Acute Poisoning Management: Toxicokinetics

Management of Acute Poisoning

• The main objectives are to describe the supportive care steps for poisoned patients, identify toxic syndromes, understand the importance of anion and osmole gaps, describe decontamination methods, and list available antidotes.

Toxicokinetics

• It is the the disposition of poisons in the body
• It is important to know the toxin's ADME: absorption, distribution, metabolism, and elimination
• Allows for an accurate evaluation of the procedures to remove the toxin from the skin or GI tract.
• Drugs with large volumes of distribution (antidepressants and antimalarials) are not easily removed through dialysis
• Drugs with low volume of distribution (lithium, phenytoin, salicylates) are more readily removed by dialysis and diuresis
• Renal elimination of weak acids uses urinary alkalinization (sodium bicarbonate)
• Renal elimination of weak bases uses urinary acidification (NH4Cl, vitamin C)

Toxicodynamics

• It is the injurious or pharmacodynamic effects of toxins in the body
• Knowledge of the toxin's toxicodynamics can be useful in the diagnosis and management of poisoning
• Hypertension and tachycardia are typically seen in amphetamines and cocaine overdose
• Hypotension and bradycardia is seen in overdose of calcium channel blockers and sedative-hypnotics

Cause of Death

• Common causes of death from drug overdose reflect the drug groups that are frequently selected for abuse or for suicide
• Sedative-hypnotics and opioids cause respiratory depression, coma, and aspiration of gastric contents
• Cocaine, phencyclidine (PCP), tricyclic antidepressants, and theophylline cause seizures, which may lead to vomiting, aspiration, and respiratory depression

Management of Poisoned Patient

• Includes the maintenance of vital functions, identification of the toxic substance, decontamination procedures, enhanced elimination, and administration of a specific antidote if available

Vital Functions

• The most important aspect of treatment of a poisoned patient
• Supportive initial treatment includes the ABCDs:
  • A: Open and protect the airway
  • B: Ensure effective ventilation (breathing)
  • C: Evaluate and support circulation
  • D: Administer 50% IV Dextrose to comatose patients immediately due to brain damage risk from hypoglycemia
• Administer thiamine to patients with suspected alcoholism or malnourishment to prevent Wernicke syndrome

Identification of Poisons

• Intoxicants cause a syndrome of clinical and laboratory changes
• Clinicians rely on indirect means to identify intoxication type and therapy progress when the toxic agent cannot be directly examined
• History and physical examination are useful in responsive patients
• General tests such as the anion and osmole gap can be useful for comatose patients

Toxic Syndromes

• Antimuscarinic drugs (anticholinergics) cause delirium, hallucinations, seizures, coma, tachycardia, hypertension, hyperthermia, mydriasis, decreased bowel sounds, and urinary retention; control hyperthermia and physostigmine may be helpful
• Cholinomimetic drugs cause anxiety, agitation, seizures, coma, bradycardia or tachycardia, pinpoint pupils, salivation, sweating, and hyperactive bowel; support respiration and treat with atropine and pralidoxime, as well as decontamination
• Opioids cause lethargy, sedation, coma, bradycardia, hypotension, hypoventilation, pinpoint pupils, cool skin, decreased bowel sounds, and flaccid muscles; provide airway and respiratory support

Toxic Features of Agents

• Acetaminophen causes mild anorexia, nausea, vomiting, delayed jaundice, hepatic, and renal failure
• Carbon monoxide causes coma, metabolic acidosis, and retinal hemorrhages
• Cyanide has a bitter almond odor and can cause seizures, coma, and abnormal ECG
• Ethylene glycol causes renal failure, crystals in urine, increased anion and osmole gap, and initial CNS excitation
• Iron causes bloody diarrhea, coma, radiopaque material in the gut, high leukocyte count, and hyperglycemia
• Lead causes abdominal pain, hypertension, seizures, muscle weakness, metallic taste, anorexia, encephalopathy, delayed motor neuropathy, and changes in renal and reproductive function
• Lysergic acid diethylamide (LSD) causes hallucinations, dilated pupils, and hypertension
• Mercury causes acute renal failure, tremor, salivation, gingivitis, colitis, erethism, and nephrotic syndrome
• Methanol causes rapid respiration, visual symptoms, osmole gap, and severe metabolic acidosis

Osmole Gap

• It is the difference between measured and predicted serum osmolality based on sodium, glucose, and blood urea nitrogen concentrations
• The gap is normally zero, but high concentrations of ethanol, methanol, and ethylene glycol can produce a significant gap

Anion Gap

• It is the difference between the sum of serum concentrations of primary cations (Na+, K+) and primary anions (Cl-, HCO3-)
• It is normally 12–16 mEq/L
• Drugs that cause an anion gap include cyanide, ethanol, ethylene glycol, ibuprofen, isoniazid, iron, methanol, phenelzine, salicylates, tranylcypromine, valproic acid, and verapamil

Decontamination

• Removal of any unabsorbed poison from the skin or GI tract
• Topical exposure requires removal of clothing and washing the patient to remove any chemical present
• Medical personnel must be careful not to contaminate themselves during this process

Activated Charcoal

• Given orally or by stomach tube for ingested toxins
• Most effective when given within one hour of ingestion
• Removes amitriptyline, barbiturates, carbamazepine, digitalis glycosides, theophylline, tricyclic antidepressants, and valproic acid
• Does not bind to iron, lithium, or potassium and binds poorly to alcohols and cyanide

Gastric Lavage

• Less commonly used
• "Stomach pumping" using a large-bore tube to remove non-corrosive drugs from the stomach
• Indicated for responsive patients
• Contraindicated for individuals at risk of GI hemorrhages, in cases of caustic ingestion, and when the airway is unprotected

Whole Bowel Irrigation

• Polyethylene-glycol electrolyte solution to enhance gut decontamination
• Used for decontamination of iron tablets, enteric-coated pills, and illicit drug-filled packets
• Cathartics like sorbitol can decrease the absorption and hasten the removal of toxins from the GI tract

Enhanced Elimination

• Possible for some toxins
• Manipulating urine pH as a method to accelerate renal excretion of weak acids and bases
• Urinary alkaline diuresis is effective for toxicity caused by fluoride, isoniazid, fluoroquinolones, phenobarbital, and salicylates
• Hemodialysis allows removal of many toxins and is commonly used for ethylene glycol, lithium, metformin, procainamide, salicylates, and valproic acid, and to correct fluid and electrolyte imbalances.

Important Antidotes

• Acetylcysteine is given for Acetaminophen overdose within 8 – 10 hrs
• Atropine is given for Cholinesterase inhibitors and rapid-onset mushroom poisoning with muscarinic effects
• Deferoxamine is given for Iron salts
• Digoxin Antibodies is given for Digoxin and related cardiac glycosides
• Esmolol is given for Caffeine, theophylline, and sympathomimetics
• Ethanol is given for Methanol and ethylene glycol; fomepizole is better tolerated
• Flumazenil is given for Benzodiazepines and zolpidem but can trigger seizures
• Fomepizole is given for Methanol and ethylene glycol
• Glucagon is given for Beta-adrenoceptor blockers
• Glucose is given for Hypoglycemics
• Hydroxocobalamin is given for Cyanide
• Naloxone is given for Opioid analgesics
• Oxygen is given for carbon monoxide

Acidification and Alkalinization for Elimination

• Used for enhanced elimination of poisonings
• Acidification of urine includes NH4Cl, Vitamin C, and cranberry juice
• Alkalinization consists of Sodium bicarbonate