Download Emergency Management of Seizures

Emergency Management of
Seizures
Sarah A. Murphy, MD
Pediatric Critical Care Fellow, MGH
• This presentation will review emergency
management of seizure/convulsions
• We will begin with a review of the approach
to a child who presents with:
– lethargy
– unconsciousness OR
– convulsions/seizures
Assess for Coma or Convulsions:
AVPU
• Is the child:
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Alert?
Responding to Voice?
Responding to Pain?
Unconscious?
• A child who is not alert but responding to voice is
lethargic
• A child who does not respond to pain is
unconscious
Unconscious or Convulsion:
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Manage Airway
Give diazepam or paraldehyde if convulsing
Position unconscious child
Give IV glucose:
Obtain History:
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Fever?
Head Injury?
Drug or Toxin exposure?
Birth asphyxia or injury if newborn?
Examination:
• AVPU score
• General:
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Pallor
Jaundice
Edema
Petechial Rash
• Head and Neck:
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Stiff neck
Signs of trauma
Pupilary reactions
Fontanelle
Posture
Laboratory Investigations:
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Blood glucose
Blood smear for malaria
Blood pressure
Urine microscopy
Electrolytes
Differential Diagnosis of Lethargy,
Unconscious, or Convulsions:
• Meningitis: irritable, stiff neck or bulging fontanelle,
petechial rash
• Cerebral Malaria: jaundice, anemia, pallor, convulsions,
hypoglycemia
• Febrile convulsions: history of same, seziure associated
with fever, age 6 mos to 5 years, normal blood smear
• Hypolycemia: responds to treatment with glucose, check
for malaria
• Head injury: signs of trauma
Differential Diagnosis of Lethargy,
Unconscious, or Convulsions:
• Poisoning: suggested by history
• Shock: unlikely to cause seizures, poor capillary
refill, rapid weak pulse
• Glomerulonephritis with encephalopathy:
raised BP, edema, decreased urine, blood in urine
• DKA: high blood sugar, polydipsia and polyuria,
deep breathing
Differential Diagnosis of lethargy,
unconsciousness or convulsions IN
NEONATE
• Birth Asphyxia: difficult delivery, onset in 1st
three days of life
• Intracranial hemorrhage: low-birth weight
or pre-term infant with onset in 1st three days of
life
• Hemolytic disease of newborn/
kernicterus: jaundice, pallor, bacterial
infection, onset in 1st three days of life
Differential Diagnosis of lethargy,
unconsciousness or convulsions IN
NEONATE
• Neonatal tetanus: onset from 3-14days of life,
irritability, difficulty breast-feeding, trismus,
spasms, seizures
• Meningitis: high-pitched cry, tense fontanelle,
apneic episodes
• Sepsis: fever or hypothermia, shock, seriously ill
Emergency Management of
Seizures?
Clinical Diagnosis of Seizure
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Altered Mental Status
Hypotonia
Emesis
Eye deviation
Tonic-clonic movements
Incontinence
Pathophysiology of Seizures
• Cellular Mechanisms responsible for Status
Epilepticus
• Natural progression of Status Epilepticus
• Systemic complications of Status Epilepticus
• Neuropathology
• CNS mechanisms for neuronal damage/death
Cellular Mechanisms
• A group of neurons in the CNS become
depolarized with abnormal synchrony and
fire action potentials repetitively,
interfering with normal brain function
• This abnormal paroxysmal activity is
intermittent and usually self-limited,
lasting seconds to a few minutes
Cellular Mechanisms
• Cellular explanation likely multifactorial:
– Increased release of excitatory
Neurotransmitters (Glutamate)
– Decreased release of inhibitory
neurotransmitters (GABA)
– Increased/decreased neurotransmitter
sensitivity
– Changes affecting ionic and voltage-gated
channels at neuronal synapses  membrane
instability
Natural History of SE
• As the duration of SE progresses, there is a
distinct evolution with predictable effects in the
human body
• Systemic changes occur in phases
– Phase I (<30 mins)
– Phase II (30-60 mins) – severe systemic distress
– Phase III (>60 mins) – Refractory SE
Systemic Complications of SE (Rogers, ch.22)
Parameter
Early
Late
Complications
20C
Hypotension
Hypoxia
Increased ICP
Acidosis
Fever
Arrhythmias
Atalectasis
Arrhythmias
Renal failure
Blood Pressure
Arterial oxygen
Arterial CO2
Serum pH
Temperature
10C
Autonomic activity
Lung fluids
Serum K+
Serum CPK
/nl
nl
Cerebral blood flow
900%
200%
Cerebral O2 consumption
300%
300%
Cerebral bleed
Ischemia
Neuropathology
Autopsy findings include:
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Hippocampal necrosis
Widespread cerebellar necrosis
Degeneration of Purkinje cells
Necrosis and neuronal loss in the cerebral
cortex.
Cause of neuropathologic changes:
– Perhaps due to systemic physiologic alteration
(hypotension, hypoxia, hyperpyrexia, acidosis)
– Perhaps intrinsic CNS mechanisms related to
electrical activity
Neurologic Damage
• In animal models, irreversible
neurologic damage in 90-120 mins
• With prolonged tonic-clonic activity:
hypoxia, hypoglycemia, hyperkalemia,
hyperkalemia, increased ICP
• Even with control of BP, oxygenation,
ventilation, glucose and fever,
neuronal cell death occurs
Hypothesized CNS mechanisms
of neuronal damage/death
• Excessive presynaptic release of
excitatory transmitter  intracellular
postsynaptic changes  dendritic swelling
and cell death.
• Inhibitory-excitatory interaction: overexcitation combined with decrease of
GABA-mediated inhibition.
• Possible unmasking of excitatory glutamate
receptor channel-mediated events
Initial Emergency Management
of Seizures
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Stabilize the patient
Address underlying causes of seizure
Treat seizures
Choices of anti-epileptic drugs
Stabilize the patient
Maintain Cardiovascular and Respiratory
Function:
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airway protection
maintain ventilation, oxygenation
support circulation
establish vascular access
Stabilize the patient
• Position the patient to avoid
aspiration, suffocation, physical
injury
– Elevate HOB
– Turn patient on side after seizure event
to prevent aspiration
– Suction available for vomitus, secretions
– Bars, rails and close monitoring to
prevent physical harm
Stabilize the patient
Assess A, B, C, D’s ……
Stabilize the patient
– Airway protection
• 100% oxygen on all patients
• attempt to open airway with jaw thrust if
needed
• oral or nasopharyngeal airway if easily placed
• suctioning of emesis/secretions
• ETT if necessary (RSI)*
Stabilize the patient
– Breathing
• support by using muscle relaxation if
necessary
Stabilize the patient
– Circulation
• verify good BP
• secure PIV
• NS 20cc/kg
Stabilize the patient
– Dextrose
• Check blood sugar
• If suspecting low bood sugar, give 25%
dextrose in water, 2-4ml/kg
• 10 mL/kg D10 in neonates
RSI for Status Epilepticus
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AIRWAY
Airway obstruction
Loss of cough/gag
Hypoventilation
Hypoxemia
Risk of aspiration
Preoxygenate w/ 100% O2 (avoid PPV)
Atropine 0.02mg/kg (0.1mg min-1mg max)
Cricoid pressure
Sedative
Paralytic
-Thiopental 3-5mg/kg or
-Succinylcholine 1-2mg/kg or
-Versed 0.05-0.1mg/kg or
-Vecuronium 0.1-0.3mg/kg
-Propofol 1-3mg/kg
Address underlying causes
• Elicit quick history
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Trauma
Antecedent illness
Fever
Ingestion
Skipped meds
• Obtain critical labs
– Chem 7, Ca, Phos, CBC, tox screen, AED
levels
Address underlying causes
– Correct and then prevent metabolic
derangements:
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Hydration
Electrolytes
Glucose
Lactate
Common Causes of Seizures
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Fever
Hypoglycemia
Hypoxia
Poisoning
Head Trauma
Meningitis
Idiopathic
Treat Seizures
1. Evaluate and treat underlying cause
2. Stop clinical/electrical seizure activity
(using Anti-Epileptic Drugs)
The longer the seizure, the more
difficult to control so…ACT FAST!
• Lowenstein and Alldredge:
– Seizures stopped by 1st line therapy in
80% of patients if started in the 1st 30
mins
– But 1st line drugs stopped seizures in
only 40% of patients if started > 2hrs
after seizure
Implementing Drug Therapy
“It’s not the particular choice of drug but rather the
timing, route, and vigor of therapy that are major
determinants of duration of status epilepticus and
subsequent morbidity.” Rogers et al.
“When treating status epilepticus, the therapeutic
endpoint is not the production of a particular drug
concentration but rather a clinical and/or electrical
endpoint.” Rogers et al.
Implementing Drug Therapy
• Anticipate consequences of therapy
– Respiratory depression
– Hypotension
Anticonvulsants: Based on availability
• First-line
• Diazepam, or Lorazepam
• Paraldehyde
• Second-line
• Phenytoin or
• Phenobarbitol
• Third-line
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Thiopental
Midazolam
Isoflurane
Propofol
Diazepam (Valium)
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Can be administered IV/PR
• Avoid repeated doses  accumulation of drug and metabolites
• Pharmacokinetics :
– Highly lipid-soluble  easily passes across blood brain barrier, and large
volume of distribution
• Rapid distribution into brain (10 sec)
• CSF concentrations reach ½ maximum value in 3 minutes
• Then, with redistribution, rapid drop in serum concentration
• Pharmacodynamics:
• Depresses all levels of the CNS, including the limbic and
reticular formation by binding to the benzodiazepine site on
the gamma-aminobutyric acid (GABA) receptor complex and
modulating GABA, which is a major inhibitory neurotransmitter
in the brain
• Onset of action ~2 mins
• Duration of action ~15 mins
• Low toxicity: sedation, hypotension, respiratory depression,
laryngospasm, CV collapse, arrest
• Use: seizure activity compromising vital functions
• IV diazepam + LD phenytoin
• Can be given:
Paraldehyde
– IM: The usual intramuscular dose of paraldehyde for
status epilepticus is 0.15 to 0.3 ml/kg. Can give additional
dose (0.05 ml/kg). The dose may be repeated in 2 to 6
hours and no more than 5 milliliters should be administered
in one site (AMA Department of Drugs, 1986).
– IV: 1) The usual dose 0.1 to 0.15 ml/kg. The intravenous
solution should be well-diluted in normal saline. Higher
doses 0.3ml/kg increase the incidence of adverse effects
2) Administration of intravenous paraldehyde is not
recommended
– PR: The usual rectal dose is 4-8 ml diluted with an equal or
double amount of oil or isotonic sodium chloride. The
paraldehyde should be diluted 2:1 in olive or cottonseed oil
or mixed in 200 ml of NS. Rectal absorption is slow and
peak plasma levels will not occur for 2 to 4 hours (Coniglio &
Garnett, 1989).
Paraldehyde
Pharmacokinetics :
– Metabolism by LIVER, 70% to 80%, with the rate of elimination slowed
by hepatic insufficiency (Gilman et al, 1985)
Pharmacodynamics:
Onset: intramuscular: 2 to 3 minutes, oral: 10 to 15 minutes
Peak Response: intramuscular: 5 to 15 minutes
Use:
Paraldehyde is a rapidly acting hypnotic, with sleep normally
ensuing in 10 to 15 minutes. It has no analgesic properties and may
produce excitement or delirium in the presence of pain.
Paraldehyde is effective for all types of convulsions and delirium at
high doses. Respiratory depression and hypotension also occur in
high doses, but little effect on respiration and blood pressure
occur at therapeutic doses (Gilman et al, 1985).
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Lorazepam (Ativan)
Given over 2 minutes
• may repeat Q10 mins x 2
• Beware of tachyphylaxis with successive doses
Pharmacokinetics
• Lipid-solubility and volume of distribution half that of
diazepam
• Half-life twice that of diazepam
• Longer onset of action (2 mins)
Pharmacodynamics
• Depresses all levels of the CNS, including the limbic and
reticular formation, by binding to the benzodiazepine site on
the gamma-aminobutyric acid (GABA) receptor complex and
modulating GABA, which is a major inhibitory neurotransmitter
in the brain
• Onset of action
• Oral: Within 60 minutes
I.M.: 30-60 minutes
I.V.: 15-30 minutes
• Duration of action 4-6 hrs
• Half-life significantly prolonged in newborns (40hrs vs 10)
• Low toxicity: sedation, hypotension, respiratory depression,
badycardia, CV collapse, arrest
Phenobarbital
• Pharmacokinetics:
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The least lipid-soluble
Peak brain concentration 60 minutes
Predictable elimination kinetics
Very long half-life: up to 120 hrs
• Pharmacodynamics:
– Inhibits reticular activating system (interferes w/ NA, K
transport across membranes)
– Onset of action: 20 minutes
– Duration of action: 24-48 hours
– Beware of prolonged sedation, respiratory depression
Dilantin (Phenytoin)
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Pharmacokinetics:
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Pharmacodynamics
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Low lipid solubility, enters brain slowly
Peak brain drug concentration: 10-30 mins
Side effects: hypotension, cardiac arrythmias
Cannot be given with glucose (will precipitate)
Stabilizes neuronal membranes and decreases seizure activity
by increasing efflux or decreasing influx of sodium ions across
cell membranes in the motor cortex creating delay in
neuronal electrical recovery
Prolongs effective refractory period and suppresses
ventricular pacemaker automaticity, shortens action potential
in the heart
• Selectively blocking the neurons that are firing at high
frequency
• Prevents the electrical spread of a focus of irritable
tissue
Dilantin (Phenytoin)
• Not water-soluble, dissolved in propylene glycol
• Or benzoic acid (benzoate), a metabolite of benzyl alcohol;
large amounts of benzyl alcohol which has been associated
with a potentially fatal toxicity ("gasping syndrome") in
neonates; metabolic acidosis, respiratory distress, gasping
respirations, CNS dysfunction (including convulsions,
intracranial hemorrhage), hypotension and cardiovascular
collapse
• Toxicity depends on the route of administration, duration,
exposure, and dose
– Hypotension, bradycardia, arrhythmias, cardiovascular collapse
(especially with rapid I.V. use)
– Risk of necrosis and limb ischemia from infusion (purple
glove syndrome)
(Fos)phenytoin
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Fosphenytoin is pro-drug of phenytoin (hydrolyzed into
phenytoin)
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Pharmacokinetics:
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Pharmacodynamics
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Low lipid solubility, enters brain slowly
Peak brain concentration in 20-60 mins
Hepatic metabolism (P-450 system)
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Stabilizes neuronal membranes (flux of Na, Ca ions)
Onset of action: 10 mins
Duration of action: 24 hrs w/ single dose
Does NOT depress respiratory drive or alter MS
Toxicity: depends on rate of administration not dose
– bradycardia, hypotension, cardiac arrhythmia
– Monitor HR, BP, ECG during LD
– Avoid extravasation (flush w/ NS, use large PIV)
Incidence of Status Epilepticus
• Status Epilepticus (SE): seizure that lasts for
greater than 30 mins or multiple seizures going on
for 30 mins without return to baseline in between
• Status Epilepticus occurs as 1st seizure in 12% of
children with seizures
• Refractory Status Epilepticus (RSE): Seizures
that do no respond to 1st line therapy and persist
for > 60 minutes
Refractory Status Epilepticus
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Inadequate drug treatment
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Uncorrected medical and metabolic
complications:
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Metabolic acidosis
Electrolyte imbalance
Hypoglycemia
Infections
Hyperthermia
Large cerebral lesion
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Hypercarbia
Fluid Imbalance
Pulmonary Edema
Renal Failure
DIC
Therapy for Refractory SE
• Therapeutic objective in this stage changes to
cerebral protection by suppression of CNS
activity and metabolism by means of GA
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Pentobarbital
Isoflurane
Midazolam
Propofol
• Continuous EEG monitoring
• Be prepared for hypotension, neurogenic
pulmonary edema
Pentobarbital
– Directly depresses neuronal activity through enhanced
GABA receptor responses
– More lipid soluble than Phenobarbital: penetrates brain
faster, redistribution into body tissues
– Elimination half-life 15-60 hrs
– Hypotension is significant complication
Drugs that Cause Seizures
• Antimicrobials
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Isoniazid
Penicillins
Nalidixic acid
Metronidazole
• Psychopharm drugs
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Antihistamines
Antidepressants
Antipsychotics
Phencyclidine
TCA
• Anesthetics
- Halothane
- Enflurane
- Cocaine
• Narcotics
- Fentanyl
- Meperidine
• Analgesics
- Ketamine
Treatment in Relation to Age
• Neonates
– Unpredictable relationship between dose and
theraputic drug effect
• Less protein binding
• Variable ability to eliminate drug
– Lorazepam  Phenobarb  fosphenytoin
• Infants
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Be ready to intubate
Phenobarbital elimination half-life VERY long
4-5 days to reach steady-state
“Therapeutic” level = what works!
Simple Febrile Seizures
• Occurs with fever in a child aged 6 months to 5 years
• A convulsion associated with an elevated temperature
greater than 38ºC
• Single seizure
• Last less than 15 minutes, have no focal features, and, if
they occur in a series, the total duration is less than 30
minutes.
• The child is otherwise neurologically healthy and without
neurological abnormality by examination or by developmental
history
• No central nervous system infection or inflammation
• No acute systemic metabolic abnormality that may produce
convulsions
• No history of previous afebrile seizures
Management of 1st non-febrile
seizure
• If well-appearing in ED, patient can
be discharged to home
• Outpatient EEG and MRI within 1
month
• Outpatient Neurology Consult
• Only 30% will have second seizure
Take Home Points
• The longer the seizure, the more difficult it becomes to stop
so…ACT FAST!
• The endpoint is NOT a particular drug concentration BUT rather a
clinical and/or electrical endpoint.
• It is not the particular choice of drug but rather the timing, route
and vigor of therapy that determines mortality and morbidity.
• Early therapy is far more effective that later therapy.
• Rate of administration of a drug is more important than total
amount administered in terms of toxicity.
• Intubate early; do not wait for florid systemic complications to
occur.