Emergency Management (Diagnosis and Treatment) of Seizures in Children beyond the Neonatal Period

 A seizure is a transient occurrence of signs &/or symptoms due to abnormal excessive or synchronous neuronal activity of the brain. Brief seizures are defined as seizures lasting less than 5 minutes, while prolonged seizures last between 5 & 30 minutes. A seizure that is provoked by a transient factor acting on an otherwise normal brain that temporarily lower the seizure threshold is not diagnosed as epilepsy (reactive seizure or acute symptomatic seizure). Epilepsy is a disease of the brain defined by any of the following conditions:

1.  At least two unprovoked (or reflex) seizures occurring > 24 hours apart.

2.  One unprovoked (or reflex) seizure & a probability of further seizures similar to the general recurrence risk (at least 60%)

3. Diagnosis of an epilepsy syndrome.

Status epilepticus is defined as more than 30 minutes of either, continuous seizure activity or two or more sequential seizures without full recovery of consciousness between them. The 30 - Minute’s definition is based on the duration of convulsive status epilepticus that may lead to permanent neuronal injury by itself. Since the majority of seizures are brief, and once a seizure lasts more than 5 minutes it is likely to be prolonged. Continuous Generalized convulsive SE in adults and children older than 5 years was operationally defined as 5 min or more clinical and/or electrographic seizure activity or (ii) recurrent seizure activity without recovery (returning to baseline) between seizures. Status treatment protocols have used a 5 - minute definition to minimize both the risk of seizures reaching 30 minutes and the adverse outcomes associated with needlessly intervening on brief, self-limited seizures.

 This guideline focuses on prevention and management of seizures in children in Egypt and the prevention of their complications.

 ➡️Guideline development process and methods

After reviewing all the inclusion and exclusion criteria and quality appraisal results, the GDG/ GAG recommended using the following source original clinical practice guidelines (CPGs):

1-     Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. American Epilepsy Society Guideline (2016).

2-     Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. International League Against Epilepsy (2015).

3-     Treatment of convulsive status epilepticus in childhood: Recommendations of the Italian League Against Epilepsy. ITALIAN LEAGUE (LICE) (2013).

4-     Guidelines for the Evaluation and Management of Status Epilepticus Neurocritical Care Society Status Epilepticus Guideline (2012).

5-     Evidence-Based Guidelines for EEG Utilization at the University Teaching Hospital (UTH). Neurologic & Psychiatric Society of Zambia (2011).

We conducted Adolopment for these guidelines: (Adoption, Adaptation, and Development)

         -  Adoption for most of the guideline recommendations.

         -  Development of Good Practice Statements

Recommendations and Good Practice Statements (GPS)

This version of the CPG includes recommendations and good practice statements on the following:

A. Diagnosis of Acute epileptic seizures in children.

The guideline covers children beyond the neonatal period (from 1-month to 18-years of age).

This guideline emphasis on diagnosis of children having convulsive (motor) seizures of any type and including serial fits, seizure clustering, and status epilepticus

-   Excluding the underlying etiology and co-morbid conditions

 B. Management of Acute epileptic seizures in children beyond the neonatal period (from 1-month to 18-years of age)

This section includes recommendations and good practice statements on treatment of acute epileptic seizures among different healthcare professionals in different healthcare settings. Also to provide healthcare professionals with easy-to-apply acute treatment protocol of epileptic seizures in children that will allow immediate and appropriate seizure control and prevention of complications.

 C. Prevention of acute seizures attacks & secondary prevention of:

-    Injury -         Recurrence     -        Development of status

-      Aspiration     -       vascular insult         -        Cardiac arrhythmia

-        SUEDP

 We can summarize the guidelines’ recommendations for management of acute epileptic seizures in children beyond the neonatal period (from 1-month to 18-years of age) in the following:

·   We recommend that the first stage in clinical management is to recognize if abnormal movement or behavior has an epileptic origin (strong recommendation).

·   We recommend ruling out febrile seizures (strong recommendation).

·  We recommend asking about prior history of epilepsy (strong recommendation).

·   We suggest asking about AED non-compliance, or known allergies (weak (conditional) recommendation).

· We suggest to address history of Ingestion of a toxin or drug abuse as possible etiologies of SE (weak (conditional) recommendation).

·  We suggest assessment of vital signs: O2 saturation, BP, HR in the immediate (0–2 min) to establish and support baseline vital signs (weak (conditional) recommendation).

·  We suggest that neurologic exam is urgent (5–10 min) to evaluate for mass lesion, acute intracranial process (weak (conditional) recommendation).

·   We recommend to address respiratory monitoring to prevent cardiopulmonary arrest, during anticonvulsant drug treatment in status epilepticus in children (strong recommendation).

·  We suggest that laboratory tests should be ordered based on individual clinical circumstances that include suggestive historic or clinical findings such as vomiting, diarrhea, dehydration, or failure to return to baseline alertness (weak (conditional) recommendation).

·  We suggest for all patients, order laboratory tests: blood glucose, complete blood count, calcium (total and ionized), magnesium, AED levels (weak (conditional) recommendation).

·   We suggest to consider based on clinical presentation, Lumbar puncture (LP) :

-  Should be performed in the very young child (<6 months), in the child of any age with persistent (cause unknown) alteration of mental status or failure to return to baseline, or in any child with meningeal signs. If increased intracranial pressure is suspected, the LP should be preceded by an imaging study of the head (weak (conditional) recommendation).

-Comprehensive toxicology panel including toxins that frequently cause seizures (i.e. isoniazid, tricyclic antidepressants, theophylline, cocaine, sympathomimetics, alcohol, organophosphates, and cyclosporine. Other laboratory tests: liver function tests,  coagulation studies, arterial blood gases, and inborn errors of metabolism (weak (conditional) recommendation).

·  In the PICU we suggest that EEG is indicated in all unconscious patients suspected of non-convulsive status epilepticus or subclinical seizures. This includes comatose or obtunded inpatients of unclear etiology especially those in whom seizures preceded the onset of coma

EEG is recommended after a first unprovoked seizure as it might offer insights into recurrence risk and/or the need for further neuroimaging (weak (conditional) recommendation).

·  In the treatment of convulsive status epilepticus in children, we suggest that continuous EEG monitoring is indicated if second therapy fails to stop seizures, and treatment consideration involves the use of anesthetic doses of either thiopental, midazolam, pentobarbital, or propofol (weak (conditional) recommendation).

·  We suggest that the use of continuous EEG (cEEG) is usually required for the treatment of SE & that continuous EEG monitoring should be initiated within 1 h of SE onset if ongoing seizures are suspected. The duration of cEEG monitoring should be at least 48 h in comatose patients to evaluate for non-convulsive seizures (weak (conditional) recommendation).

·   We suggest that the use of this cEEG is encouraged to be available at tertiary care facilities where the optimum standard of care is provided (Good practice statement).

·  We recommend that the use of a brain CT scan or MRI in the emergency room is indicated when specific interventions may be needed.

A CT scan is strictly indicated when a structural lesion is suspected or when the etiology of the seizure cannot be easily identified. Structural lesions include, among others, post-traumatic complications, cerebral hemorrhage, brain edema, and space-occupying lesions, which may be suggested by post-ictal deficits and/or persisting impairment of consciousness.

In the emergency room, MRI is not indicated, except for selected circumstances, to be evaluated on an individual basis (strong recommendation).

·  We recommend that the etiology of SE should be diagnosed as soon as possible and occur simultaneously and in parallel with treatment for evaluation for mass lesions, meningitis, encephalitis (strong recommendation).

·  We suggest that all patients with SE should have Head computed tomography (CT) scan (good practice statement).

·  We suggest considering Brain magnetic resonance imaging (MRI)based on clinical presentation (Good practice statement).

· We recommend that Benzodiazepines are the most efficient group of drugs to be initially used in the treatment of acute convulsion after 5 minutes from the start of seizures (strong recommendation).

·  Pre-hospital Treatment:

As early as possible by Trained personal whether medical\Para medical or caretaker. We recommend that drugs of Choice are:

Midazolam (intra-muscular – buccal – nasal)

Diazepam (rectal)

(Only one dose, not to be repeated) (strong recommendation).

·   Hospital Emergency Room:

We recommend that history of pre-hospital use of benzodiazepines must be considered as well as timing.

Doses given within one hour  before ER presentation must be regarded as an initial dose

-  Midazolam:

It is the most appropriate type of benzodiazepines to be used.  

In the hospital the whole full dose to be given as a single dose better than broken into multiple doses (strong recommendation).

-  Diazepam:

IV diazepam could be repeated after 5 minutes convulsion continued (strong recommendation).

-  Alternatively:

IF VENOUS ACCESS UNAVAILABLE;

Use midazolam: buccal or intranasal.

Use diazepam: rectal

Follow up for signs of respiratory depression  as hypoventilation, pallor, decrease oxygen saturation

Respiratory support and intubation may be needed (strong recommendation).

· - Non Benzodiazepine Therapy: we recommend

-  Phenytoin and Phenobarbitone

First Phase therapy: 5 - 20 minutes

-  Both phenytoin and phenobarbital are recommended (strong recommendation).

-  Phenytoin followed by phenobarbital is recommended if benzodiazepines fail (strong recommendation).

-  Phenobarbital is recommended in the absence of benzodiazepines (strong recommendation).

Second phase therapy: 20 - 40 minutes

-  Phenytoin and Phenobarbital are recommended (strong recommendation).

- They are not used sequentially but alternating. Generally, phenytoin precedes phenobarbital on account of a better safety profile (strong recommendation).

- Valproate

-  IV Sodium valproate is an option in the second-therapy phase and should begin when the seizure duration reaches 20 minutes (strong recommendation).

-  The use of IV Sodium valproate is dependent on its availability especially in tertiary care centers where optimum care is provided (Good practice statement).

- Valproic acid offers a valid alternative to phenytoin and phenobarbital.  It should be used with extreme caution, however, particularly in young children, when a possible metabolic etiology has not been ruled out (strong recommendation).

-  Pyridoxine

-  Consider vitamin-dependent diseases (pyridoxine or pyridoxal-phosphate) in the early myoclonic epilepsy group (Good practice statement).

- Young children with epilepsy (under 3 years) who develop SE lasting 30 minutes, especially if myoclonic should receive pyridoxine trial in case they have pyridoxine dependent/responsive seizures (weak (conditional) recommendation).

-  Levetiracetam

-  IV Levetiracetam or oral through a nasogastric tube could be given in the second phase therapy for SE (weak (conditional) recommendation).

- This drug can be used for continued oral therapy, does not cause significant side effects, and needs no preliminary check of renal function (weak (conditional) recommendation).

 Guideline Registration

PREPARE (Practice guideline REgistration for transPAREncy), WHO Collaborating Center for Guideline Implementation and Knowledge Translation, EBM Center, University of Lanzhou, Lanzhou, China. Registration Number: ((submitted and in process)). Link: http://www.guidelines-registry.org/