Definition

Status epilepticus is defined as 5 min of continuous seizures, or two seizures without regaining consciousness in between for more than 5 min.

Common etiologies

See Table 15.1 .

Management

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  Treatment algorithm ( Fig. 15.1 )

  
  

  
  

  
  

  

  
  

  
  

  Treatment Algorithm for Status Epilepticus by 2016 American Epilepsy Society Guidelines.

  
  

  ECG, Electrocardiogram; EEG, Electroencephalography; IV, Intravenous Level A, Established as effective; Level B, Probably effective; Level U, Data inadequate or insufficient.

  
  

  From Glauser T, Shinnar S, Gloss D, Arya R, Bainbridge J, Bare M, Bleck T, Dodson WE, Garrity L, Jagoda A, Lowenstein D, Pellock J, Riviello J, Sloan E, Treiman DM. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society. Epilepsy Currents. 2016;16(1):48-61.

  
  

  
  

  

  
  
  
  
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  Pharmacotherapy ( Table 15.2 )

  
  
  
  

  Table 15.2

  
  

  Drug Regimens for Generalized Status Epilepticus

  
  

  Adapted from Brophy GM, Bell R, Claassen J, et al.; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care . 2012;17(1):3–23; Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society. Epilepsy Currents . 2016;16(1):48–61.

  
  

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

  DRUG	USUAL DOSE	PD/PK	METABOLISM	COMMENTS
  First-Line Therapy (Emergency): Benzodiazepine
  Lorazepam	0.1 mg/kg IV (up to 4 mg/dose), MR in 5–10 min NTE: 2 mg/min	Onset: 10 min Duration: 6–8 h Half-life: 14 h	Hepatic	IV formulation contains propylene glycol ADR: sedation, hypotension, respiratory depression
  Midazolam	0.2 mg/kg IM up to 10 mg/dose	Onset: 15 min Duration: up to 6 h Half-life: 3 h	Hepatic; active metabolite	Short duration with IV ADR: sedation, hypotension, respiratory depression
  Diazepam	0.15 mg/kg IV up to 10 mg/dose, MR in 5 min NTE: 5 mg/min If IV not available, 0.2–0.5 mg/kg PR up to 20 mg/dose	Onset: IV: 1–3 min PR: 2–10 min Duration: 15–30 min Half-life: IV: parent 33–45 h; desmethyl-diazepam: 100 h PR: parent 45–46 h; desmethyl-diazepam: 71–99 h	Hepatic Active metabolites: N-desmethyl-diazepam, temazepam, and oxazepam	IV formulation contains propylene glycol Not recommended as first-line therapy due to short duration of seizure control ADR: sedation, hypotension, respiratory depression
  Second-Line Therapy (Urgent): Initiate After Benzodiazepine if Seizures Persist or if a Maintenance Needed
  Valproate	20–40 mg/kg IV, up to 3000 mg/dose	Time to peak: at the end of 1 h infusion Half-life: 9–19 h	Hepatic	Therapeutic level: 50–100 mcg/mL
  Phenytoin	20 mg/kg IV, may give additional 5 mg/kg 10 min after LD NTE: 50 mg/min	Onset: 0.5–1 h Half-life: 7–42 h	Dose-dependent (Michaelis-Menten) PK	Enzyme inducer; several DDIs IV formulation contains propylene glycol and ethanol ADR: hypotension, arrhythmia, phlebitis, purple glove syndrome, hepatotoxicity Only compatible in saline
  Fosphenytoin	20 PE mg/kg IV, may give additional 5 mg/kg 10 min after LD Max: 1500 mg PE/dose NTE: 150 mg/min May also give IM	Time to peak: 15 min Half-life: Fosphenytoin: 15 min Phenytoin: 12–29 h	Hepatic; fosphenytoin is rapidly converted to phenytoin via hydrolysis	Enzyme inducer; several DDIs ADR: hypotension, arrhythmia, hepatotoxicity
  Phenobarbital	20 mg/kg IV, may give additional 5–10 mg/kg 10 min after LD NTE: 100 mg/min	Onset: 5 min Duration: >6 h Half-life: 53–118 h	Hepatic	IV formulation contains propylene glycol Enzyme inducer ADR: sedation, hypotension, respiratory depression
  Levetiracetam	1–3 g or 60 mg/kg IV up to 4500 mg/dose NTE: 5 mg/kg/min	Time to peak: 1 h Half-life: 6–8 h	Enzymatic hydrolysis (24% of dose) Renal excretion (66% as unchanged and 27% as inactive metabolites)	ADR: sedation, paradoxical excitation, irritability Renally eliminated
  Third-Line Therapy (Refractory): Initiate if Seizures Persist After First- and Second-Line Therapy
  Midazolam high-dose infusion	0.05–0.2 mg/kg/h	Onset: 3–5 min Half-life: 1.8–6.8 h (prolonged in renal failure, cirrhosis, CHF, obesity, and elderly)	Hepatic, active metabolite	Requires intubation before starting therapy ADR: sedation, hypotension, respiratory depression
  Pentobarbital	25 mg/kg LD followed by 0.5–5 mg/kg/h	Onset: 3–5 min Half-life: 15–50 h (dose dependent)	Hepatic	Requires intubation before starting therapy IV formulation contains propylene glycol Enzyme inducer; several DDIs ADR: sedation, hypotension, respiratory/cardiac depression, paralytic ileus, immunosuppression
  Propofol	20–200 mcg/kg/min Titrate by 5 mcg/kg/min q5min	Onset: 9–51 s Half-life: Biphasic: Initial: 40 min Terminal: 4–7 h (after 10-day infusion, may be up to 1–3 days)	Hepatic	Requires intubation before starting therapy ADR: sedation, hypotension, respiratory depression, pancreatitis, cardiac failure, rhabdomyolysis, metabolic acidosis, propofol infusion syndrome Lipid formulation provides 1.1 kcal/mL
  Valproate	20–40 mg/kg IV, may give additional 20 mg/kg 10 min after LD NTE: 5 mg/kg/min	Time to peak: at the end of a 1 h infusion Half-life: 9–19 h	Hepatic	For nonintubated Many DDIs, avoid in patients with a TBI ADR: hyperammonemia, thrombocytopenia, hepatotoxicity, pancreatitis
  Lacosamide	200–400 mg IV NTE: 200 mg/15 min	Time to peak: 1–4 h Half-life: 13 h	Renal excretion (95%)	For nonintubated ADR: dizziness, bradyarrhythmia, PR prolongation, hypotension
  Topiramate	200–400 mg PO/NG ×1 then 300–1600 mg/day PO/NG (divided two to four times daily)	Time to peak: 2 h Half-life: 19–23 h	Renal excretion (70% as unchanged drug)	For nonintubated ADR: metabolic acidosis No IV formulation available
  Ketamine	0.5–5 mg/kg/h	Onset: 30 s Half-life: α: 10–15 min β: 2.5 h	Hepatic	ADR: excitation, hypertension, possible neurotoxicity, hallucinations

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