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tox 3

Cholinergic Toxicity (Organophosphate and related agents)

  • Key idea: cholinergic toxicity results from acetylcholine excess due to acetylcholinesterase inhibition (e.g., organophosphate pesticides) and can also arise from certain muscarinic mushrooms. The term CHOL is used as a memory aid for acetylcholine–related toxicity.

  • Common etiologies mentioned:

    • Organophosphate poisoning (insecticides, pesticides)

    • Certain mushrooms with muscarinic properties (even small amounts can cause toxicity)

    • Other potential cholinergic sources include some pesticides and muscarinic toxins in mushrooms

  • Clinical manifestations (the classic cholinergic “sludge”)

    • DUMBBELSS/SLUDGE mnemonics describe muscarinic effects:

    • DUMBBELS: Diarrhea, Urination, Miosis, Bronchorrhea, Bronchospasm, Emesis, Lacrimation, Salivation

    • SLUDGE: Salivation, Lacrimation, Urination, Defecation, Gastrointestinal cramping, Emesis

    • Other signs described in the talk:

    • Wet skin and body fluids (wet Willy concept)

    • Bronchorrhea and bronchospasm (the ‘killer bees’ triad)

    • Bradycardia

    • Lacrimation (tearing)

    • Miosis (pinpoint pupils) versus mydriasis (dilated pupils) in other toxidromes

  • Pupillary findings (differential):

    • Pinpoint pupils (miosis) common in cholinergic and opioids

    • Dilated pupils (mydriasis) seen in stimulants and anticholinergics

  • Hypotheses and differential concepts:

    • Pinpoint pupils point toward cholinergic or opioid toxidromes

    • Mydriasis points toward stimulants or anticholinergic toxidromes

  • Typical features (summary for field assessment):

    • Urination, Defecation, GI cramping, Emesis, Diaphoresis (sweating), Lacrimation, Salivation

    • Bradycardia, bronchorrhea, bronchospasm

    • Pupillary constriction (miosis)

  • Prehospital management notes (as described):

    • Antidote: Atropine (and sometimes supportive care with fluids)

    • Atropine dosing guidance from the talk: may require several milligrams; examples cited include 2 mg or 4 mg, with titration until symptoms improve

    • Ensure airway, breathing, circulation; fluids to combat dehydration from secretions

    • Emphasize that prehospital care can be lifesaving and needs to be ongoing until symptoms resolve

  • Mnemonics and group dynamics:

    • Dumbbells mnemonic for D: Diarrhea, Urination, Miosis, etc. (and other teachers/peers used ‘dumbbells’ and ‘sludge’ and ‘killer bees’ in the discussion)

  • Important caveat:

    • The presenter emphasizes not relying on a single sign (e.g., pinpoint pupils) and to consider the broader toxidrome pattern; prompt atropinization and fluids are key

  • Connections to prior knowledge:

    • Links to other toxidromes with pinpoint pupils (opioids) and dilated pupils (stimulants/anticholinergics)

    • Recognition of wet, drooling, sweating, and GI/GU overactivity as core cholinergic signs

Acetaminophen (Tylenol) Overdose

  • Key idea: Tylenol overdose is the leading cause of acute liver failure in the US; time-sensitive management with a specific antidote is critical.

  • Toxic dose reference:

    • Toxic dose threshold: 150\ ext{mg/kg} within 24 hours

    • The antidote (N-acetylcysteine) is most effective when given early

  • Pathophysiology (brief): acetaminophen hepatotoxicity occurs via a reactive metabolite causing hepatic injury; liver failure may progress through defined stages

  • Stages of acetaminophen overdose:

    • Stage 1 (<24 hours): nonspecific symptoms (nausea, malaise); patients may under-recognize the danger; early presentation can be deceptive

    • Stage 2 (24–36 hours): abdominal pain, nausea, vomiting; signs begin to worsen; antidote most beneficial if given before this stage advances

    • Stage 3 (2–4 days): peak liver injury; acidosis; potential MODS/ARDS; death may occur; some patients’ livers may regenerate, but mortality is highest in this stage

  • Dosing and threshold calculations (illustrative):

    • Toxic if exposure exceeds 150\ \text{mg/kg} within 24 h

    • Example calculation for a patient of weight W: the amount toxic = W \times 150\ \text{mg}

    • If tablet strength is 500 mg: approximate number of tablets to reach toxic dose = \frac{W \times 150}{500} (round up)

    • If tablet strength is 325 mg: approximate number = \frac{W \times 150}{325}

  • Antidote and decontamination:

    • N-acetylcysteine (NAC) is the antidote; timing is critical

    • Activated charcoal can be given early to reduce absorption if within an appropriate time window

    • In the hospital, labs are used to monitor liver function tests; NAC is continued as indicated by the clinical course and labs

  • Prehospital and practical notes:

    • If a Tylenol-containing product is suspected (including combination products), think about acetaminophen overdose

    • Tylenol-containing products discussed: DayQuil/NyQuil, Excedrin, Alka-Seltzer, Robitussin, Theraflu, Vicks; combination analgesics such as Hydrocodone/acetaminophen (Lortab, Norco), Oxycodone/acetaminophen (Percocet), and Tylenol 3

    • The concept of synergy is discussed: acetaminophen combined with opioids allows for reduced doses of each while achieving effect

  • Case takeaway guidance:

    • If overdose is suspected, obtain history (including recent days’ intake, not just today)

    • If early, administer activated charcoal as appropriate; anticipate NAC in hospital with timely communication

    • If significant overdose is suspected, rapid transport is essential due to risk of liver injury

  • Practical anecdote from the talk:

    • A caregiver’s real-life example highlighted rapid evaluation, the importance of not delaying antidote by waiting on lab results, and using NAC promptly if acetaminophen overdose is suspected

Salicylate (Aspirin) Overdose

  • Key idea: salicylate toxicity can occur from aspirin-containing products (including Pepto-Bismol) and some essential oils like wintergreen oil; symptoms can be delayed and require prompt evaluation

  • Notable sources mentioned:

    • Pepto-Bismol (salicylates)

    • Wintergreen oil (methyl salicylate)

  • Presentation and symptoms:

    • Hyperthermia (fever)

    • Hyperventilation (tachypnea) due to metabolic acidosis and respiratory compensation

    • Tinnitus and hearing loss (can be temporary)

    • Vomiting and possible acidosis

    • Possible CNS symptoms with high levels

  • Toxic dose and pediatric relevance:

    • Lethal dose for a 3-year-old about 7500\ ext{mg}

    • A sick/toxic level can start around 500\ \text{mg} (varies with weight and chronicity)

    • Baby aspirin tablets are 81 mg each; calculation example: lethal dose ~ 7500\text{ mg} / 81 \approx 92 tablets

  • Management notes:

    • Activated charcoal if early and within the window for ingestion

    • Sodium bicarbonate therapy to alkalinize serum and urine, promote salicylate excretion, and correct acidosis

    • Fluids and electrolyte management as supportive care

    • Assess for acid-base disturbances and monitor for signs of CNS involvement

    • Transportation to ED for definitive care is recommended for suspected overdose

  • Case-oriented guidance:

    • When a child ingests a salicylate-containing product, call poison control for guidance due to variability in product content and timing

    • The talk emphasizes not delaying definitive care while awaiting lab results; but labs will guide further treatment

Opioid Overdose

  • Key signs and differential:

    • Pinpoint pupils (miosis) commonly observed

    • Respiratory depression and bradycardia

    • Skin and bowel findings may be variable; not a reliable sole indicator

    • In overdose scenarios, consider co-ingestants (e.g., methadone, typical opioids, or mixed with other CNS depressants)

  • Critical prehospital management points:

    • Naloxone (Narcan) is used to reverse opioid-induced respiratory depression

    • Route and dosing:

    • Intranasal: initial dose often 2 mg (per nostril, total 2 mg if per-dose pack or 4 mg total depending on device). In some protocols, 2 mg per nostril is standard; in others, initial 0.4–0.5 mg IV/IO may be used with cautious titration

    • Intravenous/IM: 0.4–0.5 mg is a common starting IV dose; can be repeated every 2–3 minutes until adequate respiration resumes

    • Duration of action: Narcan duration is approximately 20$-$60\ ext{minutes}; relapse is possible if the opioid effect persists longer than the antagonist

    • If respiratory drive is present, do not over-activate counterproductive reversal; avoid fully waking the patient if there is still risk of airway compromise

    • Reassess and transport for continued observation and potential repeat dosing

  • Important considerations:

    • Do not give Narcan to every overdose patient solely based on respiratory status; ensure there is respiratory depression before administration

    • Be aware that many ODs are unintentional; adjust treatment based on clinical assessment and partner with the receiving facility for continuity of care

  • Additional notes from the talk:

    • In opioid overdoses with CNS depression, you may bag/ventilate and administer Narcan incrementally

    • The speaker emphasizes practical administration technique and ongoing assessment during transport

Sympathomimetic and Stimulant Toxidromes (Cocaine, Ecstasy, Meth)

  • Key features of stimulants:

    • Tachycardia, hypertension, hyperthermia

    • Agitation and anxiety; patient may be very combative or highly restless

    • Chest pain and potential for myocardial ischemia or infarction even in young patients due to increased oxygen demand

    • Possible wide complex tachycardias or arrhythmias due to conduction system effects (sodium channel effects can widen QRS)

    • Hyperthermia with ecstasy/metamphetamine/molly can lead to dangerous hyperthermia and rhabdomyolysis; aggressive cooling is essential

  • ECG and cardiac considerations:

    • Cocaine/meth can cause ischemic changes; QRS widening due to sodium-channel blockade can mimic other arrhythmias

    • In stimulant-related STEMI, treatment still centers on stabilizing the patient and mitigating sympathetic surge; aspirin is appropriate if STEMI is suspected

    • Benzo use is key to calming sympathetic overdrive; benzodiazepines help reduce heart rate, agitation, and temperature

  • Management principles:

    • Aggressive supportive care: IV fluids, oxygen as needed, cooling measures for hyperthermia

    • Benzodiazepines (e.g., Versed) to reduce sympathetic overdrive and prevent seizures

    • Avoid excessive vasodilators or nitroglycerin in certain tachyarrhythmias unless explicitly indicated; primary aim is CNS/adrenergic calming

    • If a true myocardial infarction pattern is suspected due to ischemia, follow STEMI protocol which may include aspirin

    • Consider airway management and continuous monitoring given the risk of rapid deterioration

  • Practical prompts from the talk:

    • Cocaine can produce a pattern that resembles Brugada on ECG in some cases, but clinicians should interpret ECGs in the clinical context

    • For stimulant-associated tachyarrhythmias, benzodiazepines are preferred to calm the patient and reduce sympathetic drive

  • Mnemonics and educational cues:

    • Stimulants include cocaine, methamphetamine, MDMA (ecstasy), caffeine, Ritalin, LSD, etc.

    • The overarching tactic is calming the patient with benzos and aggressive cooling when hyperthermia is present

Sedatives, Depressants, and Cannabinoids

  • Barbiturates and other CNS depressants:

    • CNS depressants slow down respiration and heart rate; management is largely supportive

    • Treatment focuses on maintaining ABCs and providing supportive care, including ventilation as needed

  • Benzodiazepines as a common agent class:

    • Used to reverse or treat overdose effects of other sedatives and to calm hyperactive patients with stimulant exposure when appropriate

  • Cannabis (marijuana):

    • Generally not associated with severe toxidrome by itself, but contamination or heavy use can cause problematic symptoms

    • Cannabinoid hyperemesis syndrome is noted; hot tubs/hot showers may help reduce vomiting symptoms

Other Important Toxidromes and Conditions Mentioned

  • Beta-blocker overdose and calcium channel blocker overdose:

    • Treatments can include glucagon (especially for beta-blocker overdose) and vasopressors to support blood pressure

    • Calcium channel blocker overdose may involve calcium administration and vasopressors; attempt to override effects with Epi/dopamine and other supportive therapies

  • Digoxin overdose:

    • ECG finding: a distinctive “ice-cream scoop” pattern; symptoms include nausea, vomiting, blurred vision, and halos

  • Tricyclic antidepressants (TCAs) overdose:

    • Mechanism: sodium channel blockade leading to QRS widening

    • Treatment: sodium bicarbonate (often 1 mEq/kg IV bolus, repeated until QRS normalization); monitor for seizures; avoid harm

  • Carbon monoxide and cyanide exposure; hydrofluoric acid exposure:

    • These exposures are noted as important toxidromes to review; standard treatments vary by substance

Case Highlights and Practical Takeaways

  • Case 1: Suspected acetaminophen overdose in an elderly patient on multiple meds

    • Key actions highlighted: consider acetaminophen OD even with combination products; use NAC early; consider activated charcoal if early; education on avoiding acetaminophen-containing meds on the counter

  • Case 2: Three-year-old ingested Pepto-Bismol (salicylate-containing)

    • Emphasized: call poison control; recognize salicylate symptoms (hyperthermia, tachypnea, tinnitus, acidosis); calculate potential lethal dose; use activated charcoal early; consider sodium bicarbonate and fluids

  • Case 3: Opioid overdose in a pulseless patient; Narcan considerations

    • Emphasized: Narcan is not first-line for cardiac arrest; focus on CPR; administer Narcan if there is respiratory depression; titrate doses and transport for observation

    • Discussed the importance of not over-reversing in a way that could cause withdrawal or airway instability

Quick Reference: Key Dosing and Formulas (LaTeX)

  • Acetaminophen toxic dose: 150\ \text{mg/kg} within 24 hours

  • Acetaminophen antidote: N-acetylcysteine (NAC); activated charcoal early if appropriate

  • Narcan (naloxone) dosing (prehospital guidance as discussed):

    • Intranasal: typically 2\ \text{mg} per nostril (total 4 mg in some devices) or a single 2 mg dose

    • IV/IO/IM: start with 0.4$-$0.5\ \text{mg}, titrate to resp. effort; multiple doses may be needed; total duration of Narcan effect is about 20$-$60\ \text{min} and re-dosing may be required

  • Atropine dosing for cholinergic toxicity (as discussed): often multiple milligrams; examples cited include 2\ \text{mg} or 4\ \text{mg}, with repeat dosing until signs of cholinergic excess abate

  • Salicylate lethal dose for a child (example given): 7500\ \text{mg} (3-year-old)

    • Sick/toxic level may begin around 500\ \text{mg}; baby aspirin 81 mg tablets imply a large number of tablets would be required for lethality

  • Sodium bicarbonate in TCA overdose: intravenous bolus of 1\ \text{mEq/kg}, repeated until QRS duration normalizes

  • Toxic thresholds for acetylcysteine and charcoal: administer NAC as soon as possible when acetaminophen OD is suspected; activated charcoal is used if ingestion was recent and within the absorption window

Practical Exam Prep Tips

  • Always consider a toxidrome pattern and use history to guide differential diagnosis

  • Call poison control early when unsure about ingestion or product contents

  • Treat life-threatening toxidromes first (airway, breathing, circulation), then address the underlying toxin

  • Use the right antidotes promptly when indicated (e.g., NAC for acetaminophen, atropine for cholinergic toxicity, defer Narcan to those with respiratory depression due to opioid overdose)

  • Remember common product contents that may contain toxins (acetaminophen in many OTC meds; salicylates in Pepto-Bismol; various stimulants and antidepressants across OTC/prescription products)

  • Keep in mind the duration of action differences between antidotes and the need for transport for ongoing care and monitoring

Notes for Review

  • The lecture emphasizes practical recognition of toxidromes through a constellation of signs and symptoms rather than relying on a single hallmark

  • There is emphasis on prehospital action: you can and should initiate certain antidotes and decontamination efforts prior to hospital arrival when safe and indicated

  • Effective prehospital care includes teamwork (e.g., call Poison Control, coordinate with receiving facility, and ensure patient transport for continued monitoring)

  • Mnemonics and visual patterns (DUMBBELSS/SLUDGE; killer bees; dumbbells) are used to aid memory and rapid recognition in the field