INTERESTING CASE

ROUNDSAlyssa Morris

Emergency Medicine R3

Objectives

DDX for toxin induced seizures

DDX for toxin induced status epilepticus

Indications for pyridoxine

Review methylxanthine toxicity

Review MDAC

CASE

19M took an unknown ingestion and had a seizure.

What is your quick ddx for drugs that cause seizure?

DDX Drug induced Seizure

OTIS CAMPBELL

O- organophosphates

T- TCAI- Isoniazid, insulinS-

sympathomimetics

C- camphor, cocaine

A- anticholinergic, amphetamines, anticholinergic, antidepressants

M- Methylxanthines

P- PCPB- Benzo w/dE- EtOH w/dL- Lithium,

lidocaineL- lead, lindane

DDx-Toxin induced Status

INH

Insulin/hypoglycemic agents

TCA

Theophylline

Wellbutrin

CO

Pyridoxine Indications

INH

Ethylene glycol

Gyromitra Mushrooms

Methylxanthines*

CASE

19M who ingested 112 caffeine tablets (100mg/tab) who was brought in by friend for intractable nausea and vomiting• Total ingestion >11g (175mg/kg)

O/E: P=131,BP= 164/67, T= 37.6, 02= 98%, agitated, vomiting ++

CASE

Labs:• APAP/ASA –• CK 14• Na 140, K 2.2, Cl 101, CO2 17, AG:

22• Lactate 8.8• pH 7.23• Caffeine level 429mmol/L

ECG: Sinus tach, no dysrhythmias

CASE CONT

Continued to be tachy, ++ vomitting, no seizure and no dysrhythmias

Course in ED:• zofran 12mg• Maxeran 10g (still vomiting)• Stemitil 10mg (still vomiting)• MDAC • Central line to replace K+• Zantac 50mg • Ativan 2mg IV x 2

CASE CONT

Labs in am• CK- 2280• PO4 0.29• K- 3.1• Caffeine level 295mmol/L• Lactate 3.9

Still vomiting and agitated

CAFFEINE

Methylxanthine Similar to theophylline

Cause release of endogenous catecholamines Stimulates B1 and B2 R

Structural analogue of Adenosine NE and epinephrine release

Inhibit phosphodiesterase (degrades cAMP) Effects like adrenergic stimulation

PHARMACOKINETICS

Routes: oral, IV, SC, IM, rectal

Oral almost 100% bioavailability

Peak concentration 30-60min

Diffuses readily into total body water and all tissues

Readily crosses BBB

Metabolized by Cytochrome P450 systemActive metabollite is theophylline

TOXICOKINETICS

Range of toxicity varies greatly

No definite conclusions from serum levels can be drawn

Lethal dose estimated: 150-200mg/kg or 5-10g

Death associated serum levels >80mm0l/L Fatalities <200mmol/L Survivial >400mmol/L

OUR PT: 175mg/kg, serum 429mmol/L

CLINCIAL EFFECTS

Occur as a result of:1 Adenosine antagonism2 Release of endogenous

catecholamines3 Phosphodiesterase inhibiton

Toxicity affects: GI system Cardiovascular system CNS MSK

GI

Nausea and protracted emesis

• Severe and difficult to control despite use of multiple anti-emetics

Increase in gastric acid secretion and smooth muscle relaxation

• Gastritis and esophagitis (more common with chronic use)

Transiently elevated liver enzymes

CARDIOVASCULAR

Tachydysrhythmias Sinus tach SVT MAT Afib PVCs VT

MI

Peripheral vasodilation (wide pulse pressure)

Hypertension or hypotension

PULMONARY

Stimulates CNS respiratory centre Increased RR Resp Alkalosis

Respiratory failure

Acute lung injury

CNS

H/AAnxietyAgitationInsomnia

TremorIrritabilityHallucinationsSeizures*

MSK

Increases intracellular Ca++

Smooth muscle relaxation

Tremor

Fasiculations

Myoclonus

Rhabdomyolysis

METABOLIC

HypoK Shift into cells from B2 stimulation

HypoMg

HypoPO4

HypoNa

Hyperglycemia

AGMA (lactate)

MANAGEMENT

Basics: IV, monitored bed

Labs to followextended electrolytesLactateCK

+/- Serum caffeine level

CXR, ECGs

TREATMENT

MDAC*

Emesis Zofran, maxeran

Dysrhythmias Benzos Esmolol Lidocaine

Rhabdo Fluids and monitor u/o

TREATMENT

Electrolytes Replace, but careful b/c will become

hyperK when shift back out of cell

Hypotension Fluids Not dopamine

Seizures Benzos Phenobarb Pyridoxine

MDAC

Definition: more than 2 sequential doses of AC• In many cases, the number of doses

administered is substantially greater

MDAC serves 2 purposes:1 Prevent ongoing absorption of a drug

that persists in the GIT

2 Enhance elimination by either disrupting enterohepatic recirculation or by enteroenteric recirculation

General Indications

GI decontamination for drug or poison ingestion associated with significant risk of toxicity, where supportive care/antidote alone is insufficient to ensure a satisfactory outcome

The toxin must be able to bind to AC

Must believe that a significant amount of agent is unabsorbed and is amenable to removal

AACT Position Statement

Position statement states use MDAC only for ingestions of CarbamazepineDapsonePhenobarbitalQuinineTheophylline /Methylxanthines

Other Drugs

Shown to increase elimination of:DigoxinPhenobarbitalCarbamazepin

ePhenylbutazon

eDapsoneNadolol

TheophyllineSalicylateQuinineCyclosporinePropoxypheneNortriptylineAmitriptyline

Contraindications

Any contraindication to single-dose activated charcoal • AC known not to adsorb • Airway protective reflexes are

absent or expected to be lost and pt is not intubated

• GI perf (esp caustic ingestion)• Increases severity of injury

(hydrocarbons)• Endoscopy for dx/mx anticipated

Presence of ileus

Administration

Initial dose• 1g/kg or 10:1 ratio of ACT:toxin, whichever

is >

Repeat dose • 0.25-0.5mg/kg every 1-6hrs

Procedure• Can be administered with cathartic for

the 1st dose only• If pt vomits, repeat the dose• Can use oral, NG or OG route

*Sxn tube before removal to reduce aspiration risk

SUMMARY

DDX for toxin induced seizures OTIS CAMPBELL

Refractory seizures in toxic ingestion Think about pyridoxine

Caffeine is a methylxanthine Adrenergic stimulation Can get refractory seizures MDAC is indicated