Toxin-Induced Seizures:Toxin-Induced Seizures:Life-Threatening Forms of Life-Threatening Forms of
WithdrawlWithdrawl
ACEP Scientific Assembly 2003, Boston, MA
Steven E. Aks, DO, FACMT, FACEPFellowship Director,
The Toxikon Consortium and Department of Emergency Medicine
Cook County Hospital
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.
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
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.
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%
Steven E. Aks, DO
Life-Threatening Withdrawal Life-Threatening Withdrawal SyndromesSyndromes
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
Steven E. Aks, DO
WithdrawalWithdrawal
• Occurs when a drug or toxin is removed or reduced and adaptive changes persist producing dysfunction
Steven E. Aks, DO
Requisite for WithdrawalRequisite for Withdrawal
• Adaption to a drug or toxin
• Decreasing concentration
• Tolerance
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
Steven E. Aks, DO
Dysinhibition SyndromeDysinhibition Syndrome
• Agitation
• Tachycardia
• Hypertension
• Fever, hyperthermia
• Seizures
Steven E. Aks, DO
FlumazenilFlumazenil
• Avoid in benzodiazepine dependent patients
• 3 cases of reversal of chronic benzodiazepines leading to seizures
Spivey 1992 Clinical Therapeutics
Drinking Problem?
Steven E. Aks, DO
EthanolEthanol
• Increases inhibitory effects
• Adaptive modulation• Inhibitory (GABAa)• Excitatory (NMDA)
Steven E. Aks, DO
Mild Alcohol WithdrawalMild Alcohol Withdrawal
• Tachycardia
• Tachypnea
• Hypertension
• Tremor (“the shakes”)
• Hypereflexia
• Peak at 24 to 36 hours
Steven E. Aks, DO
Victor and AdamsVictor and Adams
• Tremulousness
• Seizures
• Hallucinations
• Delirium
Steven E. Aks, DO
Course of Neurological Course of Neurological DisturbancesDisturbances
Victor and Adams 1953
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!
Steven E. Aks, DO
HallucinationsHallucinations
• Usual visual
• Formication
• Auditory in ~20%
• May last up to three days
Steven E. Aks, DO
Why Did They Die?Why Did They Die?
• No nurses
• Dehydration
• Physical restraints
• Neuroleptics
Steven E. Aks, DO
KindlingKindling
• Withdrawal progressively becomes worse
• Treat aggressively to head off early!
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
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
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
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.
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.
Steven E. Aks, DO
SomaSoma
• Positive findings• Tachycardia 120• Horizontal nystagmus• Tongue tremors
• Lorazepam 2 mg and Diazepam 5 mg
• Outpatient lorazepam
Steven E. Aks, DO
GHBGHB
• Gamma Hydroxybutyrate
• 1,4 Butanediol
• Gamma Butyrolactone
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
Steven E. Aks, DO
GHB Withdrawal TreatmentGHB Withdrawal Treatment
• Recognition!
• Symptomatic
• Benzodiazepines
• Barbiturates
• Propofol
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."
Questions?
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