Salicylate Toxicity

Salicylate containing products

• Methyl Salicylate

  • 1mL = 1.4g of aspirin

  • 5mL = 7g which is ~21 tablets (325mg aspirin)

• Bismuth Subsalicylate

  • 15 mL = 130mg

  • salicylate 1mL = 8.7mg → can cause chronic or acute toxicity especially in infants

• Excedrin: Migraine Medication OTC

  • Acetaminophen, Aspirin, caffeine

• Alka-Seltzer: OTC hangover, heartburn, headache, stomach ache relief

  • Anhydrous citric acid, aspirin, sodium bicarb

  • 2 tablets per packet

  • 1 tablet = 325mg aspirin

  • Directions: dissolve 2 tabs in 4oz H2O

• BENGAY

  • Muscle relief

  • Topical cream

• Wart Removal

• Tiger Balm

• Teething Gel

• Aspirin:

  • Lethal dose: 150mg/kg

  • Analgesia, antipyretic, anti-inflammatory

Pathophysiology

• Inhibition of cyclooxygenase enzyme (COX)

• Inhibit oxidative phosphorylation

• Increased renal bicarbonate excretion

• Lipolysis

• Metabolic acidosis Activates the brainstem (medulla) → tachypnea / respiratory alkalosis

• Two types of ingestion

  • Acute (i.e. suicide attempt)

  • Chronic (i.e. nursing home residents

Clinical Presentation

• General

  • Tachycardia

  • Tachypnea

  • Diaphoresis

  • Hyperthermia

• Neuro

  • Tinnitus/whooshing

  • Delirium/Agitation

  • Seizure/coma

• Pulmonary

  • Pulmonary Edema

  • Tachypnea

• Gastro

  • Nausea/vomiting

  • Diarrhea

• Presentation can mimic

  • Meningitis (AMS, delirium, agitation, hyperthermia, diaphoresis)

  • Pneumonia (pulmonary edema, tachypnea, diaphoresis, hyperthermia)

  • DKA (AMS, nausea/vomiting, tachypnea)

  • Sepsis (acidosis/lactic acidosis, tachypnea, diaphoresis/hyperthermia, tachycardia, hypotension, leukocytosis/leukopenia, fevers)

• Seizure Risk

  • pH of 7.45? 7.25? Risk of seizure and cardiac arrest

  • Risk 6-18 hours post ingestion

  • Levels >100mg/dL (severely toxic) can cause damage to basement membranes → cerebral and pulmonary edema

  • Cerebral edema → seizures

Work-up

• Call poison control 1-800-222-1222

• CBC, chem10, LFTs, VBG, salicylate level, APAP levels, ETOH, Utox, CXR, +/- CT head

• FUN FACT

  • Chloride will initially be falsely elevated secondary to salicylates interfering with how chloride is measured in lab

Acid-Base

• Respiratory Alkalosis

  • Affects the respiratory drive -> tachypnea

• Anion Gap Metabolic Acidosis

  • Ketoacid, salicylic acid, lactic acid

  • Increases renal excretion of bicarb

  • Uncoupling oxidative phosphorylation → hyperthermia and increased lactic acid

• Acidosis

  • Weak acid, pKA 3.5

  • Salycilate typically exists in ionized state at physiological pH

  • However, as metabolic acidosis ensues, the non-ionized form can easily cross blood brain barrier

Timing of Salicylate Levels

• Levels peak ~6 hours post ingestion

• Note: enteric coated tablets, peak ingestion can be delayed >12h

• Chronic Ingestion

  • Toxicity may occur at lower doses than acute OD

  • Don’t underestimate the severity of the intoxication based off the serum level, as it has already accumulated in the brain

Management

• Goal is to alkalinize the urine: Increasing serum pH effectively decreases toxicity

• Non-ionized Form

  • At a lower pH, salicylate will diffuse into tissues (crossing blood brain barrier)

• Ionized form

  • s/p alkalization

  • Won’t cross BBB

  • Excreted in urine

• Alkalinization

  • Indications

    • Salicylate level > 40mg/dL

    • Symptomatic patients

    • Bicarb gtt

      • 1L D5W

      • Release 150cc

      • Add 3amp bicarb (150cc)

      • Run at ~200-250cc/hr

  • Note: replete potassium

  • Bicarb decreases K

  • So, you can add 40 meq Potassium Cl

  • Mechanism

    • Initially……. Body is losing bicarb into the urine

    • While bicarb is excreted into the urine, so is K and Na

    • If the patient is vomiting, that is an additional source of lost K

    • Since the body is losing K

    • Kidneys respond to decrease in K by increasing K reabsorption

    • Sending H+ out into urine (acidic urine)

    • By increasing serum K (fluid repletion with added K), it will slow the gradient for the Na K ATPase pump, halting the release of H into the urine

    • Thereby, increasing bicarb reabsorption, will cause the ionized form of salicylates into the urine and excreted out!

• Urine Output

  • Hydrate to maintain a urine output of 2-3mL/kg/hr

• Hemodialysis

  • Indications

  • AMS

  • Noncardiogenic pulmonary edema

  • Salicylate level:

    • >100mg/dL

    • >90mg/dL w/ renal dysfunction or despite fluid resuscitation

    • >60mg/dL chronic (nursing home patients)

    • pH <7.2 despite bicarb

Let’s review some facts

• Salicylate Toxicity

  • Found in other medications besides aspirin

• Toxicity

  • Acute ingestion vs. Chronic

• Metabolic Acidosis

  • Secondary uncoupling oxidative phosphorylation

  • Excretion of bicarb in urine

• Respiratory alkalosis

  • affects medulla -> tachypnea/hyperventilation

• Alkalinize the urine

  • Sodium bicarb drip

• Hemodialysis

  • Acute toxicity: > 90mg/dL

  • Chronic Toxicity: > 60mg/dL

References

• Swaminathan A. Salicylate Toxicity. REBEL EM - Emergency Medicine Blog. Published May 17, 2018. Accessed December 7, 2023. https://rebelem.com/salicylate-toxicity/

• Farkas J. Salicylate intoxication. EMCrit Project. Published October 1, 2021. Accessed December 7, 2023. https://emcrit.org/ibcc/salicylates/#top

• Garner H, Long B, Santos C. EM@3AM: Salicylate Overdose. emDOCs.net - Emergency Medicine Education. Published June 20, 2020. Accessed December 7, 2023. http://www.emdocs.net/em3am-salicylate-overdose/

• Kolowich S. Tox Cards: Treatment for Salicylate Poisoning. emDOCs.net - Emergency Medicine Education. Published January 31, 2017. Accessed December 7, 2023. http://www.emdocs.net/9997-2/

Jillian Leibowitz, DO