Introduction     References     Annotated Bibliography    Questions

Pediatric Seizures and Status Epilepticus (SE): 
Epidemiology, Diagnosis and Management

Case Presentation

This presentation addresses the following topics related to pediatric seizure and status epilepticus:

1) Pre-hospital treatment

2) Emergency department treatment

3) Rapid and effective diagnosis, treatment, and disposition of patients


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Pediatric Seizures and Status Epilepticus (SE): 
Epidemiology, Diagnosis and Management

 

Introduction 

 

This document addresses pediatric seizures and SE as they relate to pre-hospital providers and the staff in the Emergency department.  The goal of this information is to facilitate the rapid and effective diagnosis, treatment, and disposition of pediatric patients with seizures and SE.

 

Overall Seizure Epidemiology

 

There are an estimated 2.5 million patients with epilepsy in the United States, a prevalence of about 6.6 per 1000 Americans.  Up to 28% of these epilepsy patients are treated in the Emergency Department annually.  Status epilepticus (SE) occurs in 50-150,000 patients per year, with a mortality of 22%.  The incidence of SE is 50 per 100,000 Americans, with the greatest incidence being at the extremes of age.  Status epilepticus is seen in up to 7% of Emergency Department seizure patients, and most emergency physicians report treating five or more cases of SE per year.  The etiology of SE in the Emergency Department is similar to that of all emergency seizure patients, with alcohol, drugs, or low anti-epileptic drug (AED) levels causing more than 50% of SE episodes treated.

 

Pediatric Seizure Epidemiology and Etiology

 

The CNS of children is more immature, making children more likely to seize but also more refractory to the consequences of an acute seizure or SE.  SE is most common in children younger than one year of age, and in children who develop SE, 50% will do so in the first year of their life.  The most common causes of SE in children are fever, CNS infection, and epilepsy, accounting for over 75% of SE episodes in children less than one year of age.  Other etiologies of SE in children include hyponatremia, inadvertent ingestions of cocaine or other toxins, and structural CNS abnormalities.  The outcome of children with SE depends on the CNS status of the child prior to the onset of the SE, the better outcomes associated with children without underlying CNS abnormalities.  The 3-6% mortality seen in pediatric SE most often is related to an acute neurologic insult or a chronic CNS condition.

 

In two studies from an urban ED, up to one percent of all patients seen in the ED were noted to be pediatric seizure patients.  Febrile seizures were noted to comprise 80% of these patients, with only 20% of pediatric patients presenting with afebrile seizures.  Febrile seizures are commonly seen in the emergency department because they occur in 2-5% of all children.  By definition, simple febrile seizures are brief (lasting less than 15 min duration), generalized, and non-recurrent.  Given the more aggressive definition of SE being used today, it is reasonable to consider children whose febrile seizures last for greater than 5-10 minutes to be complex, and diagnose the patient as having SE.

 

Seizure Classification

 

Pediatric seizures can be broadly classified into generalized and partial seizures.  Generalized seizures involve both cerebral hemispheres, while partial seizures involve only one cerebral hemisphere.  Generalized seizures either are convulsive (generalized tonic-clonic seizures) or non-convulsive (absence seizures).  Partial seizures are either simple, in that they do not involve an alteration in consciousness, or complex, when there is impaired consciousness. 

 

Simple partial seizures manifest themselves based on the location of the seizure focus, and can have focal motor movements, sensory, autonomic, or somatosensory symptoms.  When partial seizures are complex, they most often involve the temporal lobe, and cause cognitive and affective abnormalities, and psychomotor seizures.

 

Other generalized seizure types in children include neonatal seizures, benign childhood epilepsy, infantile spasms, Lennox-Gastaut syndrome, atonic seizures, and febrile seizures. These seizure types are more fully addressed in the slide presentation.

 

Status epilepticus can be divided into convulsive, non-convulsive, and subtle SE. Convulsive SE describes a generalized seizure that lasts greater than 5-10 minutes.  This more aggressive SE definition shortens the seizure duration criteria from 30 minutes, and is consistent with the treatment philosophy that prompts paramedics, nurses and emergency physicians to treat seizures early, regardless of duration.  

 

Non-convulsive SE includes a prolonged absence or complex partial seizure.  Complex partial SE may be present in a patient with waxing and waning mental status and/or intermittent bizarre or unusual behavior.  Complex partial SE patients may also develop generalized seizures after they present to the Emergency Department. 

 

Subtle status epilepticus, which is a late manifestation of prolonged SE and is a sign of profound encephalopathy, may be the diagnosis in frankly comatose patients who have only minimal focal motor activity.  In the past, a patient with subtle SE may have been considered less sick than a patient with generalized convulsive SE (GCSE) because of the absence of generalized seizure activity.  Up to 20% of comatose patients whose generalized seizures have been terminated may continue to have ictal discharges on EEG.   The absence of clinical manifestations of SE leads to the designation "subtle SE".   Patients who present with or develop subtle SE are usually elderly patients with significant co-morbidities and are more refractory to initial therapies, causing a higher mortality rate, up to 50% at 30 days.

 

 

Pre-hospital Pediatric Seizure Therapy

 

The pre-hospital treatment of pediatric SE with diazepam has been shown to reduce seizure duration by 47%, and to reduce the seizure recurrence rate by 32%.  The Chicago EMS seizure SMOs allow for multiple 0.1 mg/kg doses of diazepam in children prior to transport.  Rectal diazepam, dosed at 0.3-0.5 mg/kg, has been shown to be safe and effective in seizing children when IV diazepam cannot be given, and is often listed as a SMO alternative when IV access is not available.  Midazolam is now being used more often in EMS SMOs, since it can be used effectively via both the IV and IM routes, precluding the need for diazepam, which requires rectal use when IV access is not possible.  EMS systems that utilize midazolam recommend multiple 0.1 mg/kg doses in children. 

 

Emergency Department Evaluation

 

A complete laboratory evaluation may only be required in patients with complicated or new-onset seizures, those in SE, or in patients with significant co-morbidity and/or at the extremes of age.  One study of pediatric seizure patients established that the need for routine chemistry testing was not justified, given the low frequency of lab abnormalities.  The only significant lab abnormality that has been noted is hypoglycemia, seen in up to 2% of seizing patients.  

 

In patients who seize for prolonged periods, up to 50% may present with a temperature above 100.5, suggesting infection as the seizure etiology and prompting a lumbar puncture (LP) to be considered.  Fever, leukocytosis, and CSF pleocytosis may accompany SE even in the absence of a CNS infection, complicating the ability to determine the etiology of a prolonged seizure. 

 

In children, fevers commonly cause seizures and SE, despite the absence of meningitis.  With the use of the HIB vaccine, the risk of meningitis is greatly reduced, making meningitis as a possible cause of a prolonged febrile seizure less likely.  One study demonstrated that a simple febrile seizure was never the sole finding in a pediatric patient with meningitis. 

 

The published AAP guidelines that discuss the management of children with febrile seizures, including the need for lumbar puncture, allow for the Emergency Physician to defer most diagnostic tests except when clinically indicated.  This is appropriate given the diminished possibility of CNS Haemophilus influenzae b infection in children who have been HIB vaccinated, since it had been the most common cause of meningitis in children in the age group associated with febrile seizures.  The current ACEP guidelines also suggest that an LP is only required in the presence of immunocompromise, meningeal signs, persistent AMS, or a clinical history suggestive of a CNS infection.

 

Neuroimaging is indicated for seizures that are new-onset, complicated (including SE), and in patients with co-morbid conditions that impart a greater risk of complications.  A non-contrast head CT performed in the Emergency Department is a reasonable first imaging study, since it may diagnose space occupying lesions, mass effect, trauma, hemorrhage, and/or cerebrovascular infarcts.  Contrast-enhanced CT might only be necessary after the initial non-contrast CT suggests a space occupying lesion that is better diagnosed using contrast, such as a CNS tumor or an isodense subdural hematoma, for example. 

 

One study has demonstrated that children with complex febrile seizures, a normal neurologic exam, and afebrile seizure patients without a clear acute cause evident on history and physical rarely have a positive CT, such that this test can be deferred if appropriate follow-up can be arranged.

 

The use of electroencehalography (EEG) in the Emergency Department has been limited, despite its ability to diagnose subtle SE in seizure patients who remain comatose for prolonged periods after the termination of a generalized seizure.   Only 12% of emergency physicians report having access to EEG in the Emergency Department, and only 15% have used it in the evaluation of suspected subtle SE.  An EEG should be considered whenever subtle SE or complex partial SE is suspected, as well as in patients who require neuromuscular paralysis, intubation, pentobarbital, and/or general anesthesia for seizure control.  For example, if a child remains comatose for more than 30-40 minutes after resolution of a prolonged seizure, an EEG might be useful in detecting an ongoing seizure focus or SE.  The EEG could be performed upon arrival in the pediatric ICU if this test is not routinely available in the ED.

 

Two channel EEG monitors are available for use with Emergency Department cardiac monitors that include changeable modular ports.  This technology could allow the emergency physician to quickly determine if persistent seizure activity is taking place, so that additional therapy or consultation can take place prior to ICU disposition. 

 

 

Pediatric Seizure and SE ED Therapy

 

Recommendations regarding the treatment of SE, published by the Working Group on Status Epilepticus, provide the basis for optimal SE management in the Emergency Department.  Although these guidelines are not specific for pediatric patients, they do outline an initial diagnostic and treatment paradigm, including the time course over which drug therapies should be provided.  Important aspects of this treatment guideline for emergency physicians include the rapid implementation of an established treatment protocol, adequate dosing on a mg/kg basis, so that refractory SE can be treated as quickly as possible.

 

There are many standard and new therapies available to assist the emergency physician in terminating seizures and SE.  Most uncomplicated seizure patients, including those who develop SE, will respond to initial drug therapies in about 80% of cases.   More than the use of a specific drug, the most important factors in seizure termination are the rapid use of effective drugs in adequate doses, based on estimated weights and mg/kg requirements.  Therapy can be optimized, therefore, by the development of guidelines that include rational, sequential drug therapy that mandates appropriate dosing prior to considering any individual AED to be ineffective.

 

Benzodiazepines, which work through the GABA inhibition of repetitive firing, are easy to use, rapid acting, with efficacy of at least 79% in the treatment of SE.  Alternate benzodiazepine administration routes include intramuscular (IM), intranasal, and buccal midazolam, as well as rectal emulsified diazepam.  When administered IM, midazolam only takes 116 seconds to terminate seizures, as compared to 34 seconds when given by the intravenous (IV) route.  Intranasal and buccal midazolam have also been shown to be as effective as diazepam in randomized, controlled clinical trials.   The new form of rectal diazepam, called Diastat, comes pre-packaged as an emulsion that can be given rectally without the need to draw up the diazepam in a tuberculin syringe or to tape or hold the buttocks together while the drug is being absorbed.  At a minimum, these alternate benzodiazepine routes should make it unnecessary to infuse AEDs via the interosseous route.

 

Phenytoins work though membrane Na+ and Ca+ channel stabilization, reducing the likelihood of repetitive neuronal firing.  The standard phenytoin dose of 18-20 mg/kg is rarely exceeded in the treatment of SE, even though high dose (30 mg/kg) phenytoin therapy is recommended for SE refractory to standard phenytoin loading doses.  Fosphenytoin, the water-soluble pro-drug of phenytoin, is dosed in phenytoin equivalents, making dosing comparable to that of phenytoin.  It can be infused more rapidly than phenytoin with less pain, fewer injection site reactions, and fewer adverse events.  A loading dose of fosphenytoin can be given IM with therapeutic phenytoin within 20-30 minutes. 

 

Barbiturates are an effective class of AEDs that work through the enhancement of GABA inhibition of neuronal firing.  Although phenobarbital effectively treats seizures and SE, its formulation, administration difficulties, and long half-life all limit its usefulness in the Emergency Department.  Pentobarbital, when used as an anesthetic in the treatment of refractory SE, requires airway management, extensive cardiovascular and EEG monitoring, and neurologic consultation.

 

IV valproate, called Depacon, is now available for use in Emergency Department seizure patients who require rapid therapeutic drug level restoration.  This drug can be loaded in doses of 25-30 mg/kg at rates up to 3-6 mg/kg/min (to a maximum rate of 300 mg/min) in children as young as 2-3 months of age without significant complications.  Because many of the seizure etiologies in children warrant long-term PO divalproex therapy, it is reasonable to load pediatric patients who require protection from or therapy for SE with IV valproate.  

 

There have been case reports of the use of lidocaine in the treatment of seizing patients refractory to conventional therapies.  Although this Na+ channel drug is not likely to terminate most cases of SE, it can be used safely and should be considered when the use of the initial therapies fail to terminate SE. 

 

Refractory SE, defined as SE non-responsive to initial therapy with benzodiazepines, phenytoins, phenobarbital, and valproate, occurs in up to 22,000 patients per year.  In a case report of an actively seizing pediatric patient, propofol was successfully used to treat the refractory SE.  It is an anesthetic agent that may be used to treat SE because it provides burst suppression through GABA inhibition.  Besides pentobarbital and propofol, midazolam can be given as constant IV infusion for refractory SE, or inhalation anesthetics can be used to achieve EEG burst-suppression.

 

Special Considerations in Pediatric Seizures and SE

 

In pediatric head trauma patients, it has been shown that patients with a GCS of 3-8 are at greatest risk for developing seizures.  Although long-term seizures are not prevented through the prophylactic use of AEDs such as phenytoin or valproate in these patients, the occurrence of early seizures (during the acute hospitalization) can be prevented with seizure prophylaxis.

 

As was stated previously, many of the seizure etiologies that cause seizures and SE in children and adolescents can be optimally treated long term with PO divalproex.  It is reasonable, therefore, to consider IV valproate as one of the initial therapies to be used when treating pediatric patients.  One specific seizure etiology that highlights this treatment guideline is juvenile myoclonic epilepsy (JME).   College students who are often sleep deprived and who have ingested alcohol, may present with an early morning generalized seizure.  These patients might have a history consistent with absence seizures as a child, but no specific work-up or seizure therapy.  In these patients, valproate is the optimal drug to be used if an ED load is required, since phenytoin can, in fact, worsen the symptoms of JME when it is used long term.  

 

 

Conclusions

 

Pediatric seizures and SE are neurologic emergencies that require prompt and effective treatment by emergency care providers.  Outcome can be enhanced for all of these patients by providing consistent care that follows a protocol, using effective drugs in adequate doses.  Future research will continue to establish how pediatric patient outcome can be improved through better use of current treatment modalities and the development of new therapies that can be effectively used in the emergency setting.

 

 

Emergency Drugs:  Pediatric Seizures and Status Epilepticus (SE)

 

 

Diazepam

 

            IV            0.1-0.2 mg/kg per dose            10 kg = 1-2 mg

            PR            0.5 mg/kg per dose             10 kg = 5 mg

 

Diazepam Rectal Gel

 

            PR            0.5 mg/kg per dose             10 kg = 5 mg

 

Lorazepam

 

            IV            0.05-0.1 mg/kg per dose     10 kg = 0.5-1 mg

 

Midazolam

 

            IV            0.05-0.1 mg/kg per dose     10 kg = 0.5-1 mg

            IM            0.08-0.2 mg/kg per dose     10 kg = 0.8-2 mg

            Buccal            0.2 mg/kg per dose             10 kg = 2 mg

 

Fosphenytoin

 

            IV            20 mg PE/kg x 1.5 doses   10 kg = 200 mg

                        Rate up to 2 mg/kg/min            10 kg = 20 mg/min (10 min load)

                        For each 1 mg/kg given, level goes up 1 microgr/ml

                        Therapeutic level = 10-20 microgr/ml

 

            IM            Same dose.  May be given in 1-4 IM injections.

 

Valproate

 

            IV            10-30 mg/kg                           10 kg = 100-300 mg

                        Rate up to 3-6 mg/kg/min  10 kg = 30-60 mg/min (5-10 min)

                        Maximum infusion rate = 300 mg/min

                        For each 1 mg/kg given, level goes up 5 microgr/ml

Therapeutic level = 50-150 microgr/ml         

 
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Pediatric Seizures and Status Epilepticus (SE): 
Epidemiology, Diagnosis and Management

Reference List

 

1.    Pashko S, McCord A, Sena MM. The cost of epilepsy and seizures in a cohort of Pennsylvania Medicaid patients.  Medical Interface 1993;Nov:79-84.

2.    DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG. Epidemiology of status epilepticus.  J Clin Neurophysiol 1995;12:316-325.

3.    DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia.  Neurology 1996;46:1029-1035.

4.    Gibbs M, Slovis C.M., Huff JS, et al. Seizures in Emergency Department Patients:  Multicenter Descriptive Study.  Ann Emerg Med 98 A.D.;32:S19-S20.

5.    Krumholz A, Grufferman S, Orr ST, Stern BJ. Seizures and seizure care in an emergency department.  Epilepsia 1989;30:175-181.

6.    Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s.  Neurology 1993;43:483-488.

7.    Lowenstein DH, Alldredge BK. Status epilepticus.  N Engl.J Med 1998;338:970-976.

8.    Working Group on Status Epilepticus. Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America’s Working Group on Status Epilepticus.  JAMA 1993;270:854-859.

9.    Kaplan PW. Nonconvulsive status epilepticus in the emergency room.  Epilepsia 1996;37:643-650.

10.DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus.  Epilepsia 1998;39:833-840.

11.Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group.  N Engl J Med 1998;339:792-798.

12.American College of Emergency Physicians. Clinical policy for the initial approach to patients presenting with a chief complaint of seizure, who are not in status epilepticus. American College of Emergency Physicians.  Ann Emerg Med 1993;22:875-883.

13.American College of Emergency Physicians, American Academy of Neurology, American Association of Neurological Surgeons, and American Society of Neuroradiology. Practice parameter: neuroimaging in the emergency patient presenting with seizure (summary statement). Ann Emerg Med 27, 114-118. 1996.

14.Appleton R, Sweeney A, Choonara I, Robson J, Molyneux E. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus.  Dev Med Child Neurol 1995;37:682-688.

15.Giroud M, Gras D, Escousse A, Dumas R, Venaud G. Use of injectable valproic acid in status epilepticus.  Drug Investigation 1993;5:154-159.

16.Leppik IE, Derivan AT, Homan RW, Walker J, Ramsay RE, Patrick B. Double-blind study of lorazepam and diazepam in status epilepticus.  JAMA 1983;249:1452-1454.

17.LeDuc TJ, Goellner WE, el-Sanadi N. Out-of-hospital midazolam for status epilepticus [letter].  Ann Emerg Med 1996;28:377-377.

18.Orebaugh SL, Bradford SM. Intravenous versus intramuscular midazolam in treatment of chemically induced generalized seizures in swine.  Am J Emerg Med 1994;12:284-287.

19.Raines A, Henderson TR, Swinyard EA, Dretchen KL. Comparison of midazolam and diazepam by the intramuscular route for the control of seizures in a mouse model of status epilepticus.  Epilepsia 1990;31:313-317.

20.Walsh-Kelly CM, Berens RJ, Glaeser PW, Losek JD. Intraosseous infusion of phenytoin.  Am J Emerg Med 1986;4:523-524.

21.Ramsay RE, DeToledo J. Intravenous administration of fosphenytoin: options for the management of seizures.  Neurology 1996;46:S17-9.

22.Jagoda A, Riggio S. Psychogenic convulsive seizures.  Am J Emerg Med 1993;11:626-632.

23.Walker IA, Slovis CM. Lidocaine in the treatment of status epilepticus.  Acad Emerg Med 1997;4:918-922.

24.Jagoda A, Riggio S. Refractory status epilepticus in adults [published erratum appears in Ann Emerg Med 1993 Nov;22(11):1771].  Ann Emerg Med 1993;22:1337-1348.

25.Borgeat A, Wilder-Smith OH, Jallon P, Suter PM. Propofol in the management of refractory status epilepticus: a case report [see comments].  Intensive Care Med 1994;20:148-149.

26.Kuisma M, Roine RO. Propofol in prehospital treatment of convulsive status epilepticus.  Epilepsia 1995;36:1241-1243.

27.Jagoda A, Riggio S. Psychogenic convulsive seizures.  Am J Emerg Med 1993;11:626-632.

28.Kumar A, Bleck TP. Intravenous midazolam for the treatment of refractory status epilepticus.  Crit.Care Med 1992;20:483-488.

29.Labar DR, Ali A, Root J. High-dose intravenous lorazepam for the treatment of refractory status epilepticus.  Neurology 1994;44:1400-1403.

30.Jagoda A, Riggio S. Emergency department approach to managing seizures in pregnancy [see comments].  Ann Emerg Med 1991;20:80-85.

31.Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial [published erratum appears in Lancet 1995 Jul 22;346(8969):258] [see comments].  Lancet 1995;345:1455-1463.

32.Arboix A, Comes E, Massons J, Garcia L, Oliveres M. Relevance of early seizures for in-hospital mortality in acute cerebrovascular disease.  Neurology 1996;47:1429-1435.

33.So EL, Annegers JF, Hauser WA, O’Brien PC, Whisnant JP. Population-based study of seizure disorders after cerebral infarction.  Neurology 1996;46:350-355.

34.Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures.  N Engl.J Med 1990;323:497-502.

35.Alldredge BK, Lowenstein DH. Status epilepticus related to alcohol abuse.  Epilepsia 1993;34:1033-1037.

36.D’Onofrio G. Lorazepam for the prevention of recurrent seizures related to alcohol.  N Engl J Med 1999;340:915-919.

37.Alldredge B, Gelb A, Isaacs M, et al. Evaluation of out-of-hospital therapy for status epilepticus.  AES Proceedings 1995;44-44.(abst)

38.Alehan FK, Morton LD, Pellock JM. Treatment of absence status with intravenous valproate.  Neurology 1999;52:889-890.

39.Fountain NB, Lothman EW. Pathophysiology of status epilepticus.  J Clin Neurophysiol 1995;12:326-342.

40.Lewis RJ, Yee L, Inkelis SH, Gilmore D. Clinical predictors of post-traumatic seizures in children with head trauma.  Ann Emerg Med 1993;22:1114-1118.

41.Parent JM, Lowenstein DH. Treatment of refractory generalized status epilepticus with continuous infusion of midazolam.  Neurology 1994;44:1837-1840.

42.Privitera MD, Strawsburg RH. Electroencephalographic monitoring in the emergency department.  Emerg Med Clin North Am 1994;12:1089-1100.

43.Towne AR, DeLorenzo RJ. Use of intramuscular midazolam for status epilepticus.  J Emerg Med 1999;17:323-328.

44.Treiman DM. Clinical trials for status epilepticus.  Adv Neurol 1998;76:173-178.

45.Wilder BJ, Campbell K, Ramsay RE, et al. Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery.  Arch Neurol 1996;53:764-768.


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Pediatric Seizures and Status Epilepticus (SE): 
Epidemiology, Diagnosis and Management

Annotated Bibliography

 

1.      Practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. American Academy of Pediatrics. Provisional Committee on Quality Improvement, Subcommittee on Febrile Seizures.  Pediatrics 1996;97:769-772.

This document outlines specific recommendations by the AAP regarding the treatment of simple febrile seizures.  Fortunately, it does not state that an LP is mandatory, but rather that it should be considered, especially in the youngest children (< 1year old).

2.      Cereghino JJ, Mitchell WG, Murphy J, Kriel RL, Rosenfeld WE, Trevathan E: Treating repetitive seizures with a rectal diazepam formulation: a randomized study. The North American Diastat Study Group.  Neurology 1998;51:1274-1282.

This study documented the efficacy of rectal diazepam gel as a means of treating seizures in the out of hospital setting and reducing the need for ED visits in patients with repetitive seizures.

3.          Chiulli DA, Terndrup TE, Kanter RK: The influence of diazepam or lorazepam on the frequency of endotracheal intubation in childhood status epilepticus [see comments].  J Emerg Med 1991;9:13-17.

This study documents that intubation rates are higher in children when diazepam is used to treat SE, as compared to lorazepam.  This data confirms the use of lorazepam in the treatment of seizures and SE in children.

4.      Green SM, Rothrock SG, Clem KJ, Zurcher RF, Mellick L: Can seizures be the sole manifestation of meningitis in febrile children?  Pediatrics 1993;92:527-534.

This study found that a simple febrile seizure never is the sole manifestation of meningitis in children.  All of the children with meningitis had either other focal neurologic  findings or altered mental status.  We therefore do not need to do an LP to rule out meningitis in children with simple febrile seizures.

5.      Harrison AM, Lugo RA, Schunk JE: Treatment of convulsive status epilepticus with propofol: case report [see comments].  Pediatr.Emerg.Care 1997;13:420-422.

This case report documents the use of propofol in the treatment of refractory SE in a child.  It is one option to consider in children with SE refractory to our main therapies, benzodiazepines, phenytoins, phenobarbital, and valproate.

6.      Hauser WA: The prevalence and incidence of convulsive disorders in children.  Epilepsia 1994;35 Suppl 2:S1-6.

This is a good epidemiologic study from an expert in this field.  The incidence of epilepsy is about 50 to 100 per 100,000.

7.      Holmes GL, Riviello JJJ: Midazolam and pentobarbital for refractory status epilepticus [published erratum appears in Pediatr Neurol 1999 Jul;21(1):511].  Pediatr.Neurol. 1999;20:259-264.

This article outlines the use of midazolam and pentobarbital in the treatment of refractory SE in children.

8.      Lacroix J, Deal C, Gauthier M, Rousseau E, Farrell CA: Admissions to a pediatric intensive care unit for status epilepticus: a 10-year experience.  Crit.Care Med 1994;22:827-832.

This is a case series of pediatric ICU admits for SE in Montreal, Canada.  The most common cause of SE was Epilepsy was the most common cause of the SE episodes, and the mortality rate was 6%.

9.      Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M: Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study [see comments].  BMJ.2000.Jul.8.;321.(7253.):83.-6. 321:83-86.

This is a randomized study that demonstrates that intranasal midazolam at 0.2 mg/kg is as effective as IV diazepam in the treatment of children with prolonged febrile seizures.

10.    Lewis RJ, Yee L, Inkelis SH, Gilmore D: Clinical predictors of post-traumatic seizures in children with head trauma.  Ann Emerg Med 1993;22:1114-1118.

In the pediatric head trauma patient, a GSC score of 3 to 8 is predictive of post-traumatic seizures.  These patients, therefore, could be prophylaxed with phenytoin (or valproate) in order to reduce the incidence of acute seizures.

11.    Maytal J, Krauss JM, Novak G, Nagelberg J, Patel M: The role of brain computed tomography in evaluating children with new onset of seizures in the emergency department.  Epilepsia 2000.Aug.;41.(8.):950.-4. 41:950-954.

This study looked at children with first time seizures in the ED, excluding simple febrile seizures.  Children with an acute symptomatic cause or a focal siezure had up to a 21% positive CT rate.  In contrast, no children with complex febrile seizures, a normal neuro exam, or the lack of an acute cause had a positive CT.  This data suggests that we can defer a CT in children with uncomplicated first time generalized seizures if an acute cause is excluded, there is a normal neurologic exam, and there is appropriate follow-up.

 

12.        Maytal J, Shinnar S: Febrile status epilepticus [see comments].  Pediatrics 1990;86:611-616.

         In this study, 44 children with febrile seizures lasting more than 30 minutes were followed for two years.  In children with a normal CNS prior to the episode of febrile SE, the risk of a subsequent febrile or afebrile seizure was no greater at two years than in children with simple febrile seizures.

13.    Nypaver MM, Reynolds SL, Tanz RR, Davis AT: Emergency department laboratory evaluation of children with seizures: dogma or dilemma?  Pediatr Emerg Care 1992;8:13-16.

This study looked at lab testing in 308 children with febrile or afebrile seizures in the ED.  Very few laboratory abnormalities that changed therapy were noted, such that  the authors conclude that routine testing for serum chemistry, calcium, and magnesium is not mandatory.

14.    Scott RC, Besag FM, Neville BG: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial.  Lancet 1999;353:623-626.

This study compared buccal midazolam with rectal diazepam, As with the study in reference 9, this randomized trial again showed that midazolam delivered through a non-IV route is as effective in the treatment of prolonged seizures in the pediatric population as is rectal diazepam.

15.    Shinnar S, Berg AT, Moshe SL, et al: Risk of seizure recurrence following a first unprovoked seizure in childhood: a prospective study.  Pediatrics 1990;85:1076-1085.

This study followed 283 children who had a first unprovoked seizure.  A subsequent seizure was noted in 36% of these children.  The recurrence rate was lowest in children with an idiopathic first and a normal EEG.  This data suggests that in the ED, a child with an uncomplicated first seizure may not require long term AED therapy, and should be referred to a neurologist for an EEG prior to initiating this therapy. 

16.    Venkataraman V, Wheless JW: Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients.  Epilepsy Res. 1999;35:147-153.

This study documents the use of IV valproate in dosed up to 28 mg/kg at rates up to 6 mg/kg/minute in epilepsy patients as young as 2 years of age. The most rapid infusion rate in this study was 300 mg/minute.  There were no BP or ECG changes noted in any of these patients.

17.   White JR, Santos CS: Intravenous valproate associated with significant hypotension in the treatment of status epilepticus.  J.Child Neurol. 1999;14:822-823.

This is a single case report that documents hypotension during an infusion of valproate at a rate of 0.5 mg/kg/min.  The hypertension resolved with IV fluids and pressors without complication, and the patient improved clinically.  This report confirms the need to be careful with all drugs, even when large case series document safe use.  

18.    Working Group on Status Epilepticus.: Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus.  JAMA 1993;270:854-859.

If you can only read one article on SE, this might be the one.  Although it is a bit dated and doesn’t deal specifically with pediatric patients, it very well reinforced the need to have a clear treatment plan for SE, and to use your chosen drugs rapidly and in adequate mg/kg doses.

 

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Pediatric Seizures and Status Epilepticus (SE): 
Epidemiology, Diagnosis and Management

Questions

 

1.)    A seven year-old boy presents to the ED with a history of staring spells, some shaking movements, and headache over the past day.  He has no history of seizures or epilepsy.  In the ED, he has three episodes of tachycardia, staring and confusion that last several minutes and resolve without therapy.  He then has a similar episode associated with diaphoresis and urinary incontinence.  His most likely diagnosis is:  

 

a.  Absence status epilepticus.

b.  Complex partial status epilepticus.

c.  Benign childhood epilepsy.

d.  Lennox-Gastaut syndrome.

e.  Generalized convulsive status epilepticus.

 

2.)     Assuming that the above episodes in the seven year-old represent repeated seizures, all of the following are acceptable initial therapies except:

 

a.       Rectal diazepam

b.      Rectal diazepam gel

c.       IM midazolam

d.      IV lorazepam

e.       IV phenobarbital

 

3.)     A 13 year old female presents at mid-morning to the ED with a one day history of a frontal headache, consistent with prior migraines, that was relieved with ibuprofen.  She also was noted by family members to be restless in bed, and was noted to “thrash about” for a brief period of time.  The family denied that this was a generalized seizure, and denied any history of epilepsy, trauma, drug ingestions, or similar episodes.  The patient has a similar episode in the ED, and then has a generalized seizure.  The most likely diagnosis is:

 

a.  Primary generalized seizure.

b.  Absence seizure.

c.  Complex partial seizure with secondary generalization.

d.  Juvenile myoclonic epilepsy.

e.  Non-convulsive status epilepticus.

 

  

4.)    A 21 year old male college student presents in the early morning to the ED with a one day history of having a generalized seizure upon awakening.  The patient had been partying after final exams, and had not been getting much sleep for several days.  Over the phone, his mom noted that he had a history of “staring spells” as a child.  The most likely diagnosis is:

 

a.  Secondarily generalized seizure.

b.  Absence seizure.

c.  Complex partial seizure with secondary generalization.

d.  Juvenile myoclonic epilepsy.

e.  Non-convulsive status epilepticus.

 

5.)     The above 21 year-old patient had two seizures in the ED which were controlled with lorazepam.  If a load of a longer acting AED was to be given in the ED in order to prevent status epilepticus, what would be the optimal drug to administer?

 

a.  IV midazolam.

b.  IV phenytoin.

c.  IV fosphenytoin.

d.  IV valproate.

e.  IV phenobarbital.

 

6.)   What is the optimal loading dose of IV valproate in patients at risk for SE?

 

a.  1-5 mg/kg.

b.      10-15 mg/kg.

c.       20-30 mg/kg.

d.      90-100 mg/kg.

 

7.)     If an IV valproate load of 25 mg/kg were given to this patient, what would be the expected valproate level be once the infusion had ended :

a.       25 mg/L

b.      50 mg/L

c.       75 mg/L

d.      100 mg/L

e.       125 mg/L

 

  

8.)     If this patient were to develop status epilepticus, what is the fastest time of infusion possible for a loading valproate infusion of 2500 mg (25 mg/kg x 100 kg)?

 

a.   4 minutes (6 mg/kg/minute).

b.   8 minutes (3 mg/kg/minute).

c.       24 minutes (1 mg/kg/minute).

d.      72 minutes (0.3 mg/kg/minute).

e.   216 minutes (0.1 mg/kg/minute).

 


Answers

 

1.)        b.         In this patient, the repeated several minute episodes that came in a flurry and were are associated with altered mental status and autonomic symptoms are consistent with complex partial status epilepticus.

 

2.)        e.         The benzodiazepines are the optimal drugs to be utilized to terminate complex partial status epilepticus.

 

3.)        c.         In this patient, the altered mental status episode that is followed by a generalized seizure is consistent with a complex partial seizure with secondary generalization.

 

4.)       d.          In this patient, the clinical presentation and history are consistent with the diagnosis of juvenile myoclonic epilepsy.

 

5.)       d.          IV valproate would be the drug of choice for an acute load, given that it is the drug of choice for the treatment of JME.  Phenytoin, in fact, often worsens the ongoing symptoms in patients with JME.

 

6.)       c.          Many epileptologists recommend loading valproate at 20-30 mg/kg, in order to quickly obtain a therapeutic level above 100 mg/L.

 

7.)       e.          The level of valproate sodium is expected to rise 5 mg/L for each 1 mg/kg of the valproate load, giving a level in this patient of 125 mg/L.

 

8.)       b.          Although loading rates as fast as 6 mg/kg/minute have been reported, the maximum rate of infusion ever reported is 300 mg/min, such that this infusion would take approximately 8 minutes.  The use of this most rapid rate would be reasonable only for use for patients in or at significant risk for status epilepticus.

 

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