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Difficulty: HardGeneral Internal Medicine

An 68-year-old woman is brought to the emergency department by her daughter due to progressive confusion, agitation, and nausea over the past 24 hours. The daughter notes that the patient has had a mild upper respiratory illness for the last few days and has been taking an over-the-counter remedy frequently. The patient has a medical history of severe osteoarthritis and hypertension. Current home medications include lisinopril and multiple daily doses of an over-the-counter pain reliever.

Temperature is 37.8°C (100.0°F), blood pressure is 110/65 mm Hg, pulse is 114/min, and respirations are 28/min. Pulse oximetry shows 98% on ambient air. Physical examination reveals a diaphoretic, agitated woman who is oriented only to person. She occasionally complains of a "ringing" sound in her ears. The lungs are clear to auscultation bilaterally. Cardiac examination shows tachycardia with a regular rhythm. There is mild, diffuse epigastric tenderness.

Laboratory studies show the following:

Serum chemistry:
Sodium: 140 mEq/L
Potassium: 3.6 mEq/L
Chloride: 104 mEq/L
Bicarbonate: 14 mEq/L
Blood urea nitrogen: 24 mg/dL
Creatinine: 1.3 mg/dL
Glucose: 112 mg/dL

Complete blood count:
Leukocyte count: 14,500/mm³

Arterial blood gas analysis (room air):
pH: 7.42
PaCO2: 21 mm Hg
PaO2: 96 mm Hg

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

  1. Intravenous sodium bicarbonateAnswer
  2. B
    Endotracheal intubation and mechanical ventilation
  3. C
    Intravenous ceftriaxone and azithromycin
  4. D
    Intravenous furosemide
  5. E
    Measurement of serum thyroid-stimulating hormone

Answer

The most appropriate next step is the administration of intravenous sodium bicarbonate to alkalinize the serum and urine.
The patient's presentation is highly characteristic of acute salicylate (aspirin) toxicity. Key clinical features include tinnitus (the "ringing" sound), hyperventilation (tachypnea), hyperthermia, and agitation. The laboratory results reveal a classic mixed acid-base disorder: a primary respiratory alkalosis and a primary high anion gap metabolic acidosis.

The anion gap is elevated: AG=Na+−(Cl−+HCO3−)=140−(104+14)=22AG = Na^+ - (Cl^- + HCO_3^-) = 140 - (104 + 14) = 22.
For a primary metabolic acidosis with a bicarbonate of 1414 mEq/L, Winter's formula predicts respiratory compensation: Expected PaCO2=(1.5×14)+8=29±2Expected\ PaCO_2 = (1.5 \times 14) + 8 = 29 \pm 2 mm Hg.
Because the patient's actual PaCO2PaCO_2 (2121 mm Hg) is significantly lower than the expected range (27−3127-31 mm Hg), a concurrent primary respiratory alkalosis is present. This occurs because salicylates directly stimulate the medullary respiratory center.

The cornerstone of management for moderate-to-severe salicylate toxicity is intravenous sodium bicarbonate. This therapy has a dual purpose: 1) Serum alkalinization keeps the weak acid (salicylate) in its ionized, deprotonated state, preventing it from crossing the blood-brain barrier into the central nervous system. 2) Urine alkalinization traps the ionized salicylate in the renal tubules, profoundly enhancing its excretion.

Step-by-Step Solution

1
Interpret the basic metabolic panel and arterial blood gas results.
Identification of a high anion gap (AG=140−(104+14)=22AG = 140 - (104 + 14) = 22) metabolic acidosis. Using Winter's formula (Expected PaCO2=1.5×14+8=29±2Expected\ PaCO_2 = 1.5 \times 14 + 8 = 29 \pm 2), the actual PaCO2PaCO_2 of 2121 mm Hg is significantly lower than expected, confirming a concurrent primary respiratory alkalosis.
To accurately characterize the underlying pathophysiology of the patient's acute systemic disturbance.
2
Synthesize the laboratory findings with the clinical presentation.
Diagnosis of acute salicylate (aspirin) toxicity, supported by the classic acid-base disturbance, tinnitus, tachypnea, fever, and recent heavy use of an over-the-counter pain remedy for osteoarthritis.
To establish a definitive diagnosis before initiating potentially dangerous therapies.
3
Determine the optimal acute therapeutic intervention.
Selection of intravenous sodium bicarbonate infusion.
Sodium bicarbonate alkalinizes the blood (trapping salicylate in the ionized form so it cannot cross the blood-brain barrier) and alkalinizes the urine (dramatically increasing renal excretion of the toxin).

Key Concept

Salicylate toxicity classically presents with tinnitus, tachypnea, and a mixed primary respiratory alkalosis and high anion gap metabolic acidosis. Management centers on serum and urine alkalinization with intravenous sodium bicarbonate.
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General Internal Medicine

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