Status Epilepticus in Children

Approach & Management

Pratibha Singhi,

Advanced Pediatrics

Centre,

Postgraduate Institute

of Medical Education

& Research

Chandigarh.

Pellock JM. Journal of Child Neurology / 2007;22(Supple):9S-13S

Epidemiology

42 000 deaths among the estimated 152 000 cases of

status epilepticus in United States each year. (DeLorenzo RJ,, et al. Neurology. 1996;46:1029-1035)

Costs from $3.8 to $7 billion per year in inpatient

expenses (Sirven JI, Waterhouse E. Am Fam Phys.

2003;68:469-476).

Most deaths in patients whose seizures are caused

by acute injuries to the brain, such as anoxia,

hypoxia, or trauma. (DeLorenzo RJ, et al.Neurology.

1996;46:1029).

The mortality rate associated with seizures lasting

30 minutes or more may be as high as 19% (DeLorenzo RJ, et al. Epilepsia. 1999;40:164-169).

PLAN OF THE TALK

Case Presentation

Definitions

Types

Clinical Features

Causes / Outcomes

Pathophysiology

Management *

General

Drugs

CASE

Patient - 14 month female

PMH: - Recurrent GTC seizures since neonatal

period, lasting up to 1 hour

- On meds: Carbamazepine, & Topiramate, -

Family had detailed instructions regarding

management of her seizures

HX: -Unwell all day- frequent vomiting, fever

- Generalized tonic-clonic seizures, began half

an hour ago

O/E: having gen convulsions

- Pale, warm, diaphoretic

- -VS: P 180, R 28, T 40.3, Sat 88%

CASE - continued

Management:

AT HOME:

Had been given Diazepam PR 0.2 mg/kg by

father

repeated Diazepam PR, and also gave

Midazolam IM 0.2 mg/kg

Is there a role for treatment at home? If so,

what is most appropriate?

Is This child in Status Epilepticus?

What treatment now to abort the seizure?

Effect of Delays on Response to Therapy

In rats, delaying treatment of a seizure with

diazepam from 10 to 45 minutes increased the

dose requirement by 10-fold (from 4.2mg/kg to

40 mg/kg) to stop the seizure in 50%.

(Kapur J, Macdonald RL. J Neurosci. 1997;17:7532)

Lesser the time from seizure onset to initiation

of treatment , higher the percentage of

patients who responded to first-line therapy.

(Lowenstein and Alldredge Neurology. 1993;43:483 )

Early treatment prevents Status epilepticus Lowenstein and Alldredge, Neurology. 1993;43:483

Usual delays Jordan KG. Neurosurg Clin N Am. 1994;5:671

The total average time from seizure onset to

treatment was 85 minutes.

From onset seizure to arrival of EMS -30 minutes

(range, 15-140 minutes), and

Arrival of EMS to patient arrival at ED - 20 minutes

(range, 10-40 minutes)

Arrival at ED until the initiation of a treatment

protocol -35 minutes (range, 15-83 minutes).

Out-of-hospital treatment of status epilepticus

may in many cases be necessary.

Effectiveness of prehospital

treatment of SE in children

Prehospital treatment with IV Diazepam was

associated with shorter seizure duration (32

minutes vs 60 minutes, P = .007) compared with

that of patients whose treatment was delayed until

arrival at the ED

Prehospital treatment was associated with a

reduction in the likelihood of recurrent seizures

observed in the emergency department (58% vs

85%, P =.045) compared with cases where

treatment was postponed.

Alldredge BK, et al. Pediatr Neurol. 1995;12:213.

Rectal diazepam 0.5mg/kg

Sublingual Lorazepam 0.1mg/kg (rpt.

after 10 mins)

IM Midazolam 0.2mg/kg

Buccal Midazolam

Intranasal Midazolam

Benzodiazepines: other options

Rectal diazepam

In two studies, rectal diazepam gel was superior

to placebo in efficacy variables and global

assessments of treatment outcome.

0.5 mg/kg for patients 2 to 5years of age,

0.3 mg/kg for patients 6 to 11 years of age, and

0.2 mg/kg for patients older than 12 years.

Dreifuss FE, et al. N Engl J Med. 1998;338:1869-1875.

Cereghino JJ, et al. Neurology.1998;51:1274-1282..

.

Rectal administration of diazepam offers families a safe and

effective means of treating seizure emergencies when intravenous

lorazepam therapy is delayed.

Dreifuss FE, et al. N Engl J Med. 1998;338:1869-1875

Buccal midaz Vs rectal diazepam

“Buccal midazolam was more effective than

rectal diazepam for children presenting to

hospital with acute seizures and was not

associated with an increased incidence of

respiratory depression”

“Buccal midazolam was as safe as and more

effective than rectal diazepam for the treatment

of seizures in Ugandan children, although

benefits were limited to children without

malaria”

Lancet. 2005 Jul 16-22;366(9481):205-10.

Pediatrics. 2008 Jan;121(1):e58-64

Intranasal midazolam therapy for

pediatric status epilepticus

Delivers antiepileptic medication

directly to the blood and

cerebrospinal fluid via the nasal

mucosa, is safe, inexpensive, easy

to learn by parents and paramedics,

and provides better seizure control

than rectal diazepam.

Wolfe TR, Macfarlanc TC, Am J Emerg Med. 2006; 24: 343-6

Intramuscular versus Intravenous Therapy for

Prehospital Status Epilepticus:

N Engl J Med. 2012

Conclusion: IM midazolam is at least as safe and effective as IV lorazepam for prehospital seizure cessation

Intranasal versus intravenous lorazepam for

control of acute seizures in children:

Epilepsia, 52:788–793, 2011

Conclusion: Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.

Preferred route of administration

i.v. lorazepam 0.05 – 0.15 mg/kg/dose

i.m. midazolam 0.1mg/kg max 0.5mg/kg

Buccal (0.3mg/kg) or intranasal Midazolam(0.2 to 0.5 mg/kg)

Per rectal Diazepam (0.2 to 0.5mg/kg)

Definition - Status Epilepticus

Continuous or rapidly repeating seizures

No consensus on exact definition - “abnormal prolonged”

“no recovery between attacks”

“20-30 min” --> injury to CNS neurons

more practical definition: since isolated tonic - clonic seizures rarely last > few minutes ... - treat as S.E if

seizure > 5 min or

If seizure persists > twice the duration of usual

If continuous seizures in ER-S.E.

2 discrete seizures with no regaining of consciousness

vs. serial seizure - close together – regained consciousness in between

Classification of SE

Seizure type:

Convulsive SE

NCSE

Etiologic classification:

Remote symptomatic

Acute symptomatic

Febrile

Cryptogenic

Progressive encephalopathy

Convulsive SE

Can be generalized, focal, myoclonic

GCSE:

Constitutes 73% - 98% of SE, Primary or

secondary GCSE

TC movement of all 4 limbs

FCSE:

Epilepsia partialis continua

Involve a single limb or face

Less frequent;associated with focal pathology

Myoclonic SE: small amplitude repetitive

myoclonic jerking

Non – convulsive SE

Continuous electrographic seizures lasting 30

minutes without clinical convulsive activity

Nonconvulsive status epilepticus may follow

convulsive status epilepticus –acutely ill

apparently self-limited seizures

may present de novo with altered mental

status or coma.

NCSE ranges between 23-34% of children who

underwent long-term electroencephalogram

monitoring in PICU or emergency departments

Wandering confused patient/

Chronic epileptic syndromesTypes :

Absence

Complex partial

Risk factors:

Age <18yrs

Coma, Convulsive SE prior EEG monitoring

H/O epilepsy

Non – convulsive SE

Pediatr Neurol 2005;32:162-5

Temporal Changes During the

Course of Untreated SE

Compensated Transitional Decompensated

Phase Phase Phase

Motor seizures

15 30 45 60

Time (min) Hours

(a) Systemic

Homeostasis (b) Cerebral BF and Energy Metabolism

(c) Cerebral Damage

Cerebral blood flow –

Cerebral O2 requirement

Blood pressure

Blood flow

O2 requirement

Seizure duration

Hyperdynamic

phase CBF meets

metobolic

requirment

Exhaustion

phase CBF drops as

hypotension sets in

Autoregulation

exhausted

Neuronal damage

ensues

Glucose G

luco

se

Seizure duration

30 min

SE

SE + hypoxia

Hyperdynamic

phase Hyperglycemia

Exhaustion

phase Hypoglycemia

develops

Hypoglycemia

appears earlier in

presence of

hypoxia

Neuronal

damage ensues

STATUS EPILEPTICUS

Immediate action (first 5 mins)

Airway protection

Administration of 100% oxygen

Support breathing if needed

Circulation: intravenous (or intraosseous) access

Draw blood for glucose, BUN, electrolytes, calcium, phosphate, toxicology, anticonvulsant levels and CBC.

Give 2-4 ml/kg of 25% GDW as bolus if there is documented or suspected hypoglycemia

CASE - continued

MANAGEMENT IN EMERGENCY:

-Bag ventilation --> O2 sat 100%

-Diazepam 0.3 mg/kg IV

-Phenytoin 20 mg/kg IV over 20 min

-Paracetamol 15 mg/kg supp

-Allowed body cooling by exposure

-ABG, labs drawn

......still seizing

CASE - continued

MANAGEMENT IN ER - continued:

-Diazepam 0.3 mg/kg repeat

-Consultation sought from -

- Ped Neurologist and ICU

-O2 sat still 100%

-ordered Phenobarbital 20 mg/kg IV

......still seizing

Is it appropriate to use Diazepam, Phenytoin

and consider phenobarbitone?

Randomized, Controlled Clinical Trials

Double-blind trial comparing IV lorazepam, 2 mg (n = 66), IV diazepam, 10 mg (n = 68), and IV placebo in 205 adults with continuous or repeated seizures lasting more than 5 mins. A second dose was administered after 4 minutes as needed

Lorazepam was superior to placebo (lorazepam, 59.1% vs placebo, 21.1%; odds ratio, 4.8) and

Diazepam was superior to placebo (diazepam, 42.6% vs placebo,21.1%; odds ratio, 2.3)

Alldredge BK, et al. N Engl J Med. 2001;345:631

Four Arm RCT Treiman DM, et al. N Engl J Med. 1998;339:792

570 patients who had either overt status epilepticus (continuous generalized tonic-clonic seizures lasting > 10 minutes or> 2 generalized seizures without full recovery of consciousness) or subtle status epilepticus (coma and ictal electroencephalogram changes with or without subtle convulsive movements).

Intravenous lorazepam (0.1 mg/kg),

Intravenous phenobarbital (15 mg/kg),

IV diazepam (0.15 mg/kg) phenytoin (18 mg/kg)

Intravenous phenytoin (18 mg/kg)

Treiman DM, Meyers PD, Walton NY, et al. N Engl J Med. 1998;339:792-8

Lorazepam was significantly more effective than phenytoin

Class I studies indicate that benzodiazepines

are an appropriate first-line therapy for either

prehospital or hospital-based treatment of

prolonged seizures or status epilepticus

No class I or class II trials in children with

prolonged seizures or status epilepticus;

however, at least 10 class III trials have

examined the efficacy and safety of diazepam,

midazolam, and lorazepam in children with

prolonged seizures.

Glauser TA, J Child Neurology, 2007;22 (Suppl):38S-46S

Midazolam appeared to stop seizures more quickly than did diazepam, but differences are of uncertain clinical significance.

Some studies found midazolam had greater

efficacy than diazepam (Shah I, Deshmukh CT.Indian J

Pediatr. 2005;72:667, McIntyre J, et al. Lancet. 2005;366:205;.

Fisgin T, et al. J Child Neurol. 2002;17:123; Bhattacharyya M,

et al. Pediatr Neurol 2006;34:355) but others did

not.(Baysun S, et al. Clin Pediatr (Phila). 2005;44:77;

Chamberlain JM, et al. Pediatr Emerg Care. 1997;13:92; Scott

RC, et al.Lancet. 1999;353:623; Lahat E, et al. Br Med J.

2000;321:83)

All 3 benzodiazepines - well tolerated, and no clear superiority in efficacy or effectiveness.

Cloyed J. J Child Neurol 2007;22(Suppl): 47S-52S

Lorazepam or diazepam in pediatric SE Choudhery and Townsend, 2006

Reviewed 65 papers that reported

using the two drugs, of which two

presented the best evidence.

Diazepam and lorazepam are

equally effective at seizure control

in children.

Emergency Medicine Journal 2006; 23: 472-473

Fosphenytoin

A prodrug of Phenytoin

it has no anticonvulsant action itself, but

is rapidly converted to Phenytoin

Dosage: in “Phenytoin Equivalents”

Can safely give at 3x rate of Phenytoin,

resulting in 2x amount of Phenytoin

delivered

COST Approx 20x that of Phenytoin

CASE - continued

MANAGEMENT IN ER - continued:

-Phenobarbital given (from previous

order)

-ABG: pH 7.01, pCO2 elevated

-Thiopental 5 mg/kg

-Intubated (with size 5 uncuffed ET

tube)

...... seizure activity stopped.

CASE - continued

MANAGEMENT IN ER - continued:

Repeat ABG: pH 7.4 pO2 359 sat 99

pCO2 18 HCO3 13 Lactate 3.8 Gluc 8.3

CBC OK

Na 144 K 3.2 Cl 108 CO2 12

Anion Gap = 24

-transferred to ICU

CONTINUUM

SEIZURE

STATUS EPILEPTICUS

REFRACTORY STATUS

EPILEPTICUS

STATUS EPILEPTICUS

Management of RSE

Stabilize and maintain vital functions

Drug therapy with monitoring

Identify and treat underlying

condition

Treat complications

Management of RSE

consider....

Thiamine

Glucose

Pyridoxine 5 gm IV (70 mg/kg)

STATUS EPILEPTICUS

Drug therapy of RSE: Thiopental

Dose: 2-5 mg/kg IV

rapid onset: 30 - 60 sec

short duration: 20 - 30 min

S/E:

CV depression and hypotension in

almost 50-60%, arrhythmias

Respiratory depression & apnea

requiring ventilation –almost all

STATUS EPILEPTICUS

Drugs for RSE: Diazepam Infusion

57/62 Consecutive RSE

Mean age 2.8 years (1.5-11.5)

60% CNS infection; 16% epilepsy

Diazepam infusion 0.01 mg/kg/min

by 0.005 mg/kg/min every 15 min.

Max. 0.03 mg/kg/min or until seizure

control

Taper after 24 hrs seizure free period

(Singhi et al, J.Child Neurol 1998; 13(1):23-26)

STATUS EPILEPTICUS

Diazepam Infusion in RSE

Seizure control 49/57 (86%)

median duration 30 min. (10-120)

Mean infusion time 68 hrs (12-120)

Mechanical ventilation -11/49 (22%)

Hypotension 1/49

Survival 42/49 (86%)

[Singhi et al, J.Child Neurol 1998; 13(1):23-26]

STATUS EPILEPTICUS

Drug for RSE: Midazolam Infusion

Both equally effective:more recurrence with Midazolam

Midazolam Diazepam Total (n=21) (n=19) Seizures controlled 18 (85.7%) 17(89.5%) 35(87.5%)

Time for seizure 15.9± 9.6 15.79±13.0 15.85 ±11.26

control Initial (minutes)

Final (median) 135 ±227 53.95 ±105 96.8 ±182

Seizure recurrence 12 (57.1) 3 (15.7) 15 (37.5)

while on infusion

(Singhi et al, J.Child Neurol 2002)

Efficacy of i.v. midazolam

Retrospective multicenter study

Subjects : 358 inpatients who received

intravenous midazolam therapy for status

epilepticus

Midazolam was administered as a bolus dose

(0.25 ± 0.21 mg/kg), followed if necessary by

continuous infusion (0.26 ± 0.25 mg/kg/hr)

Conclusion: midazolam is highly effective for the

management of status epilepticus, if used

sufficiently early after seizure onset

Efficacy of intravenous midazolam for status epilepticus in childhood. Pediatr Neurol 2007;36:366-372.

Sodium valproate in Pediatric SE

Randomized study : 40 children, assigned

to Valproate or Diazepam infusion

Loading Dose: 20 mg/kg/IV;

1:1 dilution in NS or 5% GDW

Infusion: 5 mg/kg/hour

Reported effectiveness 78% in RSE

Mehta V, Singhi and Singhi, J Child Neurology 2007

Role of valproate in children:

Current status

A meeting of team of experts- general

“consensus” was that

intravenous (i.v.) valproate is a useful

agent in the treatment of non-convulsive

status epilepticus (SE).

valproate is an interesting, underutilized

alternative in convulsive SE but more

controlled studies are needed.

a possible role for intravenous valproate

Aldenkamp A, et al Acta Neurol Scand Suppl. 2006; 184: 1-13.

Shearer P, Riviello JEmerg Med Clin North Am. 2011 29:51-64.

STATUS EPILEPTICUS

Propofol

Dose: 1-2 (3-5) mg/kg, Onset: 2-4 min, if necessary continuous infusion, guided by EEG

Half-life: 30-60 min

Continue for 12 h after seizure control, slowly tapered over 12h

does not accumulate --> rapid recovery

Very rapid onset of action and rapid recovery. Few haemodynamic side- effects -hypotension, metabolic acidosis, hypertriglyceridemia

Use requires assisted ventilation , intensive care and monitoring.

Of questionable value in children_-Propofol infusion syndrome

Propofol and thiopental for RSE in

children: which one

Reviewed 34 episodes of RSE

Thiopental was effective in most

patients,but there were serious side

effects.

Propolol was used according to a strict

protocol. It was effective in most patients.

Side effects were infrequent.

Authors suggest the use of propofol

before thiopental.

van Gestel JP, et al. Neurology 2005; 65: 591-2.

Pentobarbital Infusion of for RSE Barberio M, et al. J Child Neurol. 2011 Dec 7. [Epub]

30 patients (age = 6.5 ± 5.1 years; 67% male) received

a mean loading dose of 5.4 ± 2.8 mg/kg, initial infusion

of 1.1 ± 0.4 mg/kg/h. Max infusion- 4.8 ± 2 mg/kg/h.

33% patients achieved sustained burst suppression

without relapse; 20 experienced relapse, 12( 60%)

eventually re-achieved burst suppression.

90 % of patients required inotropes; 66% acquired an

infection; 10% had metabolic acidosis; and 10%

experienced pancreatitis. Poor outcomes (death,

encephalopathy) were observed in 33% of patients.

STATUS EPILEPTICUS

Paraldehyde

IV doses effective for RSE

1.75 ml (1gm/ 1 ml) paraldehyde in 35ml 5% GDW

Loading dose 150-200 mg/kg over 15-20 mins

Continuous infusion 20 mg/kg/hour;

titrate with EEG monitoring

Need fresh solution protect from light, avoid plastic

Side effects:

Drowsiness, coma, myocardial depression

Pulmonary embolism, pulmonary hemorrhage

hepatic/Renal toxicity

No longer recommended by some

STATUS EPILEPTICUS

Lidocaine

Considered highly effective by some

Initial dose: 1-2 mg/kg/IV

Infusion: 2-4 mg/kg/hour with ECG

monitoring

Side effects:

Hypotension, heart block, arrhythmias,

CNS toxicity

May aggravate seizures at higher

doses

Intravenous Levetiracetam

“intravenous levetiracetam may be an effective

and safe antiepileptic drug in a variety of clinical

situations requiring the IV administration of

antiepileptic drugs”

Retrospective 73 patients, 5.6+5.6 yrs, dose of 29.4

+13.5 mg/kg. 67% received additional AEDs. 79%

received levetiracetam for serial seizures

89% of patients remained seizure-free at 1 hour

71%) were placed on maintenance levetiracetam

Doses 20-60mg/kg

Levetiracetam was well tolerated at the

doses studied

Pediatr Neurol 2008;38: 177-180.

Reiter PD, et al, Pediatr Neurol. 2010;43:117-21.

Lacosamide as a new treatment option in Refractory Status Epilepticus

Available as an intravenous solution since

2009

Pub Med lists 19 studies

10 single case reports and 9 case series

(Adult studies)

Overall success rate was 56% (76/136)

Adverse events 25% mild sedation, few-

hypotension

Level of evidence: class IV

Hofler J & Trinka E, Epilepsia 1-12, 2013

STATUS EPILEPTICUS

Treatment

Chlormethiazole

I.V. Infusion 0.8% solution (8 mg/ml)

Usual dosage: Initially 0.1 ml/kg/min.

(0.08 mg/kg/min) increasing

progressively every 2-4 h as required.

Clonazepam

Usual dosage: 1-2 mg/bolus injection

over 30 seconds

STATUS EPILEPTICUS

Etomidate

Loading dose: 0.3 mg/kg

Infusion: 20 mcg/kg/min

Side effects:

Hypotension, drug induced myoclonus

and adrenal suppression

Corticosteroid co-administration

required

Pathophysiology of Refractoriness

in SE

Progressive Impairment -Internalization of

GABA receptors

( less responsiveness to GABA ergic

medications)

Increased AMPA and NMDA receptors

(increased sensitivity to excitatory

neurotransmitters)

Use of NMDA channel blockers

Cortical spreading depolarization -CSD

Ketamine in SE

blocks NMDA receptors - this may protect brain from effects of excitatory NT’s

may be neuroprotective as well as antiepileptic

some animal studies have demonstrated control of refractory SE with Ketamine:

Ketamine Controls Prolonged SE - DJBorris Epilepsy Research 42 (2000): 117-22

A ketamine–diazepam combination might be a clinically useful therapeutic option for the treatment of refractory SE. (Martin and Kapur Epilepsia, 2008; 49:248)

more efffective than Phenobarb in LATE SE (>60 min); not as effective in EARLY SE

Management of SE

Treat underlying condition

1. Blood

C.B.C., Glu, Ca, Mg, AED levels

A.B.G., Urea & Electrolytes

Toxicology screen, Culture-if febrile

2. Urine - Analysis, Toxicology

3. C.T. or M.R.I.

4. L.P - if suspected meningitis

5. Others - acc. To suspected etiology.

INVESTIGATIONS

Evaluation of the Status epilepticus

What is the value of:

Serum laboratory studies?

Lumbar puncture and CSF analysis?

EEG?

Neuroimaging?

Role of routine investigation in

SE – what’s the evidence

AAN - Recommendations for the Diagnostic

Evaluation of the Child with Status Epilepticus.

American Family Physician Volume 75, Number

10 May 15, 2007

What is the value of serum

laboratory studies?

In the absence of a history or

findings suggestive of disease,

serum laboratory tests have

NOT been shown to be of value

in evaluating a first non-febrile

seizure

Laboratory tests should be

ordered based on individual

circumstances

Value of lumbar

puncture and CSF analysis?

Should be performed in

children <6 months-old,

children with persistent mental status changes, or

children with meningeal signs

In the child >6 months with a first non-febrile seizure, LP is of limited value and should be used primarily when there is concern about meningitis or encephalitis

What is the value of EEG?

Continuous seizure monitoring

Achieving burst suppression/flat

EEG

Detection of non convulsive

seizures

Value of neuroimaging?

Emergent imaging study: CT scan

Non-emergent imaging study: MRI

HOWEVER, only 2% of all

abnormalities influence

treatment or management

Value of neuroimaging? • The purpose of an emergent study -

detection of a condition requiring

immediate intervention - a child with

focal deficits or prolonged post-ictal state

• The purpose of a non-emergent study -

detection of abnormalities that may

affect prognosis and treatment - a child

who has motor or cognitive impairments,

abnormal neurological exam, a seizure of

focal onset, or is less than one year old

STATUS EPILEPTICUS

Treat complications

Circulatory support: IV fluids, inotropes Hemodynamic monitoring

Metabolic:Hypoglycemia, hypocalcemia, hyponatremia

Acidosis: Fluids and pressor, ventilation, control seizures

Pulmonary oedema: Ventilation, diuresis, vasoactive drugs

Hyperpyrexia: Cooling blankets, IV fluids

Renal failure: Appropriate management

Cerebral oedema: IV mannitol

STATUS EPILEPTICUS

Treat underlying condition

Try to find out underlying condition for RSE

If CNS infection is suspected, antibiotics

and or acyclovir for Herpes

CT, MRI or LP at appropriate time- therapy

For drug ingestion or toxicity appropriate

therapy including dialysis

Metabolic disorders

STATUS EPILEPTICUS EEG and prognosis

Periodic epileptiform discharges (PED)

at any time during or after SE, are

associated with poor outcome.

PED not related to etiology or structural

abnormality.

No predictable sequence of EEG

changes during SE. (Epilepsia 1999, Feb: 40(2):157-63)

Outcome of SE

Depends on cause -- acute vs chronic

Acute - difficult to control / higher mortality

Sepsis, CNS infections ,CNS - stroke, head trauma, neoplasm,drug toxicity, hypoxia, metabolic encephalopathy - abn electrolytes, renal failure

Chronic causes - better response to Rx known epilepsy - breakthrough seizure +/- low

anticonvulsant levels, drug abuse / withdrawal

Remote CNS process (eg brain surgery / CVA / trauma) --> SE after long latent period

Outcome of SE

Mortality presently- 5%

Refractory status epilepticus mortality is still

around 30%

Time taken to start and quality of treatment-

early, intensive care improves outcome

Neurologic sequelae is more in infants (29%)

compared to older children (6% after 3 years)

Increase risk future SE / chronic seizure

Worse outcome if prolonged / severe

physiologic disturbance

Evidence-based status of Rx Emergent treatment Urgent treatment Refractory

treatment

Lorazepam, Class I, level A

Valproate , Class IIa, level A

Midazolam, Class IIa, level B

Midazolam, Class I, level A

Phenytoin/fosphenytoin, Class IIa, level B

Valproate, Class IIa, level B

Diazepam, Class IIa, level A

Midazolam (continuous infusion), Class IIb, level B

Propofol, Class IIb, level B

Phenytoin/fosphenytoin, Class IIb, level A

Phenobarbital, Class IIb, level C

Pentobarbital/thiopental, Class IIb, level B

Phenobarbital, Class IIb, level A

Levetiracetam, Class IIb, level C

Levetiracetam, Class IIb, level C

Valproate, Class IIb, level A

Phenytoin/fosphenytoin, Class IIb, level C

Levetiracetam, Class IIb, level C

Lacosamide, PHB, TPM, Class IIb, level C

Brophy GM, Neurocrit Care. 2012 Aug;17(1):3-23.

Guidelines for Diagnosis and Management of Childhood Epilepsy, Indian pediatrics Aug 2009

Valproate infusion

TAKE HOME-POINTS

Status Epilepticus in childhood.

Status epilepticus is associated with high

morbidity and mortality,

Better outcome if seizure stopped earlier

Complications can be reduced through

appropriate, prompt, and aggressive

intervention.

Benzodiazepines remain the first-line drug

therapy. Lorazepam/ diazepam - best 1st

line.

Buccal midazolam is more effective and

easier to rectal diazepam.

TAKE HOME-POINTS

Status epilepticus in childhood.

Phenytoin/ fosphenytoin (and phenobarb) administered intravenously remain the second-line treatments of choice.

Barbiturates and midazolam /Diazepam infusion are used for RSE treatment.

IV Valproate is useful in RSE

Levetiracetam is an option

? Ketamine for v pronged seizures

Thank You

Questions, Comments, Concerns

Intramuscular versus Intravenous Therapy for

Prehospital Status Epilepticus:

N Engl J Med. 2012

Conclusion: IM midazolam is at least as safe and effective as IV lorazepam for prehospital seizure cessation

Intranasal versus intravenous lorazepam for

control of acute seizures in children:

Epilepsia, 52:788–793, 2011

Conclusion: Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.

Evidence-based status of Rx Emergent treatment Urgent treatment Refractory

treatment

Lorazepam, Class I, level A

Valproate , Class IIa, level A

Midazolam, Class IIa, level B

Midazolam, Class I, level A

Phenytoin/fosphenytoin, Class IIa, level B

Valproate, Class IIa, level B

Diazepam, Class IIa, level A

Midazolam (continuous infusion), Class IIb, level B

Propofol, Class IIb, level B

Phenytoin/fosphenytoin, Class IIb, level A

Phenobarbital, Class IIb, level C

Pentobarbital/thiopental, Class IIb, level B

Phenobarbital, Class IIb, level A

Levetiracetam, Class IIb, level C

Levetiracetam, Class IIb, level C

Valproate, Class IIb, level A

Phenytoin/fosphenytoin, Class IIb, level C

Levetiracetam, Class IIb, level C

Lacosamide, PHB, TPM, Class IIb, level C

Brophy GM, Neurocrit Care. 2012 Aug;17(1):3-23.

Lacosamide as a new treatment option in Refractory Status Epilepticus

Available as an intravenous solution since

2009

Pub Med lists 19 studies

10 single case reports and 9 case series

(Adult studies)

Overall success rate was 56% (76/136)

Adverse events 25% mild sedation, few-

hypotension

Level of evidence: class IV

Hofler J & Trinka E, Epilepsia 1-12, 2013