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

CASE 5: Ethylene Glycol and Methanol

Setting: ED

CC: “I feel drunk.”

VS: BP: 110/70 mm Hg; P: 84 beats/minute; T: 100.2°F; R: 24 breaths/minute

HPI: A 28-year-old man is brought to the ED by his friends because he tried to kill himself with something he drank in the garage. The patient is clearly drunk and unable to provide a clear history. It is not clear how much vodka he may have drunk as well.

PMHX:

Image Depression

Medications:

Image Alprazolam

Image Paroxetine

Orders:

Image Naloxone, thiamine, dextrose

PE:

Image General: disoriented, visibly intoxicated

Image HEENT: red eyes, hard to visualize retinas

Image Neurologic: unable to complete the examination because of inability to cooperate

Image Abdomen: soft, nontender

Interval History: “No response to naloxone/dextrose. Patient remains disoriented with mental status changes.”

Initial Orders:

Image CHEM-7

Image UA

Image Complete blood count (CBC)

Image Urine toxicology screen

Image Serum osmolarity

Delirium Etiology

• Sodium level up/down

• Glucose level down

• Calcium level up

• Osmolar changes

• Liver or renal failure

• Hypoxia

Altered mental status is one of those symptoms for which treatment is started before getting tests.

The worst form of confusion is a seizure.

On CCS, do not get a neurology consultation until after these simple tests have been done. You are not supposed to need a neurology consultation to know to check the levels of calcium, glucose, oxygen, sodium, and to test for liver or renal failure.

Move the clock forward only far enough to get the test results. You will not know what type of hospital admission you need for this patient until you know the severity of his illness.

Reports:

Image CHEM-7:

Image Sodium 140 mEq/L

Image Glucose 90 mg/dL

Image Chloride 100 mEq/L

Image BUN 9 g/dL

Image Bicarbonate: 16 mEq/L (normal 22–26 mEq/L)

Image UA: No white blood cells (WBCs), “envelope-shaped” crystals present

Image CBC: WBCs 14,200/μL; 78% neutrophils

Image Urine toxicology screen: no cocaine, opiate, marijuana, benzodiazepines

Image Serum osmolarity 360 mOsm/kg

Serum Osmolarity = 2 × Sodium + Glucose/18 + BUN/2.8

Which laboratory test result tells you that there must have been a toxic ingestion?

a. WBC count elevation

b. Osmolar gap

c. Metabolic acidosis

d. Decreased anion gap

Answer b. Osmolar gap

The measured osmolarity is 360 mOsm/kg.

The calculated osmolarity is 287 mOsm/kg.

The difference between the osmolarity you measure and the osmolarity you calculate means that there must be an additional toxic substance in the bloodstream. A mild elevation in WBC could mean very little. Any form of “stress” for the body can lead to a mild elevation in WBC count. Fifty percent of WBCs are in circulation and 50% are on the “margins” or edges of the blood vessels. It is easy to double the WBC count just from “stress.” Also, this patient has an increased anion gap of 24 mmol/L, not a decreased anion gap. The normal gap is 6 to 12 mmol/L. Ethylene glycol leads to the increase in osmolar gap.

Envelope crystals are calcium oxalate.

Stress Leukocytosis

• Epinephrine

• Cortisol

Both pull WBCs off the endothelial lining.

Which of these would not be a cause of this metabolic acidosis?

a. Diarrhea

b. Sepsis

c. Hypotension

d. Methanol

e. Ethylene glycol

Answer a. Diarrhea

Diarrhea causes a GI tract loss of bicarbonate with an increased serum chloride. This is why diarrhea and renal tubular acidosis (RTA) have normal anion gaps. An increased anion gap in metabolic acidosis results from the insertion, or addition, of a new substance into the body. This decreases the bicarbonate and does not allow the chloride to rise.

Any form of hypoperfusion or hypotension increases lactate production. Methanol increases formic acid and is the insertion of a new anion.

Methanol Poisoning

• Increased anion gap

• Toxic to the eye and retina

• “Blind drunk”

• Fomepizole for drug therapy

• Dialysis to remove

Isopropyl alcohol: normal anion gap acidosis

Alcohol dehydrogenase metabolizes methanol to formic acid (Figure 11-2). Formic acid burns the eye.

imgae

Figure 11-2. A. Metabolism of methanol. B. Metabolism of ethylene glycol. NAD+, oxidized form of nicotinamide adenine dinucleotide; NADH, reduced form of nicotinamide adenine dinucleotide. (Reproduced with permission from Tintinalli JE, et al. Tintinalli’s Emergency Medicine, A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill; 2011.)

Metabolic Acidosis + Elevated Gap + Envelope Crystals = Ethylene Glycol

All patients who have metabolic acidosis need an ABG assay to determine the severity of decrease in pH. You should wait for the ABG results and ethylene glycol level to start treatment.

Orders:

Image ABG

Image Ethylene glycol level

Image Calcium levels

Image Repeat CHEM-7

Why is ethylene glycol toxic to renal function?

a. Hydrogen ions damage the glomerulus.

b. Ethylene glycol causes sloughing of the proximal tubule cells.

c. Oxalic acid and glycolic acid have direct cytotoxic effects.

d. Ethylene glycol lowers calcium levels.

e. The mechanism is unknown.

Answer c. Oxalic acid and glycolic acid have direct cytotoxic effects.

The entire point of the basic science correlate of this case is knowing that it is the metabolite of ethylene glycol and methanol that causes their toxic effects. Ethylene glycol is not directly toxic to the kidney. Ethylene glycol is metabolized to glycolic acid and oxalic acid. It is the metabolites that are dangerous to the kidney tubules by their direct cytotoxic effects.

Gastric lavage is never the correct treatment for toxic alcohols.

The patient remains intoxicated and difficult to interview.

Reports:

Image ABG: pH 7.34; PCO2 24 mm Hg; PO2 90 mm Hg

Image Ethylene glycol level: elevated

Image Calcium levels: 6.5 mg/dL (decreased)

Image Repeat chemistry: serum bicarbonate 18 mEq/L; creatinine 1.7 mg/dL

Renal toxicity takes 1 to 2 days after the ingestion of ethylene glycol.

Calcium complexes with oxalic acid

• Lowers blood calcium levels

• Precipitates in the kidneys

Orders:

Image Fomepizole

Image Bicarbonate drip if pH < 7.2

Image Transfer to ICU

Fomepizole

• Blocks alcohol dehydrogenase

• Prevents production of oxalic acid from ethylene glycol

• Prevents formic acid production from methanol

The patient is moved to the ICU if there is severe metabolic acidosis (pH < 7.2) or an overdose bad enough to need:

Image Bicarbonate drip

Image Fomepizole

Image Dialysis

• Fomepizole inhibits alcohol dehydrogenase.

• Alcohol dehydrogenase makes toxic metabolites.

• Only dialysis removes toxic alcohol from the blood.



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