MANAGEMENT OF TONIC- CLONIC SE:(1,2)
Time from initiation
of observation and
treatment (min) Procedure
=================================================
0 Assesss cardiorespiratory function
as the presence of tonic clonic sta
tus is verified.If ensure of diagnosis
observe one tonic-clonic attack and
verify the presence of unconcious
ness after the end of the tonic clo
nic attack.Insert oral airway and ad
minister 02,if necessary.Insert an in
travenous catheter.Draw venous
blood to determine anticonvulsant
levels,glucose,BUN,electrolytes,and
complete blood count stat.Draw ar
terial blood for stat pH,PO2,PCO2,
HCO3-.Monitor respiration,blood
pressure,and electrocardiograph.
If possible monitor encephalograph.
5 Start iv infusion with NS contain-
ing with B complex. Give a bolus
injection of 50 ml of 50% glucose.
10 Infuse 1 mg lorazepam over 5 mi
nutes also give fosphenytoin to a
total of 17 mg/kg(level >20 mcg
per ml). If hypotension develops
slow infusion rate.Phenytoin 50
mg/ml in propyleneglycol may be
placed in a 100 ml volume control
set and diluted with normal saline.
the rate of infusion should be
watched. Alternatively phenytoin
may be injected slowly by iv.
20 If seizures persist give 1mg lorazepam
intravenously.
30 If seizures persist consider pseudo
seizures if no CNS infection or
trauma.Otherwise, phenobarbital 20
mg/kg iv no faster than 100 mg/min
until seizures stop or to a loading of 20
mg/kg(level > 40 mcg/ml).
60 If seizure continue, general anesthesia
with pentobarbital is instituted.
120 If SE continue a neurologist and
anesthesiologist with expertise in SE
should be consulted. Advice from a
regional epilepsy center on the
management of intractable SE also
should be sought Push pentobarbital
until seizures stop or hypotension
arises.With cessation of seizures if
still twitching assess EEG to rule out
subtle SE.
Generalized convulsive SE is considered a neurologic emergency.
Treatment to secure the airway, provide oxygen,and maintain circulation must be initiated within the first fiew minutes to prevent complications such as hypoxaemia,
systemic hypertension,tachydysrythmia.
Protocols for the treatment of convulsive SE remain somewhat individualized by institution and specialty.
Recent trends have pushed aggressive treatment beginning as soon as 10 minutes into continuous convulsive state.
In practice this intervention can rarely be effected except in hospital. One of many approaches to control SE is shown as mention above.
This protocol reflects the current widespread use of lorazepam titrated to effect (0,03 to 0,22 mg/kg) as a subtitute for diazepam.
Parke Davis has withdrawn phenytoin(Dilantin) in favor of the prodrug fosphenytoin(Cerebyx).This a water soluble preparation with pH of 9 is converted in 15 minutes to the active drug phenytoin by tissue phosphatases. It is equally as effective as phenytoin but without complications of the propyleneglycol solvent and higher alkalinity (pH 12).
It can be delivered intramuscularly and more stable in the iv form but it can also precipitate hypotension if adminis-
tered too rapidly.
Phenobarbital as alternative drug when seizure persist after lorazepam. Physicians are using thiopental much earlier in the treatment of SE when phenobarbital is not available.
When phenytoin and phenobarbital are ineffective, a benzodiazepine is often suggested. Midazolam and diazepam have a shorter onset time than lorazepam although lorazepam generally has a longer duration of action with a lower likelihood of severe respiratory depression making it the preferred agent of some clinicians.
Diazepam is the fastest onzet (1-3 minutes) and hystoricaly was the treatment of choice because is known as the fastest medication to terminate seizures. However because of its lipholicity diazepam has a very short duration in CNS (10-20 min). For this reason lorazepam has replaced diazepam as the drug of choice. Its onset in only slower (2-3 min) but its anticonvulsant action typically last for more than 4 hours.
Diazepam has been reported to be effective rectally, and midazolam to be effective intramuscularly and intranasally in children.
If seizures continue to be refractory to treatment with the previously noted drugs, pentobarbital usually can be used some times thiopental.
Alternatively,volatile anesthetics can also be used.
Intravenous valproate (depakene) is now available which being tried in refractory status. Any of the other non iv formulated AEDs can be administered via nasogastric tube.
Propofol has been used in ambulances for patient refractory to iv benzodiazepine, given in 30 mg boluses every 30 seconds until the seizure are terminated.There may be a future role for alpha 2 agonist therapy as such drugs become clinically available.
Dexmedetomidine confered brain protection in an animal
seizure model.
Other protocol for tonic clonic generalized SE based on stage :
Stage General measures AEDs Usual route of adm
Premonitory Continued neurolo Diazepam 10mg iv bolus
gic observation,dia max 5mg/min
agnostic SE by ob Lorazepam 4mg iv bolus
serving continued max 2mg/min
seizure activity of Midazolam 5mg iv bolus
one additional sei max 4m/min
zure. Paraldehyde 5- 10 ml in
5- 1 ml water or oil
by rectal First line
Early Ensure adequate Diazepam 10mg iv bls
(0-30 mins) cardiorespiratory Lorazepam 4- 8mg iv
function,iv line,ad-
minister 02,initiate Second line
regular ECG,and BP Midazolam 5-10 mg iv
monitoring,draw Phenytoin 15-18 mg/kg
blood for emergen- iv loading
cy investigations,in- dose(max.
tubation may be 50mg/min.
considered. Paraldehyde solution 4%
in saline,50-100ml/h
iv solution
Lidocaine:iv bolus and
short infusion.
Established Set second iv line First line
(large veins)admi- Phenytoin repeate
nister thiamine 100 7mg /kg iv.
mg iv and glucose Phenobarbital
D50W-50 ml iv, 10-20 mg/kg iv
treat acidosis,estab loading dose
lished etiology,admis- (<100mg/m)
sion to ICU,intubation second line
ICU,intubation has to Diazepam iv infusion
be considered,EEG/ Midazolam iv infusion
ECG monitoring. Paradeldehyde iv infusion
Refractory Full anesthesia needed First line
(>120 min) EEG/ECG monitoring,ar- Pentobarbital iv/infus
terial line,initiate pres- Propofol iv/infusion
sor therapy when requi-
red monitoring of AEDs Second line
levels intracranial pres- Isoflurane inhalation
sure monitoring where
appropriate.
In a patient who is actively seizing a lateral position may help prevent aspiration.The choice of iv fluids should include normal saline if phenytoin will be used because phenytoin will precipitate in glucose containing solution
After 8 mg of lorazepam if seizures have not been aborted
use of another anticonvulsant medication is indicated.
If benzodizepine are effecive in seizure control further seizures need to be prevented with a long acting anticonvulsant.
A loading dose of phenytoin is 18-20 mg /kg ,even at the recomended rate of administration (50mg/min),hypotension is the most common side effect and mandates decreasing the infusion rate.
to be continued
Time from initiation
of observation and
treatment (min) Procedure
=================================================
0 Assesss cardiorespiratory function
as the presence of tonic clonic sta
tus is verified.If ensure of diagnosis
observe one tonic-clonic attack and
verify the presence of unconcious
ness after the end of the tonic clo
nic attack.Insert oral airway and ad
minister 02,if necessary.Insert an in
travenous catheter.Draw venous
blood to determine anticonvulsant
levels,glucose,BUN,electrolytes,and
complete blood count stat.Draw ar
terial blood for stat pH,PO2,PCO2,
HCO3-.Monitor respiration,blood
pressure,and electrocardiograph.
If possible monitor encephalograph.
5 Start iv infusion with NS contain-
ing with B complex. Give a bolus
injection of 50 ml of 50% glucose.
10 Infuse 1 mg lorazepam over 5 mi
nutes also give fosphenytoin to a
total of 17 mg/kg(level >20 mcg
per ml). If hypotension develops
slow infusion rate.Phenytoin 50
mg/ml in propyleneglycol may be
placed in a 100 ml volume control
set and diluted with normal saline.
the rate of infusion should be
watched. Alternatively phenytoin
may be injected slowly by iv.
20 If seizures persist give 1mg lorazepam
intravenously.
30 If seizures persist consider pseudo
seizures if no CNS infection or
trauma.Otherwise, phenobarbital 20
mg/kg iv no faster than 100 mg/min
until seizures stop or to a loading of 20
mg/kg(level > 40 mcg/ml).
60 If seizure continue, general anesthesia
with pentobarbital is instituted.
120 If SE continue a neurologist and
anesthesiologist with expertise in SE
should be consulted. Advice from a
regional epilepsy center on the
management of intractable SE also
should be sought Push pentobarbital
until seizures stop or hypotension
arises.With cessation of seizures if
still twitching assess EEG to rule out
subtle SE.
Generalized convulsive SE is considered a neurologic emergency.
Treatment to secure the airway, provide oxygen,and maintain circulation must be initiated within the first fiew minutes to prevent complications such as hypoxaemia,
systemic hypertension,tachydysrythmia.
Protocols for the treatment of convulsive SE remain somewhat individualized by institution and specialty.
Recent trends have pushed aggressive treatment beginning as soon as 10 minutes into continuous convulsive state.
In practice this intervention can rarely be effected except in hospital. One of many approaches to control SE is shown as mention above.
This protocol reflects the current widespread use of lorazepam titrated to effect (0,03 to 0,22 mg/kg) as a subtitute for diazepam.
Parke Davis has withdrawn phenytoin(Dilantin) in favor of the prodrug fosphenytoin(Cerebyx).This a water soluble preparation with pH of 9 is converted in 15 minutes to the active drug phenytoin by tissue phosphatases. It is equally as effective as phenytoin but without complications of the propyleneglycol solvent and higher alkalinity (pH 12).
It can be delivered intramuscularly and more stable in the iv form but it can also precipitate hypotension if adminis-
tered too rapidly.
Phenobarbital as alternative drug when seizure persist after lorazepam. Physicians are using thiopental much earlier in the treatment of SE when phenobarbital is not available.
When phenytoin and phenobarbital are ineffective, a benzodiazepine is often suggested. Midazolam and diazepam have a shorter onset time than lorazepam although lorazepam generally has a longer duration of action with a lower likelihood of severe respiratory depression making it the preferred agent of some clinicians.
Diazepam is the fastest onzet (1-3 minutes) and hystoricaly was the treatment of choice because is known as the fastest medication to terminate seizures. However because of its lipholicity diazepam has a very short duration in CNS (10-20 min). For this reason lorazepam has replaced diazepam as the drug of choice. Its onset in only slower (2-3 min) but its anticonvulsant action typically last for more than 4 hours.
Diazepam has been reported to be effective rectally, and midazolam to be effective intramuscularly and intranasally in children.
If seizures continue to be refractory to treatment with the previously noted drugs, pentobarbital usually can be used some times thiopental.
Alternatively,volatile anesthetics can also be used.
Intravenous valproate (depakene) is now available which being tried in refractory status. Any of the other non iv formulated AEDs can be administered via nasogastric tube.
Propofol has been used in ambulances for patient refractory to iv benzodiazepine, given in 30 mg boluses every 30 seconds until the seizure are terminated.There may be a future role for alpha 2 agonist therapy as such drugs become clinically available.
Dexmedetomidine confered brain protection in an animal
seizure model.
Other protocol for tonic clonic generalized SE based on stage :
Stage General measures AEDs Usual route of adm
Premonitory Continued neurolo Diazepam 10mg iv bolus
gic observation,dia max 5mg/min
agnostic SE by ob Lorazepam 4mg iv bolus
serving continued max 2mg/min
seizure activity of Midazolam 5mg iv bolus
one additional sei max 4m/min
zure. Paraldehyde 5- 10 ml in
5- 1 ml water or oil
by rectal First line
Early Ensure adequate Diazepam 10mg iv bls
(0-30 mins) cardiorespiratory Lorazepam 4- 8mg iv
function,iv line,ad-
minister 02,initiate Second line
regular ECG,and BP Midazolam 5-10 mg iv
monitoring,draw Phenytoin 15-18 mg/kg
blood for emergen- iv loading
cy investigations,in- dose(max.
tubation may be 50mg/min.
considered. Paraldehyde solution 4%
in saline,50-100ml/h
iv solution
Lidocaine:iv bolus and
short infusion.
Established Set second iv line First line
(large veins)admi- Phenytoin repeate
nister thiamine 100 7mg /kg iv.
mg iv and glucose Phenobarbital
D50W-50 ml iv, 10-20 mg/kg iv
treat acidosis,estab loading dose
lished etiology,admis- (<100mg/m)
sion to ICU,intubation second line
ICU,intubation has to Diazepam iv infusion
be considered,EEG/ Midazolam iv infusion
ECG monitoring. Paradeldehyde iv infusion
Refractory Full anesthesia needed First line
(>120 min) EEG/ECG monitoring,ar- Pentobarbital iv/infus
terial line,initiate pres- Propofol iv/infusion
sor therapy when requi-
red monitoring of AEDs Second line
levels intracranial pres- Isoflurane inhalation
sure monitoring where
appropriate.
In a patient who is actively seizing a lateral position may help prevent aspiration.The choice of iv fluids should include normal saline if phenytoin will be used because phenytoin will precipitate in glucose containing solution
After 8 mg of lorazepam if seizures have not been aborted
use of another anticonvulsant medication is indicated.
If benzodizepine are effecive in seizure control further seizures need to be prevented with a long acting anticonvulsant.
A loading dose of phenytoin is 18-20 mg /kg ,even at the recomended rate of administration (50mg/min),hypotension is the most common side effect and mandates decreasing the infusion rate.
to be continued
