Management of Acute Poisoning

Management of Acute Poisoning

• The topic is on the management of acute poisoning, presented by Carmen Ortiz-Sánchez from the Department of Pharmacology.

Objectives

• Describe the steps involved in the supportive care of a poisoned patient.
• Identify toxic syndromes associated with overdose of major drugs or drug groups frequently involved in poisoning.
• Understand the importance of the anion gap and osmole gap in managing poisoned patients.
• Describe the decontamination methods available for managing poisoned patients and increasing the elimination of toxic compounds.
• List the antidotes available for managing poisoned patients.

Toxicokinetics

• Toxicokinetics refers to the disposition of poisons in the body or their pharmacokinetics
• Knowing a toxin's ADME (absorption, distribution, metabolism, and elimination) allows for an accurate evaluation of 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 involves urinary alkalinization with sodium bicarbonate.
• Renal elimination of weak bases involves urinary acidification with NH4Cl or vitamin C.

Toxicodynamics

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

Causes of Death in Intoxicated Patients

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

Management of the Poisoned Patient

• Management includes 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 for a poisoned patient involves maintaining vital functions.
• Supportive initial treatment includes the ABCDs (Airway, Breathing, Circulation, Dextrose).
• Open and protected airway must be established.
• Effective ventilation (breathing) must be ensured.
• Circulation should be evaluated and supported as needed.
• Due to the danger of brain damage from hypoglycemia, 50% IV Dextrose should be administered immediately to comatose patients.
• In patients with suspected alcoholism or malnourishment, thiamine should be administered to prevent Wernicke syndrome.

Identification of Poisons

• Many intoxicants cause a characteristic syndrome of clinical and laboratory changes.
• When the toxic agent cannot be directly examined and identified, the clinician must rely on indirect means to identify the type of intoxication and the progress of therapy.
• History and physical examination are useful in responsive patients.
• General tests such as the anion and osmole gap can be useful for a comatose patient.

Toxic Syndromes

• Antimuscarinic drugs (anticholinergics) present with delirium, hallucinations, seizures, coma, tachycardia, hypertension, hyperthermia, mydriasis, decreased bowel sounds, and urinary retention. Control hyperthermia. Physostigmine may be helpful, but not for tricyclic overdose.
• Cholinomimetic drugs (carbamate or organophosphate cholinesterase inhibitors) present with anxiety, agitation, seizures, coma, bradycardia or tachycardia, pinpoint pupils, salivation, sweating, hyperactive bowel, muscle fasciculations, then paralysis. Support respiration and decontaminate; treat with atropine and pralidoxime.
• Opioids (e.g., heroin, morphine, methadone) present with lethargy, sedation, coma, bradycardia, hypotension, hypoventilation, pinpoint pupils, cool skin, decreased bowel sounds, and flaccid muscles. Provide airway and respiratory support, administer naloxone as required.
• Salicylates (e.g., aspirin) present with confusion, lethargy, coma, seizures, hyperventilation, hyperthermia, dehydration, hypokalemia, anion gap, and metabolic acidosis. Correct acidosis and fluid/electrolyte imbalance; use alkaline diuresis or hemodialysis to aid.
• Sedative-hypnotics (barbiturates, benzodiazepines, ethanol) initially cause disinhibition, later progressing to lethargy, stupor, and coma. Nystagmus is common, along with decreased muscle tone, hypothermia, small pupils, hypotension, and decreased bowel sounds in severe overdose. Provide airway and respiratory support. Avoid fluid overload and consider flumazenil for benzodiazepine overdose.
• Stimulants (amphetamines, cocaine, PCP), bath salts present with agitation, anxiety, seizures, hypertension, tachycardia, arrhythmias, mydriasis, vertical and horizontal nystagmus with PCP, warm and sweaty skin, hyperthermia, increased muscle tone, possible rhabdomyolysis. Control seizures with benzodiazepines (e.g., lorazepam), hypertension, and hyperthermia.
• Selective serotonin reuptake inhibitors cause mild symptoms like shivering, hyperreflexia, and diarrhea. Severe cases may involve muscle rigidity, fever seizures, and cardiovascular instability. Stop the offending drug and provide supportive management, along with an antidote like cyproheptadine.
• Tricyclics cause antimuscarinic effects. Control seizures and correct.
• Acetaminophen presents with mild anorexia, nausea, vomiting, delayed jaundice, and may progress to hepatic and renal failure.
• Carbon monoxide presents with coma, metabolic acidosis, and retinal hemorrhages.
• Cyanide presents with a bitter almond odor, seizures, coma, and abnormal ECG.
• Ethylene glycol presents with renal failure, crystals in urine, increased anion and osmole gap, initial CNS excitation. Eye examination results in a normal state.
• Iron presents with bloody diarrhea, coma, radiopaque material in the gut (seen on X-ray), high leukocyte count, and hyperglycemia.
• Lead presents with abdominal pain, hypertension, seizures, muscle weakness, metallic taste, anorexia, encephalopathy, delayed motor neuropathy, changes in renal and reproductive function.
• Lysergic acid diethylamide (LSD) presents with hallucinations, dilated pupils, and hypertension.
• Mercury presents with acute renal failure, tremor, salivation, gingivitis, colitis, erethism (fits of crying, irrational behavior), and nephrotic syndrome.
• Methanol presents with rapid respiration, visual symptoms, osmole gap, and severe metabolic acidosis.

Identification of Poisons: Anion & Osmole Gap Calculations

• Osmole gap is the difference between the measured serum osmolality and the osmolality predicted by measured serum concentrations of sodium, glucose, and blood urea nitrogen.
  • Gap = Osm (measured) - [(2 × Na+ [mEQ/L]) + (Glucose [mg/dL] ÷ 18) + (BUN [mg/dL] ÷ 3)]
• It is normally zero.
• High serum concentrations of ethanol, methanol, and ethylene glycol can produce a significant gap.
• Anion gap is the difference between the sum of the serum concentrations of the 2 primary cations (Na+, K+) and the sum of the measured serum concentrations of the 2 primary anions (Cl-, HCO3-).
  • Anion gap = (Na+ + K+) – (HCO3- + Cl-)
• The normal range is 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

• Decontamination is the removal of any unabsorbed poison from the skin or gastrointestinal tract.
• For topical exposure, remove clothing and wash the patient to remove any chemical present on the skin. Medical personnel must be careful not to contaminate themselves during this process.
• Activated charcoal can be given orally or by stomach tube for ingested toxins, most effective when given within one hour of toxin ingestion.
• Poisons removed include amitriptyline, barbiturates, carbamazepine, digitalis glycosides, theophylline, tricyclic antidepressants, and valproic acid
• Activated charcoal does not bind to iron, lithium, or potassium and binds poorly to alcohols and cyanide.
• Gastric lavage is less commonly used, and involves "stomach pumping" using a large-bore tube, which removes non-corrosive drugs from the stomach. It is indicated for responsive patients.
• Gastric lavage is contraindicated in individuals at risk of GI hemorrhages, in cases of caustic ingestion (i.e., ingestion of strongly acidic or alkaline substances), and when the airway is unprotected (when essential reflexes are lost, and no endotracheal intubation was performed beforehand).
• Whole bowel irrigation involves polyethylene-glycol electrolyte solution to enhance gut decontamination and is used for decontamination of iron tablets, enteric coated pills, and illicit drug-filled packets.
• Cathartics such as sorbitol can decrease absorption and hasten removal of toxins from the GI tract.

Enhanced Elimination

• Enhancement of elimination is possible for some toxins.
• Manipulation of urine pH can be used to accelerate renal excretion of weak acids and bases.
• Urinary alkaline diuresis is effective in toxicity caused by fluoride, isoniazid, fluoroquinolones, phenobarbital, and salicylates.
• Hemodialysis allows the removal of many toxic compounds.
• It is commonly used to remove toxins such as ethylene glycol, lithium, metformin, procainamide, salicylates, and valproic acid, and to correct fluid and electrolyte imbalances.

Important Antidotes

• Acetylcysteine is an antidote for acetaminophen, best given within 8-10 hours of overdose.
• Atropine is an antidote for cholinesterase inhibitors and rapid-onset mushroom poisoning with muscarinic effects.
• Deferoxamine is an antidote for iron salts.
• Digoxin antibodies are an antidote for digoxin and related cardiac glycosides.
• Esmolol is an antidote for caffeine, theophylline, and sympathomimetics.
• Ethanol is an antidote for methanol and ethylene glycol (fomepizole is better tolerated).
• Flumazenil is an antidote for benzodiazepines and zolpidem.
• Fomepizole is an antidote for methanol and ethylene glycol.
• Glucagon is an antidote for beta-adrenoceptor blockers.
• Glucose is an antidote for hypoglycemics.
• Hydroxocobalamin is an antidote for cyanide.
• Naloxone is an antidote for opioid analgesics.
• Oxygen is an antidote for carbon monoxide.

Measures for Decontamination and Enhanced Elimination

• Decontamination measures involve removing affected clothing, washing affected skin, performing gastric lavage, administering activated charcoal, whole bowel irrigation, and using cathartics.
• Enhanced elimination measures involve administering an antidote that reacts with the toxin or speeds its metabolism, performing hemodialysis, and manipulating urine pH (alkalinize or acidify).
• Acidification of urine involves using NH4Cl, Vitamin C, or Cranberry juice.
• Alkalinization involves using sodium bicarbonate.