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?