toxicity

Airway & Breathing

• Airway (Is the throat open and clear?)

  • Symptoms: trouble breathing (dyspnea), trouble speaking (dysphonia), “air hunger,” hoarseness

  • Signs: noisy breathing (stridor), pulling in chest/neck muscles when breathing (retractions), blue lips/skin (cyanosis)

  • Treatment: secure the airway right away if these are present

• Breathing (Is oxygen getting in?)

  • Check oxygen with pulse oximeter

  • Treatment: give 100% oxygen via facemask

    • Exception: if CO₂ is already high (elevated pCO₂), oxygen needs to be adjusted carefully

Circulation & Coma Cocktail

• Circulation (Heart & blood flow)

  • Check pulse and blood pressure

  • Treatment: place an IV line, give fluids if needed (fluid bolus)

• Drug-Induced CNS Depression (Coma Cocktail)

  • Used when patient is unresponsive from unknown drug overdose

What is used to treat a “Coma Cocktail”

• Dextrose: 50 mL of 50% IV dextrose

• Thiamine: 100 mg IV

• Naloxone: 0.4–2.0 mg IV

History of Exposure

• When evaluating a poisoned patient, always ask about the exposure details:

  • What happened? → Events and symptoms that occurred

  • Other substances? → Were there co-ingestions (multiple drugs/chemicals)?

  • First aid/therapy? → Was anything already done to treat it?

  • What substance? → Agents involved (any physical evidence like pill bottles, chemicals, etc.)

  • How was it taken? → Route (swallowed, inhaled, injected, skin, etc.)

  • How much? → Amount taken/administered

  • When? → Time since exposure

Medical History

• When assessing a poisoned patient, collect their medical background:

  • Allergies → to meds or substances

  • Medications → current prescriptions, over-the-counter, supplements

  • Past medical history → chronic illnesses (e.g., asthma, diabetes, seizures)

  • Situation prior to event → what was happening before poisoning (suicidal intent, accident, etc.)

  • Height & weight → important for dosing treatments

Physical Examination

• Check the patient from head to toe:

  • Look at the patient → general appearance, alertness, distress

  • Look at the skin → color, rashes, needle marks, sweating, cyanosis

  • Smell the breath → certain toxins have distinctive odors (alcohol, garlic, fruity, bitter almonds)

  • Listen to the lungs → wheezing, crackles, decreased air movement

  • Listen to the heart → abnormal rate or rhythm

  • Examine the abdomen → tenderness, distention, bowel sounds

  • Check extremities & do neuro exam → reflexes, strength, tremors, seizures, pupils

Laboratory Tests

• Key labs to order in a poisoned patient:

  • Metabolic profile/chemistries → kidney/liver function, glucose

  • Electrolytes → sodium, potassium, chloride, bicarbonate

  • CBC (Complete Blood Count) → infection, anemia, platelets

  • Anion gap → helps detect metabolic acidosis (poisonings like methanol, ethylene glycol)

  • Osmolal gap → screens for toxic alcohols (methanol, ethylene glycol)

  • Serum tox screen → checks blood for common toxins/drugs

  • Urine tox screen → detects drugs/poisons in urine

  • Quantitative analysis → measures exact toxin level (when possible)

Toxicokinetics

• How the body handles a drug/poison at toxic doses

• It looks at:

  • Absorption → how the toxin enters the body

  • Distribution → where it spreads (blood, tissues, fat, organs)

  • Metabolism → how the body breaks it down

  • Excretion → how the body gets rid of it (urine, bile, breath, sweat)

Pathophysiologic Alterations in Poisoning

• GI motility → slower stomach emptying or delayed absorption

  • Management: late gastric evacuation, repeated activated charcoal, whole bowel irrigation (WBI)

• Enterohepatic recirculation (toxin reabsorbed from intestines back to blood)

  • Management: multiple doses of activated charcoal

• Kidney elimination problems → toxins not cleared normally

  • Management: forced diuresis (more urine), ion trapping (change urine pH to trap drug)

• Other impacts:

  • Cardiovascular/pulmonary function

  • Acid-base balance

  • Kidney/liver function

  • Hypothermia

Ipecac Syrup

• Induces vomiting

Ipecac Syrup only works when exposure is within 

• 4-6 hrs 

Ipecac Syrup (< 1year)

• 5-10 mL

• x1 in 20 min. if no response

Ipecac Syrup (1-11 years)

• 15 mL

• x1 in 20 min. if no response

Ipecac Syrup (>12 years)

• 30 mL

• x1 in 20 min. if no response

Gastric Lavage

• A tube is put into the stomach through the mouth or nose, then water or saline is flushed in and sucked back out to remove the poison

• Only in very serious, life-threatening poisonings, usually within 1 hour of ingestion

Activated Charcoal 

• Binds (adsorbs) toxins in the stomach/intestines → prevents absorption into the blood

• Excellent for many drugs/poisons (but NOT all)

• Do NOT use if intestinal obstruction, risk of aspiration, or unprotected airway

T/F: activated charcoal has excellent efficacy

• True

Activated Charcoal (< 1 y/o)

• 1 g/kg

Activated Charcoal (1-12 y/o)

• 25-50 g

Activated Charcoal (adolescent or adult)

• 25-100 g

Cathartics

• Sometimes given with charcoal to speed toxin elimination, but use is controversial

Whole Bowel Irrigation

• PEG-3350

• Flushes entire GI tract, used for sustained-release drugs, “body packers,” or substances charcoal can’t bind

GI Decontamination & Enhanced Elimination

• Multiple-Dose Activated Charcoal

• Diuretics

  • Forced diuresis: increase urine output to wash out toxins

  • Alkalinization of urine: give bicarbonate to trap weak acids (like aspirin, phenobarbital) in urine

• Extracorporeal Removal

  • Hemodialysis

  • Hemoperfusion

  • Peritoneal dialysis

Does the patient have to be concious/awake to give activated charcoal?

• YES

First thing to do with an overdose patient?

• ABC

• Check airway 

• Check breathing 

• Check circulation 

Is acetaminophen toxic?

• Yes, at high doses, it overwhelms the liver’s ability to safely break it down

• Normally: acetaminophen is metabolized into safe products

• In overdose: too much gets converted into a toxic byproduct (NAPQI)

  • NAPQI damages liver cells → can lead to acute liver failure

Acetaminophen Overdose

• 400 fatalities/year involve acetaminophen

• Majority are intentional (suicide attempts)

• In most overdose cases, measured acetaminophen (APAP) blood levels are well above the toxic threshold

Acetaminophen→ NAPQI

• Most acetaminophen (APAP) is broken down in the liver into harmless products:

  • Glucuronide conjugates

  • Sulfate conjugates

• Small percentage:

  • Converted into NAPQI (N-acetyl-p-benzoquinone imine)

  • NAPQI facts:

    • Highly toxic metabolite

    • Normally, glutathione (a natural liver antioxidant) quickly detoxifies NAPQI into harmless products (cysteine & mercapturate conjugates)

NAPQI

• More acetaminophen is converted into NAPQI (toxic metabolite)

• Glutathione stores deplete (<30% remaining)

• Excess NAPQI kills liver cells → centrilobular necrosis (classic liver damage pattern)

• About 20% of patients with toxic levels don’t get severe liver injury (differences in metabolism)

• Without treatment, 1–2% of overdoses lead to fatal liver failure

Who is at higher risk of liver injury from acetaminophen overdose?

• Alcoholism

• Starvation/malnutrition

• AIDS

• Race

• Liver disease

• Pregnancy

• Drug-induced alterations

  • Anticonvulsants and isoniazid → increase metabolism toward toxic pathways, raising NAPQI levels

N-acetylcysteine

• Replaces glutathione (the liver’s natural defense)

• Detoxifies the toxic metabolite NAPQI before it can destroy liver cells

N-acetylcysteine (starting dose)

• 140 mg/kg

N-acetylcysteine (maintenance dose)

• 70 mg/kg given every 4 hours (17 doses) for 72 hours

• If vomits within 1 hour → repeat the dose (vomit is common side effect)

N-acetylcysteine must be diluted

• Use a 5% solution for administration

  • NAC usually comes as 10–20% solution → must be diluted

  • Can mix with beverages (Fresca works well to mask taste)

• Vomiting is a common side effect

0–24 hours APAP Toxicity

• Symptoms: nausea, vomiting, loss of appetite, sweating

• BUT many patients may have no symptoms → why APAP is called the “Silent toxin”

1–3 days APAP Toxicity

• Symptoms may temporarily improve (latent phase)

• Liver enzymes and bilirubin start to rise

• May feel liver tenderness or abdominal pain

3–6 days APAP Toxicity

• Peak liver damage: ↑ liver enzymes, RUQ pain, jaundice

• Hypoglycemia, confusion (encephalopathy)

• Clotting problems (like DIC)

• Other issues: pancreatitis, myocarditis, low phosphate

7–8 days APAP Toxicity

• Severe damage: coma, hepatorenal syndrome, possible death

• BUT if patient survives, liver has strong ability to heal

1–7 months APAP Toxicity

• Recovery phase → liver can return to normal function

< 4 hours after ingestion (Acetaminophen (APAP) Overdose Management)

• Give Activated Charcoal (if patient is awake/protected airway) → stops more drug from being absorbed

• Start N-acetylcysteine (NAC) → protects the liver

4–8 hours after ingestion (Acetaminophen (APAP) Overdose Management)

• Draw APAP blood level

• If APAP level is high → continue NAC

• If APAP level is low → stop NAC (not needed)

N-acetylcysteine (NAC) in Acetaminophen Overdose

• It is a Sulfhydryl compound

• Replenishes glutathione, which is the liver’s shield

  • Glutathione binds/detoxifies the toxic metabolite NAPQI

  • NAC can also directly bind to toxic metabolites

• Most effective if given early (before liver damage builds up)

• Best if started within 8–10 hours of ingestion

• Some benefit may still occur up to 72 hours later → may slow down liver failure

IV N-acetylcysteine

• Used in Europe for years, approved in US in 2004

• Expensive (≈ $3000)

• Best option for patients with significant nausea & vomiting (who can’t tolerate oral NAC)

IV N-acetylcysteine Dosing

• 150 mg/kg in 200 mL D5W

Infuse over 15 minutes

• 50 mg/kg in 500 mL D5W

Infuse over 4 hours

• 100 mg/kg in 1000 mL D5W

Infuse over 16 hours

N-acetylcysteine Side Effects

Oral: 

• Unpleasant odor/taste (like rotten eggs) → using a straw may help (also better to put in a drink)

• Rare: Sulfhemoglobinemia → cyanosis (blue skin) but without breathing problems

IV: 

• Anaphylactoid reactions (3–9%) → rash, wheezing, hypotension

• Usually mild and can be fixed by slowing the infusion rate

Salicylate Poisoning

• Overdose of aspirin or similar drugs (salicylates)

• Causes acid–base problems (first breathing faster → then metabolic acidosis)

• Affects the brain (confusion, agitation, seizures)

• Affects the stomach (nausea, vomiting)

• Can raise body temperature

Salicylate Poisoning – Mechanism of Toxicity

• Breathing changes

  • Aspirin stimulates the brain’s breathing center

  • This makes the patient breathe too fast (hyperventilate)

  • Breathing out too much CO₂ → respiratory alkalosis (blood becomes more basic)

  • Body tries to fix this → later causes metabolic acidosis

  2. Energy problems in cells

  • Salicylates “uncouple” energy production (oxidative phosphorylation)

  • This means cells waste energy → they burn fuel but don’t make enough ATP (the body’s energy currency)

  3. Lactic acid buildup

  • Because cells aren’t making enough energy, they switch to anaerobic metabolism

  • This makes extra lactic acid → leads to lactic acidosis

  4. Glucose (sugar) problems

  • Normal sugar breakdown (glucose & fat metabolism) gets blocked

  • Brain runs low on glucose → confusion, seizures, coma

  5. Fluid leakage

  • Aspirin can damage small blood vessels (capillaries)

  • This makes them “leaky” → fluid leaks into the brain (cerebral edema) and lungs (pulmonary edema)

Pathophysiology of Aspirin Overdose

• Stimulates respiratory center → hyperventilation

• Respiratory alkalosis develops

• Uncouples oxidative phosphorylation → energy production fails

• ↑ Heat production → fever

• ↑ Tissue glycolysis (sugar breakdown speeds up)

• Mobilization of fats → free fatty acids + ketones

• Mobilization of glycogen stores → backup sugar used up

• Result = energy depletion

Salicylate-Induced Acid-Base Changes

• Early: Respiratory alkalosis

  • Caused by fast breathing (hyperventilation) → blowing off too much CO₂

• Middle: Mixed acid-base disturbance

  • Combination of respiratory alkalosis + metabolic acidosis happening together

• Late: Metabolic acidosis

  • From lactic acid buildup, energy failure, and acid accumulation

Salicylate Poisoning – Clinical Presentation

• Early symptoms

  • Vomiting

  • Fast breathing (hyperpnea)

  • Ringing in ears (tinnitus)

  • Lethargy (tiredness)

  • Fever

• Lab findings (ABGs)

  • Mixed respiratory alkalosis + metabolic acidosis

• Severe intoxication

  • Coma

  • Seizures

  • Low blood sugar (hypoglycemia)

  • High body temperature (hyperthermia)

  • Fluid in lungs (pulmonary edema)

• Cause of death

  • CNS failure + cardiovascular collapse

Salicylate Poisoning – Diagnosis

• Acute ingestion

  • Serum level > 90–100 mg/dL → usually severe toxicity

  • Need multiple blood levels (drug absorption may be delayed by bezoars)

  • Done nomogram exists but not widely used

• Chronic intoxication

  • Symptoms don’t match blood levels well

  • Must rely more on clinical presentation than numbers

Salicylate Poisoning - Management 

• 1 mEq/kg IV bolus sodium bicarbonate

• Start continuous infusion of sodium bicarbonate

  • Mix 3 ampules (44 mEq each) in 1 L D5W

  • Infuse at 200 mL/hr

  • Goal: keep urinary pH > 7.5

• Add IV potassium (40 mEq/L) to the same IV bag

• Needed because low potassium makes alkalinization less effective

Salicylate Poisoning – Hemodialysis Indications

• Severe intoxication → seizures, coma

• Metabolic acidosis + kidney failure

• Risk for pulmonary edema

  • Older age

  • Smoking history

  • Acute on chronic ASA intoxication

  • Ineffective diuresis

• High ASA level > 100 mg/dL

Ethylene Glycol

• Found in antifreeze and some solvents

• Clear + no smell

• Sweet taste → people or kids may accidentally drink it

• The chemical itself (ethylene glycol) is not very toxic

• But the body breaks it down into toxic acids

  • Glycolic acid → causes severe acidosis (blood too acidic)

  • Oxalic acid → combines with calcium → forms crystals in kidneys → kidney damage

• Even 100 mL (about half a small cup) can be deadly

Ethylene Glycol - Mechanism of Toxicity

• Ethylene glycol → broken down by alcohol dehydrogenase

• Produces glycolic acid + oxalic acid

• These acids + lactic acid → cause anion gap metabolic acidosis

• Oxalate + calcium → form insoluble calcium oxalate crystals

• Crystals deposit in kidneys and tissues

• Damage from both crystals + toxic acids

• Leads to organ failure (especially kidney failure)

Stage 1 (30 min – 12 hrs) Ethylene Glycol Poisoning

• Looks like alcohol intoxication (inebriation)

• Nausea/vomiting

• ↓ Reflexes (hyporeflexia)

• Seizures, coma

• Eye findings: ophthalmoplegia, nystagmus, papilledema

Stage 2 (12 - 24 hrs) Ethylene Glycol Poisoning

• Fast heart rate (tachycardia)

• High blood pressure (hypertension)

• Fluid in lungs (pulmonary edema)

Stage 3 (>24 hrs) Ethylene Glycol Poisoning

• Flank pain

• ↓ Urine output (oliguria → anuria)

• Renal failure

Ethylene Glycol – How & When to Treat

• Lab testing is slow → don’t wait for results

• Start treatment immediately if poisoning is suspected

• Use clinical findings to guide decisions

• Ethylene glycol is a deadly poison → even small amounts can be fatal

Ethylene Glycol – Treatment Strategies

• Stabilize patient first

  • Airway, breathing, circulation

• Activated charcoal

  • May help if given early

• Correct acidosis

  • IV sodium bicarbonate

  • Hemodialysis if severe

• Antidotes (block alcohol dehydrogenase)

  • Fomepizole (preferred)

  • Ethanol (alternative)

• Vitamins

  • Help enhance breakdown of toxic metabolites

Ethanol (alternative)

• Blocks alcohol dehydrogenase

• Prevents ethylene glycol → toxic metabolites

Ethanol dosing 

• 1000 mg/kg/hr IV over 1–2 hrs

• Then: 100 mg/kg/hr continuous infusion

Fomepizole brand name

• Antizol

Fomepizole (perferred)

• Blocks alcohol dehydrogenase → stops conversion of ethylene glycol into toxic acids

Fomepizole Doisng

• 15 mg/kg IV over 30 min

• Then: 10 mg/kg IV every 12 hrs × 4 doses

What is the first line treatment for Ethylene Glycol overdose?

• Fomepizole

Ethylene Glycol – Hemodialysis

• Removes both ethylene glycol and its toxic metabolites

• Helps correct

  • Acid-base disturbances

  • Electrolyte abnormalities

• Not all patients need dialysis → reserved for severe cases

• Treatment goal

  • Continue until:

    • Ethylene glycol level < 20 mg/dL

Methanol

• Common in windshield washer fluid and Sterno (camping fuel)

• Methanol itself is not very toxic.

• The liver breaks it down into:

  • Formaldehyde → very toxic

  • Formic acid → damages the optic nerve and causes blindness

Methanol Treatment

• Fomepizole (best)

• Ethanol

• Bicarbonate

• Dialysis

Big difference between Methanol and Ethylene Glycol

• Methanol → Eyes (Blindness)

• Ethylene Glycol → Kidneys (Renal failure)

Lithium – Classification of Exposure

• This happens when someone who already takes lithium (for a long time) accidentally or intentionally takes too much more. They are not new to lithium

Acute Intoxication of Lithium

• Happens when someone who has never taken lithium before suddenly takes it (accidentally or on purpose)

• Early symptoms: nausea, vomiting

• More serious symptoms: often delayed for hours because lithium takes a long time to spread through the body

• Key point: Blood levels of lithium don’t match the severity of symptoms right away. (A patient might have high levels but not show signs until later)

Chronic Intoxication of Lithium

• Happens in someone who already takes lithium regularly, but their levels rise over time (not from a one-time overdose)

• Why it happens (causes):

  • Higher dose (on purpose or by mistake)

  • Drug interactions (e.g., NSAIDs, thiazide diuretics → make kidneys hold onto more lithium)

  • Kidney problems (kidneys can’t clear lithium properly)

  • Low body fluid (dehydration/volume depletion): body holds onto more sodium and lithium, causing toxicity

Normal (therapeutic) Blood Levels of Lithium

0.4 – 1.3

Mild toxicity (too high) Blood Levels of Lithium

• >1.5

• Symptoms: vomiting, diarrhea, tremor, unsteady walking, vision problems

Serious toxicity Blood Levels of Lithium

• >2.5

• Life-threatening: seizures, heart rhythm problems

Emergency Blood Levels of Lithium

• >3.5

• Dialysis (machine cleans lithium out of blood) is usually needed

Management of Lithium Poisoning

• “In like a Lamb, Out like a Lion”

• Lithium poisoning may start quietly (mild at first) but can become very severe later

• Replace lost fluids aggressively (dehydration makes lithium worse)

• Activated charcoal does NOT work for lithium (but can be used if another drug was also swallowed)

• Ipecac (to make someone vomit) can be used only if it’s within minutes of swallowing lithium (more common in kids)

• Whole bowel irrigation (flushing out the intestines with solution) may help if the person took sustained-release (SR) lithium tablets

Lithium Poisoning - Hemodialysis

• Main treatment for severe cases

• Used if:

  • Lithium blood level is ≥ 2.5 mEq/L (especially in Acute-on-Chronic or Chronic exposures)

  • Severe symptoms (coma, seizures, dangerous heart rhythms)

• Problem: lithium leaves tissues slowly → after dialysis, lithium in the blood can rebound (rise again)

• Because of this, prolonged or repeated dialysis is often needed