emergency management of seizures final 3-1

8/9/2019 Emergency Management of Seizures Final 3-1

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Emergency Management ofSeizures

Sarah A. Murphy, MDPediatric Critical Care Fellow, M!


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• This presentation will review emergency

management of seizure/convulsions

• We will begin with a review of the approach

to a child who presents with: – lethargy

– unconsciousness OR

– convulsions/seizures


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ssess for !oma or !onvulsions:

"#$• %s the child:

– lert&

– Responding to "oice&

– Responding to #ain&

– $nconscious&

• child who is not alert but responding to voice islethargic

• child who does not respond to pain isunconscious


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$nconscious or !onvulsion:

• 'anage irway

• (ive diazepam or paraldehyde if convulsing

• #osition unconscious child

• (ive %" glucose:


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Obtain )istory:

• *ever&

• )ead %n+ury&

• ,rug or To-in e-posure&

• .irth asphy-ia or in+ury if newborn&


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-amination:

• "#$ score

• (eneral:

– #allor – 0aundice

– dema

– #etechial Rash

• )ead and 1ec2: – 3tiff nec2

– 3igns of trauma – #upilary reactions

– *ontanelle

– #osture


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4aboratory %nvestigations:

• .lood glucose

• .lood smear for malaria

• .lood pressure

• $rine microscopy

• lectrolytes


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,ifferential ,iagnosis of 4ethargy5

$nconscious5 or !onvulsions:• 'eningitis: irritable5 stiff nec2 or bulging fontanelle5

petechial rash

• !erebral 'alaria: +aundice5 anemia5 pallor5 convulsions5hypoglycemia

• *ebrile convulsions: history of same5 seziure associatedwith fever5 age 6 mos to 7 years5 normal blood smear

• )ypolycemia: responds to treatment with glucose5 chec2for malaria

• )ead in+ury: signs of trauma


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,ifferential ,iagnosis of 4ethargy5

$nconscious5 or !onvulsions:• #oisoning: suggested by history

• 3hoc2: unli2ely to cause seizures5 poor capillaryrefill5 rapid wea2 pulse

• (lomerulonephritis with encephalopathy:raised .#5 edema5 decreased urine5 blood in urine

• ,8: high blood sugar5 polydipsia and polyuria5deep breathing


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,ifferential ,iagnosis of lethargy5

unconsciousness or convulsions %1

1O1T

• .irth sphy-ia: difficult delivery5 onset in 9st

three days of life• %ntracranial hemorrhage: lowbirth weight

or preterm infant with onset in 9st three days oflife

• )emolytic disease of newborn/2ernicterus: +aundice5 pallor5 bacterialinfection5 onset in 9st three days of life


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,ifferential ,iagnosis of lethargy5

unconsciousness or convulsions %1

1O1T

• 1eonatal tetanus: onset from ;9


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mergency 'anagement of

3eizures&


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Clinical Diagnosis of Seizure

" Altered Mental Status

" !ypotonia

" Emesis

" Eye de#iation

" $onic%clonic mo#ements" &ncontinence


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Pathophysiology of Seizures

" Cellular Mechanisms responsi'le for Status

Epilepticus

" (atural progression of Status Epilepticus

" Systemic complications of Status Epilepticus

" (europathology" C(S mechanisms for neuronal damage)death


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Cellular Mechanisms

" A group of neurons in the C(S 'ecomedepolarized with a'normal synchrony andfire action potentials repetiti#ely,interfering with normal 'rain function

" $his a'normal paro*ysmal acti#ity isintermittent and usually self%limited,

lasting seconds to a few minutes


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Cellular Mechanisms

" Cellular e*planation li+ely multifactorial- &ncreased release of e*citatory

(eurotransmitters lutamate/- Decreased release of inhi'itoryneurotransmitters A0A/

- &ncreased)decreased neurotransmitter

sensiti#ity- Changes affecting ionic and #oltage%gatedchannels at neuronal synapses mem'raneinsta'ility


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(atural !istory of SE

" As the duration of SE progresses, there is adistinct e#olution with predicta'le effects in the

human 'ody

" Systemic changes occur in phases- Phase & 123 mins/

- Phase && 23%43 mins/ - se#ere systemic distress

- Phase &&& 543 mins/ - 6efractory SE


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Systemic Complications of SE


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Systemic Complications of SE (Rogers, ch.22)Parameter Early Late Complications

.lood #ressure )ypotension

rterial o-ygen )ypo-ia

rterial !O= %ncreased %!#

3erum p) cidosis

Temperature *ever utonomic activity rrhythmias

4ung fluids talectasis

3erum 8 > rrhythmias3erum !#8 Renal failure

!erebral blood flow !erebral bleed

!erebral O= consumption %schemia

)nl

nl

7338 9338

2338 2338

:3! 93!


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(europathology

Autopsy findings include- !ippocampal necrosis- ;idespread cere'ellar necrosis

- Degeneration of Pur+in


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(eurologic Damage

" &n animal models, irre#ersi'leneurologic damage in 73%:93 mins

" ;ith prolonged tonic%clonic acti#ityhypo*ia, hypoglycemia, hyper+alemia,hyper+alemia, increased &CP

" E#en with control of 0P, o*ygenation,#entilation, glucose and fe#er,neuronal cell death occurs


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!ypothesized C(S mechanismsof neuronal damage)death

" E*cessi#e presynaptic release of e*citatorytransmitter intracellular postsynaptic

changes

dendritic swelling and cell death." &nhi'itory%e*citatory interaction o#er%e*citation com'ined with decrease ofA0A%mediated inhi'ition.

" Possi'le unmas+ing of e*citatory glutamatereceptor channel%mediated e#ents


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&nitial Emergency Management

of Seizures" Sta'ilize the patient

" Address underlying causes of seizure

" $reat seizures

" Choices of anti%epileptic drugs


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Stabilize the patient

Maintain Cardio#ascular and 6espiratoryFunction

" airway protection" maintain #entilation, o*ygenation

" support circulation

" esta'lish #ascular access


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Sta'ilize the patient

" Position the patient to a#oidaspiration, suffocation, physical

in


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Assess A, 0, C, D>s ??


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- Airway protection" :338 o*ygen on all patients

" attempt to open airway with


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- 0reathing" support 'y using muscle rela*ation if

necessary


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- Circulation" #erify good 0P

" secure P&" (S 93cc)+g


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- De*trose" Chec+ 'lood sugar

" &f suspecting low 'ood sugar, gi#e 9B8de*trose in water, 9%ml)+g

" :3 m)+g D:3 in neonates

6S& for Status Epilepticus


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6S& for Status Epilepticus

A&6;A- Airway o'struction

- oss of cough)gag- !ypo#entilation- !ypo*emia- 6is+ of aspiration

Preo*ygenate w) :338 =9 a#oid PP/

Atropine 3.39mg)+g 3.:mg min%:mg ma*/

Cricoid pressure

Sedati#e%$hiopental 2%Bmg)+g or

%ersed 3.3B%3.:mg)+g or%Pro ofol :%2m )+

Paralytic%Succinylcholine :%9mg)+g or

%ecuronium 3.:%3.2mg)+g


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Address underlying causes

" Elicit uic+ history- $rauma

- Antecedent illness

- Fe#er- &ngestion

- S+ipped meds

" ='tain critical la's- Chem G, Ca, Phos, C0C, to* screen, AED

le#els


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- Correct and then pre#ent meta'olicderangements

" !ydration

" Electrolytes

" lucose

" actate

Address underlying causes


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Common Causes of Seizures

" Fe#er

" !ypoglycemia

" !ypo*ia" Poisoning

" !ead $rauma" Meningitis

" &diopathic


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$reat Seizures

:. E#aluate and treat underlying cause

9. Stop clinical)electrical seizure acti#ityusing Anti%Epileptic Drugs/


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$he longer the seizure, the more

difficult to control so?AC$ FAS$H


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" owenstein and Alldredge- Seizures stopped 'y :st line therapy in

I38 of patients if started in the :st 23mins

- 0ut :st line drugs stopped seizures in only38 of patients if started 5 9hrs afterseizure


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&mplementing Drug $herapy

J&t>s not the particular choice of drug 'ut rather the timing,route, and #igor of therapy that are ma


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&mplementing Drug $herapy

" Anticipate conseuences of therapy- 6espiratory depression

- !ypotension


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Anticon#ulsants 0ased on a#aila'ility" First%line

" Diazepam, or orazepam

" Paraldehyde

" Second%line" Phenytoin or" Pheno'ar'itol

" $hird%line" $hiopental" Midazolam" &soflurane" Propofol


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Diazepam alium/


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Diazepam alium/" Can 'e administered &)P6

" A#oid repeated doses accumulation of drug and meta'olites

" Pharmaco+inetics - !ighly lipid%solu'le easily passes across 'lood 'rain 'arrier, and large

#olume of distri'ution

" 6apid distri'ution into 'rain :3 sec/" CSF concentrations reach L ma*imum #alue in 2 minutes" $hen, with redistri'ution, rapid drop in serum concentration

" Pharmacodynamics" Depresses all le#els of the C(S, including the lim'ic and

reticular formation 'y 'inding to the 'enzodiazepine site onthe gamma%amino'utyric acid A0A/ receptor comple* andmodulating A0A, which is a ma


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Paraldehyde

" Can be given:- I: $he usual intramuscular dose of paral!ehy!e for

status epilepticus is 3.:B to 3.2 ml)+g. Can gi#e additionaldose 3.3B ml)+g/. $he dose may 'e repeated in 9 to 4hours and no more than B milliliters should 'e administeredin one site AMA Department of Drugs, :7I4/.

- I": #) $he usual dose 3.: to 3.:B ml)+g. $he intra#enoussolution should 'e well%diluted in normal saline. !igherdoses 3.2ml)+g increase the incidence of ad#erse effects

2) Administration of intra#enous paral!ehy!e is notrecommended- %R: $he usual rectal dose is %I ml diluted with an eual or

dou'le amount of oil or isotonic sodium chloride. $heparal!ehy!e should 'e diluted 9: in oli#e or cottonseed oilor mi*ed in 933 ml of (S. 6ectal a'sorption is slow and

pea+ plasma le#els will not occur for 9 to hours Coniglio arnett, :7I7/.

P ld h d


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Paraldehyde

Pharmaco+inetics - Meta'olism 'y &E6, G38 to I38, with the rate of elimination slowed

'y hepatic insufficiency ilman et al, :7IB/

Pharmacodynamics =nset intramuscular 9 to 2 minutes, oral :3 to :B minutesPea+ 6esponse intramuscular B to :B minutes

Nse%aral!ehy!e is a rapidly acting hypnotic, with sleep normallyensuing in :3 to :B minutes. &t has no analgesic properties and mayproduce e*citement or delirium in the presence of pain.%aral!ehy!e is effecti#e for all types of con#ulsions and delirium athigh doses. 6espiratory depression and hypotension also occur inhigh doses, 'ut little effect on respiration and 'lood pressureoccur at therapeutic doses ilman et al, :7IB/.

Ati /


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orazepam Ati#an/" i#en o#er 9 minutes

" may repeat Q:3 mins * 9" 0eware of tachyphyla*is with successi#e doses

" Pharmaco+inetics" ipid%solu'ility and #olume of distri'ution half that of diazepam" !alf%life twice that of diazepam" onger onset of action 9 mins/

" Pharmacodynamics" Depresses all le#els of the C(S, including the lim'ic and reticular formation,

'y 'inding to the 'enzodiazepine site on the gamma%amino'utyric acid

A0A/ receptor comple* and modulating A0A, which is a ma


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Pheno'ar'ital

" Pharmaco+inetics

- $he least lipid%solu'le- Pea+ 'rain concentration 43 minutes- Predicta'le elimination +inetics- ery long half%life up to :93 hrs

" Pharmacodynamics- &nhi'its reticular acti#ating system interferes w) (A,

transport across mem'ranes/- =nset of action 93 minutes- Duration of action 9%I hours- 0eware of prolonged sedation, respiratory depression


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Dilantin Phenytoin/

" Pharmaco+inetics

" ow lipid solu'ility, enters 'rain slowly" Pea+ 'rain drug concentration :3%23 mins" Side effects hypotension, cardiac arrythmias" Cannot 'e gi#en with glucose will precipitate/

" Pharmacodynamics

- Sta'ilizes neuronal mem'ranes and decreases seizure acti#ity 'yincreasing efflu* or decreasing influ* of sodium ions across cellmem'ranes in the motor corte* creating delay in neuronal electricalreco#ery

- Prolongs effecti#e refractory period and suppresses #entricular pacema+erautomaticity, shortens action potential in the heart" Selecti#ely 'loc+ing the neurons that are firing at high freuency

" Pre#ents the electrical spread of a focus of irrita'le tissue


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Dilantin Phenytoin/

" (ot water%solu'le, dissol#ed in propylene glycol" =r 'enzoic acid 'enzoate/, a meta'olite of 'enzyl alcoholT

large amounts of 'enzyl alcohol which has 'een associatedwith a potentially fatal to*icity Ugasping syndromeU/ in

neonatesT meta'olic acidosis, respiratory distress, gaspingrespirations, C(S dysfunction including con#ulsions,intracranial hemorrhage/, hypotension and cardio#ascularcollapse

" $o*icity depends on the route of administration, duration,

e*posure, and dose- !ypotension, 'radycardia, arrhythmias, cardio#ascular collapse

especially with rapid &.. use/

- 6is+ of necrosis and lim' ischemia from infusion purpleglo#e syndrome/

Fos/phenytoin


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/p y

" Fosphenytoin is pro%drug of phenytoin hydrolyzed into phenytoin/

" Pharmaco+inetics

" ow lipid solu'ility, enters 'rain slowly" Pea+ 'rain concentration in 93%43 mins" !epatic meta'olism P%B3 system/

" Pharmacodynamics" Sta'ilizes neuronal mem'ranes flu* of (a, Ca ions/" =nset of action :3 mins

" Duration of action 9 hrs w) single dose" Does (=$ depress respiratory dri#e or alter MS" $o*icity depends on rate of administration not dose

- 'radycardia, hypotension, cardiac arrhythmia- Monitor !6, 0P, EC during D- A#oid e*tra#asation flush w) (S, use large P&/


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&ncidence of Status Epilepticus

" Status Epilepticus SE/ seizure that lasts forgreater than 23 mins or multiple seizures going onfor 23 mins without return to 'aseline in 'etween

" Status Epilepticus occurs as :st seizure in :98 ofchildren with seizures

" 6efractory Status Epilepticus 6SE/ Seizuresthat do no respond to :st line therapy and persistfor 5 43 minutes


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6efractory Status Epilepticus

" &nadeuate drug treatment

" Nncorrected medical and meta'olic complications- Meta'olic acidosis- Electrolyte im'alance- !ypoglycemia- &nfections- !yperthermia

" arge cere'ral lesion

% !ypercar'ia

% Fluid &m'alance

% Pulmonary Edema

% 6enal Failure% D&C


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$herapy for 6efractory SE

" $herapeutic o'


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Pento'ar'ital

- Directly depresses neuronal acti#ity through enhancedA0A receptor responses

- More lipid solu'le than Pheno'ar'ital penetrates 'rainfaster, redistri'ution into 'ody tissues

- Elimination half%life :B%43 hrs

- !ypotension is significant complication


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Drugs that Cause Seizures

" Antimicro'ials- &soniazid- Penicillins

- (alidi*ic acid

- Metronidazole

" Psychopharm drugs

- Antihistamines- Antidepressants

- Antipsychotics

- Phencyclidine

- $CA

" Anesthetics% !alothane% Enflurane% Cocaine

" (arcotics% Fentanyl% Meperidine

" Analgesics% etamine

$ t t i 6 l ti t


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$reatment in 6elation toAge

" (eonates- Nnpredicta'le relationship 'etween dose and theraputic

drug effect" ess protein 'inding

" aria'le a'ility to eliminate drug- orazepam Pheno'ar' fosphenytoin

" &nfants

- 0e ready to intu'ate- Pheno'ar'ital elimination half%life E6 long- %B days to reach steady%state- J$herapeuticK le#el V what wor+sH


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Simple Fe'rile Seizures" =ccurs with fe#er in a child aged 4 months to B years" A con#ulsion associated with an ele#ated temperature greater

than 2IWC" Single seizure

" ast less than :B minutes, ha#e no focal features, and, if theyoccur in a series, the total duration is less than 23 minutes." $he child is otherwise neurologically healthy and without

neurological a'normality 'y e*amination or 'y de#elopmentalhistory

" (o central ner#ous system infection or inflammation" (o acute systemic meta'olic a'normality that may producecon#ulsions

" (o history of pre#ious afe'rile seizures


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Management of :st non%fe'rile

seizure" &f well%appearing in ED, patient can

'e discharged to home

" =utpatient EE and M6& within :month

" =utpatient (eurology Consult

" =nly 238 will ha#e second seizure


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$a+e !ome Points


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$a+e !ome Points" $he longer the seizure, the more difficult it 'ecomes to stop so?AC$ FAS$H

" $he endpoint is (=$ a particular drug concentration 0N$ rather a clinicaland)or electrical endpoint.

" &t is not the particular choice of drug 'ut rather the timing, route and #igorof therapy that determines mortality and mor'idity.

" Early therapy is far more effecti#e that later therapy.

" 6ate of administration of a drug is more important than total amountadministered in terms of to*icity.

" &ntu'ate earlyT do not wait for florid systemic complications to occur.


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emergency management of seizures final 3-1

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