Treatment administration during a seizure in home-settings: Time to treat (TT)

Abstract

Background and objective

Early intervention on prolonged and cluster seizures can avoid serious consequences such as irreversible neuronal damage, late onset epileptogenesis, sudden unexpected death, and premature death, among others. In addition, it can prevent progression to status epilepticus, which has a mortality rate of 20%. However, prehospital diagnosis and treatment of seizures is often delayed, as patients receive treatment 30 min past seizure onset even though most seizures last less than 2 min. The aim of this consensus was to determine the time at which rapid and early seizure termination (REST) drugs should be administered in home-settings.

Materials and methods

Eleven epileptologists reviewed and discussed the scientific literature in face-to-face work meetings, followed by individual work. Recommendations for the management of prolonged and cluster seizures in the home-setting were established.

Results

Patients with epilepsy should be considered candidates to receive REST treatment in home-seeting if they are at risk of prolonged seizures or clusters, as well as if they experience prodromal symptoms, auras, or epileptic seizures that alert of a more severe seizure that lead to impaired consciousness or generalize tonic-clonic.

Additionally, this treatment should be considered for individuals who, despite not having epilepsy, are at risk of experiencing a seizure, such as those with a history of febrile seizures, acute brain injuries with seizures, or patients undergoing withdrawal from anti-seizure treatment.

The general recommendation is to administer REST treatment two minutes after the onset of a seizure or when clustered seizures occur at twice the usual frequency within an eight-hour period. In cases of generalized tonic-clonic seizures, intervention should be even more prompt.

Treatment timing should always be individualized for each patient, considering the characteristics of their usual seizures. The neurologist must prescribe the medication with instructions for it to be administered in the patient's home setting.

Conclusions

In general, the administration of REST medications by non-healthcare personnel should follow these recommendations: medication should be given for epileptic seizures lasting 2 min or in cases where the frequency of seizures doubles compared to usual. This is crucial in most cases, while always considering the recommendations of the physician.

Resumen

Antecedentes y objetivo

La intervención precoz sobre crisis epilépticas prolongadas y en racimo puede evitar graves consecuencias como daño neuronal irreversible, epileptogénesis de aparición tardía, muerte súbita inesperada y muerte prematura, entre otras. Además, puede prevenir la evolución a status epilepticus, que tiene una tasa de mortalidad del 20%. Sin embargo, el diagnóstico y tratamiento prehospitalario de las crisis suele retrasarse; los pacientes tardan más de 30 minutos en recibir tratamiento desde el inicio de la crisis, aun cuando la mayoría duran menos de 2 minutos. El objetivo de este consenso fue determinar el tiempo en que se deben administrar medicamentos de acción rápida para la finalización precoz de crisis epilépticas (REST, del inglés rapid and early seizure termination) en ámbitos no sanitarios.

Materiales y métodos

Once epileptólogos revisaron y discutieron la bibliografía científica en reuniones de trabajo presenciales, seguidas de trabajo individual. Se establecieron las recomendaciones para tratar las crisis epilépticas prolongadas y en racimo en el ámbito no sanitario.

Resultados

Los pacientes con epilepsia se deben considerar tributarios de recibir tratamiento para REST en el ámbito no sanitario si tienen riesgo de sufrir crisis prolongadas o en racimos, así como si tienen síntomas prodrómicos, auras o crisis epilépticas premonitorias de crisis con alteración del nivel de conciencia o convulsivas. También, se debe considerar en aquellas personas que aunque no tengan epilepsia tengan riesgo de sufrir una crisis, como aquellos con antecedentes de crisis febril, lesiones cerebrales agudas con crisis epilépticas o pacientes en retirada de tratamiento anticrisis.

La recomendación general es administrar medicamentos para REST a los dos minutos del inicio de la crisis o cuando las crisis en racimo se presentan con una frecuencia el doble de lo habitual dentro de un margen de 8 horas. Se debe actuar con mayor precocidad en los casos de convulsión tónico-clónica generalizada. Siempre se debe individualizar los tiempos para cada paciente, teniendo en cuenta las características de sus crisis habituales. El neurólogo debe prescribir la medicación con las indicaciones para poder ser administradas en el ámbito familiar del paciente.

Conclusiones

De forma general, se recomienda la administración de medicamentos para REST por parte de personal no sanitario en crisis epilépticas de más de 2 minutos de duración o ante un incremento del doble de la frecuencia habitual de las mismas, teniendo siempre en cuenta las recomendaciones de su médico.

Introduction

Epilepsy is one of the most common neurological diseases and can affect people of all ages.¹ According to the World Health Organisation (WHO), around 5 million people are diagnosed with epilepsy worldwide each year and the total number of people suffering from epilepsy is estimated at 50 million.¹ In Spain, the annual incidence in adults is estimated at 37.7 cases per 100,000 inhabitants,² while the active and lifetime prevalence are estimated at 5.8 and 14.9 cases per 1,000 inhabitants ≥18 years, respectively.³ The risk of mortality associated with patients with epilepsy is up to 4 times higher compared to the general population.²

An epileptic seizure (EC) is the transient appearance of signs and/or symptoms generated by abnormal, excessive or synchronous neuronal activity in the brain.^4,5 Although most ECs resolve spontaneously in less than 2 min,^6–9 prolonged seizures and cluster seizures are relatively common in patients with epilepsy, with a higher prevalence among patients with drug-resistant epilepsy.^10–12 There is no set time to define a prolonged seizure, so in practice such seizures are understood as those that last longer than the average typical seizure in a given individual, without reaching status epilepticus. The International League Against Epilepsy (ILAE) Commission on Classification and Terminology defines status epilepticus as abnormally long seizures (t1) that may have serious long-term consequences (t2).¹³ The onset of status epilepticus (t1) is determined at 5 min for generalised tonic-clonic seizures, at 10 min for focal seizures with altered consciousness and at 10−15 min for absences.¹³

Cluster seizures consist of a series of clustered seizures with short intercritical periods but are not included in the ILAE classification.⁵ In the absence of an agreed definition of cluster seizures, the most widely accepted definitions include groups of 2 or more seizures in 24 h, of 3 or more seizures in 24 h, and of 2 or more seizures in 6 h, and 2 or more seizures in 6 h, always with recovery to baseline between seizures and not meeting the criteria for status epilepticus (EE)12. The frequency of these seizures ranges from 22 to 43% in the outpatient setting depending on the definition used.^14,15 In a study based on patient diaries, it was found that almost half of the outpatients had such a seizure within 24 h.¹⁴

Often, prolonged and cluster FBs are preceded by prodromal symptoms in the form of behavioural changes, cognitive difficulty, mood disturbances or patient self-perceptions that can be anticipated hours to days before the onset of seizures.¹⁶ In addition, epileptic auras are subjective sensations that sometimes precede EC. Both prodromes and auras can alert to the development of SCD with altered consciousness or generalised seizure.

Occasionally, there are some types of short-lasting ECs such as clonus or absences that may be a premonitory symptom of a generalised seizure in some epileptic syndromes.¹⁷ In these situations, action could be taken to try to prevent the progression of the crisis, the risks and benefits having to be assessed on a case-by-case basis.

Both prolonged seizures and cluster seizures can have serious physical and social consequences for patients and families if not treated in time.¹⁸ The use of rapid and early seizure termination drugs (REST) is recommended to prevent the recurrence and progression to EE.^19,20 Early recognition and intervention of these crises is essential to reduce the risks and morbidity associated with them.²¹ Early treatment of these crises would allow for:

• –Reduce the risk of EE? Prolonged and cluster ECs are a risk factor for developing EE, considered a neurological emergency with an associated mortality rate of 20%.¹⁹ EE occurs more frequently in patients with cluster seizures than in patients without cluster seizures (44% vs. 12.5%).²²

• –To prevent irreversible neuronal damage and late epileptogenesis. Long-term ECs that progress to EE can lead to irreversible neuronal damage including neuronal death.¹³ Classical neurodegeneration, excitotoxicity and apoptosis can cause permanent damage to neuronal networks.²³ Evidence indicates that cell loss resulting from ECs in childhood can affect learning and memory functions in adulthood.²³ In addition, it has been reported that prolonged febrile seizures can lead to changes in the brain that increase the severity and duration of subsequent seizures.²⁴

• –Reducing sudden death in epilepsy (SUDEP sudden unexpected death in epilepsy). Evidence indicates that patients with a history of cluster seizures have a 2.5 times higher risk of SUDEP than those without cluster seizures (8% vs. 3%).¹⁵ In the MORTEMUS study, where cardiorespiratory arrest was analysed in patients admitted to epilepsy monitoring units, one third of SUDEP patients had experienced accumulations of 2 or more generalised tonic-clonic seizures 24 h prior to their death.²⁵

• –Reduce early mortality. In a population-based study of patients with childhood-onset epilepsy, followed for approximately 40 years, a 3.5-fold increased risk of premature mortality was found in patients who started having cluster seizures during treatment, with a prevalence of 42% compared to 14% in those without cluster seizures.¹⁵

• –To reduce the risk of injury and trauma from falling during periods of disconnection. Patients with sudden motor manifestations or tonic-clonic seizures may present a 3% risk of fractures or other traumatic injuries.²⁶

• –Reduce physical, psychiatric and cognitive co-morbidities. Prolonged crises are associated with systemic complications, including cardiovascular, respiratory and metabolic complications.²⁷ Cluster attacks may also predispose to psychiatric and/or cognitive disorders. In a study of patients with SCD for at least one year, 13% of patients with post-critical psychosis (episode of psychosis occurring after SCD) developed intercritical psychosis,²⁸ the latter associated with a high frequency of cluster seizures.²⁹ Both status epilepticus and the repetition of 10 or more tonic-clonic seizures may predispose to the onset of cognitive impairment.³⁰

• –Reduce emergency department visits and hospitalisations for crisis-related complications. CE-related hospitalisations are more common in patients with cluster seizures.³¹ In addition, and because these crises can be precursors of an EE, cluster crises are associated with a higher consumption of health resources, especially emergency department visits.^10,12

• –To reduce the loss of quality of life for patients and their families, who are usually their carers. A high percentage of patients and caregivers report negative effects of these crises on their activities of daily living, impairing their independence, recreational activities and social life. The labour productivity of both is also affected, necessitating reduced working hours and even cessation of work.^10,31 Most patients report feeling depressed, stressed, helpless and fearful in relation to ECs.¹⁰ Additionally, it has been observed that the impact on quality of life is higher in patients with cluster seizures compared to those with single seizures.³¹

Although early intervention plays a key role in the prognosis of patients with SC, pre-hospital diagnosis and treatment is often delayed. According to the results of the literature review by Gaínza-Lein et al. (2019), the median time to first treatment is above 30 min.²¹ According to evidence from different studies, in about half of the patients treated before arrival at the hospital, treatment was administered by emergency services and in about 13% by their relatives.²¹ The use of drugs for STEMI in the out-of-hospital setting is notoriously low, with only 20% of patients with EC reporting the use of drugs for STEMI when experiencing a cluster seizure.¹⁰ This is due, in part, to the lack of clear indications on when to administer these drugs and the lack of information in clinical practice guidelines (CPGs) on the management of EC in the out-of-hospital setting.³²

In Spain, the Spanish Society of Neurology (SEN) CPG highlights the importance of early administration of medication by both family and caregivers and out-of-hospital emergency services in patients with urgent SCD.³³ Urgent ECs include EE, cluster seizures and seizures with a high risk of recurrence or progression to EE.^33,34 In a consensus document for the treatment of patients with urgent CE, García Morales et al. (2019) recommend the use of benzodiazepines (BZD) as initial treatment, emphasising their early use for better seizure control and reduced risk of adverse consequences.³⁴ However, there is no consensus on the indications for early treatment of EC. Currently, in Spain, oral midazolam up to the age of 18 years and rectal diazepam for both children and adults are approved for the treatment of prolonged or cluster seizures by non-medical personnel. There are other alternatives not available in Spain, such as midazolam, tetrazepam or nasal and buccal lorazepam. None of them specify exactly how long it should be administered. Other recommendations include taking an extra dose of the patient's usual anti-crisis medication for the risk of recurrence. In the healthcare environment, there are other medicines for REST that require more advanced action.³²

In response to this situation, the development of a consensus document with clear and consensual recommendations on the treatment of EC in the non-health domain is considered necessary. The main objective of this consensus is to establish the duration of an EC from which medicines should be used for non-health REST in the non-health setting. Hereafter, this time will be referred to as treatment time (TT). As a secondary objective, this consensus document provides guidance on prescribing and administering medicines for REST.

Material and methods

First, a working group of neurology and neuropaediatric specialists specialised in the management of patients with epilepsy was created. This working group comprised a total of 11 people, 2 of whom had an additional coordinating role. In the initial phase, a literature review was conducted in Pubmed® with the search strategy ((("seizure duration") AND (min OR minutes OR sec* OR seconds)) limited to scientific articles published in the last 10 years. In addition, specific CPGs and articles on standard treatment times currently in use were reviewed.

At the first working meeting, held on 14 June 2023, the working group discussed the scientific evidence gathered in the previous literature review, in order to establish the TT, as well as the exceptions to this TT and the target population. Subsequently, the information discussed during the meeting was synthesised and an electronic questionnaire was developed to record the level of agreement/disagreement of each member of the working group with the proposals drawn from the first meeting, as well as any suggestions for modification. Their responses were then analysed to assess the level of consensus. To ensure the robustness of the recommendations, a consensus threshold of 100% was used, i.e. consensus on a recommendation was considered to exist only when all members of the working group agreed with the recommendation.

"At the second working meeting, held on 28 September 2023, the results of the questionnaire were presented and discussed in order to reach a consensus. In addition, recommendations related to the prescription of medicines for REST were discussed and agreed upon. The recommendations agreed upon by the working group were translated into a first draft of the consensus, which was critically reviewed by all members of the working group to generate this final consensus. Fig. 1 presents an abbreviated description of the methodological process followed for the development of this consensus. With the scientific endorsement of the Spanish Society of Neurology (SEN) and the Spanish Epilepsy Society (SEEP)

Figure 1.

Phases for the elaboration of the consensus document.

Results and discussion

Preliminary considerations

Target population

The target population to which the recommendations of this consensus apply are patients with known epilepsy and patients at risk of having a recurrent seizure, i.e. those who have had a previous EC associated with a history of risk such as febrile seizures, traumatic brain injury, stroke or withdrawal of anti-crisis drugs, among others. No recommendations are set out for patients with first EC or actions in the healthcare setting, where there may be more advanced measures for action.

Population out of range

The population outside the scope of the consensus, i.e. the population to which the recommendations of this consensus do not apply, are patients with:

• –Onset seizure.

• –Age less than 6 months.

• –Epileptic spasms.

• –Not knowing whether they have epilepsy or not.

• –History of non-epileptic seizures.

• –BZD contraindication.

• –History of BZD misuse or abuse.

• –History of lack of efficacy to BZD.

• –Epilepsies and epileptic syndromes with prolonged and cluster seizures on a regular basis, where the use of REST medications would not resolve an urgent situation.

• –High demand for REST drugs, which could lead to a BZD dependence syndrome.

Scope

This consensus is intended for clinicians in general (i.e. not necessarily specialised in epilepsy) and the recommendations it includes have been developed to be applied only in the non-healthcare setting by family members and/or caregivers of patients.

Typification of prolonged epileptic seizures with the aim of applying medication for REST

In order to facilitate the understanding of this document, a simplified EC classification has been adopted. This classification is described in Table 1.

Table 1.

Classification of epileptic seizures according to seizure semiology.

Crisis with motor component

With impaired consciousness

Without altered consciousness

Crisis without motor component

With impaired consciousness

Without altered consciousness

Generalised tonic-clonic seizuresGeneralised tonic-clonic seizures

Primary

With bilateral progression

Typification of cluster epileptic seizures with the aim of applying medication for REST.

For the present work and for future reference, the working group has agreed to define cluster seizures as an increase of double or more the usual frequency of EC within 8 h in each individual patient. As an illustrative example, in a patient with a usual frequency of 2 seizures in 8 h, from a therapeutic point of view, the recurrence of 4 or more seizures in that period would be considered a cluster amenable to treatment in the home setting.

Duration of epileptic seizures

According to the studies reviewed, the average duration of EC is generally less than 2 min (Table 2). Larsen et al. (2023) analysed almost 3,000 EEGs recorded by electroencephalography and calculated their duration according to the different types of EEGs. Their results show a mean duration for generalised tonic-clonic seizures (GTCS) of 79.5 seconds (1.3 min) and 103.5 seconds (1.7 min) for focal to bilateral tonic-clonic seizures (FBTCS).⁹ Other studies report a mean duration of 96 seconds (1.6 min) for generalised secondary tonic-clonic seizures,⁷ of 102,2 seconds (1.7 min) for CTCFB⁸ and 76.7 seconds (1.3 min) for non-generalised focal seizures.⁸

Table 2.

Average duration of epileptic seizures in studies published between 2013 and 2023.

Source	Sample	Type of crisis	Average duration in seconds	Average duration in minutes
Larsen et al. (2023)^9	2,742 EC	CTCG	79.5	1.3
		CTCFB	103.5	1.7
Zhang et al. (2022)^35	105 patients with ELT	ELT negative for MRI positive for PET	75.9	1.3
		Temporal lobe lesion TLE	71.7	1.2
Damien et al. (2021)^36	111 patients, 995 EC	Non-motor	87	1.5
Kaufmann et al. (2020)^8	69 patients with unifocal epilepsy	CFTCB	102.2	1.7
		CF	76.7	1.3
Cardenas et al. (2020)^6	19 patients, 23 EC	CTCG	56.2	0.9
Zibrandtsen et al. (2019)^37	14 patients, 24 EC	CF	57.2−60.6	0.9−1.0
Sala-Padro et al. (2019)^38	5 patients	Focal insular start	42	0.7
Gibbs et al. (2018)^39	58 patients	Front start	38.5	0.6
		Extrafrontal onset	61.8	1.0
Kessler et al. (2017)^40	416 patients; 1,932 EC	Absences	10.2	0.2
Dobesberger et al. (2015)^7	200 patients; 1,796 EC	CFS	42	0.7
		CFC	62	1.0
		CTCSG	96	1.6
Dlugos et al. (2013)^41	446 patients	Absence	10.8	0.2

CF: non-generalised focal seizures; CFC: complex focal seizures; CFS: simple focal seizures; CTCG: generalised tonic-clonic seizures; CTCFB: focal to bilateral tonic-clonic seizures; CTCSG: secondary generalised tonic-clonic seizures; EC: epileptic seizure; ELT: temporal lobe epilepsy; MRI: magnetic resonance imaging; PET: positron emission tomography.

Consensus recommendations

The following recommendations, which are the consensus of the working group, are a general guideline and therefore an individualised treatment plan is required for each patient.

Treatment times (Figs. 2 and 3)

The following baseline recommendation, understood as TT, is established to promote early treatment of EC in the non-health setting: Figs. 2 and 3.

Figure 2.

Acute treatment of prolonged epileptic seizures.

TT: treatment time; REST: rapid and early seizure termination.

*The times have been considered according to the average seizure duration times. However, each treatment should be individualised and even the time of administration reduced if a high risk of progression to tonic-clonic seizures or previous recognisable pattern of onset is considered.

**To individualise treatment on the basis of the patient's medical history, according to the duration and evolution of the patient's usual crises.

Figure 3.

Acute treatment of cluster attacks. No alteration of consciousness.

TT: treatment time; REST: rapid and early seizure termination.

*The usual seizure frequency should be individualised and the medication recommended for REST should be based on the risk of recurrence or progression of disabling seizures.

**The impact of this type of seizure on the patient should be considered and treatment should be individualised on the basis of the patient's clinical history, according to the duration and evolution of the patient's usual seizures.

Recomendación base: TT. In general, treatment should be given 2 min after the onset of the EC but should be individualised according to the frequency and duration of the usual seizures, and treatment of the seizure can be advanced on a case-by-case basis.

The TT of 2 min applies to prolonged EC with motor component and generalised primary or bilaterally progressive generalised tonic-clonic. Even so, TT with REST medications in these prolonged seizures may be less than 2 min if the treating physician believes there may be an individualised benefit over risk in each patient, for example:

• –In patients with a history of more than one prolonged seizure with a recognisable pattern of onset, the ideal scenario would be to administer a REST medication as soon as possible, before it becomes prolonged.

• –In patients with a history of bilateral tonic-clonic seizures, medication for REST should be administered as soon as possible to prevent spread, considering the severity of this type of seizure.

The TT of 2 min does not apply to prolonged EoC without motor component (whether or not the patient has altered consciousness) for which it is recommended that treatment be individualised on the basis of the patient's clinical history, according to the duration and evolution of their usual seizures. In other words, the administration of the medicine can be brought forward or delayed for REST, for which we give the following examples:

• –Patient with frequent absence seizures usually lasting more than 2 min to resolution: a time from which to use the medicine for REST should be recommended.

• –Patient with frequent prolonged sensory seizures usually lasting 5 min and having no impact on the patient's consciousness or subsequent functioning: REST medication would be applicable only in case of longer duration or occurrence of other unusual symptoms.

Additionally, in the TT for cluster seizures the seizure recurrence interval is more relevant than the seizure duration and varies according to the type of seizure:

• –Cluster seizures with motor component, with or without altered consciousness: treatment is recommended if an increase of twice the patient's usual seizure frequency is observed within 8 h. Generalised tonic-clonic cluster seizure: it is recommended to treat at the second seizure regardless of its usual frequency within 24 h.

• –Cluster seizures without motor component, without alteration of consciousness: it is recommended to individualise the treatment according to the patient's medical history, taking into account the usual progression of the patient."

• –Cluster seizures without motor component, with altered consciousness: treatment is recommended if you have an increase of twice the usual frequency within 8 h.

These recommendations are summarised in Table 3 distinguishing by type of crisis.

Table 3.

Treatment time according to seizure type.

Type of epileptic seizure	Treatment
Protracted crises
Seizures with motor component, with or without impairment of consciousness.	TT: treat at 2 min from the onset of the crisis^a.
Seizure without motor component, with or without altered consciousness	Treat on an individualised basis according to the patient's medical history
Generalised tonic-clonic seizure, primary or with bilateral progression	TT: treat at 2 min from the onset of the crisis^a.
Cluster crisis
Cluster seizures with motor component, without alteration of consciousness.	TT: Treat if you have an increase of twice the usual frequency in a period of 8 h
Cluster seizure with motor component, with altered consciousness	TT: Treat if you have an increase of twice the usual frequency in a period of 8 h
Generalised tonic-clonic cluster seizure	TT: Treat at second seizure within 24 h regardless of their usual frequency
Cluster seizures without motor component, without alteration of consciousness.	Treat on an individualised basis according to the patient's medical history, taking into account the patient's usual progression.
Cluster seizures without motor component, with altered consciousness.	TT: Treat if you have an increase of twice the usual frequency in a period of 8 h

TT: treatment time; REST: rapid and early seizure termination.: treatment time.

a

TT with REST medications in these prolonged seizures may be less than 2 min if the treating physician considers that there may be a benefit over risk for each patient assessed on an individual basis.

Prescription of medicines for REST

Who should prescribe medicines for REST

Prescribing REST medications for patients with EC can be done by any physician with the ability to prescribe REST medications who is familiar with the particularities of this type of medication, the medical history and the patient's circumstances. The specific medication to be prescribed shall be that authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS).

Who should be prescribed medicines for REST

The following patients are recommended to be prescribed medication for REST:

• –Patients with epilepsy at risk of prolonged or cluster EC.

• –Patients with epilepsy who normally suffer from prodromal symptoms, epileptic auras, sensory seizures, psychic, absence or cluster myoclonus preceding a seizure with altered consciousness or generalised tonic-clonic seizures.

• –Patients who have had previous FBs and who are at risk of recurrence (children with a history of febrile seizures, patients with a history of acute symptomatic seizures such as stroke, traumatic injury, central nervous system infection or autoimmune encephalitis).

• –Patients who have had epilepsy on preventive anti-crisis drugs and are in the process of withdrawing anti-crisis drugs.

In what other situations should medicines for REST be prescribed?

Prescription of REST medications is recommended when there are risk factors for prolonged or cluster EC:

• –Patient with epilepsy and a previous history of prolonged seizures, cluster seizures or EE.

• –Patient with a history of febrile EE or atypical febrile crisis.

• –Patient with a diagnosis of epilepsy refractory to treatment.

It is also recommended that REST medications be prescribed during periods of increased vulnerability to prolonged or cluster EC, such as:

• –Sleep-wake cycle disturbances or sleep deprivation (due to travel, holidays, bereavement days, insomnia…).

• –Feverish illness, infection or situations that may affect drug absorption.

• –Situations of severe emotional stress.

• –Poor adherence to medication.

• –Menstrual cycle in catamenial epilepsies.

Contraindications of medicines for REST

The use of medicines for REST is not recommended in the following cases:

• –Patients under 6 months of age.

• –Patients with contraindication to BZD use.

• –Patients at risk of developing a BZD dependence syndrome.

• –Patients with a history of BZD ineffectiveness.

In addition, although not recommended, the use of drugs for REST could be considered in the following cases, provided that the treating physician sees a clinical benefit to the patient (relative contraindication):

• –Patients with epilepsy and epileptic syndromes with prolonged and cluster seizures on a regular basis, where the use of REST drugs would not resolve an urgent situation.

• –Patients without certainty of diagnosis of epilepsy.

Drug delivery for REST

It is recommended to administer REST medications to the patient with EC in the non-health care setting, following the times described in the "treatment times" section. Medication may be administered by health personnel with adequate knowledge of EC care, but also by:

• –The patient himself, if he maintains the ability to safely self-administer medication."

• –Relatives and caregivers of the patient.

• –Authorised staff of educational, occupational, training, recreational and sports centres, which the patient attends regularly and under detailed medical prescription.

Implementation of TT

In order to translate the recommendations outlined in this consensus into practice, the promotion of early management of the patient with CHD in patient associations, as well as by health education nurses, would be useful. In a complementary way, the development of biometric monitoring tools for the detection and measurement of EC duration would be very useful to optimise early treatment of EC patients.

Conclusions

The administration of RESTs by non-healthcare workers should follow these recommendations, which state that they should be administered in ECs of 2 min duration or at twice the usual frequency as crucial in most cases. Early intervention on prolonged and cluster ECs can prevent serious consequences and progression to status epilepticus.

Ethical considerations

The following document has the scientific endorsement of the Spanish Society of Neurology and the Spanish Society of Epilepsy.

Funding

This work has been funded by UCB Pharma S.A., which was not involved in the design of the study; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Acknowledgements

The authors would like to thank Pirgit M Larsen for providing data from her study for this paper.