Toxin-Induced Seizures: Life-Threatening Forms of Withdrawl ACEP Scientific Assembly 2003, Boston, MA

Steven E. Aks, DO, FACMT, FACEP Fellowship Director, The Toxikon Consortium and Department of Emergency Medicine Cook County Hospital

Steven E. Aks, DO Trauma - Tox A 40 year old male presents to the trauma unit at Cook County Hospital after jumping from the 4 th 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 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 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 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%

Steven E. Aks, DO Life-Threatening Withdrawal Syndromes

Steven E. Aks, DO Benzodiazepine Withdrawal Similar to ethanol, barbiturate Onset may be delayed Long T ½ Resolution may take up to 10 days

Steven E. Aks, DO Withdrawal Occurs when a drug or toxin is removed or reduced and adaptive changes persist producing dysfunction

Steven E. Aks, DO Requisite for Withdrawal Adaption to a drug or toxin Decreasing concentration Tolerance

Steven E. Aks, DO Human Action is Dysinhibition Drugs as inhibitors Benzodiazepines on GABAa Opioids on opioid receptor Clonidine on the alpha 2 receptor

Steven E. Aks, DO Dysinhibition Syndrome Agitation Tachycardia Hypertension Fever, hyperthermia Seizures

Steven E. Aks, DO Flumazenil 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 Ethanol Increases inhibitory effects Adaptive modulation Inhibitory (GABAa) Excitatory (NMDA)

Steven E. Aks, DO Mild Alcohol Withdrawal Tachycardia Tachypnea Hypertension Tremor (“the shakes”) Hypereflexia Peak at 24 to 36 hours

Steven E. Aks, DO Victor and Adams Tremulousness Seizures Hallucinations Delirium

Steven E. Aks, DO Course of Neurological Disturbances Victor and Adams 1953

Steven E. Aks, DO 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 > 100 CCH 1150!

Steven E. Aks, DO Hallucinations Usual visual Formication Auditory in ~20% May last up to three days

Steven E. Aks, DO Why Did They Die? No nurses Dehydration Physical restraints Neuroleptics

Steven E. Aks, DO Kindling Withdrawal progressively becomes worse Treat aggressively to head off early!

Steven E. Aks, DO 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

Steven E. Aks, DO The Dosing Champions DrugDoseAuthor Diazepam2640 mg over 56 hours Nolop, 1985 Midazolam2850 mg over 5 days Lineaweaver, 1985 Diazepam2335 mg over 48 hours Woo, 1979

Steven E. Aks, DO 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

Steven E. Aks, DO 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.

Steven E. Aks, DO 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 Soma Positive findings Tachycardia 120 Horizontal nystagmus Tongue tremors Lorazepam 2 mg and Diazepam 5 mg Outpatient lorazepam

Steven E. Aks, DO GHB Gamma Hydroxybutyrate 1,4 Butanediol Gamma Butyrolactone

Steven E. Aks, DO Sedative Hypnotic Withdrawal SubstanceOnset / Duration Autonomic Instability Mechanism (Loss of inhibition) GHBHours / 5 – 12d Mild GHB, GABAa, GABAb Benzos1-3 d / 5-9 dModerateGABAa EthanolHours / d Moderate to Severe GABAa, NMDA dysinhib Baclofen12-96 h / 8dModerateGABAb Dyer: 2001 Annals EM

Steven E. Aks, DO GHB Withdrawal Treatment Recognition! Symptomatic Benzodiazepines Barbiturates Propofol

Steven E. Aks, DO 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."

Questions?