General
Drugs
Epidemiology - SE
life threatening
USA: -102,000 -152,000 cases / year
- 52,000 deaths / year
of new cases of epilepsy, 12 -30%
present in Status
generalized Status is most common
form - and subject of this review
Clinical - Generalized SE
at onset - usually obvious tonic / clonic
as continues often subtle - slight twitch of
face / extremities, nystagmoid eye
movements
may be NO observable motor sz, still risk
for CNS injury - assume still seizing if SE pt
not waking
Outcome of SE
overall adult mortality 20% (>80 yr : 50%)
>90% mortality is due to underlying disease
children - better outcomes - mortality 2.5 %
increase risk future SE / chronic sz
worse outcome if prolonged / severe
physiologic disturbance
outcome depends on cause - acute vs chronic
Outcome of SE
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Outcome of SE
continued
Pathophysiology - SE
Pathophysiology - SE contd
Pathophysiology - SE
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Pathophysiology - SE
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Pathophysiology - SE
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Pathophysiology - SE
continued
OUTLINE - Management of SE
General approach
Anti - Epileptic Drugs:
Benzodiazepines
Phenytoin / Fosphenytoin
Barbiturates
Propofol
others / new possibilities
Management of SE
ABCs (+ monitor / O2 / large IVs)
START PHARMACOTHERAPY ASAP
Metabolic acidosis common - if severe, give
Bicarb
if intubating / ventilating - avoid longacting n-m blockers - masks sz activity
beware hyperthermia
Management of SE
continued
Management of SE
continued
Management of SE
continued
consider....
Thiamine
Glucose
Pyridoxine 5 gm IV (70 mg/kg kids)
reverses INH action inhibiting GABA
synthesis
now recommended routinely by NYC Poison
Control in REFRACTORY SE d/t frequency
of INH OD
OUTLINE - Management of SE
General approach
Anti - Epileptic Drugs:
Benzodiazepines
Phenytoin / Fosphenytoin
Barbiturates
Propofol
others / new possibilities
Drug Rx of SE
Drug Rx of SE
easy to administer
prompt onset, long-acting
100% effective vs seizures
no depression of cardio-resp function or mental
status
no other adverse effects
Drug Rx of SE
Drug Rx of SE
1st - Benzodiazepines
* Lorazepam, Diazepam
2nd - Phenytoin, Fosphenytoin
3rd - Phenobarbital
Drug Rx - Refractory SE
Non - IV Rx of SE
Lorazepam
1st agent to use
Dose: Adults 4 -10 mg (.1 mg/kg) IV
Peds .05 - .1 mg/kg (to 4 mg) IV
less lipid soluble than Diazepam --> smaller
volume of distribution / longer T1/2
effects last 12 - 24 hr
S/E: resp depression, hypotension, confusion,
sedation (but less than diazepam)
Diazepam
Dose: Peds .1-1.0 (.2-.5) mg/kg IV
Adults 10 - 20 mg (.2 mg/kg) IV
Duration of action: < 1 hr
Lorazepam
Diazepam
*1224hr
*<1hr
23min
13min
++
Midazolam
Dose: .2 mg/kg IV
5-10 mg IM
0.2 mg/kg Intranasal
Dose for refractory SE - continuous IV
infusion @ 0.1 - 2.0 mg/kg/hr - titrated
Onset: IV 2 - 3 min / other routes 15 min
Duration: 1 - 4 hr
Phenytoin (Dilantin)
still the standard 2nd IV Rx after Benzo
dose: 18 - 20 mg/kg (better than 1 gram)
IV solution is highly alkaline - dissolved in
propylene glycol, alcohol, and NaOH
- pH is 12
-give in large vein, dilute N/S, flush
rate: 50 mg / min (Peds: 1 mg/kg/min)
onset of action: 10 - 30 min
duration of action: 12 - 24 hr
Phenytoin
continued
Fosphenytoin
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
Molecular wt = 1.5 x Phenytoin ... so
1.5 mg Fosphen --> 1 mg Phenytoin
can safely give at 3x rate of Phenytoin,
resulting in 2x amount of Phenytoin delivered
Fosphenytoin
Fosphenytoin
Negative considerations:
COST Approx 20x that of Phenytoin
CONFUSION of ordering in Phenytoin
equivalents
can give IV at rate of 150 PE/min, which
delivers 100 mg/min of Phenytoin
750 mg Fosphen = 500 mg PE
- One
UK hospital expresses orders in both
units ie 500 mg PE (750 mg Fosphen)
Fosphenytoin
confusion:
case report
25 yo female given infusion of Phenytoin
(mistaken for Fosphenytoin) at 150 mg/min
bradycardia to 34
BP dropped to 45/0
asystole
oops.
resuscitated with CPR ( x 15 min),
intubation, atropine, isoproterenol
Fosphenytoin
NOTES both Fosphen (Cerebyx) and Dilantin are
marketed by Parke-Davis
Fosphen was developed to solve problems
associated with parenteral Phenytoin, and
eventually replace it
P-D have stopped making IV Dilantin - but
generic IV Phenytoin still available
Fosphenytoin
Barbiturates
in use since 1912
general CNS depressant activity
Phenobarbital
Dose: 20 mg/kg IV (range 10-40 mg/kg)
-usu maximum 1 gm
Maximum rate: 100 mg/min
onset of action: 10 - 20 min
duration of action: 1 - 3 days
Phenobarbital
Pentobarbital
Dose: 5 - 12 mg/kg
Rate: 5 - 20 mg/min
Thiopental
Dose: 2-5 mg/kg IV
rapid onset: 30 - 60 sec
short duration: 20 - 30 min
S/E:
Thiopental
Propofol
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:
Propofol
Propofol
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
Paraldehyde
Consensus Guidelines
Rx of Status Ep. in Children
by the Status Epilepticus Working Party Britain 2000
based on literature search of Ped SE papers
in English ; >1100 found, though only 2
were pediatric RCTs
Consensus Guidelines:
if IV Access
1. Lorazepam 0.1 mg/kg (over 30-60 sec)
2. Lorazepam - repeat
3. Phenytoin 18 mg/kg (over 20 min)
OR Phenobarbital 20 mg/kg (over 10
min) if already on Phenytoin
AND Paraldehyde rectally 0.4 ml/kg in
same volume olive oil
4. RSI - Thiopental induction 4 mg/kg
Consensus Guidelines:
if NO IV Access
1. Diazepam 0.5 mg/kg rectally
2. Paraldehyde 0.4 ml/kg rectally
start intraosseous if still no IV
then follow IV algorithm
4. RSI using Thiopental
3. Phenytoin / Phenobarb; plus Paraldehyde
rectally
Thank you