Status EpilepticusMohsen Saidinejad, MD, MBA, FAAP, FACEP

Associate Professor of Pediatrics & Emergency Medicine

David Geffen School of Medicine at UCLA

Director, Institute for Health Services and Outcomes Research

Los Angeles Biomedical Research Institute

Department of Emergency Medicine

Harbor UCLA Medical Center

Conflicts/disclosures

None

Case

2 year-old female brought by EMS in status epilepticus. First line agent was used in the field but patient continues to seize.

What is the next agent to consider?

What is the airway management strategy?

Outline

Definition Epidemiology Classification Pathophysiology Complications Status febrile seizure Assessment Treatment Case discussion Conclusion

Definitions

Duration

Seizure activity > 5 minutes

Multiple seizures without return to baseline

Neuronal damage (>30 minutes)

Refractory: > 30 minutes

Response to intervention

Within 10 minutes

20-30 minutes

> 30 minutes

Quality

Convulsive

Non-convulsive

Refractory

Complications

Refractory

Epidemiology

Most common neurologic emergency in children

Incidence of SE in children: ~10-40/100,000

Mortality rate as high as 3%

Most in first year of life

Complication of an acute illness (e.g. meningitis) or activation of epilepsy

Most common cause of SE is febrile seizure (25% of all SE)

Traumatic SE is not common but can indicate severe anoxic injury

Classification

Convulsive SE

Generalized tonic-clonic

Non-convulsive SE

Absence

Complex Partial

Refractory SE – Prolonged convulsive

Pathophysiology

Isolated seizures:

Failed mechanism to inhibit neurotransmission

Inhibition of GABA

blockage of N-methyl-D-aspartate (NMDA) channels (Mg++)

Excessive excitation

Excessive activation of glutamate, aspartate, and acetylcholine receptors

Calcium ion-dependent potassium ion current

Risk factors

Having underlying epilepsy – 10-20% of children with epilepsy develop SE

Partial seizures occurring in clusters

Age < 1 year

Febrile seizure

Focal seizures with secondary generalization

Ongoing background EEG epileptiform activity

Previously healthy patient with first seizure presentation as SE

Previous SE

Presence of abnormal findings on MRI

Etiology

Manifestation of acute infectious illness (encephalitis, meningitis)

Febrile seizure

Drug ingestions

Traumatic brain injury (including acute hypoxic/anoxic insult)

Anti-epileptic medications (e.g. carbamazepine)

Electrolyte abnormalities

Metabolic diseases (e.g. inborn errors of metabolism)

Complications

Acidemia

Hypoxemia

Carbon dioxide retention

↑ intracranial pressure (ICP) and cerebral edema

Electrolyte abnormalities (including glucose)

Initial catecholamine release tachycardia, hypertension, ↑ cerebral blood flow followed by hypotension and ↓ cerebral blood flow

Leukocytosis (especially if febrile seizure)

Mortality 3-4%

Long term neuro-behavioral consequences

Febrile Status Epilepticus

Occurs in ~ 5% of all febrile seizures

One of the most common causes of SE

Not related to same long-term consequences as epileptic non febrile seizure

Not an independent risk factor for future afebrile seizure

Febrile infection-related epilepsy syndrome (FIRES) - new-onset refractory SE in the setting of a prodromal febrile illness (two weeks - 24 hours prior to onset of refractory SE, with or without fever at onset of SE)

Treatment can be initiated in the similar fashion as afebrile, but consider:

etiology related to infection

Rapid temperature change - antipyretic

Assessment

History

Prior known seizures?

Febrile (now or last 24 hours)?

How long has the seizure lasted?

Patient age?

What treatments have been given at home/pre-hospital?

Etiology?

Physical exam

Airway, breathing, circulation

Brief neurologic exam

Obvious seizure, post-ictal, or residual

Vitals (including pulse oximetry)

Diagnostic testing

Point of care glucose

Serum electrolytes including Na+, Ca++, Mg++, PO4-

Arterial blood gases

End tidal CO2

A complete blood count (CBC)

Urine and blood toxicology

Serum anti-epileptic drug levels

(1/3 SE have sub-therapeutic levels)

Other tests

CT/LP

MRI (deferred)

EEG (usually deferred)

Management consideration

Response to previous therapy

Compliance with maintenance medication

Use of alternative therapies

Recent change in medication dose

Paradoxical effect of anticonvulsant medication

The goal is to stop convulsive SE in under 30 minutes – Neuronal injury and death occurs and irreversible damage is inevitable

Kindling phenomenon – time sensitivity of achieving seizure control

Management consideration - Airway

If patient is maintaining airway, aggressive approach such as intubation is not indicated. Start with simple measures Blow by oxygen

Oxygen by nasal cannula

Airway re-positioning

Oral airway

Nasal trumpet

Endotracheal intubation may be indicated in respiratory failure Rising PCO2 (>60)

Circulatory Shock

Apnea/bradypnea

Management consideration

Out of hospital/pre-hospital

Depends on IV access

Midazolam 0.1 mg/kg (IM), 0.2 mg/kg (PR), 0.2 mg/kg Buccal

5 mg max for up to 40 kg weight, 10 mg max for > 40 kg weight

Lorazepam 0.1 mg/kg IV

Diazepam PR (0.5mg/kg – max 20 mg)

IM midazolam or IV lorazepam?

IM lorazepam (not a preferred route – depo effect - prolonged sedation)

Management consideration

First line – in hospital – up to 2 doses

IV lorazepam (0.1 mg/kg) – Max 4 mg

IV diazepam (0.1-0.2 mg/kg) – Max 8 mg

IV midazolam (0.1 mg/kg) – max 4-6 mg –

if no IV access – e.g. pre-hospital, IM Midazolam is an option

Second line – in hospital – after 10 minutes of continued SE – dose can be repeated once if needed but lower dose recommended

IV forphenytoin (20mg PE/kg loading dose) – Max 150 mg PE/min

IV Valproic acid (40 mg/kg loading dose)

IV Levetiracetam (60 mg/kg loading dose)

IV phenytoin (20 mg/kg loading dose – slower pushed at 1mg/kg/min)

**Note: For age > 28 days and for Convulsive or partial motor SE

Management considerations

Third line – in hospital - typically needs airway to be protected first

Pentobarbitol – 5-15 mg/kg initial dose

Followed by infusion 0.5-5 mg/kg/hour (typical infusion 0.5-1 mg/kg/hour)

Caution: Myocardial depression, decreased cardiac output

Propofol – short acting, but tricky

No more than 5 mg/kg/hour (to reduce risk of toxicity)

Not used if patient on ketogenic diet

Phenobarbitol- Initial dose of 20mg/kg (can be first agent if no response to benzo)

Followed by

2 mg/kg/minute infusion (max 50mg/minute)

8-10 mg/kg doses every 30 minutes

Status epilepticus – role of continuous EEG monitoring

Convulsive status epilepticus

Continuous EEG helps detect sub-clinical seizure after the apparent seizure has stopped. This can guide further antiepileptic agent and avoid further neuronal damage.

In non-convulsive SE, continuous EEG can guide treatment decision

In traumatic brain injury and continued/fluctuating altered mental status

In acutely ill patient with altered mental status Patients with SE who require pharmacologic sedation/paralysis

Paroxysmal events thought to be seizure activity

Neonatal status epilepticus

Herman S, Abend N, Bleck T, Chapman K, Drislane F, Emerson R, et al. . Consensus statement on continuous EEG in critically ill adults and children, part I: indications. J Clin Neurophysiol. (2015) 32:87–95.

Special considerations – Neonatal status epilepticus Neonatal seizure rate: 2-4/1000, 20-60/1000 in premies < 1500 gram

Treatment options: Phenytoin and phenobarbital (50% effective)

Recent options: levetiracetam and topiramate

Slaughter L. A., Patel A. D., Slaughter J. L. (2013). Pharmacological treatment of neonatal seizures: a systematic review. J. Child Neurol. 28 351–364.

Special considerations – Neonatal status epilepticus

Special considerations – Neonatal status epilepticus

Special considerations – Neonatal status epilepticus

Special considerations

Ketamine – emerging as an alternative option (1.5 mg/kg loading dose)

Lacosamide – ~6-10 mg/kg with a max 50-100 mg dose (*limited data)

Topiramate – Limited data or guidelines on its use for refractory SE

Prolonged refractory SE treatment

Suppression bursts 24-48 hours – Pentobarbitol, midazolam, or propofol induced coma with continuous EEG monitoring

Case review

2 year-old female is brought to the ED in status epilepticus.

After first line agents (benzodiazepines) are used, patient continues to seize. What is the second line therapy agent to consider?

What is the airway management strategy?

Conclusion

For the purpose of ED treatment, SE is 5 minutes of continuous convulsion or failure to return to baseline after seizure ends. Definitions vary, however.

SE is most common in first year of life, or with febrile seizures

SE lasting longer than 30 minutes is a risk factor for irreversible neuronal damage and death

Serious complications of SE include acidemia, hypoxia, and CO2 retention

Management options should consider individual risk, prior response, and medication adherence

Benzodiazepines are first line therapy to stop SE

Accepted second line includes fosphenytoin, valproic acid, and levetiracetam

Airway protection should be considered for refractory SE and prior to third line therapy (Phenobarbitol, Propophol, Pentobarbitol, etc.)

If on continuous drips, suppression bursts of 24-48 hours are considered prior to reassessment

References

1. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia 1993; 34:592.

2. Raspall-Chaure M, Chin RF, Neville BG, et al. The epidemiology of convulsive status epilepticus in children: a critical review. Epilepsia 2007; 48:1652.

3. Novak G, Maytal J, Alshansky A, Ascher C. Risk factors for status epilepticus in children with symptomatic epilepsy. Neurology 1997; 49:533.

4. Raspall-Chaure M, Chin RF, Neville BG, Scott RC. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol 2006; 5:769.

5. McTague A, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev 2018; 1:CD001905.

6. Sofou K, Kristjánsdóttir R, Papachatzakis NE, et al. Management of prolonged seizures and status epilepticus in childhood: a systematic review. J Child Neurol 2009; 24:918.