Post on 24-Aug-2020
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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.