management of status epilepticus in children

• Definition• EPIDEMIOLOGY• Pathology• Classification• Risk factors• Immediate assessment

• Immediate Treatment• Laboratory studies• Stabilization• Monitoring • PHARMACOLOGIC

AGENTS• Prognosis

Definition

Status Epilepticus: The International League Against Epilepsy (ILAE) and the World

Health Organization currently define SE as a “condition characterized by an epileptic seizure that is

so frequently repeated or so prolonged as to create a fixed and lasting condition”

Definitionpractical definition of SE

has emerged as any seizure that lasts more than 5 minutes

continuous seizure activity or recurrent seizure activity without regaining of consciousness lasting for more than 5 min

Definitionpractical definition of SE

has emerged as any seizure that lasts more than 5 minutes

Nonconvulsive SE (NCSE) refers to ongoing EEG seizure activity without associated clinical

signs.

DefinitionRefractory Status Epilepticus :

failed to respond to therapy, usually with at least 2 (such as a benzodiazepine and another medication) medications.

New-onset refractory status epilepticus (NORSE): refractory status epilepticus in a patient without prior epilepsy

ILAE Definitions of Status EpilepticusTime after which if seizures do not terminate patient is considered in

status epilepticus (t1)

Time after which ongoing seizures have long term

consequences (t2)Convulsive status epilepticus 5 min 30 minFocal status epilepticus with

impaired consciousness 10 min 60 min

Absence status epilepticus 10–15 min unknownOther Definitions of Status Epilepticus

Established statusepilepticus Status epilepticus that persists after treatment with a benzodiazepine (1st line treatment)

Refractory status epilepticus

Status epilepticus that persists after a 1st line agent (benzodiazepine) and 2nd linesagent (additional agent such as levetiracetam, phenytoin, valproic acid) have failed

Definition New-onset refractory status epilepticus (NORSE):

refractory status epilepticus in a patient without prior epilepsy

fever-induced refractory epileptic encephalopathy in school age children

(FIRES)

is a syndrome of refractory status epilepticus that is associated with

acute febrile infections, appears to be parainfectious in nature, and to

be highly drug resistant but responsive to the ketogenic diet.

Definition*

several clinical studies have been published using durations of 5 minutes

More information is needed to clarify and allow acceptance of a standard operational definition for SE.

• incidence of status epilepticus ranges between 10 and 60 per 100,000 population

• Status epilepticus is most common in children younger than 5 yr of age, with an incidence in this age group of >100 per 100,000 children.

EPIDEMIOLOGY

• Approximately 30% of patients presenting with status epilepticus are having their first seizure, and approximately 40% of these later develop epilepsy

EPIDEMIOLOGY

• Febrile status epilepticus is the most common type of status epilepticus in children.

• In the 1950s and 1960s, mortality rates of 6-18% were reported after status epilepticus; currently, with the recognition of status epilepticus as a medical emergency, a lower mortality rate of 4-5% is observed, most of it secondary to the underlying etiology rather than to the seizures.

• Status epilepticus carries an approximately 14% risk of new neurologic deficits, most of this (12.5%) secondary to the underlying pathology.

EPIDEMIOLOGY

1. convulsive SE (CSE)2. nonconvulsive SE (NCSE) : There are

10-20%

1. Neuronal (Cerebral) 2. Systemic Effects.

Cerebral Injury

DISTURBANCE EQUALIBRIMExcitation >inhibitory mechanisms

PROLONGED : SE

Systemic Complications.

+vE

Precipitating factors

+vE

1. Downregulation Of GABAA Receptors May Reduce The Efficacy Of Benzodiazepines In RSE

2. Extrusion Of Anticonvulsants Across The Blood-brain Barrier (BBB) May Limit Anticonvulsant Activity.

3. Over Expression Of The Transporter's Multidrug Resistance Gene

1. Ensure adequate brain oxygenation , cardiorespiratory function2. Terminate clinical , electrical seizure activity as rapidly as possible3. Prevent seizure recurrence4. Identify precipitating factors such as hypoglycemia, electrolyte

imbalance, lowered drug levels, infection, and fever5. Correct metabolic imbalance6. Prevent systemic complications7. Further evaluate and treat the etiology of SE

Out of hospital management – Community education – Patients must be brought to the hospital at the earliest

Hospital emergency management PICU management

– It is helpful to have a protocol in every hospital.

1. Look for medical identification.2. Protect the person from nearby hazards.3. Loosen ties or shirt collars.4. Protect the head from injury.5. Turn the person on his side to keep the airway clear.6. Time record7. Reassure when consciousness returns.8. Ask whether hospital evaluation is wanted, call an ambulance

1. Do not put any hard implement in the mouth.2. Do not try to hold the tongue. It cannot be swallowed.3. Do not try to give liquids during or just after the seizure.4. Do not use artificial respiration unless breathing is absent after muscle

jerks subside, or unless water has been inhaled.5. Do not restrain the person.6. The person should be transferred to a medical center as soon as

possible if their – seizure continues beyond 5 minutes– if after ceasing, it begins again

• The therapeutic window – for most effective treatment with benzodiazepines may have already passed

by the time that hospital treatment starts, which is usually more than 20 min after the onset of GTC-SE.

• administer drugs by 1. Buccal2. Rectal3. Nasal 4. other non-invasive routes

• if appropriately instructed and if proper “rescue medications” are available for emergency use

1. Rectal diazepam (0.5 mg/ kg for children )2. Buccal midazolam (0.4–0.5 mg/kg in children )3. Intranasal midazolam (0.2 mg/Kg in children ) For any of these medications a repeat dose can be

given at least 10 min after the first dose.

1. the seizure has happened in water.2. there's no medical I.D., and no way of knowing whether the seizure is caused

by epilepsy.3. the person is

1. Pregnant2. Injured3. diabetic.

4. the seizure continues for more than five minutes.5. a second seizure starts shortly after the first has ended.6. consciousness does not start to return after the shaking has stopped.

DEFINITIONContinuous tonic-clonk seizure activity lasting more than 5 minutes or Two or more seizures without regaining consciousness in between seizures

This gaud line in india

AT CLINIC OR OUTSIDE HOSPHALMaintain airways and assess cardio-respiratory functionBrief history and examinationInject rectal diazepam -0.5 mg/kg (children) orGive buccal midazolam - 0.2 mg/kg (children)If seizures persist, shift the patient to the nearest hospital

IN HOSPITAL SETTING•A.B.C and assess cardio-respiratory function , take history , physical exam•Take blood samples for glucose, urea, AED levels and others as appropriate•Inject PHT: 15 - 20 mg/kg IV at maximum rate of 50 mg/min•CT scan,lumbar puncture if indicated ,Consult neurologist if seizures persist

OVERVIEW OF ASSESSMENT The evaluation includes:

1. General assessment(ABC); the pediatric assessment triangle

appearance work of breathing circulation

2. Primary assessment: rapid evaluation of 1. Cardiopulmonary 2. Neurologic function

3. Secondary assessment : focused medical history and thorough head to toe physical exam

4. Tertiary assessment :1. Laboratory2. Radiographic3. other ancillary studies

32

Appearance (TICLS)1. Tone : abnormal tone2. Interactiveness : decreased

interactiveness3. Look/gaze : poor color4. Consolability : abnormal stare

Consolability 5. Speech/cry : weak cry.

Breathing:1. Abnormal airway sounds2. position of comfort that

maximizes airway opening3. use of accessory muscles

Circulation Assessment1.Heart rate2.Pulse3.capillary refill4.Blood pressure5.End organ profusion•Urine output•Level of consciousness •Muscle tone

Primary assessmentrapid sequence assess (ABCDE):1.Airway:

Patent patent with maneuvers/adjuncts partially or completely obstructed

2.Breathing: respiratory rate Effort tidal volume lung sounds pulse oximetry

3.Circulation:4)Disability

CNS function Level of conscious ; AVPU pediatric response scale:

Dextrose hypoglycemia :rapid bedside glucose or response to empiric

administration of dextrose6.Exposure :

fever or hypothermia, skin findings, trauma

Has the child ever had a seizure before?

History of :

Trauma?

Fever?

Ingestion?

Was the child his usual self prior to this event?

What medications child take?

Past- History:

Any medical problems?

Any neurologic ?

developmental problems?

If child has known epilepsy

Name and dosage of medications!!! Calculate if this is appropriate dosage.

Has the child missed dosage of medication

If so, consider loading with that medication

Be aware of paradoxical side effects of ACDS

• Phenytoin and carbamazepine toxicity may precipitate SE

1. Serum glucose and a rapid "finger-stick" glucose2. Serum electrolytes, calcium, and magnesium levels3. Arterial blood gases and pH , RFT , LFT4. A complete blood count and general chemical screen5. Urine and blood toxicology6. Serum antiepileptic drug (AED) levels

7. Other testing in specific clinical circumstances may include 1. Blood cultures and lumbar puncture (LP)2. Metabolic studies for inborn errors of

metabolism3. Neuroimaging is generally deferred until the

patient is stabilized.

Ancillary studies in children with status epilepticusPatient

population Studies All patients

Serum electrolytesSerum calcium, phosphate, and magnesiumBrain imaging (CT or MRI)EEG

Patient population Studies

Epilepsy pts on anticonvulsants

Anticonvulsant level

Patient population Studies

Febrile patients

CBC with differential , Blood cultureUrinalysis, urine cultureCSF culture (once seizures stopped and if brain imaging excludes increased intracranial pressure)

Patient population Studies Poisoned patient Urine screen for cocaine, amphetamines,

and PCPAspirin levelVenous or arterial pH and pCO2ECG once seizures stop

Patient Studies Infants <6 months of

age*

Blood gas , Plasma ammonia , Plasma amino acidsPT, PTTSerum AST, ALT, LDH, Alkaline phosphataseBlood lactate and pyruvateUrinalysis ,Urine for reducing substancesUrine organic acids ,Urine amino acidsCheck newborn urine screening results if infant from country where instituted

C. Electrocardiographic (ECG)

D. EEG monitoring

At 0 min On presentation to hospital, initiate ABCs: A – support airway B – 100% oxygen, assess ventilation, SpO2 monitor C – cardiorespiratory monitor, check pulses, do IV access • History (SAMPLE) , Examination• Investigations • Suspect and treat raised ICP as needed, CT scan when warranted • Keep normothermic, acetaminophen/ibuprofen as appropriate

At 5 min IV access?

Mistake Made In The Treatment Of SE

inadequate doses of drugs are given initially

physicians wait for more seizures to occur before administering the necessary total dose

1. Previous response2. Missed medication 3. Paradoxical effects 4. Nonprescription medications5. Alternative routes of administration6. Nonepileptic seizures

1. Rapid Onset Of Action2. Broad Spectrum Of Activity3. Ease Of Administration Including Intravenous (IV) And

Intramuscular (IM) Preparations4. Minimal Redistribution From The CNS5. Wide Therapeutic Safety Margin

Lorazepam vs. Diazepam ,MidazolamLorazepam Diazepam Midazolam

Duration of

action

6-8 hours 20-30 minutes Mean: 2 hours

Onset of action 5 minutes 1-3 min 3-5 minutes

Sedation + ++ +++

• Mechanism of Action – Depresses all levels of the CNS, including the

limbic and reticular formation, by binding to the benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex and modulating GABA, which is a major inhibitory neurotransmitter in the brain

• Dose : – 0.05-0.1 mg/kg

– (maximum: 4 mg/dose)

• Rate : – slow I.V. over 2-5 minutes

– (maximum rate: 2 mg/minute)

• Frequency : – may repeat every 10-15 minutes if needed

• Onset of action: – Oral: Within 60 minutes – I.M.: 30-60 minutes – I.V.: 15-30 minutes

• Duration: – 8-12 hours

• more effective than diazepam• Longer duration of action (6-12 hours vs. <1 hour)• Less respiratory depression than diazepam• Not available rectally

• dose: • Loading dose: 0.15-0.2 mg/kg• Continuous I.V. infusion:

• Initial rate: 0.06-0.12 mg/kg/hour (1-2 mcg/kg/minute); • increase rate every 5-15 minutes in increments of 0.06-0.24

mg/kg/hour (1-4 mcg/kg/minute) until seizure activity ceases• maximum dose: 3 mg/kg/hour (50 mcg/kg/minute)

• Onset of action: – Oral: Children: Within 10-20 minutes – I.M.:

• Children: Within 5 minutes • Adults: Within 15 minutes

– I.V.: Within 1-5 minutes – Intranasal: Within 5 minutes

• Maximum effect: – I.M.:

• Children: 15-30 minutes • Adults: 30-60 minutes

– I.V.: 5-7 minutes – Intranasal: 10 minutes

• Duration: – I.M.: Mean: 2 hours, up to 6 hours – I.V.: 20-30 minutes – Intranasal: 30-60 minutes – Note: Full recovery may take more than 24

hours

– Dose– Children 2-5 years: 0.5 mg/kg– Children 6-11 years: 0.3 mg/kg – Children ≥12 years and Adults: 0.2 mg/kg– Infants >30 days and Children: I.V: 0.1-0.3

mg/kg/dose given over 3-5 minutes, every 5–10 minutes

– (maximum: 10 mg/dose)

– Onset of action: – I.V.: 1-3 minutes – Rectal: 2-10 minutes – Duration: – 15-30 minutes

– Highly effective in rapidly terminating seizures

– However, redistribution into adipose tissue limits

anticonvulsant effect to less than 20 minutes

– Available in rectal gel, which can be given outside

the ED


At 5 min IV access?

At 10 min

At 15 min Phenytoin 20 mg/kg IV/IO, max 1 g, over 20 minutes, in 0.9% NaCl (NS)

Phenobarbital 20 mg/kg IV/IO, max 1 g, over 5-10mins

At 25 min

• The order of Phenytoin and Phenobarbital may be interchanged • Phenytoin should be used in head trauma • Phenobarbital should be used 1st if patient already on phenytoin maintenance • Rapid Sequence Intubation if compromised airway at any point

• Ventilate to normal parameters • Sedation and muscle relaxants only if necessary to ventilate or protect airway

At 35 min

Early referral to PICU if any of following: • airway/ventilation/cardiovascular compromise• seizure refractory to 2nd line medications • seizure >30 minutes • initiating Midazolam or Thiopental infu

Midazolam 0.15 m g/k g IV bolus, then 2 mcg/kg/min by IV infusion

o seizure refractoryo prevent recurrance If seizures continue for 10 minutes after at least two injections

of lorazepam, begin treatment with fosphenytoin

dose of 20 mg phenytoin equivalents (PE)/kg IV at a rate of 3 mg/kg per minute (maximum rate 150 mg/min). The maximum dose in 24 hours is 1500 mg PE General rule of thumb: for each 1 mg/kg phenytoin (or 1PE/kg

fosphenytoin) expect level to rise by 1)

1. Alternative to second Line drugs Phenobarbital phenytoin4. Third Line medication

1. Valproic acid2. Levetiracetam

Alternative to second Line drugs 1. phenytoin (If fosphenytoin is unavailable)

dose :18 to 20 mg/kg IV , give in large vein, dilute with N/S rate of 1 mg/kg per minute maximum rate 50 mg/min. Maximum dose 1500mg/day onset of action: 10 - 30 min duration of action: 12 - 24 hr

2. Phenobarbital dose : 20 mg/kg rate 2 mg/kg per minute or 50 mg/min followed by repeated increments of approximately 8 to 10 mg/kg

every 30 minutes Maximum dose 1500mg/d

• Loading dose: – 15-18 mg/kg in a single or divided doses

• Maintenance dose : – usually starts 12 hours after the loading dose: – Infants and Children: Initial: 5-10 mg/kg/day in 2-3 divided

doses• onset of action may be delayed for 10 to 30 minutes

• Mechanism of Action• Stabilizes neuronal membranes and decreases seizure

activity by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses; prolongs effective refractory period and suppresses ventricular pacemaker automaticity, shortens action potential in the heart

• S/E - (most avoided if slower administration)1. hypotension2. arrhythmias - (must monitor)3. respiratory depression4. venous irritation5. extravasation -->tissue injury / necrosis6. “purple glove syndrome”: progressive limb edema,

discoloration and pain 2-12 hr post IV admin

• a prodrug of Phenytoin– it has no anticonvulsant action itself, but is

rapidly converted to Phenytoin– Dosage: in “Phenytoin Equivalents” to

attempt to avoid confusion– can safely give at 3x rate of Phenytoin,

resulting in 2x amount of Phenytoin delivered

• Advantages over Phenytoin:– does not require solvent (Phenytoin is dissolved in

propylene glycol)• can give IM when no IV access• IV: - less potential for irritation - can give faster

- no risk of tissue necrosis if goes interstitial - does not precipitate in IV solutions

– lower risk of hypotension and dysrhythmias

• Negative considerations:– COST Approx 20x that of Phenytoin

Third Line Medication :if necessary

1. Valproic acid2. Levetiracetam

Valproic acid third-line treatment. loading dose of 20 to 40 mg/kg IV (diluted 1:1 with normal

saline or 5 percent dextrose in water) over 5 to 10 minutes may be repeated after 10 to 15 minutes This is followed by an IV infusion of 5 mg/kg per hour

continued seizures after 2 or 3 line antiepileptic drugs have failed Will usually need EEG monitoring at this point The goal is to stop electrographic seizure activity before reducing

the therapyUsually this implies achievement of complete flattening of the

EEG. a burst suppression pattern may be enough, and the periods of

flattening in such a case need to be >8-20 sec

hemodynamically stable1. pentobarbital : Short acting barbiturate with a rapid onset of actionoRequires

1. intubation2. mechanical ventilation3. vasopressor agents.

oDose initial bolus infusion of 5 to 15 mg/kg IV followed by a continuous infusion of 0.5 to 5.0 mg/kg per hour .

• Maintenance of pentobarbital anesthesia is continued for approximately 4 h by an infusion of 1–3 mg/kg/hr.

• The patient is then checked for the seizure activity – If clinical seizures and/or generalized discharges persist on EEG, the

procedure is repeated;– if not, the pentobarbital is tapered over 12–24 hours.

Significant side effects: 1. respiratory depression2. Hypotension3. myocardial depression4. reduced cardiac output5. pulmonary edema6. ileus

2. Midazolam

• Dose: 2-5 mg/kg IV• rapid onset: 30 - 60 sec• short duration: 20 - 30 min• S/E:

– CV depression, hypotension, arrhythmias – resp depression, apnea

• Thiopental - negative aspects:– accumulates in fatty tissues– an active metabolite - Pentobarbital – long recovery time after infusion– hemodynamic instability

hemodynamically unstableMidazolam may be better tolerated Dose

initial bolus infusion of 0.15 to 0.2 mg/kg IV followed by continuous infusion of 1 mcg/kg per min the infusion is increased by 1 mcg/kg per min every 15 minutes until

seizures are controlled or max dose(50 mcg/kg/minute)

3 mg × body wt (in kg), added to diluent to make 50 mL→ 1 mL/h delivers 1 μg/kg/min

hemodynamically unstablePropofol :Intravenous anesthetic

• Dose: 1-2 (3-5) mg/kg• Rate: 5-10 mg/min (1-15 mg/kg/hr)• Onset: 2-4 min• Half-life: 30-60 min• does not accumulate --> rapid recovery• Mechanism:

– stimulates GABA receptors– suppresses CNS metabolism

Risk of 1. Hypotension2. Apnea 3. Bradycardia4. Fatal Acidosis 5. Rhabdomyolysis of the skeletal and cardiac muscles6. Contraindicated in child on ketogenic diet

Advantages over Barbiturates– less hypotension– more rapid onset of action– rapid elimination

• “Pro-convulsant effect” - is now thought to be myoclonus, unlikely a significant problem

Inhalational anesthesia :- isoflorane is preferable because

halothane can increase intracranial pressure enflurane can induce seizures

Valproic acid Levetiracetam Keppra Consider IV pyridoxine if age <18 month

nelson2016• After the emergent therapy usually with a benzodiazepine,

the subsequent urgent therapy medication is usually fosphenytoin,

• The subsequent medication is ofen phenobarbital.• Ideally, emergent and urgent therapies should have been

received within less than 30 min so as to initiate the subsequent therapy soon,

nelson2016• Currently, the level of the evidence for refractory treatment

is strongest for midazolam and valproate, followed by propofol and pentobarbital/thiopental, followed by levetiracetam, phenytoin/fosphenytoin, lacosamide, topiramate, and phenobarbital.

nelson2016• Current evidence for the urgent therapy is strongest for

valproate, followed by phenytoin/fosphenytoin and midazolam continuous infusion, followed by phenobarbital and levetiracetam, the last of which are currently being increasingly used

Tim Assessment Supportive care Seizure treet 0 to 5 minutesprehospital

Obtain initial vital signs, including temperature

Lateral position, Open airwaySuction secretionsAdminister 100 percent O2

Benzodiazepine (first line):Lorazepam 0.05 to 0.1 mg/kg IV or IO, maximum 4 mg IV or IO access not achieved within 3 minutes:Rectal diazepam (Diastat® gel or injection solution given rectally) 0.5 mg/kg, maximum 20 mg OR Buccal midazolam 0.2 mg/kg, maximum 10 mg OR IM midazolam 0.1-0.2 mg/kg, maximum 10 mg

Identify airway obstruction and hypoxemia

Place continuous cardiorespiratory monitors and pulse oximetry

Identify impaired oxygenation or ventilation

Perform bag-valve-mask ventilation, as neededPrepare for RSI*

Obtain rapid bedside blood glucose and other studies

Establish IV or IO access

Evaluate for signs of sepsis/meningitis

Treat hypoglycemia (IV dextrose 0.25 to 0.5 gm/kg)

Evaluate for signs of head trauma

Treat fever (acetaminophen 15 mg/kg rectally)

Tim Assessment Supportive care Seizure treet 5 to 10 minutesER

Reevaluate vital signs, airway, breathing, and circulation

Maintain monitoring, ventilatory support, and vascular access

Benzodiazepine: second dose

Evaluate for signs of trauma, sepsis, meningitis, encephalitis

Give antibiotics if signs of sepsis or meningitisΔ

10 to 15 minutes



Fosphenytoin (second line):20 mg PE per kg IV or IO◊ ORPhenobarbital:20 mg/kg IV or IO, maximum 1 gram, if toxin-induced seizure (expect respiratory depression with apnea)§

Place second IVRSI potentially indicated*

Tim Assessment Supportive care

Seizure treet

15 to 30 minutesPICU



Phenobarbital (third line):20 mg/kg IV or IO, maximum 1 gram, (10 mg/kg if phenobarbital given as second line)§ ORValproic acid 20 to 40 mg/kg IV or IOANDPyridoxine 100 mg IV or IO in infants <1 year of agePyridoxine 70 mg/kg IV or IO, maximum 5 grams, if INH poisoning suspectedObtain pediatric neurology consultation (see Refractory status epilepticus algorithm)

Obtain continuous EEG monitoring, if available

Tim Assessment Supportive care

Seizure treet

>35 to 30 minutesPICU



Pentobarbital anesthesia (patient already intubated)Loading dose: 5-7 mg/kg; may repeat 1- to 5-mg/kg boluses until EEG exhibits burst suppressionMaintenance dose: 0.5-3 mg/kg/h; monitor EEG to keep burst suppression pattern at 2-8 bursts per min


Tim Assessment Supportive care Seizure treet >35 to 30 minutesPICU



Midazolam* infusion loading dose is 100-300 mcg/kg followed by infusion of 1-2 mcg/kg/min; increase by 1-2 mcg/kg/min q15min if seizures persist (effective range 1-24 mcg/kg/min). When seizures stop and/or burst suppression is achieved, continue same dose for 48 h then wean by decrements of 1-2 mcg/kg/min q15min.Propofol* initial bolus is 2 mg/kg IV; repeat if seizures continue and follow by infusion of 5-10 mg/kg/h, if necessary, guided by EEG monitoring. Taper dose 12 h after seizure activity stops.



At 5 min IV access?

At 10 min

At 15 min Phenytoin 20 mg/kg IV/IO, max 1 g, over 20 minutes, in 0.9% NaCl (NS)

Phenobarbital 20 mg/kg IV/IO, max 1 g, over 5-10mins

At 25 min

• The order of Phenytoin and Phenobarbital may be interchanged • Phenytoin should be used in head trauma • Phenobarbital should be used 1st if patient already on phenytoin maintenance • Rapid Sequence Intubation if compromised airway at any point

• Ventilate to normal parameters • Sedation and muscle relaxants only if necessary to ventilate or protect airway

At 35 min

Early referral to PICU if any of following: • airway/ventilation/cardiovascular compromise• seizure refractory to 2nd line medications • seizure >30 minutes • initiating Midazolam or Thiopental infu

Midazolam 0.15 m g/k g IV bolus, then 2 mcg/kg/min by IV infusion

Midazolam increase by 2 mcg/kg/min q 5 min,0.15 mg/kg bolus as needed, Max50 mcg/kg/min

If stops x 48 hrs

Midazolam taper by 1 mcg/kg/min q 30 minAt 90 min

Thiopental 4 mg/kg IV bolus, then 1 mg/kg/hr IV infusion Discontinue Midazolam Infusion

Thiopental increase by 1 mg/kg/hr q 30 min, 2 mg/kg bolus as needed, max 6 mg/kg/hr

Thiopental taper by 25% q 12 hrs

If stops x 48 hrs

At 35 min

Initial assessmentNeurologic examinationGeneral evaluation with attention to

respiratory and circulatory status02 *-/- mechanical ventilation PRNIV catheters inserted (at least two)Blood work: electrolytes, glucose, toxicology, CBC, LFTS, Ca, Mg, ABG, Flngerstfck glucoseCardiac monitoring with pulse oximetryFrequent vital signsConsider glucose + thiamine IV

Initial therapyIn first IV:

Lorazepam 0.02-0.03 mg/kg IVAlternatives: Diazepam 0.1 mg/kg IVMidazolam 0.05 mg/kg IVWait l minute for response then additionalLorazepam PRN: max dose 0.1 mg/kg;max rate 2 mg/min

in second IV:Phenytoin 20 mg/kg at 25-50 mg/min* ORFosphenytoin 20 mg/kg PE at 50-125 mg PE/min*

Correct metabolic abnormalities if presentSecond-line therapy Phenytoin or Fosphenytoin dose: 10 mg/kg PEintubate, mechanical ventilation ,Continuous blood pressure, cardiac monitoring

Risk for prolonged ventilation Propofol infusion l to 2 mg/kg per hour, titrated to seizure free state. Rates may be as high as 10 to 12 mg/kg per hour After seizures controlled, maintain for 24 hours, then taper at 5 percent per hour If seizures persist after 45 to 60 minutes, then pentobarbital infusion Maintain therapeutic levels of phenytoin and/or phénobarbital

• Patients who are at high risk for prolonged mechanical ventilation (eg, those with severe COPD, severe debilitation, or cancer) should be treated with propofol in an attempt to minimize the duration of sedation

• The term "malignant" status epilepticus has been introduced to refer to status epilepticus that either fails to respond to the therapies discussed above or recurs quickly on tapering these medications

• It has been reported that as many as 20 percent of patients with refractory status epilepticus evolve into malignant status epilepticus, a transition that is associated with a very poor prognosis

• SE can be 1. fatal ( mortality)2. Morbidity associated with long-term morbidity,

including:seizure recurrence neurologic problems.

PrognosisOUTCOME

Depend onAge, etiology, and duration correlate directly

with mortalityThe highest mortality is seen in the elderly;

fortunately, children have a far lower mortality rate than do adults

Prognosis

OUTCOMEMortality :can result from

1. Underlying condition 2. Respiratory3. Cardiovascular4. metabolic complications of SE

mortality rates of SE in children varies between 3 and 9 percent The underlying etiology is the main predictor of mortality

mortality rates of SE in adult 20 percent

OUTCOME Morbidity Neurologic sequelae of SE include;

1. focal motor deficits2. mental retardation3. behavioral disorders4. chronic epilepsy.

morbidity other than epilepsy occurred in 15 percent of patients Neurologic sequelae are usually caused by the underlying condition rather than the seizures

rates of neurologic sequelae are increased in younger patients with a longer duration of seizures, Patients with cryptogenic SE and those with febrile SE do not have an increased

incidence of recurrent seizures or other neurologic sequelae over baseline

OUTCOME-Morbidity Recurrent seizures

The risk for having future seizures of any type : Is high when SE is the child's first seizure, up to 50 percent in two reports Recurrent SE also was more likely to occur in children who presented with

SE (21 versus 1 percent in those with a brief initial seizure. Other risk factors for recurrence include :

1. Remote symptomatic etiology2. Abnormal electroencephalogram3. Seizure during sleep4. History of prior febrile seizures5. Focal post-ictal deficits, including Todd's paresis

OUTCOMENeurologic sequelae more with :

prolonged inadequately treated

OUTCOME Refractory status epilepticus high mortality and morbidity. mortality ; 33% to 52% More in :

Younger patients (<5 years) multifocal abnormalities on EEG generalized abnormalities on EEG

Morbidity In survivors, recurrent seizures were common (31 to 97 percent) new neurologic deficits (71 to 100 percent).

Treatmentposttreatment subtle SE isidentical to that of refractory SEcentral theme to improving outcome is early

recognition intensive EEG monitoring.

Neonatal Status EpilepticusTreatment• Phenobarbital

– Usually used first– Prolonged half life—100 hours after day 5-7; therefore watch for toxicity– 20 mg/kg IV (up to 40 mg); repeat 10/kg every 15-30 minutes times two

• Phenytoin/Fosphenytoin– 20 mg/kg (over 30-45 minutes)– Half-life 100 hours– Nonlinear kinetics; redistribution, variable rate hepatic metabolism require

individuallization of maintenance dosing• Benzodiazepine

– Diazepam• 0.25mg/kg IV bolus or 0.5 mg/kg PR

– Lorazepam• 0.05 mg/kg IV over2-5 minutes

• Midazolam infusion

References1. UpToDate 21.62. Text book of pediatric_epilepsy-diagnosis_and_therapy_3rd

3. CLINICAL PEDIATRIC NEUROLOGY: A SIGNS AND SYMPTOMS APPROACH ; 20094. Pediatric Neurology ;20105. Neurocrit Care society6. EPILEPSY: GLOBAL ISSUES FOR THE PRACTICING NEUROLOGIST7. Atlas of Pediatric EEG8. eMedicine Medical 9. A Clinical Guide to Epileptic Syndromes and their Treatment10. Current Management in Child Neurology, Third Edition11. Nelson_Textbook_of_Pediatrics__19th_Edition12. Rudolph's Pediatrics13. epilepsyfoundation.org14. Nelson_Textbook_of_Pediatrics__20th_Edition15. Child Neurology 6th edition : by John H. Menkes (Editor), Harvey B. Sarnat, Samat By

Lippincott, Williams & Wilkins

management of status epilepticus in children

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