Toxin-Induced Seizures: Life-Threatening Forms of Withdrawl

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Toxin-Induced SeizuresLife-Threatening Forms of
Withdrawl
ACEP Scientific Assembly 2003, Boston, MA
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Steven E. Aks, DO, FACMT, FACEPFellowship
Director, The Toxikon Consortium and Department
of Emergency MedicineCook County Hospital
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Trauma - Tox

• A 40 year old male presents to the trauma unit at
  Cook County Hospital after jumping from the 4th
  story of a burning hotel.
• There are obvious bilateral fracture/dislocations
  of his ankles, and he complains of back pain.

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PE/Work up

• T 99 P 110 RR 24 BP 110/60
• Alert, in moderate distress secondary to pain
• CT head, chest, abdomen/pelvis negative
• L-S L4 compression fracture
• bilateral fracture dislocations

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Day 2

• Patient becomes increasingly anxious and
  agitated, noted to be diaphoretic.
• HR 130 BP 160/90 RR 24 T 101
• HEENT PERRL at 6 mm
• Ht RRR S1S2 tachycardic
• Neuro Diffuse tremors noted bil UEs, followed
  by brief tonic clonic seizure.

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Punchline

• Patient taking multiple benzodiazepines
  prescribed by several practitioners.
• 100 mg diazepam required to achieve light
  sedation
• 400 mg total over next 2 days
• Taper of 10

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Life-Threatening Withdrawal Syndromes
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Benzodiazepine Withdrawal

• Similar to ethanol, barbiturate
• Onset may be delayed
• Long T ½
• Resolution may take up to 10 days

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Withdrawal

• Occurs when a drug or toxin is removed or reduced
  and adaptive changes persist producing dysfunction

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Requisite for Withdrawal

• Adaption to a drug or toxin
• Decreasing concentration
• Tolerance

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Human Action is Dysinhibition

• Drugs as inhibitors
• Benzodiazepines on GABAa
• Opioids on opioid receptor
• Clonidine on the alpha 2 receptor

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Dysinhibition Syndrome

• Agitation
• Tachycardia
• Hypertension
• Fever, hyperthermia
• Seizures

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Flumazenil

• Avoid in benzodiazepine dependent patients
• 3 cases of reversal of chronic benzodiazepines
  leading to seizures

Spivey 1992 Clinical Therapeutics
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Drinking Problem?
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Ethanol

• Increases inhibitory effects
• Adaptive modulation
• Inhibitory (GABAa)
• Excitatory (NMDA)

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Mild Alcohol Withdrawal

• Tachycardia
• Tachypnea
• Hypertension
• Tremor (the shakes)
• Hypereflexia
• Peak at 24 to 36 hours

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Victor and Adams

• Tremulousness
• Seizures
• Hallucinations
• Delirium

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Course of Neurological Disturbances
Victor and Adams 1953
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Seizures

• Usually begin 6-8 hours after last consumption of
  alcohol.
• May be seen prior to autonomic symptoms
• Self-limited
• Can be seen at Etoh of gt 100
• CCH 1150!

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Hallucinations

• Usual visual
• Formication
• Auditory in 20
• May last up to three days

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Why Did They Die?

• No nurses
• Dehydration
• Physical restraints
• Neuroleptics

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Kindling

• Withdrawal progressively becomes worse
• Treat aggressively to head off early!

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Lorazepam Vs. Diazepam

• 2mg IV Q15 min
• IM OK
• Lack of hepatic metabolism good for cirrhotics
• Shorter T ½

• 5 mg IV Q 15 min
• IM not OK
• Long T ½ with active metabolites
• May accumulate in cirrhotics

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The Dosing Champions
Drug Dose Author
Diazepam 2640 mg over 56 hours Nolop, 1985
Midazolam 2850 mg over 5 days Lineaweaver, 1985
Diazepam 2335 mg over 48 hours Woo, 1979
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Miscellaneous

• Phenobarbital 5 mg/kg initially
• Bolus with 260 mg over 5 min, then 130 mg Q 30
  min until light sedation
• Pentobarbital
• Intubate patient
• 3-5 mg/kg bolus
• 100 mg/hour to maintain sedation
• Propofol

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Soma

• A 31 year old male and his 29 year old female
  companion presented to the ED with severe
  tremulousness that began 6 hours after they had
  discontinued daily use of Soma Solution, or 1,4
  Butanediol.
• They were taking 1 oz doses nightly as a sleep
  aid 5 weeks before, but they had gradually
  increased amounts and were taking 16 oz/day.

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Soma

• They stopped use 4 days prior and 6 hours later
  they developed abdominal cramping, palpitations,
  tremors and anxiety.
• Attempted treating symptoms with vodka for 4 days
  before presentation.

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Soma

• Positive findings
• Tachycardia 120
• Horizontal nystagmus
• Tongue tremors
• Lorazepam 2 mg and Diazepam 5 mg
• Outpatient lorazepam

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GHB

• Gamma Hydroxybutyrate
• 1,4 Butanediol
• Gamma Butyrolactone

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Sedative Hypnotic Withdrawal
Substance Onset / Duration Autonomic Instability Mechanism (Loss of inhibition)
GHB Hours / 5 12d Mild GHB, GABAa, GABAb
Benzos 1-3 d / 5-9 d Moderate GABAa
Ethanol Hours / 10-14d Moderate to Severe GABAa, NMDA dysinhib
Baclofen 12-96 h / 8d Moderate GABAb
Dyer 2001 Annals EM
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GHB Withdrawal Treatment

• Recognition!
• Symptomatic
• Benzodiazepines
• Barbiturates
• Propofol

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Homer Simpson

• "To alcohol! The Cause of AND solution to all
  of life's problems. Alcohol is a way of life.
  Alcohol is my way of life, and I aim to keep it."
  

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Questions?