Treatment Of Acute Seizures Research Articles

Safety and tolerability of intravenous undiluted levetiracetam in pediatrics: A retrospective cohort study.

Time is critical in executing acute seizure treatment, and efforts to minimize operational delays with medication preparation confer potential logistical and practical advantages. Multiple studies have demonstrated the safety and tolerability of intravenous (IV) undiluted levetiracetam (LEV) in adults; however, published pediatric data are limited. This study aims to evaluate the safety and tolerability of IV undiluted LEV in pediatrics. This was a retrospective, dual-center, observational cohort study evaluating concentration-related adverse drug events with IV undiluted (100 mg/mL) LEV in pediatrics over a 3-year 3-month timespan. A total of 60 undiluted administrations in 52 patients were included in the study. The median age was 4 years; 58.3% of patients were younger than 5 years of age. All doses were administered via a peripheral IV line. The most common IV anatomic site and peripheral IV gauge (G) was the antecubital (66.6%) and 22G catheter (63.3%). There were no documented concentration-related adverse drug events. Regardless of IV anatomic site, IV gauge, and administered dose there were no documented concentration-related adverse effects with IV undiluted LEV in a pediatric population. IV undiluted LEV may be considered safe and tolerable in pediatrics. Prospective pediatric studies should assess the safety and tolerability of IV undiluted LEV.

Intranasal vs Buccal vs Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Egyptian Patients

Abstract Introduction: Acute convulsions in children are a common emergency worldwide. Benzodiazepines are the recommended first line of treatment. We wished to compare the efficacy, ease of administration and overall satisfaction of midazolam by the buccal, intranasal orintramuscular route in the treatment of acute seizures in Egyptian children both at homes and Emergency room (ER) Methods A prospective, randomized, trial was performed in children aged 1 months to 17 years with acute seizures lasting longer than 5 min. Children were randomly assigned to receive midazolam, 0.2 mg/kg, by the buccal, intranasal or intramuscular route. The primary endpoint was seizure cessation within 10 min of drug administration and no seizure recurrence within 30 minutes. Results There were 196 seizures analysed in home group, 67 patients received midazolam via buccal route, 60 via intranasal, 69 via intramuscular route while 105 patients were recruited from ER 37 patients received buccal midazolam, 34 received intranasal and 34 received intramuscular midazolam. Intramuscular midazolam stopped seizures within 10 min in 94.2 % in home group and 85.3 % in ER group. On the other hand, intranasal midazolam was successful to stop seizures in 93.3% in home group and 88.2 % in ER group within 10 minutes. The buccal route was effective in 91% in home group and 78.4 % in ER group. There were no significant differences in efficacy between all groups. P = 0.763 and P = 0.509 among home and ER groups respectively. Time to seizure cessation was significantly higher in the buccal group 5.11 ± 1.23minutes in home group and 5.91 ± 1.25 in ER group (P = 0.000). Highest overall satisfaction and ease of administration was seen in intranasal group especially among caretakers in home group > 7= 49 (81.7 %) P = 0.002.. Intramuscular midazolam was more preferred by physicians in ERgroup >7=32 (94.1%) (P = 0.001) There were no significant cardio-respiratory events in all groups. Conclusions Our results indicate that there is no clinically important difference between buccal, intranasal and IM routes of administration midazolam. Buccal and intranasal midazolam were safe and effective for treatment of acute seizures in children.

Intranasal Versus Buccal Versus Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Patients: A Randomized Controlled Trial

BackgroundBenzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER). MethodsA prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes. ResultsIn the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups. ConclusionsIntramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers.

Acute Abortive Therapies for Seizure Clusters in Long-Term Care.

To describe acute seizure treatment for the long-term care setting, emphasizing rescue (acute abortive) medications for on-site management of acute unexpected seizures and seizure clusters. Narrative review. People with seizures in long-term care, including group residences. PubMed was searched using keywords that pertained to rescue medications, seizure emergencies/epilepsy, seizure action plans, and long-term care. Seizure disorder, including epilepsy, is prevalent in long-term care residences, and rescue medications can be used for on-site treatment. Diazepam rectal gel, intranasal midazolam, and diazepam nasal spray are US Food and Drug Administration (FDA)-approved seizure-cluster rescue medications, and intravenous diazepam and lorazepam are approved for status epilepticus. Benzodiazepines differ by formulation, route of administration, absorption, and metabolism. Intranasal formulations are easy and ideal for public use and when rectal treatment is challenging (eg, wheelchair). Intranasal, intrabuccal, and rectal formulations do not require specialized training to administer and are easier for staff at all levels of training compared with intravenous treatment. Off-label rescue medications may have anecdotal support; however, potential disadvantages include variable absorption and onset of action as well as potential risks to patients and caregivers or care partners. Delivery of intravenous-administered rescue medications is delayed by the time needed to set up and deliver the medication and is subject to dosing errors. Seizure action plans that include management of acute seizures can optimize the quality and timing of treatment, which may reduce emergency service needs and prevent progression to status epilepticus. Seizure disorder is prevalent across all ages but is increased in older adults and in those with intellectual and developmental disabilities. Prompt intervention may reduce negative outcomes associated with acute unexpected seizures and seizure clusters. Seizure action plans that include acute seizures can improve the treatment response by detailing the necessary information for staff to provide immediate treatment.

Sublingual lorazepam as rescue therapy for seizure emergencies in adults

ObjectiveLimited acute home treatments are available for patients with prolonged (>5 minutes) or repetitive (≥2 in 24 hours) seizures. While this early seizure treatment may reduce the need for emergency care, intermittent intranasal benzodiazepine formulations are expensive and rectal diazepam administration is often socially unacceptable. We determined whether caregivers could use sublingual lorazepam oral concentrate solution effectively as acute treatment for adults with prolonged and repetitive seizures. MethodsPatients prescribed sublingual lorazepam solution at the Johns Hopkins Epilepsy Center for acute seizure treatment during a 5-year period (2012–2017) were screened. We determined clinical history of seizure patterns and number of antiseizure medications (ASMs) through patient and caregiver surveys, and we verified this history in patients’ medical records and charts. During a 2-year span (2017–2018), patients and caregivers were surveyed on responses to their most recent use of sublingual lorazepam solution, including seizure cessation (prolonged seizure stopping <5 minutes or ≤1 repetitive seizure), presence of sedation and adverse events within 24 hours of administration, and whether refrigeration limited use. ResultsIn total, 52 patients used sublingual lorazepam for treatment of acute seizures during the study period (median dose 1 mg, range 0.5 to 2 mg). Of them, 48 patients participated in treatment survey interviews. Family caregivers usually administered lorazepam (88%); 3 self-administered. Patients were surveyed on responses to their most recent use of sublingual lorazepam treatment: 66% (23/35) of patients with repetitive seizures reported no further seizure activity after administering treatment; 70% (7/10) with prolonged seizures reported seizure activity ceased within 5 minutes of treatment. Three patients treated auras and had no seizures. There were no serious adverse events during most recent use: 31% of patients developed moderate/severe sedation. Of note, 98% refrigerated lorazepam, often with coolers; 44%, however, said this limited treatment access. There was high treatment satisfaction; 79% reported that having the emergency treatment available made them feel safer. SignificanceThis patient survey and retrospective chart review demonstrates that home treatment with sublingual lorazepam solution may be effective for interrupting prolonged and repetitive seizures. No patients had sedation complications with home doses of 0.5 to 2 mg, and patients report high satisfaction with the treatment.

Clinically important intracranial abnormalities in children presenting with first focal seizure.

Management of pediatric patients presenting with first seizure is challenging, especially with regards to emergent neuroimaging. The rate of abnormal neuroimaging findings is known to be higher in focal seizures than in generalized seizures, but those intracranial abnormalities are not always clinically emergent. In this study, we aimed to determine the rate and indicators for clinically important intracranial abnormalities that change acute management in children presenting with a first focal seizure to the pediatric emergency department (PED). This study was conducted retrospectively in the PED at a University Children`s Hospital setting. The study population consisted of patients aged between 30 days and 18 years with first focal seizure and who had emergent neuroimaging at the PED between the years 2001 and 2012. There were 65 eligible patients meeting the study criteria. Clinically important intracranial abnormalities requiring emergent neurosurgical or medical intervention were detected in 18 patients (27.7%) at the PED. Four patients (6.1%) underwent emergent surgical procedures. Seizure recurrence and the need for acute seizure treatment in the PED were significantly associated with clinically important intracranial abnormalities. Neuroimaging study yielding of 27.7% shows that first focal seizure must be evaluated meticulously. From the emergency department`s point of view; we suggest that first focal seizures in children should be evaluated with emergent neuroimaging, if possible with magnetic resonance imaging. Especially patients with recurrent seizures at presentation requires more careful evaluation.

Novel variants in GABAA receptor subunits: A possible association with benzodiazepine resistance in patients with drug-resistant epilepsy

Benzodiazepines (BDZ) such as diazepam and lorazepam are popular as first-line treatment for acute seizures due to their rapid action and high efficacy. However, long-term usage of BDZ leads to benzodiazepine resistance, a phenomenon whose underlying mechanisms are still being investigated. One of the hypothesised mechanisms contributing to BDZ resistance is the presence of mutations in benzodiazepine-sensitive receptors. While a few genetic variants have been reported previously, knowledge of relevant pathogenic variants is still scarce. We used Sanger Sequencing to detect variants in the ligand-binding domain of BDZ-sensitive GABAA receptor subunits α1–3 and 5 expressed in resected brain tissues of drug-resistant epilepsy (DRE) patients with a history of BDZ resistance and found two previously unreported predicted pathogenic frameshifting variants – NM_000807.4(GABRA2):c.367_368insG and NM_000810.4(GABRA5):c.410del – significantly enriched in these patients. The findings were further explored in resected DRE brain tissues through cellular electrophysiological experiments.

Intravenous Brivaracetam in the Management of Acute Seizures in the Hospital Setting: A Scoping Review.

BackgroundClinical considerations for drug treatment of acute seizures involve variables such as safety, tolerability, drug-drug interactions, dosage, route of administration, and alterations in pharmacokinetics because of critical illness. Therapy options that are easily and quickly administered without dilution, well tolerated, and effective are needed for the treatment of acute seizures. The objective of this review is to focus on the clinical considerations relating to the use of intravenous brivaracetam (IV BRV) for the treatment of acute seizures in the hospital, focusing on critically ill patients.MethodsThis was a scoping literature review of PubMed from inception to April 13, 2021, and search of the American Academy of Neurology (AAN) 2021 Annual Meeting website for English language publications/conference abstracts reporting the results of IV BRV use in hospitalized patients, particularly in the critical care setting. Outcomes of interest relating to the clinical pharmacology, safety, tolerability, efficacy, and effectiveness of IV BRV were reviewed and are discussed.ResultsTwelve studies were included for analysis. One study showed that plasma concentrations of IV BRV 15 min after the first dose were similar between patients receiving IV BRV as bolus or infusion. IV BRV was generally well tolerated in patients with acute seizures in the hospital setting, with a low incidence of individual TEAEs classified as behavioral disorders. IV BRV demonstrated efficacy and effectiveness and had a rapid onset, with clinical and electrophysiological improvement in seizures observed within minutes. Although outside of the approved label, findings from several studies suggest that IV BRV reduces seizures and is generally well tolerated in patients with status epilepticus.ConclusionsIV BRV shows effectiveness, and is generally well tolerated in the management of acute seizures in hospitalized patients where rapid administration is needed, representing a clinically relevant antiseizure medication for potential use in the critical care setting.

Seizure Management in the Intensive Care Unit.

Purpose of this reviewThis review presents current therapy for seizures in the intensive care unit. The reader is provided with recent evidence regarding the use of EEG in determining treatment for acute seizures. Proposed treatment approaches for seizures and status epilepticus are provided. Controversies and complexity of selecting treatments are discussed.Recent findingsCritical Care EEG Monitoring Research Consortium analyzed the association of periodic and rhythmic electroencephalographic patterns with seizures and found that lateralized and generalized periodic discharges and lateralized rhythmic delta were associated with increased seizure risk. Applications using modified EEG techniques have demonstrated more rapid feedback to the ICU than was previously possible.SummaryAccurate diagnosis and efficient treatment of seizures in the ICU is challenging due to patient factors, complexities of antiepileptic drug therapy, and the required expertise for EEG interpretation. Selection of optimally effective therapy for seizures or status epilepticus depends on multiple factors, making collaboration between neurophysiologists and the ICU team of paramount importance.

Leitner (Monatsschrift f. Kinderheilkunde Bd. 48, H. 3/4, 1930)

(Monatsschrift f. Kinderheilkunde Bd. 48, H. 3/4, 1930) used luminar sodium with great success in the treatment of acute seizures in infants and infants, which proved to be the chosen remedy in the treatment of persistent convulsions in infants.

Seizure Control in Neonates Undergoing Screening vs Confirmatory EEG Monitoring.

ObjectiveTo determine whether screening continuous EEG monitoring (cEEG) is associated with greater odds of treatment success for neonatal seizures.MethodsWe included term neonates with acute symptomatic seizures enrolled in the Neonatal Seizure Registry (NSR), a prospective, multicenter cohort of neonates with seizures. We compared 2 cEEG approaches: (1) screening cEEG, initiated for indications of encephalopathy or paralysis without suspected clinical seizures; and (2) confirmatory cEEG, initiated for the indication of clinical events suspicious for seizures, either alone or in addition to other indications. The primary outcome was successful response to initial seizure treatment, defined as seizures resolved without recurrence within 30 minutes after initial loading dose of antiseizure medicine. Multivariable logistic regression analyses assessed the association between cEEG approach and successful seizure treatment.ResultsAmong 514 neonates included, 161 (31%) had screening cEEG and 353 (69%) had confirmatory cEEG. Neonates with screening cEEG had a higher proportion of successful initial seizure treatment than neonates with confirmatory cEEG (39% vs 18%; p < 0.0001). After adjusting for covariates, there remained a greater odds ratio (OR) for successful initial seizure treatment in the screening vs confirmatory cEEG groups (adjusted OR 2.44, 95% confidence interval 1.45–4.11, p = 0.0008).ConclusionsThese findings provide evidence from a large, contemporary cohort of neonates that a screening cEEG approach may improve odds of successful treatment of acute seizures.Classification of EvidenceThis study provides Class III evidence that for neonates a screening cEEG approach, compared to a confirmatory EEG approach, increases the probability of successful treatment of acute seizures.

Intra Nasal Midazolam vs. Rectal Diazepam in Management of Acute Seizures in Pediatrics, Considering the Antiepileptic Drugs Monitoring

Immediate management of children's epilepsy is essential before the patient arrives to the hospital. The purpose of this study was to compare the efficacy of intranasal midazolam vs. rectal diazepam in the management of acute pediatric seizures. In this cross-sectional study, 68 patients having acute seizure were evaluated for response to treatment after receiving intra-nasal midazolam (34 patients) or rectal diazepam (34 patients). Patents were assessed by physicians at the arrival to emergency department for history taking and examination. Blood samples were assessed for valproate, phenobarbital and phenytoin levels in serum to determine previous use of antiepileptic drugs. Seizure duration and response time to treatment were evaluated along with health care utilization and were compared between study groups, by the statistical package for the social sciences software. Mean age of study participants, sex disturbance, age at onset of a seizure, type of seizure and prehospital time had not any significant differences between two groups (p>0.05). The mean response time to diazepam was 8.0±4.9 min and 6.3±2.2 min for midazolam; which had a significant difference between groups (0.001). Linear regression of serum antiepileptic drug levels in association of response time in each group was not significant in all case (p>0.05), expect the lamotrigine serum level in midazolam group (p=0.029). Intranasal midazolam was seen to have a better effect than rectal diazepam in the management and treatment of acute seizures in children; while antiepileptic drugs monitoring want helpful in assessing the absolute effect.

Epilepsy monitoring units can be safe places; a prospective study in a large cohort

ObjectiveNo international guideline is available for minimum safety measures at epilepsy monitoring units (EMUs), although recommendations for preferred practices exist. These are mostly based on expert opinion, without evidence of effectiveness. We do not apply all of these preferred practices at our EMU setting. We audited adverse events and diagnostic utility at our EMU over one year. MethodsFrom May 2018 to May 2019, we prospectively collected data concerning adverse events and diagnostic utility of all EMU admissions (noninvasive video-electroencephalogram (EEG) recordings); during these admissions, individuals can be ambulant within their EMU room. ResultsThere were 1062 admissions comprising 1518 EMU days. In 2% of the admissions, a complication occurred, mostly a fall without injury (n = 6). In almost half of the falls, this was from the bed. Complications occurred most often during admissions for presurgical evaluation. Antiseizure medication (ASM) was tapered in 86% of presurgical cases, but no serious injury occurred, and occurring seizures were effectively treated with intranasal midazolam if needed. ConclusionsThe overall adverse event rate was low. Falls are the most common adverse event comparable with previously published fall rates at other EMUs where people are restricted to their bed. We showed that restricted ambulation at a well-monitored EMU is not necessary and possibly unwanted. No serious injury due to tapering of ASM occurred, and intranasal midazolam was shown to be effective as acute seizure treatment.

Inhaled alprazolam rapidly suppresses epileptic activity in photosensitive participants.

Treatment options for seizure clusters are limited; the need for easy-to-administer treatments remains. The Staccato system delivers drug deep into the lung via inhalation. In this phase 2a study, we investigated the ability of three different doses of Staccato alprazolam to suppress the electroencephalographic (EEG) photoparoxysmal response (PPR) compared with placebo in participants with photosensitive seizures. Adults (18-60years) with a diagnosis and history of PPR on EEG with or without an epilepsy diagnosis were eligible to participate. Participants received Staccato alprazolam 0.5, 1.0, and 2.0mg, and Staccato placebo (twice) in random order. Intermittent photic stimulation and clinical assessments were performed at one predose and seven postdose time points. The primary endpoint of the study was the change in standardized photosensitivity range (SPR) in participants receiving each dose of Staccato alprazolam. Fifteen participants with a prior epilepsy diagnosis were screened; five were enrolled, randomized, and completed the study. All participants were white females with a mean (SD) age of 27.2 (6.8) years. All doses of Staccato alprazolam reduced the SPR at 2minutes; the effect was sustained through 4hours for the 0.5-mg dose and 6hours for the 1.0- and 2.0-mg doses. The magnitude and duration of sedation and sleepiness were dose-related. Four participants (80%) experienced ≥1 adverse event (AE); none was severe or serious. Cough, diarrhea, dysgeusia, oral dysesthesia, sedation, and somnolence were experienced by two participants (40%) each. This proof-of-concept study demonstrated that Staccato alprazolam 0.5, 1.0, and 2.0mg rapidly suppressed epileptiform activity in photosensitive participants with epilepsy. The AE profile of Staccato alprazolam was similar to what has been reported for alprazolam for other indications. The results support further development of Staccato alprazolam as a rescue medication for the acute treatment of seizures.

Assessment of dose capping in phenytoin loading practices in the emergency department and the impact of an emergency medicine pharmacist

ObjectivesPhenytoin is a common anticonvulsant used for the acute treatment of seizures in the emergency department (ED). Certain patient populations, such as the obese, have been shown to present dosing challenges. Often doses are arbitrarily “capped” for fear of overdosing. Emergency medicine pharmacists (EPhs) have been shown to optimize the care of patients receiving phenytoin therapy in other settings, demonstrating reductions in seizure activity, duration of therapy, and cost.MethodsRecords of patients presenting to the ED that were at least 18 years old and were prescribed intravenous phenytoin were reviewed. Patients weighing 100 kg or more were compared with those less than 100 kg. To evaluate the impact of an EPh, intravenous phenytoin orders placed during the EPh's hours were compared with those placed outside of those hours.ResultsA total of 117 patients were included, 42 (36%) weighed 100 kg or more. No significant difference was found in the achievement of target (10‐20 μg/mL) postload concentrations between the two groups (P = 0.795). Patients weighing 100 kg or more received significantly lower weight‐based phenytoin doses (16.0 vs 18.6 mg/kg, P = 0.0001). Those 100 kg or more who received less than 15 mg/kg were found to have significantly lower postload concentrations than those that received 15 mg/kg or more regardless of total dose (11.5 vs 16.5 μg/mL; P = 0.003). The presence of an EPh was found to result in significantly higher rates of postload concentrations within the therapeutic range across all groups (72.4% vs 53.7%; P = 0.04).ConclusionsThe available data suggest that artificial total dose limitations in patients yield significantly lower postload concentrations, potentially delaying seizure control in the acute setting. The presence of EPhs at the bedside increases the success of initial phenytoin dosing strategies in this population.

F24. Evaluation of cardiovascular parameters during intravenous loading dose of lacosamide

Several recent reports have described the efficacy of intravenous (IV) lacosamide (LCS) in the management of acute seizures and status epilepticus (SE). Based on data from 3 randomized control trials LCS appeared to be well tolerated. However, previous studies of patients on maintenance LCS therapy have reported Electrocardiographic (ECG) changes including conduction disturbances and sinus node dysfunction. A study of IV LCS boluses of 200, 300, and 400 mg administered over 15 min to outpatient subjects with epilepsy showed no changes in ECG during the infusions. We performed a retrospective review of adult patients who received IV LCS of 400–1400 mg and evaluated for changes in cardiovascular parameters during and immediately after the loading dose. With IRB approval, patients were identified that received IV LCS in the ICU for acute treatment of seizures during the years 2013–2016. Data elements collected were age, gender, weight, duration of infusion, change or termination of infusion because of immediate side effects, heart rate changes, blood pressure changes, oxygen saturation changes, and use of vasopressor agents one hour before, during and up to one hour after the infusion completed. All loading doses were administered over 30–60 min. No concurrent other anti-epileptic medication was given during loading dose of LCS. Three hundred and fifty-four adult patients were identified that were treated with LCS for seizures and SE in the ICU. 318/354 patients had IV loading dose of 400–1400 mg. Demographics were male/female (130/188), average weight 83.7 kg (range 40.8–219.5), and average age was 60 yrs (18–97). Ranges of the bolus doses included 400–600 mg (210 pts), 601–800 mg (78 pts) and 801–1400 mg (30 pts). No patients required a change or discontinuation of the infusion due to acute side effects. No patients required vasopressors from blood pressure changes during the bolus. The systolic blood pressure (mm Hg) 1 h prior, during, and 1 h post bolus were 137.56 ± 25.3, 133.4 ± 24.87, and 131.6 ± 25.89 (measured with 1 standard deviation). Similarly, the diastolic measurements were 72.3.9 ± 12.87, 72.7 ± 13.78, and 69.94 ± 13.46. Similarly, the heart rate measurements were 86.98 ± 19.73, 85.92 ± 18.85, and 85.22 ± 18.25. Patients with refractory SE who require anesthetic agents or repeated doses of benzodiazepines are most vulnerable to severe hypotension which complicates the management and increases risk for organ hypo-perfusion and mortality. The choice of IV antiepileptic medications is limited since IV fosphenytoin has been associated with substantial hypotension. In our study IV bolus doses of LCS appears to have no deleterious cardiovascular effects thus favoring its use in the management of acute seizures and SE. Furthermore, we did not identify any malignant changes in heart rate related to the bolus dose ranging from 400 to 1400 mg.

Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats.

Diazepam, administered by the intravenous, oral, or rectal routes, is widely used for the management of acute seizures. Dosage forms for delivery of diazepam by other routes of administration, including intranasal, intramuscular, and transbuccal, are under investigation. In predicting what dosages are necessary to terminate seizures, the minimal exposure required to confer seizure protection must be known. Here we administered diazepam by continuous intravenous infusion to obtain near-steady-state levels, which allowed an assessment of the minimal levels that elevate seizure threshold. The thresholds for various behavioral seizure signs (myoclonic jerk, clonus, and tonus) were determined with the timed intravenous pentylenetetrazol seizure threshold test in rats. Diazepam was administered to freely moving animals by continuous intravenous infusion via an indwelling jugular vein cannula. Blood samples for assay of plasma levels of diazepam and metabolites were recovered via an indwelling cannula in the contralateral jugular vein. The pharmacokinetic parameters of diazepam following a single 80-μg/kg intravenous bolus injection were determined using a noncompartmental pharmacokinetic approach. The derived parameters Vd , CL, t1/2α (distribution half-life) and t1/2β (terminal half-life) for diazepam were, respectively, 608mL, 22.1mL/min, 13.7 minutes, and 76.8minutes, respectively. Various doses of diazepam were continuously infused without or with an initial loading dose. At the end of the infusions, the thresholds for various behavioral seizure signs were determined. The minimal plasma diazepam concentration associated with threshold elevations was estimated at approximately 70ng/mL. The active metabolites nordiazepam, oxazepam, and temazepam achieved levels that are expected to make only minor contributions to the threshold elevations. Diazepam elevates seizure threshold at steady-state plasma concentrations lower than previously recognized. The minimally effective plasma concentration provides a reference that may be considered when estimating the diazepam exposure required for acute seizure treatment.

Seizure Bootcamp: Everything You Ever Needed to Know to Manage Seizures in End Stage Disease (FR455)

•Describe common clinical presentations of seizures in advanced illness.•Implement strategies for appropriate use of antiepileptics in end stage illness.•Develop a framework for management of acute seizure activity in home and inpatient hospice settings. Seizures are a common occurrence in end stage disease, occurring in a wide range of conditions, including dementia, stroke, AIDS, end stage renal disease, and both primary brain tumors and metastatic disease. Not only are uncontrolled seizures a significant source of distress to both patient and families, but they present a significant management challenge to the hospice team, who are often faced with controlling seizures in the face of advancing disease, increasing seizure risk factors, and declining ability of the patient to take oral medications. Through use of current evidence, case studies, and interactive discussion, this session will present participants with the opportunity to establish a framework to effectively assess and manage seizures in the end stages of illness, with particular attention to management of seizures in the hospice setting. Participants will develop the bedside clinical skills necessary to detect subtle presentations of seizures and to distinguish them from common seizure mimics. Participants will also develop increased comfort with use of antiepileptics in end stage disease, including facility with non-oral routes of administration, and with treatment of acute seizures in both the home and inpatient settings. In addition, participants will develop techniques to effectively educate families and other caregivers about the safe management of acute seizures at home.

Comparing the effectiveness of intranasal Midazolam and intravenous Lorazepam for the treatment of acute seizures in children

Objective: The objective of this study was to compare the safety and efficacy of intranasal midazolam with intravenous lorazepam in acute seizures in children. Methods: Children aged 6 months–12 years with active tonic/clonic/tonic-clonic seizures coming to the pediatric emergency department were enrolled in the study after getting informed consent. Groups were randomly distributed (Group 1: Intranasal midazolam; Group 2: IV lorazepam) and the sample size was 80 (40 in each group). Under clinical and pulse oximetry monitoring, aqueous midazolam 0.2 mg/kg was administered intranasally through automated aqueous intranasal spray(Midacip 0.5mg per puff) in lying down or in 45° propped up position to Group 1, while injectable lorazepam 0.1 mg/kg was administered intravenously slow (to a maximum of 4 mg) to Group 2. Results: Both the groups were found to be comparable in baseline characteristics. Mean time to administer the drug after arrival to the doctor in intranasal midazolam and IV lorazepam was 3.65 (standard deviation [SD] 1.167) min and 7.93 (SD 3.23) min, respectively (p=0.0001). Intranasal midazolam group had significant control of seizures in &lt;5 min of arrival (p=0.0006). The control of seizures within 1 min after drug administration was also found to be more effective in midazolam group (p=0.004). No adverse effects or respiratory depression were found in any of the groups. Conclusion: The ease to administer, effectiveness, and rapid onset of action of intranasal midazolam without causing any respiratory depression enable it to be considered as a first-line drug for acute seizures in all settings including homes/day-care centers.

A comparison of buccal midazolam and intravenous diazepam in acute treatment of seizures in children

A comparison of buccal midazolam and intravenous diazepam in acute treatment of seizures in children