Emergency Management of Seizures Sarah A. Murphy, MD Pediatric Critical Care Fellow, MGH.
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Transcript of Emergency Management of Seizures Sarah A. Murphy, MD Pediatric Critical Care Fellow, MGH.
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Emergency Management of Seizures
Sarah A. Murphy, MDPediatric Critical Care Fellow, MGH
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• 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
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Assess for Coma or Convulsions: AVPU
• Is the child:– 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
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Unconscious or Convulsion:
• Manage Airway
• Give diazepam or paraldehyde if convulsing
• Position unconscious child
• Give IV glucose:
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Obtain History:
• Fever?
• Head Injury?
• Drug or Toxin exposure?
• Birth asphyxia or injury if newborn?
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Examination:
• AVPU score• General:
– Pallor– Jaundice– Edema– Petechial Rash
• Head and Neck:– Stiff neck– Signs of trauma– Pupilary reactions– Fontanelle– Posture
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Laboratory Investigations:
• Blood glucose
• Blood smear for malaria
• Blood pressure
• Urine microscopy
• Electrolytes
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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
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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
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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
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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
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Emergency Management of Seizures?
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Clinical Diagnosis of Seizure
• Altered Mental Status• Hypotonia• Emesis• Eye deviation• Tonic-clonic movements• Incontinence
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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
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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
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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
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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
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Systemic Complications of SE (Rogers, ch.22)
Parameter Early Late Complications
Blood Pressure HypotensionArterial oxygen Hypoxia
Arterial CO2 Increased ICPSerum pH Acidosis
Temperature FeverAutonomic activity Arrhythmias
Lung fluids AtalectasisSerum K+ Arrhythmias
Serum CPK Renal failure
Cerebral blood flow Cerebral bleedCerebral O2 consumption Ischemia
/nlnl
900% 200%
300% 300%
10C 20C
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Neuropathology
Autopsy findings include:– 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
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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
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Hypothesized CNS mechanisms of neuronal
damage/death• Excessive presynaptic release of excitatory transmitter intracellular postsynaptic changes dendritic swelling and cell death.
• Inhibitory-excitatory interaction: over-excitation combined with decrease of GABA-mediated inhibition.
• Possible unmasking of excitatory glutamate receptor channel-mediated events
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Initial Emergency Management of Seizures
• Stabilize the patient• Address underlying causes of seizure
• Treat seizures• Choices of anti-epileptic drugs
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Stabilize the patient
Maintain Cardiovascular and Respiratory Function:
• airway protection• maintain ventilation, oxygenation• support circulation• establish vascular access
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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
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Stabilize the patient
Assess A, B, C, D’s ……
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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)*
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Stabilize the patient
–Breathing•support by using muscle relaxation if necessary
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Stabilize the patient
–Circulation •verify good BP•secure PIV•NS 20cc/kg
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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
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RSI for Status Epilepticus
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
-Thiopental 3-5mg/kg or
-Versed 0.05-0.1mg/kg or
-Propofol 1-3mg/kg
Paralytic-Succinylcholine 1-2mg/kg or
-Vecuronium 0.1-0.3mg/kg
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Address underlying causes
• Elicit quick history– Trauma– Antecedent illness– Fever– Ingestion– Skipped meds
• Obtain critical labs– Chem 7, Ca, Phos, CBC, tox screen, AED levels
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– Correct and then prevent metabolic derangements:
•Hydration•Electrolytes•Glucose•Lactate
Address underlying causes
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Common Causes of Seizures
• Fever• Hypoglycemia• Hypoxia• Poisoning• Head Trauma• Meningitis• Idiopathic
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Treat Seizures
1. Evaluate and treat underlying cause
2. Stop clinical/electrical seizure activity (using Anti-Epileptic Drugs)
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The longer the seizure, the more difficult to control
so…ACT FAST!
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• 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
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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.
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Implementing Drug Therapy
• Anticipate consequences of therapy– Respiratory depression– Hypotension
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Anticonvulsants: Based on availability
• First-line• Diazepam, or Lorazepam• Paraldehyde
• Second-line• Phenytoin or• Phenobarbitol
• Third-line• Thiopental• Midazolam• Isoflurane• Propofol
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Diazepam (Valium)• 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
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Paraldehyde• Can be given:
– 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).
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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 minutesPeak 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
• Use: First-line therapy for SE
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Phenobarbital
• Pharmacokinetics:– 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
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Dilantin (Phenytoin)
• Pharmacokinetics:• 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)
• Pharmacodynamics– 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
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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)
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(Fos)phenytoin
• Fosphenytoin is pro-drug of phenytoin (hydrolyzed into phenytoin)
• Pharmacokinetics:• Low lipid solubility, enters brain slowly• Peak brain concentration in 20-60 mins• Hepatic metabolism (P-450 system)
• Pharmacodynamics• 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)
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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
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Refractory Status Epilepticus
• Inadequate drug treatment
• Uncorrected medical and metabolic complications:– Metabolic acidosis– Electrolyte imbalance– Hypoglycemia– Infections– Hyperthermia
• Large cerebral lesion
- Hypercarbia- Fluid Imbalance- Pulmonary Edema- Renal Failure- DIC
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Therapy for Refractory SE
• Therapeutic objective in this stage changes to cerebral protection by suppression of CNS activity and metabolism by means of GA– Pentobarbital – Isoflurane– Midazolam – Propofol
• Continuous EEG monitoring
• Be prepared for hypotension, neurogenic pulmonary edema
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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
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Drugs that Cause Seizures
• Antimicrobials– Isoniazid– Penicillins– Nalidixic acid– Metronidazole
• Psychopharm drugs– Antihistamines– Antidepressants– Antipsychotics– Phencyclidine– TCA
• Anesthetics- Halothane- Enflurane- Cocaine
• Narcotics- Fentanyl- Meperidine
• Analgesics- Ketamine
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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– Be ready to intubate– Phenobarbital elimination half-life VERY long– 4-5 days to reach steady-state– “Therapeutic” level = what works!
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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
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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
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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.
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