Question

Difficulty: Very hardGeneral Internal Medicine

A 72-year-old woman is evaluated in the hospital for progressive lethargy and confusion over the past 24 hours. She was admitted 4 days ago for an acute exacerbation of chronic obstructive pulmonary disease (COPD). On admission, she was started on intravenous methylprednisolone, nebulized ipratropium-albuterol, and empiric piperacillin-tazobactam. She was also continued on her home dose of furosemide for a history of ischemic cardiomyopathy with a left ventricular ejection fraction of 35%. Her other home medications include lisinopril and levothyroxine.

Her temperature is 37.4∘C37.4^\circ\text{C} (99.3∘F99.3^\circ\text{F}), blood pressure is 100/60 mm Hg100/60\text{ mm Hg}, pulse is 110/min110\text{/min}, and respirations are 22/min22\text{/min}. Physical examination shows dry mucous membranes. The jugular venous pressure is 4 cm H2O4 \text{ cm H}_2\text{O}. Lung auscultation reveals distant breath sounds with faint expiratory wheezes and fine bibasilar crackles. Cardiac examination shows a regular tachycardia with no murmurs or gallops.

Laboratory studies show:
Sodium: 136 mEq/L136 \text{ mEq/L}
Potassium: 2.8 mEq/L2.8 \text{ mEq/L}
Chloride: 92 mEq/L92 \text{ mEq/L}
Bicarbonate: 36 mEq/L36 \text{ mEq/L}
Blood urea nitrogen: 52 mg/dL52 \text{ mg/dL}
Creatinine: 2.3 mg/dL2.3 \text{ mg/dL} (baseline 1.1 mg/dL1.1 \text{ mg/dL})
Thyroid-stimulating hormone (TSH): 0.1μU/mL0.1 \mu\text{U/mL} (normal: 0.4–4.0μU/mL0.4–4.0 \mu\text{U/mL})
Free T4: 1.0 ng/dL1.0 \text{ ng/dL} (normal: 0.9–1.7 ng/dL0.9–1.7 \text{ ng/dL})

Arterial blood gas on 2 L/min2 \text{ L/min} oxygen by nasal cannula shows:
pH: 7.547.54
PaCO₂: 48 mm Hg48 \text{ mm Hg}
PaO₂: 68 mm Hg68 \text{ mm Hg}

Which of the following is the most appropriate next step in management?

  1. Administer intravenous 0.9% normal saline and potassium chlorideAnswer
  2. B
    Administer an additional dose of intravenous furosemide
  3. C
    Initiate noninvasive positive-pressure ventilation
  4. D
    Broaden antibiotic coverage to intravenous meropenem
  5. E
    Decrease the daily dose of levothyroxine

Answer

Administer intravenous 0.9% normal saline and potassium chloride
The correct answer is to administer intravenous 0.9% normal saline and potassium chloride. This patient presents with lethargy, tachycardia, hypotension, and laboratory evidence of severe hypokalemia, acute kidney injury (BUN to creatinine ratio > 20:1), and a primary metabolic alkalosis (pH 7.54, bicarbonate 36 mEq/L). This presentation is classic for a contraction alkalosis, a chloride-responsive metabolic alkalosis driven by aggressive loop diuretic (furosemide) use leading to severe volume depletion. The volume contraction activates the renin-angiotensin-aldosterone system, which promotes sodium reabsorption at the expense of potassium and hydrogen ion excretion, perpetuating the alkalemia. The elevated PaCO2 of 48 mm Hg represents perfect respiratory compensation (Expected PaCO2 = 40 + [0.7 × 12] = 48.4 mm Hg), definitively ruling out acute respiratory failure. The definitive treatment for chloride-responsive metabolic alkalosis is volume repletion with 0.9% normal saline (which provides chloride to enable renal bicarbonate excretion) and aggressive potassium replacement.

Step-by-Step Solution

1
Analyze the patient's volume status and renal function.
The patient is profoundly volume depleted (hypotension, tachycardia, dry mucous membranes, JVP of 4 cm H2O) with a prerenal acute kidney injury indicated by a BUN/Creatinine ratio greater than 20:1.
Establishing volume status is critical for interpreting metabolic derangements and guiding therapy.
2
Interpret the arterial blood gas and electrolyte panel.
The pH of 7.54 and elevated bicarbonate of 36 mEq/L indicate a primary metabolic alkalosis. Severe hypokalemia (2.8 mEq/L) is concurrently present.
Identifying the primary acid-base disorder dictates the subsequent calculation of expected respiratory compensation.
3
Calculate the expected respiratory compensation for the metabolic alkalosis.
Using the formula: Expected PaCO2 = 40 + [0.7 × (actual HCO3 - 24)], the expected PaCO2 = 40 + [0.7 × (36 - 24)] = 40 + 8.4 = 48.4 mm Hg. The actual PaCO2 of 48 mm Hg demonstrates appropriate compensation.
This rules out a superimposed primary respiratory acidosis (hypercapnia) that might otherwise be suspected in a COPD patient.
4
Determine the therapeutic intervention for the diagnosed pathology.
The diagnosis is chloride-responsive contraction alkalosis secondary to furosemide use. Treatment involves stopping the offending agent and administering isotonic normal saline and potassium chloride.
Saline restores intravascular volume and provides chloride, allowing the kidneys to excrete excess bicarbonate. Potassium repletion corrects the hypokalemia, which otherwise sustains metabolic alkalosis by promoting renal hydrogen ion excretion.

Key Concept

Management of contraction alkalosis (chloride-responsive metabolic alkalosis) in a medically complex patient requires volume expansion with isotonic saline and correction of associated hypokalemia.
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