Major intoxicationTraining program Intensive Care

Radboud University Nijmegen Medical Centre

Website

http://www.emedicine.com/emerg/TOXICOLOGY.htm

Diagnosis

• Make a thorough history

• Identify the poison

• Estimate the time from ingestion

• Estimate the expected severity

• Do a complete physical examination

• Airway - Breathing - Circulation - Disability - Complete evaluation

• Toxidromes

Toxidromes

• Anticholinergic

• Sympathomimetic

• Narcotic

• Sedatives/hypnotics

• Serotoninergic

• Confusion, tremor, fasciculations, extrapyramidal symptoms, hypereflexia, hyperpyrexia, diaphoresis, tachycardia

• Cholinergic

Investigations

• General biochemical tests

• Drug screening

• Quantitative blood levels

Treatment

• Maintenance of vital functions

• Give antidote

• Prevent absorption

• Drug analysis

• Increase elimination

• Observe in appropriate location

Extracorporeal techniques

• (Potential) lifethreatening intoxication

• Low volume of distribution (< 1 L/kg)

• Low protein binding

• Low endogenous clearance

• Low molecular (HD)

Hemodialysis - Hemoperfusion - Hemofiltration

Examples

• Aspirin (neurotoxic, Acid-base disturbances)

• Lithium (neurotoxic) - often multiple sessions

• Methanol/Ethylene glycol

• Valproic acid (CNS toxicity, NH4 ↑)

• Theophyline (HP)

Hemoperfusion?

• Teicoplanin and vancomycin

• Digoxin

• Theophyline

• Phenobarbital, phenytoin, carbamazepine and valproic acid

Betasorb ®

Reiter K. Blood Purif 2002;20:380-388

Analgesics

• Opioids

• CZS depression, respiratory depression, miosis, acute pulmonary oedema

• Activated charcoal, sodium bicarbonate, naloxone

• Acetaminophen

• Centrilobular liver necrosis

• Activated charcoal, N-acetylcysteine (Rumack-Matthew)

• Salicylates

• Stimulation respiratory centre, uncoupling oxidative phosphorylation

• Activated charcoal, urinary alkalinization, haemodialysis

5-Oxoproline

• High anion gap (SIG) metabolic acidosis

• Basic underlying mechanism is glutathione deficiency

• Usually during prolonged acetaminophen treatment - mostly women

• Clinically often diminished consciousness

Cell membrane

Aminoacid (AA)

Cysteine - Glycine Glutamate - AA

Gluthathione

Gluthathione Cysteine - Glycine γ-glutamyl - AA

γ-glutamyl transpeptidase

5-oxoproline

AA

Renal failure

γ-glutamylcyclotransferase

L-glutamate

FlucloxacillinNetilmycinVigabatrin

5-oxoprolinase

γ-glutamylcyclotransferase

Dipeptidase

γ-glutamyl cysteine

Cysteine

Gluthathionesynthase

Glycine

γ-glutamylcysteine synthase

Negativefeedback

AcetaminophenAlcoholDiet

MalnutritionLiver disease

γ-Glutamyl cycle

= gluthatione stores are reduced and negative feedback falls away

Sedatives

• Activated charcoal

• Supportive Care

• Flumazenil

• Alkaline diuresis/haemodilalysis

• barbiturates

ϒ-Hydroxybutyric acid

• [Peak] 40 minutes after oral ingestion

• T1/2 20-30 minutes

• Coma after 40 - 60 mg/kg

• Coma, myoclonus, hypoventilation and bradycardia

• Supportive therapy

Neuroleptic agents

• Recovery without sequelae is the rule

• Convulsions, hypotension, dysrhythmia

• Activated charcoal, supportive care

Tricyclische AD

• > 1000 mg

• Dysrhythmias, hypotension, seizures, coma, anticholinergic effects

• Activated charcoal, sodium bicarbonate, hypertonic saline

SSRI’s

• CNS depression, seizures, QT/QRS ↑, autonomic dysfunction

• Especially in combination with MAOI’s

• Supportive care

Cardiotoxins

• Calcium channel blockers

• Slowing of conduction, decreased contractility, vasodilation, hyperglycemia

• Beta-blockers

• Bradycardia, heart block, hypotension, hypoglycemia

• Activated charcoal, calcium, glucagon, insulin