Intravenous Lacosamide in Pediatric Status Epilepticus: An Open-Label Efficacy and Safety Study

IntroductionLacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus.MethodsChildren who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide.ResultsNine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient.ConclusionIn children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg.     

The Use of Lacosamide in Refractory Status Epilepticus

Background  

Case reports suggest lacosamide may have a role in status epilepticus (SE). The purpose of this case series is to describe the use of lacosamide in refractory SE (RSE) at our institution.     

Intravenous lacosamide as short‐term replacement for oral lacosamide in partial‐onset seizures

Purpose : Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial‐onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200–800 mg/day) infused over 10, 15, and 30 min as short‐term replacement for oral lacosamide in patients with partial‐onset seizures. Methods : This multicenter, open‐label, inpatient trial enrolled 160 patients from ongoing open‐label, long‐term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2–5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations. Results : A total of 160 patients received lacosamide 200–800 mg/day, i.v., for 2–5 days, of which 69% received 400–800 mg/day doses. The most common AEs (reported by ≤10% of patients) were headache, dizziness, and somnolence. There was no increase in frequency or severity of AEs with shorter durations of infusion or increased days of exposure. AEs were similar, but more frequent, with higher doses (≥400 mg/day). Injection‐site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts. Discussion : This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short‐term (2–5 days) replacement for patients temporarily unable to take oral lacosamide.     

Factors influencing response to intravenous lacosamide in emergency situations: LACO-IV study

Status epilepticus (SE) and acute repetitive seizures (ARSs) frequently result in emergency visits. Wide variations in response are seen with standard antiepileptic drugs (AEDs). Oral and intravenous (IV) formulations of lacosamide are approved as adjunctive therapy in the treatment of partial-onset seizures in adults and adolescents. The aim of the retrospective multicenter observational study (LACO-IV) was to analyze data from a large cohort of patients with SE or ARSs of varying severity and etiology, who received IV lacosamide in the emergency setting. Patient clinical data were entered into a database; lacosamide use and efficacy and tolerability variables were analyzed. In SE, IV lacosamide tended to be used mainly in nonconvulsive status epilepticus as second- or third-line treatment. The proportion of patients with no seizures when IV lacosamide was the last drug administered was 76.5% (70.9% SE and 83.7% ARSs). The rate of seizure cessation ≤ 24 h after IV lacosamide administration was 57.1% (49.1% SE and 67.4% ARSs). Of the factors analyzed, a shorter latency from seizure onset to IV lacosamide infusion influenced treatment response significantly. A nonsignificant tendency towards a higher response was seen with lacosamide dose > 200 mg versus ≤ 200 mg. Analysis of response according to mechanism of action showed no significant differences in response to IV lacosamide in patients receiving prior sodium channel blocker (SCB) or non-SCB AEDs in the overall or SE population; however, in ARSs, a tendency towards a higher response was observed in those receiving non-SCB AEDs. The frequency and nature of adverse events observed were in line with those reported in other studies (somnolence being the most frequent). In the absence of randomized prospective controlled studies of IV lacosamide, our observations suggest that IV lacosamide may be a potential alternative for treatment of SE/ARSs when seizures fail to improve with standard AEDs or when AEDs are contraindicated or not recommended.     

Intravenous lacosamide for treatment of status epilepticus

Kellinghaus C, Berning S, Immisch I, Larch J, Rosenow F, Rossetti AO, Tilz C, Trinka E. Intravenous lacosamide for treatment of status epilepticus.
Acta Neurol Scand: 2011: 123: 137–141.
© 2010 John Wiley & Sons A/S. Objectives – Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first‐line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. Methods – We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. Results – Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200–400 mg), which was administered at 40–80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. Conclusions – Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.     

The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: A meta-analysis of published studies

PurposeSystematic evaluation of published evidence-base of the efficacy of five antiepileptic drugs – lacosamide, levetiracetam, valproate, phenytoin and phenobarbital – in convulsive benzodiazepine-resistant status epilepticus.MethodsData sources included electronic databases, personal communication, and back tracing of references in pertinent studies. These were prospective and retrospective human studies presenting original data for participants with convulsive benzodiazepine-resistant status epilepticus. Interventions were intravenous lacosamide, levetiracetam, phenobarbital, phenytoin and valproate. Outcome measured is clinically detectable cessation of seizure activity. Level-of-evidence was assessed according to Oxford Centre of Evidence-Based Medicine and The Cochrane Collaboration's Tool for Assessment of Risk. Twenty seven studies (798 cases of convulsive status epilepticus) were identified and 22 included in a meta-analysis. Random-effects analysis of dichotomous outcome of a single group estimate (proportion), with inverse variance weighting, was implemented. Several sources of clinical and methodological heterogeneity were identified.ResultsEfficacy of levetiracetam was 68.5% (95% CI: 56.2–78.7%), phenobarbital 73.6% (95% CI: 58.3–84.8%), phenytoin 50.2% (95% CI: 34.2–66.1%) and valproate 75.7% (95% CI: 63.7–84.8%). Lacosamide studies were excluded from the meta-analysis due to insufficient data.ConclusionValproate, levetiracetam and phenobarbital can all be used as first line therapy in benzodiazepine-resistant status epilepticus. The evidence does not support the first-line use of phenytoin. There is not enough evidence to support the routine use of lacosamide. Randomized controlled trials are urgently needed.     

Safety and Efficiency of Intravenous Push Lacosamide Administration

Background/objective

Intravenous (IV) lacosamide use for status epilepticus has increased in recent years and is recommended for refractory status epilepticus by current guidelines. Per the lacosamide package labeling, the preferred route of administration is diluted and infused over 30–60 min; however, administration undiluted is also acceptable and recent literature demonstrated safety at a maximum rate of 80 mg per minute (Kellinghaus et al. in Acta Neurol Scand 123:137–141, 2011). Undiluted administration as an IV push has potential to increase efficiency of administration to patients needing urgent seizure control since it may be dispensed from automatic dispensing cabinets in patient care areas. This study aims to compare safety outcomes and efficiency of administration in patients receiving lacosamide IV push compared to IV piggyback.

Methods

We present a single-center, retrospective cohort study of patients receiving lacosamide via IV piggyback or IV push from June 2016 to July 2017. Baseline characteristics, data related to potential safety concerns and timing of ordering, verification, and administration were collected. The primary safety outcomes were incidence of infusion site reactions, hypotension (systolic blood pressure [SBP] < 90 mm Hg), and bradycardia (heart rate [HR] < 50 beats per minute) documented within 2 h of each lacosamide dose. Secondary safety outcomes included the incidence of PR interval prolongation in patients with at least one electrocardiogram measured. The primary efficiency outcome was the time between order verification and administration.

Results

Patients in the IV piggyback (n = 88) and IV push (n = 78) groups had similar baseline characteristics, initial dose, SBP, and HR. Hypotension (8 vs. 10.3%) and bradycardia (2.3 vs. 2.6%) rates were similar among both groups (p > 0.05). Only one patient in each group had documented PR prolongation, and no documented infusion reactions occurred. Median time from order verification to administration was significantly reduced in the IV push group (35 min vs. 1 h 49 min; p < 0.001).

Conclusions

Administration of lacosamide via IV push results in similar adverse effect rates to IV piggyback preparations with more efficient time to administration.

     

An audit of the predictors of outcome in status epilepticus from a resource‐poor country: a comparison with developed countries

Aim. Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. Methods. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. Results. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non‐convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second‐line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Conclusions. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common. Treatment delay was frequent and adversely affected the outcome.     

Successful treatment for refractory convulsive status epilepticus by non‐parenteral lacosamide

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38‐year‐old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.     

Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide‐naive patients with partial‐onset seizures

Purpose: To examine the safety and tolerability of rapidly initiating adjunctive lacosamide via a single intravenous loading dose followed by twice‐daily oral lacosamide in lacosamide‐naive adults with partial‐onset seizures. Methods: This open‐label, multicenter trial, enrolled patients with epilepsy who were taking 1–2 antiepileptic drugs (AEDs) in one of four sequential cohorts containing 25 subjects each. An intravenous lacosamide loading dose (200, 300, or 400 mg) was administered over 15 min followed 12 h later by initiation of oral dosing consisting of one‐half of the loading dose administered twice daily for 6.5 days. The first cohort was administered lacosamide 200 mg/day, followed by a cohort at 300 mg/day, and then a cohort at 400 mg/day. The results from each cohort were evaluated before enrolling the next highest dose level. The fourth cohort enrolled patients at the highest dose with clinically acceptable safety and tolerability results. Safety evaluations included treatment‐emergent adverse events (TEAEs), patient withdrawals due to TEAEs, and changes in vital signs, 12‐lead electrocardiography (ECG) studies, laboratory parameters, and clinical examinations. Postinfusion lacosamide plasma concentrations were also evaluated. Key Findings: A total of 100 patients were enrolled, 25 in each cohort. The loading dose for the repeat cohort was 300 mg; therefore, 25 patients were enrolled at 200 mg/day, 50 at 300 mg/day, and 25 at 400 mg/day. Most TEAEs occurred within the first 4 h following infusion; dose‐related TEAEs (incidence ≥10%) during this timeframe included dizziness, somnolence, and nausea. Seven patients withdrew, all due to TEAEs: three (6%) from the combined 300 mg group and four (16%) from the 400 mg group; four of these patients discontinued within 4 h following infusion. The most common TEAEs leading to discontinuation (overall incidence >1%) were dizziness (6%), nausea (5%), and vomiting (3%). No clinically relevant pattern of changes from baseline ECG, clinical laboratory parameters, or vital signs were observed. Trough plasma concentrations suggested that near steady‐state lacosamide concentrations were achieved with a single intravenous loading dose. Significance: Intravenous loading doses of 200 and 300 mg lacosamide administered over 15 min followed by oral lacosamide were well tolerated in lacosamide‐naive patients. The 400‐mg loading dose was less well tolerated due to a higher frequency of dose‐related TEAEs. These results support the feasibility of rapid initiation of adjunctive lacosamide treatment.     

Rapid loading of intravenous lacosamide: Efficacy and practicability during presurgical video‐EEG monitoring

Purpose: This study investigates immediate efficacy and safety of intravenous application of de novo lacosamide (LCM) as add‐on therapy in patients with pharmacoresistant focal epilepsy. Methods: During presurgical video–electroencephalography (EEG) monitoring, 17 adult inpatients received LCM infusion (200 mg every 12 h for 2–3 days) followed by oral formulation with the same regimen. Before and after intravenous application of LCM, seizures and interictal epileptiform discharges (IEDs) recorded with continuous video‐EEG monitoring were analyzed, and an assessment of adverse events (AEs) was performed daily. To evaluate the midterm tolerability and efficacy, follow‐up visits were conducted 1 and 3 months after discharge from hospital. Key Findings: In the acute phase, intravenous initiation of LCM was well tolerated with few mild or moderate AEs (3 of 17, 17.6%). A significant reduction of seizure frequency in the treatment phase as compared to mean seizure frequency in the 2‐day baseline phase was achieved (p < 0.05 for the first treatment day, and p < 0.005 for the second treatment day). On the first treatment day, 61.5% of the patients were seizure free, and 84.6% on the second treatment day. IED reduction after intravenous application of LCM was not significant. After 1 month, the 50% responder rate was 46.6% and after the 3‐month period, 42.8%. Significance: Our data suggest that rapid intravenous initiation of de novo LCM is safe and may protect against seizures in a rapid and midterm time window.     

Intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures

PURPOSE: This multicenter, double-blind, double-dummy, randomized, inpatient trial evaluated the safety, tolerability, and pharmacokinetics of intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures. METHODS: Patients were enrolled from an ongoing open-label extension trial of oral lacosamide and randomized (2:1) to either intravenous lacosamide and oral placebo or intravenous placebo and oral lacosamide. During the 2-day inpatient treatment period, patients received twice-daily doses of lacosamide equivalent to their current daily dose of oral lacosamide. The first 30 patients enrolled received infusions with 60-min durations and the next 30 received infusions with 30-min durations. RESULTS: Of 60 patients randomized, 59 completed the trial. Treatment-emergent adverse events (AEs) were reported by 16 patients and included dizziness, headache, back pain, somnolence, and injection site pain. The tolerability profile of intravenous lacosamide was consistent with that of oral lacosamide. All AEs were considered mild or moderate in intensity, and no serious AEs or AEs leading to withdrawal were reported. CONCLUSIONS: Intravenous lacosamide, administered as 60- or 30-min twice-daily infusions, showed a similar safety and tolerability profile to oral lacosamide when used as replacement therapy. Results from this trial support further investigation of intravenous lacosamide at shorter infusion durations.     

NEOPLASM study: Real-life use of lacosamide in patients with brain tumor-related epilepsy

BackgroundThe choice of antiepileptic drug (AED) therapy in patients with brain tumor-related epilepsy (BTRE) is complicated, and there are a lack of robust clinical trial data to date.MethodsThe NEOPLASM (Neuroncologic Patients treated with LAcoSaMide) study was a 6-month, multicenter, retrospective, observational study in patients with BTRE treated with lacosamide. Patients were started on lacosamide because of a lack of efficacy or adverse events (AEs) with prior AEDs or suitability versus other AEDs, according to clinical practice. The primary efficacy variable was the seizure-free rate at 6 months. Safety variables included the proportion of patients with an AE and the proportion with an AE that led to discontinuation.ResultsOverall, 105 patients from 14 hospital centers were included in the analysis. Treatment with lacosamide for 6 months resulted in a 30.8% seizure-free rate, and 66.3% of patients had a ≥ 50% seizure reduction (responders). In the subset of patients included because of a lack of efficacy with prior AEDs, seizure-free rates were 28.0%, and 66.7% of patients were responders. No statistically significant differences in efficacy were observed according to the mechanism of action or enzyme-inducing properties of concomitant AEDs. Adverse events were reported by 41.9% of patients at 6 months, and 4.7% of them led to discontinuation. The most common AEs were somnolence/fatigue and dizziness. Notably, 57.1% of the patients who were switched to lacosamide because of AEs with their previous therapy did not report any AE at 6-month follow-up.ConclusionsIn this open-label, observational study, lacosamide appeared to be effective and well tolerated in a large population of patients with BTRE. Lacosamide may therefore be a promising option for the treatment of patients with BTRE.     

Two years of experience in the treatment of status epilepticus with intravenous levetiracetam

Since its introduction in 2006, 43 patients with various forms of status epilepticus (SE) have been treated with the intravenous formulation of levetiracetam (LEV) in our clinic. After ineffective treatment with benzodiazepines, intravenous LEV was administered as a short infusion (nonconvulsive and subtle SE) at a dose of 1000 or 2000 mg. In cases of convulsive SE, a fractionated injection of 1000 or 2000 mg was used. When the results for both are combined, SE could be terminated in 19 of 43 patients. Intravenous LEV was more effective in simple focal SE (3/5), complex focal SE (11/18) and myoclonic status (2/2) than in nonconvulsive (2/8) and subtle (1/2) SE. In no case was (secondarily) generalized convulsive status epilepticus (0/8) terminated. Intravenous LEV was also well-tolerated when injected in fractionated form. No severe adverse reactions were observed. As a result of this investigation, intravenous LEV in moderate doses may represent an efficacious and well-tolerated alternative for the treatment of focal (simple and complex focal) and myoclonic SE. Further investigations are needed to confirm this assumption as the patient numbers are quite low.     

Tonic status epilepticus in a centenarian woman

Generalized tonic status epilepticus (TSE) is a rare epileptic condition. It occurs usually in the context of symptomatic generalized epilepsy, in particular, in subjects with a diagnosis of Lennox‐Gastaut syndrome, atypical forms of idiopathic (genetic) generalized epilepsy, or as a paradoxical effect during treatment with diverse antiepileptic drugs. Herein, we describe the case of an elderly woman on chronic treatment with psychotropic drugs who developed an episode of generalized TSE. Motor manifestations were subtle and difficult to recognize as seizures, and a detailed video‐EEG importantly contributed to accurate and prompt diagnosis. TSE was initially refractory to conventional anti‐seizure drug therapy including levetiracetam and valproate but was finally controlled with lacosamide. Our case indicates a potential therapeutic effect of lacosamide on TSE in the elderly after treatment failure with first‐line anti‐seizure drugs. [Published with video sequence on www.epilepticdisorders.com ]     

Short‐term outcomes and major barriers in the management of convulsive status epilepticus in children: a study in Georgia

Aim. Convulsive status epilepticus is the most common childhood neurological emergency in developing countries, where poor healthcare organisation could play a negative role in the management of the condition. Unavailability of second‐line injectable anticonvulsants is an additional hindering factor in Georgia. This report reflects the results of the first study aimed at evaluating the epidemiological features of convulsive status epilepticus, as well as identifying obstacles influencing the management of patients with convulsive status epilepticus in Georgia. Methods. A prospective, hospital‐based study was performed. Paediatric patients with convulsive status epilepticus, admitted to the emergency department of a referral academic hospital from 2007 to 2012, were included in the study. Results. Forty‐eight paediatric patients admitted to hospital met the criteria for convulsive status epilepticus. Seizure duration was significantly shorter among the group with adequate and timely pre‐hospital intervention. Moreover, patients with appropriate pre‐hospital treatment less frequently required mechanical ventilation (p=0.039). Four deaths were detected during the follow‐up period, thus the case fatality rate was 8%. Only 31% of patients received treatment with intravenous phenytoin. Conclusion. The study results show that adequate and timely intervention could improve outcome of convulsive status epilepticus and decrease the need for mechanical ventilation. Mortality parameters were comparable to the results from other resource‐limited countries. More than one third of patients did not receive appropriate treatment due to unavailability of phenytoin.     

Efficacy and safety of intravenous lacosamide in refractory nonconvulsive status epilepticus

Koubeissi MZ, Mayor CL, Estephan B, Rashid S, Azar NJ. Efficacy and safety of intravenous lacosamide in refractory nonconvulsive status epilepticus.
Acta Neurol Scand: 2011: 123: 142–146.
© 2010 John Wiley & Sons A/S. Background – Lacosamide (LCM) is a novel antiepileptic drug (AED) recently approved as an adjunctive therapy in the treatment of partial seizures in adults. LCM is available in oral and intravenous formulations, has linear pharmacokinetics and a unique mechanism of action. The aim of this study – To evaluate the safety and efficacy of intravenous LCM in the treatment of nonconvulsive status epilepticus (NCSE) after failure of conventional therapy. Methods – We retrospectively reviewed all patients with NCSE treated with LCM. We reviewed the clinical and electrographic changes before and after LCM administration. We also noted any reported side effects including electrocardiographic changes. Results – We report four cases of NCSE that were refractory to conventional treatment, but readily responsive to LCM. No side effects attributable to LCM were identified. Conclusions – Intravenous LCM may be safe and efficacious as an add‐on AED for the treatment of NCSE when standard therapy fails.     

Isoflurane anaesthesia in the treatment of convulsive status epilepticus

Summary Status epilepticus may be resistant to intravenous anticonvulsive drugs. In these cases treatment with the inhalation anaesthetic agent isoflurane may be helpful in the further management. We describe a 35-year-old female patient who suffered from status epilepticus with partial seizures. In spite of therapy with benzodiazepine and phenytoin the status evolved into tonic clonic seizures. Treatment with thiopentone sodium did not stop seizure activity. Anaesthesia with isoflurane (dosage up to 1.5 vol.%) carried out twice within 72 h finally led to a termination of status epilepticus. From our own experience and reports in the literature we conclude that general anaesthesia with isoflurane can and should be used in the treatment of severe status epilepticus that does not respond to intravenous anticonvulsive agents.     

Why we prefer levetiracetam over phenytoin for treatment of status epilepticus

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine‐resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time‐consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine‐resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.