Pediatric emergency medicine trisk 361

Medical Management of an Active Seizure Beyond the
Neonatal Period
Benzodiazepines are the initial drug of choice for the treatment of seizures.
Benzodiazepines work by blocking the GABA receptor, thus increasing the
seizure threshold. Lorazepam (Ativan) has a rapid onset of action (less than 5
minutes) and should be given intravenously over 2 to 4 minutes to avoid acute
respiratory decompensation. The dose is 0.1 mg/kg, with a maximal dose of 4 mg.
Its anticonvulsant effects can last for several hours. An equally effective
alternative is diazepam 0.2 mg/kg IV (maximum dose 8 mg). Intramuscular
midazolam was shown to be at least as effective as intravenous lorazepam in
terminating status epilepticus in the prehospital setting. Midazolam dosing is 0.2
mg/kg/dose (with MAX 10 mg/dose) IM or 0.1 mg/kg/dose IV (maximum 5
mg/dose). Midazolam is shorter acting than both lorazepam and diazepam. If a
first dose of benzodiazepines fails, then a second dose should be administered at 5
minutes.


FIGURE 72.2 Management of status epilepticus.


For patients with no IV access, other options are available. Midazolam is
reliably and rapidly absorbed intramuscularly at the above dosing. Diazepam can
also be given as a rectal gel PR at a dose of 0.2 to 0.5 mg/kg/dose with a
maximum dose of 20 mg/dose.
Both intranasal and buccal routes of midazolam have been described with
successful cessation of seizures, often in prehospital settings. These modes of
administration should be reserved for providers who have administered intranasal
or buccal medication in the past, rather than have their first attempt of using these
routes on an actively seizing child (Fig. 72.2 ).
Diazepam has an advantage in that it can be given rectally, which is useful
when a patient does not have IV access. A rectal gel is available in fixed doses of

5, 7.5, 10, 12.5, 15, 17.5, or 20 mg. The IV preparation of the drug may be used
alternatively. Recommended rectal dosing for children up to 5 years of age is 0.5
mg/kg.
Midazolam can be given intramuscularly (0.2 mg/kg/dose; not to exceed a
cumulative dose of 10 mg) and should be considered if there is delay in IV
access. Midazolam has a theoretical advantage in that patients will return to
baseline more quickly than with lorazepam or diazepam, thus allowing for better
assessment of mental status and the need for CT scan and/or LP.
Phenytoin (Dilantin) is a second-line agent for the treatment of seizures.
Phenytoin blocks sodium channels and thus acts by a different mechanism than
the benzodiazepines. The dose is 15 to 20 mg/kg as an initial load. It has several
limitations as compared with the benzodiazepines. First, peak CNS
concentrations may not be reached until 10 to 30 minutes after its infusion is
completed and, thus, it is much slower in onset. Furthermore, it must be
administered slowly (no faster than 1 mg/kg/min, or 20 minutes for a dose of 20
mg/kg) because of concerns of cardiac conduction disturbances. It cannot be
given in dextrose-containing solutions.
As a result of the limitations in the administration of phenytoin, fosphenytoin
(Cerebyx) was created. It is a prodrug whose active metabolite is phenytoin. The
drug is dosed as phenytoin equivalents (PEs), and the loading dose is 15 to 20 mg
PE/kg. The advantages are that it can be given much more rapidly (up to 3 mg
PE/kg/min, or 7 minutes for a dose of 20 mg PE/kg) and that it may be given in
either normal saline or a 5% dextrose-containing solution or intramuscularly.
Phenobarbital (Luminal) is another second-line agent for the treatment of
seizures. The loading dose is 10 to 20 mg/kg. Its advantage over phenytoin is that
it can be given more rapidly (2 mg/kg/min, or 10 minutes for a dose of 20 mg/kg).
However, it has an extremely long half-life (up to 120 hours) and a pronounced


sedating effect. Furthermore, it can cause significant respiratory depression,

especially when given after a benzodiazepine. One must be prepared to intubate a
patient who has received both a benzodiazepine and a barbiturate for the
treatment of seizures. It is important to remember that if a patient needs to be
intubated, a muscle relaxant can mask the motor manifestation of seizure activity.
The side-effect profile of phenobarbital and the fact that it acts on GABA
receptors (similar to the first line of benzodiazepines), make phenobarbital an
inferior choice to the fast-administered/fast-acting fosphenytoin. Therefore,
phenobarbital is now considered a third-line agent.
Valproic acid (Depakene) is a commonly used antiepileptic agent and the IV
preparation had been used in the past to rapidly attain therapeutic levels.
Recently, there have been a few case series demonstrating its effectiveness in
treating seizures in children who have been refractory to the first-line agents. As
such, many now consider it a third-line agent for the treatment of status
epilepticus. It is given intravenously at a dose of 15 to 40 mg/kg over 10 minutes.
It is generally well tolerated and is less sedating than the barbiturates.
IV levetiracetam (Keppra) has also been used for pediatric status, with a
loading dose of 40 to 60 mg/kg given over 10 minutes. There is some evidence
that phenytoin/fosphenytoin, valproate, and levetiracetam are all equally
reasonable choices in this setting. Since levetiracetam has less immediate side
effects than fosphenytoin, it is now becoming increasingly common as a second
line of treatment. Furthermore, single doses of up to 60 mg/kg have been
endorsed by at least two guideline panels and these doses were well tolerated and
appear promising. A recent randomized controlled trial involving children and
adults with SE refractory to benzodiazepines demonstrated equal effectiveness of
approximately 50% of fosphenytoin, levetiracetam, and valproate. Two recent
large trials of phenytoin versus levetiracetam also failed to demonstrate a
difference in effectiveness.
Pyridoxine deficiency is an uncommon cause of seizures in newborns. One
should consider its use (50 to 100 mg IV) primarily in patients younger than 3
months whose seizure activity is refractory to the other therapies. Rarely,

pyridoxine-dependent epilepsy may present in older patients, so some guidelines
recommend its use in refractory status epilepticus in patients up to 18 months of
age. Pyridoxine is also used in the treatment of isoniazid overdose (usual initial
dose 70 mg/kg).
If all the described therapies fail, patients may require general anesthesia to
abort the seizures. A variety of agents can be used, including inhalational
anesthetics (e.g., halothane, isoflurane), large doses of short-acting barbiturates