Internal Medicine Correlations and Clinical Scenarios (CCS) USMLE Step 3

CASE 3: Aspirin Overdose

Setting: ED

CC: “I’m puking, my head hurts, and my ears are ringing.”

VS: BP: 124/82 mm Hg; P: 114 beats/minute; T: 101°F; R: 24 breaths/minute

HPI: A 54-year-old man come to the ED because shortness of breath, headache, and ringing in his ears. He is your former roommate in medical school, who took a bottle of aspirin in the bathroom at the twenty-fifth reunion. He usually takes an aspirin a few times a day for his joint pain. He comes to the ED the day after the overdose.

PMHX:

Image Rheumatoid arthritis

Image Depression

Image Recovering alcoholic—10 years sober

Medications:

Image Aspirin

Image Etanercept

Image Methotrexate

PE:

Image General: uncomfortable, sitting up on edge of bed holding his head

Image Cardiovascular: no murmur, no gallops

Image Abdomen: soft, nontender

Image Neurological: confused

Which of the following is the most urgent test?

a. Salicylate level

b. Acetaminophen level

c. Arterial blood gas (ABG)

d. Liver function tests

e. Blood urea nitrogen (BUN) and creatinine

Answer c. Arterial blood gas (ABG)

All of these tests are important. Your job is to understand which is the most important. Metabolic acidosis and respiratory alkalosis are the most likely causes of death, as well as seizure and pulmonary edema.

Respiratory alkalosis happens first!

Initial Orders:

Image Salicylate level

Image Acetaminophen level

Image ABG

Image LFTs

Image Basic metabolic panel (CHEM-7)

Image Charcoal

Charcoal can remove absorbed poisons and lower blood level.

Respiratory Alkalosis

First: direct stimulation to the brainstem

Salicylates stimulate brainstem respiratory centers.

Move the clock forward only 10 to 20 minutes to see what the results of the tests are.

Reports:

Image Salicylate level: 70 μg/mL (markedly elevated)

Image Acetaminophen level: none detected

Image ABG: pH 7.42; partial pressure of carbon dioxide (PCO2) 22 mm Hg; partial pressure of oxygen (PO2) 68 mm Hg

Image Serum bicarbonate 18 mEq/L (decreased)

Image LFTs: normal

Image BUN 22 g/dL (elevated); creatinine 1.9 mg/dL (elevated)

Image Anion gap 20 mmol/L (normal 6–12 mmol/L)

Always get salicylate and acetaminophen levels on all pill overdoses because of high rates of co-ingestion.

Salicylates directly stimulate the medulla, causing hyperventilation.

The mechanism of tinnitus is unknown.

What is the mechanism of the metabolic acidosis?

a. Renal insufficiency

b. Lactic acidosis

c. Oxalic acid accumulation

d. Unknown

e. Ketoacids (beta-hydroxybutyric acid, acetoacetic acid)

Answer b. Lactic acidosis

Salicylate intoxication produces metabolic acidosis with increased anion gap. The source of the lactic acidosis is the loss of oxidative phosphorylation. Oxidative phosphorylation or the Krebs cycle is the aerobic method whereby large amounts of adenosine triphosphate (ATP) are produced from each molecule of glucose. Salicylate intoxication poisons this activity in the mitochondria. Poisoned mitochondria cannot make ATP from glucose and the body is dependent on glycolysis. The end product of glycolysis is lactic acidosis.

Nausea and Vomiting

• Stimulation of chemoreceptor trigger zone

• Located in the medulla: no blood–brain barrier

Now that salicylate poisoning is clearly diagnosed, you should try to lower the level as quickly as possible. Also, because death can be from pulmonary edema, you should look at the chest.

Orders:

Image Bicarbonate IV

Image Dextrose 5% in water (D5W) (or any IV fluid with glucose)

Image Urinalysis (UA): check urine pH

Image Chest x-ray

Why is bicarbonate use beneficial?

a. It corrects acidosis on ABG.

b. It increases urinary excretion.

c. It reverses cardiac effect.

d. It reverses CNS effect.

e. It restores oxidative phosphorylation in the mitochondria.

Answer b. It increases urinary excretion.

Bicarbonate prevents reabsorption of salicylates after they have been filtered at the glomerulus. Bicarbonate use in aspirin overdose is entirely about lowering the blood level as quickly as possible by increasing urinary excretion. It has nothing to do with protecting the heart. That is how it works with TCA overdose.

1. Salicylates filter at the glomerulus.

2. Bicarbonate charges salicylates in the tubule.

3. Charged molecules cannot be reabsorbed.

IV bicarbonate is started. The patient is transferred to the ICU.

If a test and a treatment are ordered at the same time on CCS, the test will not reflect the treatment. UA and IV bicarbonate ordered at the same time will not reflect the IV bicarbonate. To see that effect, you would have to move the clock forward and recheck the UA.

Reports:

Image UA: no cells, pH 5.4 (before bicarbonate)

Image Chest x-ray: pulmonary edema and acute respiratory distress syndrome (ARDS)

Weak acids lose hydrogen ions (H+) and get charged in the basic environment. Charged molecules do not pass biological membranes easily.

Salicylates cause fever by their effect on the brain.

Mechanism of Confusion

• Direct CNS toxicity of salicylates

• Decreases CNS glucose from salicylates

• Cerebral edema

Why is there lung damage in salicylate poisoning?

a. It is from vasoconstriction.

b. It is from renal failure.

c. Salicylates cause capillary leak directly.

d. It is from hyperventilation from metabolic acidosis.

Answer c. Salicylates cause capillary leak directly.

Salicylate poisoning causes direct toxicity to the lungs resulting in ARDS. No one knows precisely why people have ARDS. The noncardiogenic pulmonary edema does not occur as an effect of respiratory compensation for metabolic acidosis. If the hyperventilation were compensation for metabolic acidosis, the chest x-ray would be normal.

Always give glucose-containing IV fluids for aspirin overdose.

No one knows why CNS glucose level is low in aspirin overdose.

Serum glucose is normal, but CNS glucose is low.

The patient’s mental status starts to improve with the start of IV glucose-containing fluids. Dyspnea improves as well. Repeat the salicylate level measurement every 2 hours and do an Interval History to check mental status.

Salicylate Metabolic Acidosis = Lactate

Orders:

Image UA

Image Salicylate level

Image ABG

ATP Molecules per Molecule of Glucose

• Aerobic: 30 to 36

• Glycolysis: 2

Salicylate Poisoning = Glycolysis Only = Lactate Overproduction

Reports:

Image UA: pH 7.8

Image Salicylate level: 60 μg/mL

Image ABG: pH 7.46; PCO2 28 mm Hg; PO2 78 mm Hg

Keep the patient in the ICU until several salicylate level measurements show that the level is decreasing. Also, bicarbonate drip is something best done in the ICU. An ICU stay of 1 to 2 days should be sufficient.

Transfer the patient out of ICU when:

• Pulmonary edema and CNS effects resolve

• Salicylate level drops

• Bicarbonate drip not needed

Move the case forward 12 hours and do an Interval History.

Interval History:Confusion, tinnitus, and shortness of breath have resolved and the patient feels much better.”

Indications for Dialysis with Salicylates

• Seizures and coma

• Pulmonary edema

• Severe confusion

Salicylic acid becomes charged by basic urine.

Charged molecules cannot reenter the tubule to go back into the blood.

The patient is transferred to the hospital floor. Stop the bicarbonate drip as the patient is moved out of the ICU.



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