Sample Protocol #5: Management of status epilepticus and seizures in hospitalized patients NonConvulsive Seizure December 16, 2014

Patient presents with alteration of consciousness unexplained by other etiologies AND suspicious for non convulsive seizure OR subclinical seizures noted on EEG

ABCs Finger stick glucose

Labs: CBC w/ Diff, CMP, Urine Drug Screen, Urine Pregnancy Test If KNOWN epilepsy, order anti- seizure medication levels IF UNKNOWN, order Magnesium and Phosphate

Patient back to Seizures Yes baseline in 15-30 Terminate minutes?

No

Administer Yes meds. Is there IV access? No Order neurology consult

Order Continuous EEG Ativan (Lorazepam): 1-2 mg IV per dose, Order Non-contrast Head Midazolam: may repeat in 5 mins, CT 0.2 mg/kg IM or IV up to 0.1 mg/kg, if up to max of 10mg not controlled after 2 If imaging reveals lesion, doses, move on order neurosurgery consult

PRE No Seizures Persist? Yes Status Epilepticus

Page 1 NonConvulsive Seizure December 16, 2014

First round of medication does not cease seizures: PRE Status Epilepticus

Administer Meds: CHOOSE ONE Consider ICU transfer Fosphenytoin: PREFERRED Close monitoring of airway 20mg PE/kg IV initial bolus. Complete initial bolus. If unless patient meets any - Readiness to intubate clinical or electrographic seizures persist, may give add’l criteria below 5mg/kg. Rate of up to 150mg PE/min. Consider LP if clinically indicated PREGNANCY OR SEVERE Levetiracetam (Keppra): LIVER DISEASE 1,000-3,000 mg IV, at rate of 2.5 mg/kg/min IV If not already ordered: EEG or clinical exam Valproate Sodium (Depakote): Order neurology consult suggestive of MYOCLONIC 20-40 mg/kg IV, may give add’l 20mg/kg, up to 3-6 mg/ Order Continuous EEG SEIZURES kg/min Midazolam: Pt in ICU, PACU, or Initial dose of 0.2 mg/kg; administer at infusion rate of INTUBATED 2mg/min; followed by continuous infusion of 0.05mg/ kg/hr. Titrate to max tolerated dose.

Consider trying another Status Seizures Persist? second line agent. Epilepticus (ONLY REPEAT ONCE)

No

Seizures Terminate

Page 2 NonConvulsive Seizure December 16, 2014

Administer Meds: CHOOSE ONE Fosphenytoin: PREFERRED 20mg PE/kg IV initial bolus. Complete initial bolus. If unless patient meets any clinical or electrographic seizures persist, may give criteria below add’l 5mg/kg. Rate of up to 150mg PE/min.

PREGNANCY OR SEVERE Levetiracetam (Keppra): LIVER DISEASE 1,000-3,000 mg IV, at rate of 2.5 mg/kg/min IV

EEG or clinical exam Valproate Sodium (Depakote): suggestive of MYOCLONIC 20-40 mg/kg IV, may give add’l 20mg/kg, up to 3-6 SEIZURES mg/kg/min Midazolam: Pt in ICU, PACU, or Initial dose of 0.2 mg/kg; administer at infusion rate of INTUBATED 2mg/min; followed by continuous infusion of 0.05mg/ kg/hr. Titrate to max tolerated dose.

Return to Pathway

Page 3 NonConvulsive Seizure December 16, 2014

Status Epilepticus

Transfer to ICU with cEEG monitoring.

Consider intermittent bolus Contraindication Yes therapies of valproic acid, to intubation? leviteracitam, or fosphenytoin.

No

Intubate and consider need for pressors.

Administer Meds: CHOOSE ONE If all other therapies fail, Treatment involves continuous infusions. Goal is to titrate to seizure suppression for consider lacosamide (Vimpat). ≥ 48 hrs. If seizures persist, goal is to titrate to burst suppression for ≥ 48 hrs. Lacosamide: 200 mg IV with maintenance of 100 mg q12. Midazolam: PREFERRED Initial dose of 0.2 mg/kg; administer at infusion rate of 2mg/min; followed by infusion of 0.05-2 mg/kg/hr Cl. Propofol: Start at 20 mcg/kg/min with 1-2 mg/kg loading dose. 30- 200 mcg/kg/min Cl. Second Choice Propofol infusion rate = 30–200 mcg/kg/min CI. Use caution when administering high doses (>80 mcg/kg/ min) for extended periods of time (i.e., >48 h)

Pentobartbital: Third Choice 5-15 mg/kg, may give add’l 5-10 mg/kg: administer at infusion rate of <50 mg/min. 0.5-5 mg/kg/h Cl.

Consult epileptologist.

Consider Seizure Protocol MRI to be ordered by neuro or epileptlogist. Treatment management Refractory Seizures Persist? Yes with assistance from Status neuro consult and epileptologist. Consider neurosurgery consult. No

Initiation of maintenance anti-seizure medication. Selection guided by epileptologist. Maintenance anti-seizure medications: Consider weaning infusion anti-seizure Phenytoin, Levetiracetam, Valproate, medications/anesthetic agents if seizure free Lacosamide, Clonazepam, Phenobarbital, 24-48 hours. Topiramate, Zonisamide, Carbamazepine, Continue cEEG for 24-48 hours once IV anti- Oxcarbazepine seizure medication/anesthetic agents infusions weaned and patient remains seizure free

Transfer out of ICU per ICU transfer criteria

Within 3-4 wks

Follow up in Neurology Clinic with Epileptologist Page 4 NonConvulsive Seizure December 16, 2014 Administer Meds: CHOOSE ONE

Treatment involves continuous infusions. Goal is to titrate to seizure suppression for ≥ 48 hrs. If seizures persist, goal is to titrate to burst suppression for ≥ 48 hrs.

Midazolam: PREFERRED Initial dose of 0.2 mg/kg; administer at infusion rate of 2mg/min; followed by infusion of 0.05-2 mg/kg/hr Cl. Propofol: Start at 20 mcg/kg/min with 1-2 mg/kg loading dose. 30- 200 mcg/kg/min Cl. Second Choice Propofol infusion rate = 30–200 mcg/kg/min CI. Use caution when administering high doses (>80 mcg/kg/ min) for extended periods of time (i.e., >48 h)

Pentobartbital: Third Choice 5-15 mg/kg, may give add’l 5-10 mg/kg: administer at infusion rate of <50 mg/min. 0.5-5 mg/kg/h Cl.

Return to Pathway

Page 5 NonConvulsive Seizure December 16, 2014

Initiation of maintenance anti-seizure medication. Selection guided by epileptologist.

Consider weaning infusion anti-seizure medications/ anesthetic agents if seizure free 24-48 hours.

Continue cEEG for 24-48 hours once IV anti-seizure medication/anesthetic agents infusions weaned and patient remains seizure free

Return to Pathway

Page 6 NonConvulsive Seizure December 16, 2014

Seizures Terminate

If patient on cEEG, continue for 24-48 hours once patient remains seizure free. Return to Previous Page

No Known Epilepsy? Yes

Order Routine EEG Back to No if not already performed. baseline?

Yes Order non-contrast head CT (within 2 hours) if not already ordered. Assess for infection Consider LP if concern for or stressors. CNS infection.

Consider LP if concern for CNS infection.

Consider head CT if concern for head injury, focal neurological examination, or prolonged alteration in mental status.

If imaging reveals lesion, order neurosurgery consult Engage Social Work

Treat underlying cause.

Is risk of recurrent seizure No high?

Yes

Maintenance anti-seizure medications: Consider beginning Follow up in Neurology Clinic. Patient ready for Phenytoin, Levetiracetam, Valproate, or adjustment of If second line agent given, discharge once all acute Within 4 wks Phenobarbital, Topiramate, Zonisamide, maintenance anti- recommend follow-up with medical needs are met Carbamazepine, Oxcarbazepine seizure medication epileptologist.

Page 7 NonConvulsive Seizure December 16, 2014

If patient on cEEG, continue for 24-48 hours once patient remains seizure free.

Return to Pathway

Page 8 Convulsive Seizure Where did the patient come Patient Presents with Convulsive Seizure from?

Is this a convulsive Is finger stick Treat appropriately Check allergies Yes seizure? glucose abnormal? Consider Thiamine

Was the patient No Do you know the given any anti- time of seizure presentation? Greater than 5 medications? No Seizures cease Minutes within 5 minutes? Assess and treat for injuries from the No seizure Yes Yes Order non-contrast head CT (within 2 hours). Order Labs: CMP, CBC, Tox Known Epilepsy? Screen, Mg, Phosphate, Back to Yes No Urine Pregnancy Test baseline? Consider LP Order AED Levels. Assess for infection or stressors. Assess and treat for injuries Did imaging from seizure Order neurosurgery reveal potential Yes consult Consider Non- surgical lesion? Convulsive Seizure

No AED levels w/in No Yes normal limits?

Yes Back to Baseline No Consider Labs: CMP, Order Labs: CMP, Non- CBC, Tox Screen, CBC, Tox Screen, convulsive Urine Pregnancy Urine Pregnancy pathway Test. Consider LP Test. Consider LP Order Routine Order Urgent and Imaging and Imaging Yes Yes EEG EEG

Are there Engage Social No seizures on the No No Work EEG? Yes

Treat underlying cause, if determined

Is risk of Yes recurrent seizure No high?

Maintenance AEDs: Phenytoin, Levetiracetam, Consider beginning Patient ready for Follow up in Valproate, Phenobarbital, or adjustment of discharge once all acute Within 4 wks Neurology Topiramate, Zonisamide, maintenance AED medical needs are met Clinic Carbamazepine, Oxcarbazepine Convulsive Seizure

Seizure persists for >5 min

Must treat acutely with 1st line anti-seizure meds

Is there IV Yes No access? Lorazepam: 2-4mg IV per dose, Midazolam: may repeat in 5 mins, 0.2 mg/kg IM or IV up to 0.1 mg/kg, if up to max of 10mg not controlled after 2 doses, move on

Imaging: Order non-contrast Assess for injuries head CT, (within 2 hours) if Perform neurological exam not already ordered Assess for provoking PENDING factors Seizures Persist? Yes Status Labs: CMP, CBC, Tox Screen, Epilepticus Mg, Phosphate, Urine Pregnancy Test, AED Levels, if not already ordered. No Strongly consider LP Order Imaging, labs, EEG EEG Routine: Pt back to baseline Known Epilepsy? Yes Urgent: if altered mental status greater than 30 minutes post convulsions Order AED Levels. Assess for infection, stressors, injuries. No

Consider neuro consult. If imaging reveals AED levels w/in No Yes lesion, order normal limits? neurosurgery consult Consider Labs: CMP, Order Labs: CMP, CBC, Tox Screen, CBC, Tox Screen, Urine Pregnancy Urine Pregnancy Test. Consider LP Test. Consider LP and Imaging and Imaging

Engage social work

Maintenance AEDs: Phenytoin, Levetiracetam, Begin or alter maintenance Valproate, Phenobarbital, AED, further treatment at Yes Topiramate, Zonisamide, discretion of neurology Carbamazepine, consult and primary service Oxcarbazepine No

Patient ready for Follow up in discharge once all acute Within 4 weeks Neurology medical needs are met Clinic Convulsive Seizure First line of medication does not cease seizures: PENDING Status Epilepticus

Levetiracetam: Does the patient have 1,000-3,000 mg IV, Order Neurology Consult severe liver disease or are YES at rate of 2.5 mg/kg/ Order Continuous EEG they pregnant? min IV

No

Consider ICU transfer if: Valproate Sodium: Does the EEG or clinical - vitals unstable 20-40 mg/kg IV, may exam suggest myoclonic YES give add’l 20mg/kg, seizures? up to 3-6 mg/kg/min

No Midazolam: Initial dose of 0.2 mg/kg; administer at infusion rate of Is the patient already in the YES 2mg/min; followed ICU, PACU, or intubated? by continuous infusion of 0.05mg/ kg/hr. Titrate to No max tolerated dose.

Fosphenytoin: (cont…) 20mg PE/kg IV initial bolus. Check with pharmacy Complete initial bolus. If clinical or Monitor heart rate electrographic seizures persist, Be aware of risk of bradycardia, may give add’l 5mg/kg. Rate of up heart block, and hypertension to 150mg PE/min.

Status Seizures Persist? Yes Epilepticus

No Maintenance AEDs: Treat Underlying Cause Phenytoin, Levetiracetam, Begin or alter maintenance AED per Valproate, Phenobarbital, neurologist recommendation Topiramate, Zonisamide, If continuous EEG not yet performed, change Carbamazepine, order to Stat EEG Oxcarbazepine

Patient ready for discharge once all acute medical needs are met

Within 4 wks

Follow up in Neurology Clinic Convulsive Seizure

Status Epilepticus

Is there a strong Transfer to ICU with cEEG clinical reason to avoid monitoring. intubation?

Yes Consider No intermittent bolus therapies of valproic acid, leviteracitam, or fosphenytoin. Intubate and consider need for pressors

Administer If all other therapies continuous infusion fail, consider of 3rd line meds: lacosamide. Choose One Midazolam: Lacosamide: 200 mg Initial dose of 0.2 IV with maintenance mg/kg; administer at Pentobartbital: of 100 mg q12. infusion rate of 5-15 mg/kg, may 2mg/min; followed Preferred give add’l 5-10 mg/ Propofol infusion by infusion of 0.05-2 rate = 30–200 mcg/ kg: administer at mg/kg/hr Cl. Propofol: kg/min CI. Use infusion rate of <50 Start at 20 mcg/kg/ caution when mg/min. 0.5-5 mg/ min with 1-2 mg/kg administering high kg/h Cl. loading dose. 30-200 doses (>80 mcg/kg/ mcg/kg/min Cl. min) for extended periods of time (i.e., >48 h)

rd Consider Seizure Protocol Titrate to continuous infusion of 3 line agent to MRI to be ordered by seizure suppression based on cEEG or clinical neuro or epileptlogist. exam for ≥ 48 hrs Treatment management with assistance from neuro consult and Consult epileptologist. Consider epileptologist. neurosurgery consult.

Consider weaning Have you weaned the infusion of third line continuous infusion meds of 3rd line meds? Refractory Yes Seizures Persist? Status

No Has the patient been seizure free for 24-48hr after Yes Stop the cEEG If seizures persist, stopping infusion of rd goal is to titrate to 3 line meds? burst suppression for ≥ 48 hrs Yes No Maintain continuous Transfer out of infusion while Maintenance AEDs: Phenytoin, ICU per ICU initiating maintenance Levetiracetam, Valproate, Within Follow up in Has patient been transfer criteria AED Lacosamide, Clonazepam, 3-4 wks epilepsy clinic seizure free for & continue Phenobarbital, Topiramate, 24-48hrs? maint AED Zonisamide, Carbamazepine, Oxcarbazepine