s ep - pratibha singhi
TRANSCRIPT
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Status Epilepticus in Children
Approach & Management
Pratibha Singhi,
Advanced Pediatrics
Centre,
Postgraduate Institute
of Medical Education
& Research
Chandigarh.
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Pellock JM. Journal of Child Neurology / 2007;22(Supple):9S-13S
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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).
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PLAN OF THE TALK
Case Presentation
Definitions
Types
Clinical Features
Causes / Outcomes
Pathophysiology
Management *
General
Drugs
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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%
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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?
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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 )
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Early treatment prevents Status epilepticus Lowenstein and Alldredge, Neurology. 1993;43:483
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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.
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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.
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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
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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..
.
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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
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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
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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
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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
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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.
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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)
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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
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Classification of SE
Seizure type:
Convulsive SE
NCSE
Etiologic classification:
Remote symptomatic
Acute symptomatic
Febrile
Cryptogenic
Progressive encephalopathy
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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
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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.
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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
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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
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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
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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
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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
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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
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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?
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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
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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)
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Treiman DM, Meyers PD, Walton NY, et al. N Engl J Med. 1998;339:792-8
Lorazepam was significantly more effective than phenytoin
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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
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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.
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Cloyed J. J Child Neurol 2007;22(Suppl): 47S-52S
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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
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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
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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.
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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
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CONTINUUM
SEIZURE
STATUS EPILEPTICUS
REFRACTORY STATUS
EPILEPTICUS
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STATUS EPILEPTICUS
Management of RSE
Stabilize and maintain vital functions
Drug therapy with monitoring
Identify and treat underlying
condition
Treat complications
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Management of RSE
consider....
Thiamine
Glucose
Pyridoxine 5 gm IV (70 mg/kg)
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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
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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)
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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]
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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)
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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.
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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
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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.
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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
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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.
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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.
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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
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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
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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.
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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
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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
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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
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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
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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
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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
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Evaluation of the Status epilepticus
What is the value of:
Serum laboratory studies?
Lumbar puncture and CSF analysis?
EEG?
Neuroimaging?
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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
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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
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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
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What is the value of EEG?
Continuous seizure monitoring
Achieving burst suppression/flat
EEG
Detection of non convulsive
seizures
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Value of neuroimaging?
Emergent imaging study: CT scan
Non-emergent imaging study: MRI
HOWEVER, only 2% of all
abnormalities influence
treatment or management
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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
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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
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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
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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)
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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
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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
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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.
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Guidelines for Diagnosis and Management of Childhood Epilepsy, Indian pediatrics Aug 2009
Valproate infusion
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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.
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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
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Thank You
Questions, Comments, Concerns
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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
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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.
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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.
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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