Management of Status Epilepticus (SE)

Initial Treatment
Medications
Timing Additional Treatment
Drug Dose

Lorazepam 0.1 mg/kg IV (IV • Consult Neurology/ Neurocritical Care

- OR - route preferred) (max • ABCs: maintain airway protection
4 mg/dose) o O2 via nasal cannula
If NO IV access o Intubation for compromised
Emergent Initial
0.2 mg/kg IM airway/gas exchange or elevated
Therapy: Midazolam (max 10 mg/dose) intracranial pressure
- OR - o Fluid resuscitation and vasopressor
ADMINISTER support if SBP < 90 mmHg or MAP
BENZODIAZEPINE STAT
Weight (kg) Dose (mg) < 70 mmHg
≤62 12.5 • Vital signs (SaO2, BP, HR)
If NO IV access and IM is • Obtain peripheral IV access
63 – 75 15
not feasible
Within first 5 76 – 87 17.5 • Finger-stick blood glucose: treat if BG
minutes Diazepam rectal gel ≥88 20 < 70 mg/dl
*Dosing provided is per rectum only. o Thiamine 100 mg IV, then
50 mL dextrose 50% IV

Repeat same dose of benzodiazepine

Initial Therapy: -PLUS-
• If hypotension occurs, reduce rate of
If still seizing after Fosphenytoin 20mg PE/kg IVPB Fosphenytoin infusion.
5 minutes (no faster than 150mg/minute)
Loading Dose

If seizures continue after Fosphenytoin loading dose escalate to Urgent Control Therapy below.

• Send labs:
Fosphenytoin Give additional 5 mg PE/kg IVP o Complete blood count (CBC)
(no faster than 150 mg/minute) o Basic metabolic panel (BMP)
o Calcium (total, ionized)
Urgent Control -PLUS ONE OF THE FOLLOWING AGENTS BELOW- o Magnesium
Therapy: Levetiracetam 60 mg/kg IV o AED levels (if taking previously)
- OR - (max dose 4500 mg) o Levetiracetam, topiramate and
10 - 30 minutes (if still lamotrigine are send-outs
seizing) Valproate 40 mg/kg IV • Neurologic exam
- OR - (max dose 3000 mg) • Do not use Valproate if patient is
receiving a carbapenem
Lacosamide 400 mg IV

0.2 mg/kg bolus, then 0.05 mg/kg/hr

Midazolam infusion titrated by 0.05-0.1 mg/kg/hr
every 3-4 hours to achieve seizure
- AND/OR -
control; max rate 2 mg/kg/hr Note: Patients MUST be intubated prior
to initiation of continuous infusions
2 mg/kg bolus, then 20 mcg/kg/min
Propofol infusion titrated by 5-10 mcg/kg/min every 5 min Infusion rates should be titrated based
Advanced Management of to achieve seizure control; max rate on continuous EEG monitoring
Refractory and Super- - AND/OR - 120 mcg/kg/min)
refractory Status Within 60 minutes:
Epilepticus:
Pentobarbital 10 mg/kg bolus, then 0.5 mg/kg/hr • Order continuous EEG
If seizures persist > 30 infusion titrated by 0.5-1 mg/kg/hr every 12 • Diagnostic imaging including head CT
hours to achieve seizure control; max
minutes • ICP monitoring if elevated ICP
- AND/OR - rate 5 mg/kg/hr,
suspected
no higher than 50 mg/min
• Foley catheter placement
2.5 mg/kg bolus, then 0.5 mg/kg/hr • Medications may be used concomitantly
titrated by 0.5-1 mg/kg/hr every 1
Ketamine infusion hours to achieve seizure control;
max rate 10 mg/kg/hr
 2
• Implement and maintain standard seizure precautions
Definitions • Minimize time to administration of AEDs. For a patient in
Status Epilepticus (SE): Continuous clinical and/or active SE, AEDs should be administered STAT
electrographic seizures lasting ≥ 5 minutes or recurrent seizure • Implement seizure care plan and patient educations
activity without returning to baseline between seizures. • Continuous infusions of AEDs should NOT be stopped to
perform neurological exam and are NOT titrated to a
Convulsive SE: Convulsions associated with rhythmic jerking sedation scale (e.g., RASS)
of the extremities.
References
Nonconvulsive SE: Seizure activity on electroencephalogram
(EEG) without clinical findings associated with convulsive SE. • Lowenstein DH, et al. (1998). Status Epilepticus. New
England Journal of Medicine. 338(14): 970-976.
Refractory SE: Clinical or electrographic seizures that do not • Brophy GM, et al. (2012).Guidelines for the Evaluation and
respond after adequate doses of an initial benzodiazepine Management of Status Epilepticus. Neurocritical Care.17:
(BZD) followed by a second acceptable antiepileptic drug 3-23.
(AED). • Glauser T, Shinnar S, Gloss D, et al. Evidence-Based
Guideline: Treatment of Convulsive Status Epilepticus in
Diagnosis Children and Adults: Report of the Guideline Committee of
the American Epilepsy Society. Epilepsy Curr.
Consider additional testing based on patient history, 2016;16(1):48-61.
clinical presentation, and/or neurology recommendations: • Fang Y, Wang X. Ketamine for the treatment of refractory
status epilepticus. Seizure. 2015;30:14-20.
• Brain magnetic resonance imaging (MRI)
• Lumbar puncture (LP) Quality Measures
• Comprehensive toxicology panel (IHIS order: Toxicology
Drug Screen, Serum): • Initial dosing order for first benzodiazepines
o Isoniazid • Initial dosing order for first AED
o Tricyclic antidepressants • Mechanical ventilation > 72 hours
o Theophylline • Average time between first dose benzodiazepines and
o Cocaine administration of first line AED
o Sympathomimetics • Order Set Usage
o Alcohol
o Organophosphates Order Sets
o Cyclosporine
• Status Epilepticus Order Set
Monitoring • Pentobarbital Coma Order Set

• Immediately order spot electroencephalogram (EEG) Authors

o IHIS order: EEG Extended < 1 Hour
• Consider continuous EEG monitoring if clinically indicated • Michel Torbey, MD
(e.g., persistent encephalopathy) • Keaton Smetana, PharmD, BCCCP
o IHIS order: EEG Extended > 1 Hour • Dorina Harper, RN, CNS

Management
Guideline Approved
Goals of Treatment
• Rapid cessation of seizure activity while maintaining January 31, 2018 Second Edition.
airway, breathing, and circulation
• Identification and treatment of underlying seizure etiology Disclaimer: Clinical practice guidelines and algorithms at The
• Long-term maintenance of seizure control Ohio State University Wexner Medical Center (OSUWMC) are
standards that are intended to provide general guidance to
Continued Medical Care clinicians. Patient choice and clinician judgment must remain
central to the selection of diagnostic tests and therapy.
Order Maintenance Drug Regimen OSUWMC’s guidelines and algorithms are reviewed
• Refer to Appendix 1 for therapeutic drug monitoring and periodically for consistency with new evidence; however, new
drug dosing developments may not be represented.

Disposition Planning Copyright © 2017. The Ohio State University Wexner Medical
Center. All rights reserved. No part of this document may be
• Consider admission/transfer to Neurosciences Critical reproduced, displayed, modified, or distributed in any form
Care Unit without the express written permission of The Ohio State
• Consult Social Worker and Case Manager to assist with University Wexner Medical Center.
long-term planning

Nursing Pearls for SE

• Assess and document neurological assessment and
seizure activity
 3

Appendix 1: Therapeutic Drug Monitoring and Intermittent Dosing of

Antiepileptic Drugs for Status Epilepticus

Phenytoin (PHT)
• Free phenytoin level 2 hours after administration of the loading dose(s)
• Order free phenytoin trough level 24 hours after administration of loading dose(s)

Free PHT Level* mcg/mL No Seizure Activity Ongoing Seizure Activity

< 0.5 Reload 20 mg/kg Reload 20 mg/kg

0.5-1.0 Reload 10 mg/kg Reload 10 mg/kg

Mini-load according to the equation

1.0-2.0 No change
below to optimize level between 2-2.5**

No change or decrease maintenance No change;

2.0-2.5
regimen if AEs present Consider additional AED
No change or decrease maintenance
> 2.5 Decrease maintenance regimen
regimen if AEs present
*Trough level or 2h post load level

**Phenytoin/Fosphenytoin mini-load (mg) = (desired free level – actual free level ) x 10 x actual body weight (kg) x 0.7

Valproic acid and derivatives (VPA):

• Total valproic acid level 1 hour after administration of the loading dose(s)
• Order total valproic acid trough level 24 hours after administration of loading dose(s)

Total VPA Level* mcg/mL No Seizure Activity Ongoing Seizure Activity

< 10 Reload 20-40 mg/kg Reload 20-40 mg/kg

10-50 Reload 10-20 mg/kg Reload 10-20 mg/kg

Mini-load according to the equation

50-100 No change below to optimize level between 100-
150**
No change or decrease maintenance No change
100-150
regimen if AEs present Consider additional AED
No change or decrease maintenance
> 150 Decrease maintenance regimen
regimen if AEs present
*Trough level or 1h post load level

**VPA mini-load (mg) = (desired level – actual level) x actual body weight (kg) x 0.2
 4

Medication Table

Serious Adverse
Drug Initial Dosing Administration Pharmacokinetics Comments
Events
~90% protein-bound  Preferred BZD to be used 1st
 Dilute 1:1 with NS line in the management of SE
Preferred in patients with
due to quick onset of action and
 Up to 2 mg/min IV hepatic impairment  Hypotension
Lorazepam 0.1 mg/kg IV longer duration of action than
(Ativa®) (max 4 mg) push 88% excreted as inactive  Respiratory midazolam
 May repeat in 5- metabolite in urine depression
 IV contains propylene glycol;
10 min prolonged high-dose infusion
t1/2 ~ 14 hours
may lead to metabolic acidosis
Onset 3-5 min IV, 15 min
IM  Quicker onset of action than
lorazepam, but limited by
 IV push over 2-5 Duration < 2 hours
shorter duration of action. May
0.2 mg/kg IV/IM min t1/2 2-7 hours  Hypotension
Midazolam be used as an alternative to
max 10 mg)
(Versed®)  Repeat every 5-10 ~97% protein-bound  Respiratory achieve initial seizure control
min to a max total depression
Hepatic metabolism  IM midazolam may be
dose of 2 mg/kg
~90% excreted in the considered for patients without
urine as metabolites IV access

0.15 mg/kg IV
(max 10 mg)
Diazepam 0.2 mg/kg Rectal gel (round
(Valium®/Diastat®) dose to nearest 2.5mg
increment
• < 62kg = 12.5mg
• 63-75kg = 15mg
• 76-87kg = 17.5mg
• >88kg = 20mg
Onset: ~ 1 min
 Diazepam rectal gel may be
~95% protein bound
considered for patients without
 Up to 5 mg/min IV t1/2 ~40 hours for parent  Hypotension IV access and IM Midazolam not
push compound available
 Respiratory
 Rectal gel Hepatic metabolism depression  IV contains propylene glycol;
prolonged high-dose infusion
Excreted in the urine as
metabolites may lead to metabolic acidosis

Onset ~15 minutes to

Load: 20 mg/kg IVPB
(max 3000 mg)
Repeat Load: May give
Fosphenytoin additional 5mg PE/kg 10 min
(Cerebyx®)
after load if still seizing
Maintenance: 5-7 mg/kg/day
divided Q8H or Q12H
 Preferred over phenytoin for
become converted to
loading dose since it can be
phenytoin
 Hypotension infused at a faster rate; however
 Up to 150 mg 95-99% protein-bound it takes time to convert from the
PE/min  Arrhythmias prodrug to active drug
Hydrolyzed to active
 Compatible in NS,  Bradycardia
phenytoin, which is then  Dosed in phenytoin equivalents
dextrose, and LR metabolized by the liver (PEs)
 Cardiac toxicity
Excreted in urine as  Use actual body weight for
inactive metabolites dosing
 5

Serious Adverse
Drug Initial Dosing Administration Pharmacokinetics Comments
Events
 Up to 50 mg/min
Onset ~ 30-60 minutes
 Hypotension
 Dilute in NS only, avoid
Load: 20 mg/kg IVPB small veins; administer ~90-95% protein-bound  Arrhythmias,  IV contains propylene glycol; high
Phenytoin Maintenance: 5-7 through 0.22 micron Hepatic metabolism  Bradycardia doses may lead to metabolic
(Dilantin®) mg/kg/day divided Q8H filter. acidosis
or Q12H
t1/2 7-42 hours  Cardiac toxicity
 Cannot be  Use actual body weight for dosing
Excreted in urine as  Purple glove
administered via PICC inactive metabolites syndrome
line.
Onset ~ 1 hour to peak

Load: Protein binding < 10%

60mg/kg Not extensively  Minimal drug interactions
(max 4500 mg) metabolized, primarily by
 Somnolence  No adjustment in hepatic failure
Levetiracetam Maintenance: 3000- enzymatic hydrolysis to
 5 mg/kg/min  Therapeutic drug monitoring is
(Keppra®) 6000 mg/day divided inactive metabolites  Psychosis,
Q12H aggression NOT recommended. Send-out lab
t1/2 6-8 hours may take several days to return
(If > 4000 mg, divide  Rare elevated
Q8H) Excreted in urine (66% limiting utility of the results
unchanged drug) CK

80-90% protein-bound  Hepatotoxicity

 Hyperammonemia  Carbapenem antibiotics
Extensive hepatic significantly reduce VPA levels
metabolism  Encephalopathy resulting in inability to achieve
Valproate Load: 40 mg/kg IVPB
t1/2 9-19 hours therapeutic serum concentrations
(Depakene®) Maintenance: 5-20  Up to 6 mg/kg/min  Pancreatitis of VPA and loss of seizure control.
mg/kg Q8H Excreted 30-50% in  Thrombocytopenia
urine as glucuronide  If receiving carbapenem
and inhibition of antibiotics, choose an
conjugate platelet activity alternative agent
 Pregnancy X
Onset immediate after IV  Dose-dependent
administration, and 1-4 PR interval
hours after oral prolongation, use
 Slow IV push at a rate caution with other  Minimal drug interactions
Load: 400mg IVP not to exceed 80mg/min 15% protein-bound PR prolonging
Lacosamide
agents or known  Dose adjustment in mild to
(Vimpat®) Maintenance: 100-  May be administered Hepatic metabolism to second- or third- moderate hepatic impairment and
300mg Q12H without further dilution inactive metabolite degree AV block in patients with end stage renal
disease or CrCl <30mL/min
T1/2 ~13 hours  Hypotension

Excreted 95% in urine  Bradycardia

 6

Appendix 2: Continuous Infusion Antiepileptic Drugs for Status Epilepticus

Clinical Pearls for Continuous Infusions
• Patients MUST be intubated prior to initiation of continuous infusions
• Infusion rates should be titrated based on continuous EEG
• When converting from one continuous infusion AED to another, the drugs should be overlapped for a sufficient period of time to minimize periods without
therapeutic levels of AEDs
Breakthrough Serious Adverse
Drug Initial Dosing Pharmacokinetics Comments
Seizure Dosing Events
0.2 mg/kg bolus,  Give 0.2 mg/kg bolus,
followed by 0.05 increase infusion rate  Hypotension
Midazolam  Tachyphylaxis occurs after prolonged
mg/kg/hr IV infusion by 0.05-0.1 mg/kg/hr See Appendix 1 (page 3)
(Versed®)
every 3-4 hours  Respiratory use
depression
 Max 2 mg/kg/hr

 Hypotension  Green urine

(especially with bolus
Onset ~ 30 seconds dose)  Formulated in lipid emulsion – must
 Consider 1 mg/kg adjust daily caloric intake (1.1 kcal/mL)
bolus prior to Duration 3-10 minutes  Respiratory
2 mg/kg bolus, increasing rate depression  Risk of PRIS and adverse events
Propofol followed by 20 97-99% protein-bound increase with higher doses of propofol
(Diprivan®) mcg/kg/min IV  Increase rate by 5-10  Cardiac failure administered for prolonged period of
mcg/kg/min every 5 Hepatic metabolism
infusion  Rhabdomyolysis time (> 48 hours)
minutes. 88% excreted in the urine
 Metabolic acidosis  Consider alternative agent if serum
 Max 120 mcg/kg/hr as inactive metabolites
triglycerides > 500 g/dL or CK > 500.
 Renal failure (PRIS) Triglycerides and CK should be
 Hypertriglyceridemia monitored at least every other day.
10 mg/kg bolus,
Onset within 3-5 minutes  Hypotension  IV contains propylene glycol; high
following by 0.5  Give 5 mg/kg bolus, doses or prolonged infusions may lead
mg/kg/hr IV infusion increase infusion rate Duration: variable  Respiratory to metabolic acidosis
Pentobarbital by 0.5-1 mg/kg/h every depression
45-70% protein-bound  Paralytic ileus may occur; all patients
(Nembutal®) 12 hours
Titrate to achieve Hepatic metabolism  Cardiac depression should have standing orders for a
seizure control (max  Do not administer Paralytic ileus bowel regimen and consideration
5 mg/kg/hr, but no faster than 50 mg/min t1/2 ~ 22 hours should be given to prokinetic agents
higher than 50  Complete loss of (e.g., erythromycin, metoclopramide) if
 Max rate 5 mg/kg/hr Excreted in the urine neurological function
mg/min) no contraindications exist
Onset ~ 30 seconds  Tachycardia  Tachyphylaxis may occur after several
2.5 mg/kg bolus, then  Give 2 mg/kg bolus,
Duration ~ 5-10 minutes  Hypertension days of continuous infusion
0.5 mg/kg/hr IV increase infusion rate
Ketamine
(Ketalar®)
infusion by 0.5-1 mg/kg/hr Hepatic metabolism to  Emergence reactions  Emergence reactions after stopping
every 1 hour active metabolite (vivid dreams, continuous infusion may be prevented
hallucinations, by pre-treatment with a
 Max 10 mg/kg/hr Excreted in the urine
delirium) benzodiazepine