The correct answer is E. The patient most likely has lactic acidosis as a result of metformin treatment.
Lactic acidosis is characterized by the accumulation of excess lactic acid in the blood (>5 mmol/L) as well as decreased arterial blood pH, decreased bicarbonate, and electrolyte imbalances with an elevated anion gap (normal = 8?16 mEq/L).
In patients with renal impairment (as evidenced by the creatinine of 2.4 mg/dL), both metformin and lactic acid are cleared less effectively, leading to an accumulation of both. The complication of lactic acidosis is serious and a potentially fatal side effect of metformin. Calculation of the anion gap:
[Na+] ? ([Cl-]+[HCO3-])
= 140 ? (102 + 14)
= 24 (elevated)
Metformin:
- Biguanide oral hypoglycemic agent.
- Indicated for the first-line treatment of type 2 diabetes mellitus.
- Decreases hepatic glucose production and intestinal glucose absorption.
- Increases insulin sensitivity.
The risk of lactic acidosis with metformin administration is increased in patients with heart failure, liver disease, intravenous contrast administration, and renal insufficiency.
The condition often is subtle and is associated with malaise, myalgias, respiratory distress, somnolence, and abdominal distress. As the acidosis becomes more severe, the patient may experience hypothermia, hypotension, and bradyarrhythmias.
It is recommended that the use of metformin be avoided in men with creatinine higher than 1.5 mg/dL and in women with creatinine higher than 1.4 mg/dL. Metformin-induced lactic acidosis also occurs more frequently in patients taking nephrotoxic medications such as aminoglycosides.
None of the other options are associated with the development of lactic acidosis:
Atenolol (choice A is a beta1-receptor antagonist indicated for the treatment of hypertension. It is most commonly associated with the development of bradycardia, hypotension, increased serum lipid levels, and impotence in men.
Enalapril (choice B) is an angiotensin-converting enzyme inhibitor (ACEI) used in the management of hypertension and congestive heart failure. ACEIs are commonly associated with the development of angioedema, hyperkalemia, and chronic cough.
Furosemide (choice C) is a loop diuretic used in the management of hypertension and various edematous states. Furosemide (and other loop diuretics) can cause severe hypokalemia, metabolic alkalosis, hyponatremia, hypocalcemia, ototoxicity (in large doses), hyperuricemia, and hyperglycemia.
Glyburide (choice D) is a sulfonylurea antidiabetic agent that is used as an adjunct to diet to lower blood glucose levels in patients with type 2 diabetes. Glyburide is most commonly associated with the development of hypoglycemia, weight gain, and elevated hepatic enzymes (in a small percentage of patients).
This is a multi-step question.
What is the question asking?
You are being asked for the medication responsible for the patient?s diagnosis.
What is the first step?
We must first establish the diagnosis.
- This 51-year-old female with a history of type 2 diabetes and hypertension on unknown medications presents with marked hyperventilation.
- The patient is tachycardic, tachypneic, and hyperventilating on exam.
- Labs reveals low serum pH and bicarbonate, and high serum creatinine.
- Labs are consistent with a diagnosis of elevated anion gap metabolic acidosis. The patient is hyperventilating to compensate for the metabolic acidosis.
What is the next step?
Next, we must determine which medication (for type 2 diabetes and hypertension) can cause metabolic acidosis in chronic kidney disease (CKD).
- Metformin (choice E) can accumulate in renal insufficiency and precipitate lactic acidosis in patients.
Can other answers be eliminated?
The other answer choices can be eliminated because they are not associated with metabolic acidosis in renal impairment:
- Atenolol (choice A), enalapril (choice B), furosemide (choice C), and glyburide (choice D) do not cause metabolic acidosis in renal insufficiency.
What is the single best answer and why?
Metformin (choice E) is the single best answer because it is the only medication listed that is known to precipitate lactic acidosis in renal insufficiency. Patients can present with hyperventilation as respiratory compensation for acidosis.
MedEssentials (4th Ed.): pp. 382
First Aid (2019): pp. 348.1-349.1, 580.1, 580.2
First Aid (2018): pp. 348.1-349.1, 576.1, 576.2
First Aid (2017): pp. 340.1-341.1, 561.1, 561.2
