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 minutes) and should be given intravenously over to minutes to avoid acute respiratory decompensation The dose is 0.1 mg/kg, with a maximal dose of mg Its anticonvulsant effects can last for several hours An equally effective alternative is diazepam 0.2 mg/kg IV (maximum dose 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 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 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 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 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 mg PE/kg/min, or 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 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 ... 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