drugs (AEDs), such as diazepam (DZP); valproic acid (VPA); levetiracetam; and lacosamide and their combinations, at the prehospital and hospital stages, as well as SE therapy complications noted only in the intravenous administration of narcotics (propofol, sodium thiopental). Results and discussion. A fetal outcome due to multiple organ dysfunction indirectly related to SE was recorded in 2 (13.3%) patients with acute symptomatic status. SE was abolished in the other 13 cases. The preliminary findings may suggest that it is appropriate to prescribe VPA just at the prehospital stage. The co-administration of VPA and DZP substantially enhances the efficiency of SE therapy. The maximum acceptable doses of AEDs using the whole available therapeutic arsenal should be administered within the first hours of acute symptomatic SE.

Cost of status epilepticus in a tertiary care hospital in India

PurposeStatus epilepticus (SE) is one of the most important neurological emergencies. The present study evaluated both direct cost of SE and predictors of cost in an Indian tertiary care teaching hospital in Lucknow India. MethodsSE was defined as continuous seizure for ≥5min or recurrent seizures without regaining consciousness. Etiologies of SE were categorized as acute central nervous system (CNS) pathology, acute non-CNS pathology, chronic CNS pathology, congenital disorders and others. Patients requiring mechanical ventilation (MV) received ventilators free of cost. Mortality and disability on discharge were noted. ResultsFifty-five patients aged 8–90 years were included (males, 33). Fifty (89.3%) patients had generalized convulsive SE. The severity of SE as assessed by Status Epilepticus Scoring Scale was unfavorable (score, 3–6) in 41 (74.5%) patients. The etiology of SE was categorized as acute CNS pathology in 28 (51%) patients, non-CNS and chronic CNS pathology in 11 (19.6%) patients each, remote congenital pathology in 2 (3.6%), and others in 3 (5.6%). Thirty (53.6%) patients had comorbidities. Median duration of hospitalization was 7 (range, 1–72) days.Twenty six patients were hospitalized for >7 days. SE was controlled by 2 drugs in 47 (85.5%) patients and refractory to 2 intravenous antiepileptic drugs in 8 (14.5%). Nineteen (34.5%) patients died, and 29 (51.8%) showed favorable outcomes on discharge. Median hospital expenditure per case was INR 19,900 ($309.87; range, INR 1600–574,000). On multivariate analysis, SE hospitalization costs were determined by refractoriness of SE and mechanical ventilation (MV). Hospitalization cost of SE was lower than those of stroke. ConclusionAcute non-CNS pathology is largely responsible for the high cost of SE, particularly refractory SE requiring mechanical ventilation.

Single-dose intravenous administration of antiepileptic drugs induces rapid and reversible remodeling in the brain: Evidence from a voxel-based morphometry evaluation of valproate and levetiracetam in rhesus monkeys

Effects of the long-term use of antiepileptic drugs (AEDs) on the brains of patients with epilepsy have been previously reported. The aim of this study was to determine the rapid brain structure remodeling induced by single-dose intravenous AED administration that rules out the potential effects of epilepsy. Ten rhesus monkeys were randomly divided into two groups and were intravenously administered a single dose of valproic acid (VPA) or levetiracetam (LEV) at treatment dosages. Magnetic resonance imaging (MRI) data were recorded from every subject prior to AED administration and at 2h and 1 week after administration. Using optimized voxel-based morphometry (VBM) analysis, we measured changes in regional gray matter volume (GMV) and white matter volume (WMV) in each group over time following medication and directly compared the differences between the two groups. Both AEDs induced brain volume alterations at 2h after their administration, but these changes had reverted at 1 week. The VPA group exhibited increased GMV in the right geniculate nucleus and the right pulvinar, whereas the LEV group exhibited WMV reductions in the right pulvinar, the right parietal lobe and the right occipital lobe. Directly compared with the LEV group, the VPA group exhibited a temporally constant GMV increase in the bilateral temporal cortex and a WMV reduction in the left pedunculus cerebri. Single-dose intravenous administration of a level of VPA or LEV that mimics clinical use is associated with rapid and reversible VBM-detected GMV or WMV alterations in rhesus monkeys. This finding may provide new insights into the understanding of AED-induced brain structure remodeling and may contribute to our understanding of the brain-level mechanisms and targets of AED action.

Canine status epilepticus treated with fosphenytoin: A proof of principle study.

There are a limited number of marketed intravenous antiepileptic drugs (AEDs) available to treat status epilepticus (SE). All were first developed for chronic therapy of epilepsy, not specifically for SE. Epilepsy and canine SE (CSE) occur naturally in dogs, with prevalence, presentation, and percentage of refractory cases similar to human epilepsy. The objective of this study was to determine if CSE treated with fosphenytoin (FOS) results in a similar responder rate as for people. A randomized clinical trial was performed for dogs with CSE. Dogs who presented during a seizure or who had additional seizures after enrolling received intravenous (i.v.) benzodiazepine (BZD) followed immediately by intravenous infusion of 15 mg/kg phenytoin equivalent (PE) of fosphenytoin (FOS) or saline placebo (PBO). If seizures continued, additional AEDs were administered per the standard of care for veterinary patients. Total and unbound plasma phenytoin (PHT) concentrations were measured. Consent was obtained for 50 dogs with CSE. Thirty-one had additional motor seizures and were randomized to the study intervention (22 FOS and 9 PBO). There was a statistically significant difference in the 12 h responder rate, with 63% in the FOS group versus 22% in the placebo group (p = 0.043) having no further seizures. The unbound PHT concentrations at 30 and 60 min were within the therapeutic concentrations for people (1-2 μg/ml) with the exception of one dog. There was mild vomiting in 36% of the FOS group (7/22) within 20 min of FOS administration and none of the placebo group (0/9) (p = 0.064). This proof of concept study provides the first evidence that FOS is tolerated and effective in canine SE at PHT concentrations clinically relevant for human SE. Furthermore, naturally occurring CSE can be utilized as a translational platform for future studies of novel SE compounds.