☣️Toxicology Unit 12 – Clinical Toxicology: Poisoning Management

Key Concepts in Clinical Toxicology

• Focuses on the diagnosis, management, and prevention of poisoning and other adverse health effects resulting from exposures to drugs, chemicals, and other substances
• Encompasses a wide range of substances, including prescription and over-the-counter medications, illicit drugs, household products, industrial chemicals, and natural toxins
• Considers the route of exposure (ingestion, inhalation, dermal absorption, or injection) and the dose of the substance in determining the severity of toxicity
• Recognizes the importance of time since exposure, as the effects of toxins can vary depending on the duration and timing of exposure
• Assesses patient factors such as age, weight, underlying health conditions, and concomitant medication use, which can influence the toxicity of a substance
• Utilizes a multidisciplinary approach, involving collaboration among healthcare professionals, poison control centers, and public health agencies to provide comprehensive care and prevent further harm
• Emphasizes the importance of rapid identification of the toxic agent, prompt initiation of appropriate treatment, and ongoing monitoring of the patient's clinical status

Common Toxic Agents and Their Effects

• Acetaminophen (paracetamol) overdose can lead to severe hepatotoxicity and liver failure
  • Characterized by nausea, vomiting, abdominal pain, and elevated liver enzymes
  • N-acetylcysteine (NAC) is the antidote for acetaminophen poisoning
• Opioids (e.g., heroin, fentanyl, oxycodone) cause respiratory depression, sedation, and pinpoint pupils
  • Can result in life-threatening hypoxia and respiratory arrest
  • Naloxone is an opioid antagonist used to reverse opioid overdose
• Organophosphate and carbamate insecticides inhibit acetylcholinesterase, leading to cholinergic toxicity
  • Symptoms include salivation, lacrimation, urination, defecation, gastrointestinal distress, and emesis (SLUDGE)
  • Atropine and pralidoxime are used to counteract the effects of these insecticides
• Carbon monoxide binds to hemoglobin with high affinity, reducing oxygen-carrying capacity and causing tissue hypoxia
  • Presents with headache, dizziness, nausea, and altered mental status
  • Treatment involves immediate removal from the exposure source and administration of high-flow oxygen or hyperbaric oxygen therapy
• Ethylene glycol (found in antifreeze) is metabolized to toxic metabolites that cause metabolic acidosis, renal failure, and CNS depression
  • Fomepizole or ethanol can be used to inhibit the metabolism of ethylene glycol, and hemodialysis may be necessary to remove the toxic metabolites
• Salicylates (e.g., aspirin) in overdose can cause metabolic acidosis, respiratory alkalosis, and electrolyte disturbances
  • Presents with tinnitus, nausea, vomiting, and altered mental status
  • Treatment includes alkalinization of the urine to enhance elimination and supportive care

Toxicokinetics and Toxicodynamics

• Toxicokinetics describes the absorption, distribution, metabolism, and excretion (ADME) of toxins in the body
  • Absorption depends on the route of exposure, physicochemical properties of the substance, and patient factors
  • Distribution is influenced by the toxin's lipophilicity, protein binding, and tissue affinity
  • Metabolism occurs primarily in the liver through phase I and phase II reactions, which can activate or detoxify substances
  • Excretion occurs mainly through the kidneys, but other routes (e.g., biliary, pulmonary) may also play a role
• Toxicodynamics refers to the biochemical and physiological effects of toxins on the body
  • Toxins can interact with receptors, enzymes, or other cellular targets to disrupt normal function
  • The dose-response relationship describes the correlation between the dose of a toxin and the observed effect, which can be linear or non-linear
  • Toxins can have local effects at the site of exposure or systemic effects after absorption and distribution
• Biomarkers of exposure and effect can be used to assess the extent of toxicity and monitor treatment response
  • Examples include blood levels of the toxin or its metabolites, liver enzymes, renal function tests, and specific biomarkers (e.g., acetylcholinesterase activity for organophosphate poisoning)
• Toxicokinetic and toxicodynamic principles guide the selection of appropriate decontamination, antidote therapy, and supportive care measures

Diagnosis and Assessment of Poisoning

• Obtain a thorough history, including the substance(s) involved, dose, route, and time of exposure
  • Collect information from the patient, family members, witnesses, or emergency medical services
  • Consider the possibility of multiple exposures or co-ingestions
• Perform a focused physical examination, paying attention to vital signs, mental status, pupil size, skin findings, and signs of specific toxidromes
  • Toxidromes are constellations of signs and symptoms suggestive of a particular class of toxins (e.g., cholinergic, anticholinergic, sympathomimetic, opioid)
• Utilize appropriate diagnostic tests to confirm the diagnosis and assess the severity of poisoning
  • Toxicology screens (e.g., urine drug screen, serum drug levels) can identify the presence of specific substances
  • Electrocardiogram (ECG) to evaluate for cardiotoxicity, QTc prolongation, or other abnormalities
  • Imaging studies (e.g., chest X-ray, CT scan) to assess for complications or co-existing conditions
• Monitor laboratory parameters to guide treatment and detect end-organ dysfunction
  • Electrolytes, renal function, liver enzymes, blood gases, and coagulation studies
  • Specific tests based on the suspected toxin (e.g., acetaminophen levels, salicylate levels, methemoglobin)
• Consult poison control centers or toxicology experts for guidance on diagnosis, management, and antidote availability
• Assess the patient's airway, breathing, and circulation, and provide immediate stabilization if necessary
• Consider differential diagnoses, as the presentation of poisoning can mimic other medical conditions (e.g., sepsis, metabolic disorders, neurological events)

General Management Principles

• Prioritize stabilization of the patient's airway, breathing, and circulation (ABC)
  • Secure the airway if the patient has a decreased level of consciousness or respiratory compromise
  • Provide supplemental oxygen and ventilatory support as needed
  • Administer intravenous fluids and vasopressors to maintain adequate blood pressure and perfusion
• Prevent further absorption of the toxin through decontamination measures
  • Activated charcoal binds to many toxins in the gastrointestinal tract and reduces absorption
  • Whole bowel irrigation can be used for sustained-release or enteric-coated preparations
  • Decontaminate the skin or eyes if there has been direct contact with the toxin
• Administer specific antidotes when available and indicated based on the identified toxin
  • Examples include naloxone for opioids, N-acetylcysteine for acetaminophen, and atropine for organophosphates
• Enhance elimination of the toxin through various techniques
  • Multiple-dose activated charcoal can interrupt enterohepatic recirculation of certain toxins
  • Urinary alkalinization can increase the elimination of weak acids (e.g., salicylates, phenobarbital)
  • Hemodialysis or hemoperfusion can remove toxins that are not effectively cleared by other means
• Provide supportive care to manage symptoms and prevent complications
  • Control agitation or seizures with benzodiazepines or other sedatives
  • Treat dysrhythmias or conduction abnormalities with appropriate medications or interventions
  • Monitor and correct electrolyte imbalances, acid-base disorders, and other metabolic derangements
• Monitor the patient closely for signs of clinical improvement or deterioration
  • Repeat laboratory tests and imaging studies as needed to assess response to treatment
  • Adjust management based on the patient's evolving clinical status and laboratory parameters
• Consult with medical toxicologists, poison control centers, or other specialists for complex cases or unfamiliar toxins

Specific Antidotes and Treatments

• N-acetylcysteine (NAC) for acetaminophen poisoning
  • Replenishes glutathione stores and prevents hepatotoxicity
  • Administered orally or intravenously according to a specific protocol based on the ingested dose and time since exposure
• Naloxone for opioid overdose
  • Competitive opioid receptor antagonist that reverses respiratory depression and sedation
  • Administered intravenously, intramuscularly, or intranasally, with repeat doses as needed
• Atropine and pralidoxime for organophosphate and carbamate insecticide poisoning
  • Atropine competes with acetylcholine at muscarinic receptors, reducing cholinergic symptoms
  • Pralidoxime reactivates acetylcholinesterase, which is inhibited by these insecticides
• Fomepizole or ethanol for toxic alcohol poisoning (e.g., methanol, ethylene glycol)
  • Inhibits alcohol dehydrogenase, preventing the formation of toxic metabolites
  • Fomepizole is preferred due to its higher specificity and fewer side effects compared to ethanol
• Sodium bicarbonate for salicylate poisoning and certain drug-induced sodium channel blockade
  • Alkalinizes the urine, enhancing the elimination of salicylates
  • Overcomes sodium channel blockade caused by drugs like tricyclic antidepressants and cocaine
• Digoxin-specific antibody fragments (Fab) for digoxin toxicity
  • Binds to and neutralizes digoxin, reducing its effects on the cardiovascular system
• Glucagon for beta-blocker and calcium channel blocker overdose
  • Increases intracellular cyclic AMP, improving heart rate and contractility
  • Administered as an intravenous bolus followed by a continuous infusion
• Methylene blue for methemoglobinemia
  • Acts as an electron donor, reducing methemoglobin back to hemoglobin
  • Administered intravenously at a dose of 1-2 mg/kg over 5 minutes
• Cyproheptadine for serotonin syndrome
  • Serotonin receptor antagonist that helps to mitigate the excessive serotonergic activity
  • Administered orally or via nasogastric tube

Decontamination and Elimination Techniques

• Activated charcoal for gastrointestinal decontamination
  • Adsorbs many toxins, reducing their absorption from the gastrointestinal tract
  • Most effective when administered within 1 hour of ingestion
  • Contraindicated in patients with an unprotected airway, gastrointestinal obstruction, or perforation
• Whole bowel irrigation for decontamination of sustained-release or enteric-coated preparations
  • Uses large volumes of polyethylene glycol solution to mechanically cleanse the bowel
  • Indicated for ingestions of iron, lithium, or potassium, as these are not well adsorbed by activated charcoal
• Multiple-dose activated charcoal for enhanced elimination
  • Interrupts enterohepatic recirculation and increases the elimination of certain toxins (e.g., theophylline, carbamazepine, phenobarbital)
  • Administered at regular intervals (e.g., every 4-6 hours) until clinical improvement is observed
• Urinary alkalinization for enhanced elimination of weak acids
  • Increases the ionization and renal excretion of toxins such as salicylates and phenobarbital
  • Achieved by administering intravenous sodium bicarbonate to maintain a urine pH between 7.5 and 8.5
• Extracorporeal removal techniques for severe poisonings or toxins not amenable to other elimination methods
  • Hemodialysis is effective for removing low molecular weight, water-soluble toxins (e.g., methanol, ethylene glycol, salicylates)
  • Hemoperfusion uses activated charcoal or resin cartridges to adsorb lipophilic toxins directly from the blood (e.g., theophylline, carbamazepine)
  • Continuous renal replacement therapy (CRRT) can be used for hemodynamically unstable patients or those with concomitant renal failure
• Chelation therapy for heavy metal poisoning
  • Uses specific chelating agents that bind to and facilitate the excretion of heavy metals
  • Examples include dimercaprol (BAL) for arsenic and mercury, succimer (DMSA) for lead, and deferoxamine for iron
• Surgical decontamination for ingested drug packets or sustained-release preparations
  • Endoscopic removal of drug packets or bezoars that are not amenable to whole bowel irrigation
  • Surgical removal may be necessary for large or multiple packets, or if there are signs of intestinal obstruction or perforation

Supportive Care and Monitoring

• Airway management and ventilatory support
  • Intubate patients with respiratory failure, severe CNS depression, or inability to protect their airway
  • Provide mechanical ventilation with settings adjusted based on the patient's oxygenation, ventilation, and acid-base status
• Hemodynamic support with intravenous fluids and vasopressors
  • Administer isotonic crystalloids to maintain adequate intravascular volume and tissue perfusion
  • Use vasopressors (e.g., norepinephrine, epinephrine) for refractory hypotension or shock
• Correction of electrolyte imbalances and acid-base disorders
  • Monitor and replete electrolytes such as potassium, magnesium, and calcium
  • Administer sodium bicarbonate for metabolic acidosis or to alkalinize the urine for enhanced elimination of certain toxins
• Management of seizures and agitation with benzodiazepines or other sedatives
  • Lorazepam or diazepam are first-line agents for controlling seizures
  • Midazolam or propofol can be used for sedation in agitated or delirious patients
• Cardiac monitoring and treatment of dysrhythmias
  • Continuous ECG monitoring to detect conduction abnormalities, QTc prolongation, or other arrhythmias
  • Administer antiarrhythmic medications (e.g., lidocaine, amiodarone) or perform electrical cardioversion as needed
• Temperature regulation and cooling measures for hyperthermic patients
  • Remove excess clothing and provide external cooling with fans, cold packs, or cooling blankets
  • Administer intravenous fluids and consider neuromuscular blockade for severe hyperthermia (e.g., serotonin syndrome, sympathomimetic toxicity)
• Monitoring of liver and renal function, coagulation status, and other relevant laboratory parameters
  • Assess for end-organ damage and adjust treatment accordingly
  • Trend laboratory values to evaluate the response to therapy and detect any deterioration
• Pain management with non-opioid analgesics or regional anesthesia techniques
  • Avoid opioids in patients with respiratory depression or altered mental status
  • Consider acetaminophen, NSAIDs, or nerve blocks for pain control when appropriate
• Wound care and tetanus prophylaxis for injection drug users or those with skin lesions
  • Clean and dress wounds, and administer antibiotics if there are signs of infection
  • Provide tetanus immunization if the patient's vaccination status is unknown or out of date

Special Populations and Considerations

• Pediatric patients
  • Children have unique physiological and developmental characteristics that affect their susceptibility to toxins and response to treatment
  • Ingestions in children are often unintentional and may involve non-pharmaceutical products (e.g., household cleaners, plants, batteries)
  • Dose calculations and antidote administration must be weight-based and carefully titrated
• Pregnant women
  • Toxins can cross the placenta an