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Status Epilepticus

Status epilepticus (SE) is defined as an medical emergency associated with significant morbidity and mortality and is presented as a continuous seizure lasting more than 5 minutes, or two or more seizures without full recovery of consciousness between any of them.[1] Seizure lasting longer than 30 minutes may increase the risk of long-term damage, such as more brain damage. Aggressive treatment is strongly recommended. SE is classified into two main categories - generalized convulsive and non-convulsive. Generalized convulsive status epilepticus (GCSE) is the most common and severe form. GCSE is characterized by repeated primary or secondary generalized seizures that involve both hemispheres of the brain, which results in loss consciousness.[2] Non-convulsive status epilepticus (NCSE) is characterized by continuous "epilepticus twilight" state that produces altered consciousness and/or behavior, such as lethargy and decreased mental function.

Diagnosis

Observation, physical examination, laboratory assessment, electroencephalogram (EEG), and neurologic imaging are required for accurate diagnosis. EEG is the most important diagnostic and management tool; however, therapy should not be delayed while waiting for testing or results.[3] The diagnosis of SE must be made after the physician has observed the seizure. Clinical presentation of SE ranges from altered consciousness, ranging from lethargy to somnolence with pronounces eyes-opening unresponsiveness and waxy rigidity. The patient should be assessed for language and cognitive abilities, and the physical and neurological examinations (motor, sensory, and reflex abnormalities, pupillary response, asymmetry, and posturing). The patient should also be examined for secondary injuries (eg, tongue lacerations, shoulder dislocations, and head and facial trauma).[4] Hypoglycemia, hyponatremia, hypernatremia, hypomagnesemia, hypocalcemia, and renal failure all can cause seizures, and so assessment of baseline serum concentration and laboratory parameters such as hematology and chemistries (albumin, renal function, and hepatic function) may be useful.

Treatment

Benzodiazepines – (C-IV) IV Fosphenytoin (Cerebrex) Valproic Acid (Depakene, Depacon) Levetiracetam (Keppra) Phenobarbital – (C-IV)
  • IV Lorazepam (Ativan), IM Midazolam (Versed), Rectal Diazepam (Diastat)
  • MOA: Increases GABA
  • Boxed Warning: Concurrent use with opioids profound sedation, respiratory depression and death
  • Warnings: Serious skin reactions (SJS/TEN), hyperactive or aggressive behavior, anterograde amnesia
  • May cause physiological dependence, tolerance, drooling, pyrexia
  • Others: Clobazam (Onfi, Sympazan)
  • Prodrug of Phenytoin (Dilantin, Phenytek)
  • Others: Phenytoin (Dilantin, Phenytek)
  • MOA: Na Channel Blocker
  • Strong inducers CYP2B6, 2C19, 2C8/9, 3A4, P-gp, and UGT1A1
  • Boxed Warning: Fosphenytoin IV administration rate should not exceed 150 mg PE/minute (if given faster, cardiac arrhythmias can occur)
  • Warnings: Extravasation (Purple Glove Syndrome), avoid in patients with positive HLA-B*1502, fetal harm
  • Side Effects:
  1. Dose related: Nystagmus, Ataxia, Diplopia
  2. Chronic: Gingival hyperplasia, hair growth, hepatotoxicity
  3. Monitor: BP, LFTs, IV – cardiac and respiratory monitoring
  • Drug Interactions: Strong inducers of CYP2B6, 2C19, 2C8/9, 3A4, P-gp, and UGT1A1
  • IV:PO ratio 1:1/ use of a non-hormonal contraceptive is recommended
  • Therapeutic Range: 10-20 mcg/mL (total level), 1-2.5 mcg/mL (free level)
  • Others: Divalproex (Depakote)
  • MOA: Increases GABA
  • Boxed Warnings: Hepatic failure, fetal harm (neural tube defects and decrease IQ scores)
  • Warnings: Hyperammonemia (treat with Carnitine), dose-related thrombocytopenia
  • Side Effects: Alopecia, weight gain
  • Monitoring: LFTs, Platelets
  • Therapeutic Range: 50-100 mcg/mL
  • Drug interaction: Lamotrigine (risk of serious rash)
  • Also used for bipolar and migraine prophylaxis
  • MOA: Increase GABA and Ca channel blocker
  • Warnings: Psychiatric reactions, including psychotic symptoms, somnolence, fatigue
  • Warnings: Hyperammonemia (treat with Carnitine), dose-related thrombocytopenia
  • Side Effects: Alopecia, weight gain
  • Monitoring: LFTs, Platelets
  • No significant drug interactions
  • IV:PO ratio 1:1
  • Max: 3,000 mg/day
  • CrCL <80 mL/min – lower dose
  • MOA: Enhance/potentiate GABA effect
  • Warnings: Habit forming, respiratory depression, fetal harm
  • Side Effects: physiological dependence, tolerance, hangover effect
  • Monitoring: LFTs, CBC with diff.
  • Drug Interactions: Strong inducers of CYP1A2, 2C8/9, 3A4, and P-gp/ use of a non-hormonal contraceptive is recommended
  • Therapeutic Range: 20-40 mcg/mL (adults), 15-40 mcg/mL (children)
  1. ^ Cherian, Ajith; Thomas, Sanjeev V. (2009). "Status epilepticus". Annals of Indian Academy of Neurology. pp. 140–153. doi:10.4103/0972-2327.56312.{{cite web}}: CS1 maint: unflagged free DOI (link)
  2. ^ Alford, Elizabeth L.; Wheless, James W.; Phelps, Stephanie J. (July 2015). "Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients". The journal of pediatric pharmacology and therapeutics: JPPT: the official journal of PPAG. pp. 260–289. doi:10.5863/1551-6776-20.4.260.
  3. ^ Chang, Andrew K.; Shinnar, Shlomo (February 2011). "Nonconvulsive status epilepticus". Emergency Medicine Clinics of North America. pp. 65–72. doi:10.1016/j.emc.2010.08.006.
  4. ^ Phelps, Stephanie; Wheless, James. "Status Epilepticus". accesspharmacy.mhmedical.com. DiPiro.