Status epilepticus

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Status epilepticus
Classification and external resources
ICD-10 G41
ICD-9 345.3
eMedicine emerg/554 article/908394
MeSH D013226

Status epilepticus (SE) is an epileptic seizure of greater than five minutes or more than one seizure within a five minute period without the person returning to normal between them. The seizures can either be of the tonic-clonic type with a regular pattern of contraction and extension of the arms and legs or of types that do not involved contractions such as absence seizures or complex partial seizures. Status epilepticus is a life-threatening condition particularly if treatment is delayed.[1]

Status epilepticus may occur in those with a history of epilepsy as well as those with an underlying problem of the brain.[2] These underlying brain problems may include trauma, infections, or strokes among others.[2] Diagnosis often involves checking the blood sugar, imaging of the head, a number of blood tests, and an electroencephalogram. Psychogenic nonepileptic seizures may present similarly. Other conditions that may also appear to be SE include: hypoglycemia, movement disorders, meningitis, and delirium among others.[1]

Benzodiazepines are the preferred initial treatment after which typically phenytoin is given.[1] Possible benzodiazepines include intravenous lorazepam as well as intramuscular injects of midazolam.[3] A number of other medications may be used if these are not effective such as valproic acid, phenobarbital, propofol or ketamine. Intubation may be required to help maintain the persons airway. Between 10 to 30% of people who have status epilepticus are dead within 30 days.[1] The underlying cause, the persons age, and the length of the seizure are important factors in the outcome.[2] Status epilepticus occurs in about 40 per 100,000 people per year[2] making up about 1% of people who visit the emergency department.[1]

Signs and symptoms[edit]

Status epilepticus can be divided into two categories—convulsive and nonconvulsive (NCSE).[1]

Convulsive[edit]

Convulsive status epileptics presents with a regular pattern of contraction and extension of the arms and legs.[1]

Epilepsia partialis continua is a variant involving hour-, day-, or even week-long jerking. It is a consequence of vascular disease, tumours, or encephalitis, and is drug-resistant.

Generalized myoclonus is commonly seen in comatose people following CPR and is seen by some as an indication of catastrophic damage to the neocortex.[4]

Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the reduction or withdrawal of anaesthesia.[5]

Nonconvulsive[edit]

Nonconvulsive status epileptics is a relatively long duration change in a person level of consciousness without large scale bending and extension of the limbs due seizure activity.[6] It is of two main types with either prolonged complex partial seizures or absence seizures.[6] Up to a quarter of cases of SE are nonconvulsive.[6]

In the case of complex partial status epilepticus, the seizure is confined to a small area of the brain, normally the temporal lobe. But the latter, absence status epilepticus, is marked by a generalised seizure affecting the whole brain, and an EEG is needed to differentiate between the two conditions. This results in episodes characterized by a long-lasting stupor, staring, and unresponsiveness.

Causes[edit]

Only 25% of people who experience seizures or status epilepticus have epilepsy.[7] Causes include:

  • Stroke[7]
  • Hemorrhage[7]
  • Intoxicants[7] or adverse reactions to drugs
  • Insufficient dosage of a medication already prescribed to the person, such causes of this include:
    • Forgetfulness on the part of the person in taking scheduled doses, or failure to take doses at the scheduled times
    • Taking medicine at wrong times as a result of a time zone change while traveling
    • Dislike of the medication or its side effects
  • Sudden withdrawal from a seizure medication, such causes include:
    • Sudden lack of access to medication due to unexpected circumstances
    • Benzodiazepine withdrawal syndrome resulting from inability to acquire non-prescribed benzodiazepines that were used being abused.[8]
    • Lack of ability of person to communicate medication needs to others, leading to absence of doses
    • Physician's decision to discontinue medication
  • Consumption of alcoholic beverages while on an anticonvulsant, or alcohol withdrawal
  • Dieting or fasting while on an anticonvulsant
  • Starting on a new medication that reduces the effectiveness of the anticonvulsant or changes drug metabolism, decreasing its half-life, leading to decreased blood concentrations
  • Developing a resistance to an anticonvulsant already being used
  • Gastroenteritis while on an anticonvulsant, because the digestive system may force out the anticonvulsant, thereby rendering the body with a lack of protection
  • Developing a new, unrelated condition in which seizures are coincidentally also a symptom, but are not controlled by an anticonvulsant already used
  • Metabolic disturbances—such as affected kidney and liver[7]
  • Sleep deprivation of more than a short duration is often the cause of a (usually, but not always, temporary) loss of seizure control; those whose seizures are inherently severe but otherwise controlled by medication can regress and have severe seizures or status epilepticus even if they are still taking their medication unless they regain their rest.

Diagnosis[edit]

Definitions vary, but currently it is defined as one continuous, unremitting seizure lasting longer than five minutes,[9] or recurrent seizures without regaining consciousness between seizures for greater than five minutes. Previous definitions used a 30-minute time limit.[2]

NCSE is believed to be under-diagnosed.[10]

Treatments[edit]

Diazepam that can be inserted rectally is often prescribed to caregivers of people with epilepsy. This enables treatment of multiple seizures prior to being able to seek medical care.

Benzodiazepines are the preferred initial treatment after which typically phenytoin is given.[1] First aid guidelines for seizures state that, as a rule, an ambulance should be called for seizures lasting longer than five minutes (or sooner if this is the person's first seizure episode and no precipitating factors are known, or if SE happens to a person with epilepsy whose seizures were previously absent or well controlled for a considerable time period).

Benzodiazepines[edit]

When given intravenous, lorazepam appears to be superior to diazepam for stopping the seizure.[3] Intramuscular midazolam appears to be a reasonable option especially in those who are not in hospital.[3]

The benzodiazepine of choice in North America for initial treatment is lorazepam due to its relatively long (2–8 hr) duration of action when injected, and its rapid onset of action, which is thought to be due to its high affinity for GABA receptors and to its low lipid solubility, which causes it to remain in the vascular compartment. If lorazepam is not available, or intravenous access is not possible, then diazepam should be given.[11] In several countries outside North America, intravenous clonazepam is regarded as the drug of first choice. For instance, the Acute Boekje, a guideline for the assessment and treatment of medical emergencies used in the Netherlands, recommends clonazepam.[12] Cited advantages of clonazepam include a longer duration of action than diazepam and a lower propensity for the development of acute tolerance than lorazepam.[13] The use of clonazepam for this indication has not caught on in North America, as it is not available as an intravenous formulation there.[13]

Particularly in children, another popular treatment choice is midazolam, given into the side of the mouth or the nose.[14] Sometimes, the failure of lorazepam alone is considered to be enough to classify a case of SE as resistant to treatment.

Phenytoin and fosphenytoin[edit]

Phenytoin was once another first-line therapy,[15] although the prodrug fosphenytoin can be administered three times as fast and with far fewer injection site reactions. If these or any other hydantoin derivatives are used, then cardiac monitoring is a must if they are administered intravenously. Because the hydantoins take 15–30 minutes to work, a benzodiazepine or barbiturate is often coadministered. Because of diazepam's short duration of action, they were often administered together anyway.

Carbamazepine and valproate[edit]

Valproate is available to be given intravenously, and may be used for status epilepticus. Carbamazepine is not available in an intravenous formulation, and does not play a role in status epilepticus.[15]

Barbiturates[edit]

Before the benzodiazepines were invented, there were the barbiturates, which are still used today if benzodiazepines or the hydantoins are not an option. These are used to induce a barbituric coma. The barbiturate most commonly used for this is phenobarbital. Thiopental or pentobarbital may also be used for that purpose if the seizures have to be stopped immediately or if the person has already been compromised by the underlying illness or toxic/metabolic-induced seizures; however, in those situations, thiopental is the agent of choice.

The failure of phenobarbital therapy does not preclude the success of a lengthy comatose state induced by a stronger barbiturate such as secobarbital. Such was the case for Ohori, Fujioka, and Ohta, circa 1998, when they induced a ten-month long coma (or "anesthesia" as they called it) in a 26-year-old woman suffering from refractory status epilepticus secondary to viral encephalitis, and then tapered her off the secobarbital very slowly while using zonisamide at the same time.[16]

Others[edit]

If this proves ineffective or if barbiturates cannot be used for some reason, then a general anesthetic such as propofol[17] maybe tried; sometimes it is used second after the failure of lorazepam.[18] This also means putting the people on artificial ventilation. Propofol has been shown to be effective in suppressing the jerks seen in myoclonus status epilepticus, but as of 2002, there have been no cases of anyone going into myoclonus status epilepticus, undergoing propofol treatment, and then not dying anyway.[19]

Ketamine, an NMDA antagonist drug, can be used as a last resort for drug-resistant status epilepticus.[20]

Lidocaine has been used in cases that do not improve with other more typical medications.[21] One concerns is that seizures often begin again 30 minutes after it is stopped.[21] Additionally it is not recommended in those with heart problems or liver problems.[21]

Prognosis[edit]

Between 10 to 30% of people who have status epilepticus are dead within 30 days.[1] The great majority of these people have an underlying brain condition causing their status seizure such as brain tumor, brain infection, brain trauma or stroke. However, people with diagnosed epilepsy who have a status seizure also have an increased risk of death if their condition is not stabilized quickly, their medication and sleep regimen adapted and adhered to, and stress and other stimulant (seizure trigger) levels controlled. However, with optimal neurological care, adherence to the medication regimen, and a good prognosis (no other underlying uncontrolled brain or other organic disease), the person—even people who have been diagnosed with epilepsy—in otherwise good health can survive with minimal or no brain damage, and can decrease their risk of death and even avoid future seizures.[7]

Epidemiology[edit]

In the United States, about 40 cases of SE occur annually per 100,000 people.[2] This includes about 10-20% of all first seizures.

History[edit]

Shortly after it was introduced in 1963, diazepam became the first choice for SE. Even though other benzodiazepines such as clonazepam were useful, diazepam was relied upon almost exclusively. This began to change in 1975 with a preliminary study on lorazepam conducted by Waltregny and Dargent, who found its pharmacological effects were longer lasting than those of an equal dose of diazepam.[22] This meant it did not have to be repeatedly injected like diazepam,[23] the effects of which would wear off five to 15 minutes later in spite of its 30-hour half-life (due to extensive redistribution of diazepam outside the vascular compartment, as diazepam is highly lipid soluble).

References[edit]

  1. ^ a b c d e f g h i Al-Mufti, F; Claassen, J (Oct 2014). "Neurocritical Care: Status Epilepticus Review.". Critical care clinics 30 (4): 751–764. PMID 25257739. 
  2. ^ a b c d e f Trinka, E; Höfler, J; Zerbs, A (September 2012). "Causes of status epilepticus.". Epilepsia. 53 Suppl 4: 127–38. doi:10.1111/j.1528-1167.2012.03622.x. PMID 22946730. 
  3. ^ a b c Prasad, M; Krishnan, PR; Sequeira, R; Al-Roomi, K (Sep 10, 2014). "Anticonvulsant therapy for status epilepticus.". The Cochrane database of systematic reviews 9: CD003723. PMID 25207925. 
  4. ^ Wijdicks, Eelco F. M.; Parisi, J. E.; Sharbrough, F. W. (February 1994). "Prognostic value of myoclonus status in comatose survivors of cardiac arrest". Annals of Neurology 35 (2): 239–43. doi:10.1002/ana.410350219. PMID 8109907. 
  5. ^ A Critical Review of Available Therapies and a Clinical Treatment Protocol,Simon Shorvon, Monica Ferlisi:Brain. 2011;134(10):2802-2818.
  6. ^ a b c Chang, AK; Shinnar, S (Feb 2011). "Nonconvulsive status epilepticus.". Emergency medicine clinics of North America 29 (1): 65–72. PMID 21109103. 
  7. ^ a b c d e f Stasiukyniene, V.; Pilvinis, V.; Reingardiene, D.; Janauskaite, L. (2009). "[Epileptic seizures in critically ill patients]". Medicina (Kaunas) 45 (6): 501–7. PMID 19605972. 
  8. ^ Evans, Katie; Sullivan, Michael J. (1 March 2001). Dual Diagnosis: Counseling the Mentally Ill Substance Abuser (2nd ed.). Guilford Press. p. 52. ISBN 978-1-57230-446-8. 
  9. ^ Nair, PP; Kalita, J.; Misra, U. K. (Jul–Sep 2011). "Status epilepticus: why, what, and how". Journal of Postgraduate Medicine 57 (3): 242–52. doi:10.4103/0022-3859.81807. PMID 21941070. 
  10. ^ Rubin, Diana; Stephan, Ruegg; Stephan, Marsch; Christian, Schindler; Leticia, Grize; Raoul, Sutter (August 24, 2011). "High prevalence of nonconvulsive and subtle status epilepticus in an ICU of a tertiary care center: A three-year observational cohort study". Epilepsy Research j.eplepsyres.2011.05.018 96 (1): 140–150. 
  11. ^ Pang, Trudy; Lawrence J. Hirsch (July 2005). "Treatment of Convulsive and Nonconvulsive Status Epilepticus". Current Treatment Options in Neurology 7 (4): 247–259. doi:10.1007/s11940-005-0035-x. PMID 15967088. 
  12. ^ "22.8 Convulsieve status epilepticus". Acute Boekje (in Dutch) (4th ed.). Van Zuiden Communications B.V. 2009. p. 276. ISBN 978-90-8523-197-4. 
  13. ^ a b Lawn, Nicholas D; Wijdicks, Eelco FM (2002). "Status epilepticus: A critical review of management options". Neurol J Southeast Asia 7: 47–59. 
  14. ^ Walker, D. M.; Teach, S. J. (June 2006). "Update on the acute management of status epilepticus in children.". Curr Opin Pediatr 18 (3): 239–44. doi:10.1097/01.mop.0000193306.55635.24. PMID 16721142. 
  15. ^ a b Beran, RG. (April 2008). "An alternative perspective on the management of status epilepticus". Epilepsy Behav 12 (3): 349–53. doi:10.1016/j.yebeh.2007.12.013. PMID 18262847. 
  16. ^ Ohori, Nobuhira; Fujioka, Y; Ohta, M. (May 1998). "Experience in managing refractory status epilepticus caused by viral encephalitis under long-term anesthesia with barbiturate: a case report". Rinsho Shinkeigaku (in Japanese) 38 (5): 474–7. PMID 9806000. 
  17. ^ Pourrat, X; J .M. Serekian, D. Antier, J. Grassin (June 9, 2001). "Generalized tonic-clonic status epilepticus: therapeutic strategy". Presse Médicale 30 (20): 1031–6. PMID 11433696.  (French).
  18. ^ Marik, Paul E.; Joseph Varon (2004). "The management of status epilepticus". Chest 126 (2): 582–91. doi:10.1378/chest.126.2.582. PMID 15302747. 
  19. ^ Wijdicks, Eelco F. M. (July 2002). "Propofol in myoclonus status epilepticus in comatose patients following cardiac resuscitation". Journal of Neurology Neurosurgery and Psychiatry 73 (1): 94–5. doi:10.1136/jnnp.73.1.94. PMC 1757284. PMID 12082068. 
  20. ^ van Rijckevorsel, K.; Boon, P.; Hauman, H.; Legros, B.; Ossemanns, M.; Sadzot, B.; Schmedding, E.; van Zandijcke, M. (September 2005). "Standards of care for adults with convulsive status epilepticus: Belgian consensus recommendations". Acta Neurol Belg 105 (3): 111–8. PMID 16255149. 
  21. ^ a b c Schmutzhard, E; Pfausler, B (Oct 2011). "Complications of the management of status epilepticus in the intensive care unit.". Epilepsia. 52 Suppl 8: 39–41. PMID 21967359. 
  22. ^ Waltregny, Alain; Jérôme Dargent (September–October 1975). "Preliminary study of parenteral lorazepam in status epilepticus". Acta Neurologica Belgica 75 (5): 219–29. PMID 3939. 
  23. ^ Walker, JE; RW Homan; MR Vasko; IL Crawford; RD Bell; WG Tasker (September 1979). "Lorazepam in status epilepticus". Annals of Neurology 6 (3): 207–13. doi:10.1002/ana.410060305. PMID 43112. 

External links[edit]