Toxin-Induced Seizures: Life-Threatening Forms of Withdrawl
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Transcript of Toxin-Induced Seizures: Life-Threatening Forms of Withdrawl
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Toxin-Induced Seizures:Toxin-Induced Seizures:Life-Threatening Forms of Life-Threatening Forms of
WithdrawlWithdrawl
ACEP Scientific Assembly 2003, Boston, MA
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Steven E. Aks, DO, FACMT, FACEPFellowship Director,
The Toxikon Consortium and Department of Emergency Medicine
Cook County Hospital
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Steven E. Aks, DO
Trauma - ToxTrauma - 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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Steven E. Aks, DO
PE/Work upPE/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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Steven E. Aks, DO
Day 2Day 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 UE’s, followed by brief tonic clonic seizure.
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Steven E. Aks, DO
PunchlinePunchline
• 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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Steven E. Aks, DO
Life-Threatening Withdrawal Life-Threatening Withdrawal SyndromesSyndromes
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Steven E. Aks, DO
Benzodiazepine WithdrawalBenzodiazepine Withdrawal
• Similar to ethanol, barbiturate
• Onset may be delayed• Long T ½
• Resolution may take up to 10 days
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Steven E. Aks, DO
WithdrawalWithdrawal
• Occurs when a drug or toxin is removed or reduced and adaptive changes persist producing dysfunction
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Steven E. Aks, DO
Requisite for WithdrawalRequisite for Withdrawal
• Adaption to a drug or toxin
• Decreasing concentration
• Tolerance
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Steven E. Aks, DO
Human Action is DysinhibitionHuman Action is Dysinhibition
• Drugs as inhibitors• Benzodiazepines on GABAa• Opioids on opioid receptor• Clonidine on the alpha 2 receptor
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Steven E. Aks, DO
Dysinhibition SyndromeDysinhibition Syndrome
• Agitation
• Tachycardia
• Hypertension
• Fever, hyperthermia
• Seizures
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Steven E. Aks, DO
FlumazenilFlumazenil
• 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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Steven E. Aks, DO
EthanolEthanol
• Increases inhibitory effects
• Adaptive modulation• Inhibitory (GABAa)• Excitatory (NMDA)
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Steven E. Aks, DO
Mild Alcohol WithdrawalMild Alcohol Withdrawal
• Tachycardia
• Tachypnea
• Hypertension
• Tremor (“the shakes”)
• Hypereflexia
• Peak at 24 to 36 hours
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Steven E. Aks, DO
Victor and AdamsVictor and Adams
• Tremulousness
• Seizures
• Hallucinations
• Delirium
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Steven E. Aks, DO
Course of Neurological Course of Neurological DisturbancesDisturbances
Victor and Adams 1953
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Steven E. Aks, DO
SeizuresSeizures
• 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 > 100
• CCH 1150!
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Steven E. Aks, DO
HallucinationsHallucinations
• Usual visual
• Formication
• Auditory in ~20%
• May last up to three days
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Steven E. Aks, DO
Why Did They Die?Why Did They Die?
• No nurses
• Dehydration
• Physical restraints
• Neuroleptics
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Steven E. Aks, DO
KindlingKindling
• Withdrawal progressively becomes worse
• Treat aggressively to head off early!
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Steven E. Aks, DO
Lorazepam Vs. DiazepamLorazepam 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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Steven E. Aks, DO
The Dosing ChampionsThe 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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Steven E. Aks, DO
MiscellaneousMiscellaneous
• 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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Steven E. Aks, DO
SomaSoma
• 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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Steven E. Aks, DO
Soma 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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Steven E. Aks, DO
SomaSoma
• Positive findings• Tachycardia 120• Horizontal nystagmus• Tongue tremors
• Lorazepam 2 mg and Diazepam 5 mg
• Outpatient lorazepam
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Steven E. Aks, DO
GHBGHB
• Gamma Hydroxybutyrate
• 1,4 Butanediol
• Gamma Butyrolactone
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Steven E. Aks, DO
Sedative Hypnotic WithdrawalSedative Hypnotic WithdrawalSubstance Onset /
DurationAutonomic 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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Steven E. Aks, DO
GHB Withdrawal TreatmentGHB Withdrawal Treatment
• Recognition!
• Symptomatic
• Benzodiazepines
• Barbiturates
• Propofol
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Steven E. Aks, DO
Homer SimpsonHomer 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?