Download Seize the Day- An Update on Small Animal Seizure Therapy

Neurologic Emergencies:
status epilepticus &
clusters seizures
Todd M. Bishop, DVM, DACVIM (Neurology)
Thursday February 6th, 2014
Neurologic emergencies
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Status epilepticus and cluster seizures
Severe vestibular events
Acute spinal cord injury (ASCI)
Traumatic brain injury (TBI)
Urgent but not emergent
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Isolated seizures
Head tilt
Facial paralysis
Ambulatory paresis and or ataxia
Spinal pain*
Tremors
Goals of this lecture series
• Recognize a true neurologic emergency
• Perform initial point-of-care diagnostic
testing
• Provide initial critical therapeutic
interventions
• Prognosticate
• Know which cases to refer and when
These lectures will be …
• Uplifting … No.
• Inspiring … Maybe.
• Empowering … I hope so.
• Remember you are the first-responders!
• What you do initially can be life-saving and
significantly impact prognosis & outcome.
• But don’t worry … no pressure !
http://fbemoticonscodes.blogspot.com/2013/02/vomit-emoticon-code-for-facebook-chat.html
Seizure topics to cover
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Definitions
Classification
Diagnostic testing
Therapeutic intervention
Complications
Prognosis
When to refer
What is a seizure?
• Definition:
– Fits, convulsions, epilepsy
– Electrochemical abnormality
in the front 2/3’s of the brain
(“forebrain”)
– A group of hyperexcitable
neurons that experience
synchronous discharge
– Enlist or recruit other
surrounding neurons
psych.umn.edu
Prosencephalon
Predictability
• Paroxysmal in nature in that it tends to
appear suddenly out of background of
normality and disappears with equal
abruptness (transient)
• Can not be predicted, but owners learn to
identify earlier signs (aura)
• Typically … can not be elicited!
• “predictably unpredictable”
What clients think about
seizure triggers
• Phases of the moon
• Barometric pressure
• Mail carrier ringing doorbell
• Vacuum
• Baby crying
• Home remodeling
• In-laws visiting
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Wrist watch clicking
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Mold in the house
http://ocean1025.files.wordpress.com/2011/01/wolf-moon.jpg
What I think about
predictability
• Nights
• Weekends
• Holidays
http://kevenelliff.com/wp-content/uploads/Facebook-Thumbs-Down.jpg
Seizure Classification
• Generalized
– Tonic-clonic
– Myoclonic
– Absence
– Atonic
www.geocities.com
• Partial
– Focal (EEG)
– Simple
– Complex
cd.textfiles.com
Etiologic classification
• Idiopathic epilepsy
– no identifiable structural brain lesion
– presumed to be genetic/familial in origin
– usually age-dependent
• Symptomatic epilepsy
– seizures due to underlying structural brain disease
• Probable symptomatic epilepsy (cryptogenic)
– seizures that are believed to be symptomatic but no
etiology can be found
• Reactive seizures
– seizures caused by extracranial disorders (toxic,
metabolic)
A simplified scheme
• Idiopathic epilepsy
– “Epilepsy”
• Extracranial disease
– Metabolic/toxic
• Intracranial disease
– Structural CNS
www.epilepsynl.com
The only classification we
care about tonight
Cluster seizures
vs.
Status epilepticus
http://www.whitegadget.com/pc-wallpapers/141188-boxing-gloves.html
Cluster seizures
• Two or more seizures in a 24 hours period
Status Epilepticus
• One continuous seizure (ictus) lasting
longer than 5-10 minutes
• Frequent cluster seizures that do not allow
for regaining of consciousness between
the seizures.
Diagnostic approach
• Signalment (age, breed, etc.)
• Basic followed by a detailed medical history
• General physical followed by a neurologic
exam
• Emergency minimum database
• Basic medical work-up
• Advanced medical work-up
• Referral for intracranial work-up as needed
Basic HX/PE
IV cath
MDB
Stabilize
Complete HX/PE
Neuro exam
Adjust Tx
Basic Medical Workup:
CBC/Chem/UA/T4
CXR +/- AXR
BP +/- EKG
Refine Tx
Advanced Medical Workup:
Abd U/s
Echo
SBA
Thyroid panel
Infectious disease titers
Maintenance
Anticonvulsant
therapy
Intracranial Workup:
MRI
CSF tap
Signalment is IMPORTANT!
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1.5 yo FS Pug = Encephalitis
2 yo MI German Sheppard = Epilepsy
12 yo FS Golden Retriever = Neoplasia
3 yo M DSH = Infectious!
=
http://www.restkultur.net/boxer-dog-pictures-id-35687.html
A DETAILED seizure history
• At what age did they start?
• Ask the owner to describe what they see w/o using words like (grand
mal, seizure, convulsion).
• How often are they happening?
• How long do they last?
• Do they come in clusters?
• What happens immediately afterward?
• What anticonvulsants have been tried?
• How long have they been on these meds?
• Any recent dose changes?
• Any side-effects of the medications?
• Any recent lab tests or drug blood levels?
• WHEN WAS THE LAST DOSE OF GIVEN?
http://www.hockeydino.com/2011/08/sports-blah-blah-football-blah.html
General Physical Exam
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Arrhythmia?
Murmur?
Pulse deficits?
Muffled heart sounds?
Jugular pulses?
Adventitial lung sounds?
Peritoneal fluid wave?
Abdominal masses?
• If the answer is “yes” to any of these questions … are
the client’s really observing true seizures vs. syncope?
http://www.stritch.luc.edu/lumen/MedEd/Radio/curriculum/Medicine/Pericardial_effusion2.htm
The Neurologic exam *
• Mentation?
• Cranial nerves deficits?
• Gait abnormalities?
– Propulsive circling?
– Paresis/ataxia?
• Postural reaction deficits?
• Spinal reflexes are less important in these cases
* Use caution when interpreting the neuro exam
during the post-ictal phase.
Emergency minimum database
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Packed cell volume (PCV)
Total solids (TS)
Blood glucose (BG)
Electrolytes (Na+, K+, Cl-, Ca2+)
• If you have one … an I-stat is very helpful!
Basic Medical Work-up
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Complete Blood Cell Count (CBC)
A comprehensive biochemistry profile
Urinalysis
Total T4
Chest +/- abdominal radiographs
A BLOOD PRESSURE!
+/- EKG depending on auscultation
Advanced Medical Work-up
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Abdominal ultrasound
Echocardiogram
A complete thyroid profile
Serum bile acids
Urine protein:creatinine ratio
Infectious disease testing
– Canine: 4Dx (Idexx)
– Feline: Feline serology 2 (Antech)
Why these databases are so
important!
• Systemic/metabolic diseases can secondarily
affect the brain (remember … reactive seizures)
– Liver disease (hepatic encephalopathy)
– Kidney failure (renal encephalopathy)
– Hypertension (pheochromocytoma, hyperthyroidism, glomerular
disease, Cushing's disease)
– Hypoxemia (cardiovascular or pulmonary disease)
– RBC diseases (anemia or polycythemia)
– Hypothyroidism
– Profound electrolyte disturbances (hyper/hypoNa)
– Hypoglycemia (insulinoma, insulin overdose)
– Nutritional deficiencies (don’t forget about thiamine)
– Toxins (lead, ethylene glycol, OP’s, strychnine, metaldehyde,
mycotoxins)
Intracranial Work-up
• MRI
• CSF analysis
cinemakc.com
Stabilizing the seizure patient
• Step 1: get the current seizure stopped
• Step 2: prescribe a loading dose of an
anticonvulsant if necessary (ie. status
epilepticus)
• Step 3: start maintenance anticonvulsant
therapy if necessary (ie. cluster seizures)
The Benzodiazepines
• Diazepam (Valium)
• Midazolam (Versed)
Mother's Little Helper
• Start with a 0.5 mg/kg IV bolus
• Repeat up to 3 more times as quickly as
needed.
"Valium, Take Me Away!"
• Can be given at 1-2 mg/kg rectally or
NASALLY if no IV access or at home
karenwindness.com
Forget the calculators!
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Cats: 0.5 mL
Small Dog: 1 mL
Medium Dog: 2 mL
Large Dog: 3 mL
XL Dog: 4 mL
* You are not going to kill anything with
Valium … I promise!
ricklondon.wordpress.com
Constant Rate Infusion (CRI)
• Q: When should you consider a CRI?
• A: When a single bolus or two stops the
current seizure but the seizures recur
within minutes to hours (4-6 hrs) of the
initial bolus.
The Diazepam CRI
• Calculate the patient’s hourly maintenance
fluid rate (ie. 1.25 mL/lb/hr)
• I use 0.9% NaCl to avoid drug precipitation
• Note the volume of the Benzo that was
needed to stop the seizure(s)
• Remove that volume of NaCl from the bag
and replace it with your Benzo of choice
• Make up a 6 hour fluid complement
• Run at maintenance fluid rate
Diazepam CRI calculation
• Example: 100 lb. dog
• CRI fluid rate:100 lb. x 1.25mL/lb/hr =125
mL/hr
• Diazepam dose = 4 mL (XL dog)
• Make up a 6 hr complement: 6 hrs x 4 mL=
24 mL Diazepam.
• Remove 24 mL of NaCl and replace with 24
mL of Diazepam.
• When run at 125 mL/hr = 0.5 mg/kg/hr of
Diazepam!
Final thoughts about CRIs
• Midazolam works just as well as
Diazepam and causes less phlebitis
• A syringe pump or buretrol can be used
instead of injecting into a bag of IVF’s
• The CRI should be SLOWLY tapered by
~25% every 6 hours over 24 hours
• If seizures recur during the taper
– REPEAT the bolus injection
– Restart the CRI at the last effective dose
What if the Benzo’s aren’t working?
• Make sure you truly have venous access!
• Consider other drugs:
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Phenobarbital
Levetiracetam
Propofol
Pentobarbital (if you can get it)
Inhalant gas anesthesia (iso- or sevoflurane)
Bromide
Fos-phenytoin?
Phenobarbital (PB)
• Loading Dose
www.neurorelief.com/ images/articles/gabaci.gif
– 4 mg/kg q 4-12 hrs x 4 doses
– Total loading dose = 16 mg/kg
– Give a few minutes between injections to
allow for full effect to be realized
• Maintenance Dose
– 1.5 mg/lb BID
– 7.5 mg/cat BID
Levetiracetam (Keppra ®)
• MOA: binds to a synaptic vesicle protein (SV2A)
believed to impede nerve conduction across synapses
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Dose: 20mg/kg IV q 8hrs or faster PRN
Human levels: 5-21mcg/mL
T1/2E: 4 hours
Metabolism: partial hepatic
Excretion: renal
Side effects: behavior change,
somnolence, GI effects
pedemmorsels.com
Other CRIs to consider
• Propofol
Bolus: 1 mg/kg IV slowly
Dog CRI: 0.1-0.7 mg/kg/min
Cat CRI: 0.1-0.5 mg/kg/min (can cause Heinz body
anemia!)
* Be prepared to intubate and ventilate!!!
• Pentobarbital
Bolus: 3-15 mg/kg IV to effect (may take several
minutes for full effect!)
CRI: 2-5 mg/kg/hr
Potassium bromide (KBr)
• Loading Dose (orally or
rectally)
– Total loading dose = 400-600
mg/kg
– 100-150 mg/kg q 4-24 hours x
4 doses
– Rectal loading is … messy!
– Side-effects are often
intolerable.
• Maintenance Dose
– 30-40 mg/kg/day
http://www.canine-epilepsy.net/basics/basics_index.html
Complications
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Hyperthermia
Coagulopathies (DIC)
Hyperglycemia
Electrolyte abnormalities
Acid-base derangement
Cerebral hypoxia
Cerebral edema
Aspiration pneumonia
Kindling?
Non-cardiogenic PE
When to refer the case?
• AFTER status epilepticus or cluster
seizures are treated/stabilized!
• When typical medical therapy is failing.
• When intracranial disease is suspected.
• Before other neurologic signs develop.
Excellent resource
• http://www.canine-epilepsy.net