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Difficulty: HardGeneral Internal Medicine

A 52-year-old man is brought to the emergency department by emergency medical services after his daughter found him lethargic and confused in his apartment. The daughter reports that the patient has a history of severe osteoarthritis, major depressive disorder, and alcohol use disorder. He recently lost his job and has been drinking heavily for the past week. His current medications include fluoxetine and several over-the-counter pain relievers. On physical examination, the patient is difficult to arouse but withdraws from painful stimuli. His mucous membranes are dry.

Vital signs are as follows:
Temperature: 37.4°C (99.3°F)
Blood pressure: 105/65 mmHg
Heart rate: 112/min
Respiratory rate: 26/min
Oxygen saturation: 98% on room air

Laboratory studies reveal the following:

Serum chemistry:
Sodium: 142 mEq/L
Potassium: 3.4 mEq/L
Chloride: 106 mEq/L
Bicarbonate: 12 mEq/L
Blood urea nitrogen: 24 mg/dL
Creatinine: 1.2 mg/dL
Glucose: 88 mg/dL

Arterial blood gas (on room air):
pH: 7.44
PaCO 2_2: 18 mmHg
PaO 2_2: 102 mmHg

Which of the following is the most appropriate next step in the diagnostic evaluation of this patient?

  1. Measurement of serum salicylate concentrationAnswer
  2. B
    Measurement of serum osmolal gap
  3. C
    Measurement of serum beta-hydroxybutyrate concentration
  4. D
    Calculation of the urine anion gap
  5. E
    Measurement of serum acetaminophen concentration

Answer

The most appropriate diagnostic step is the measurement of the serum salicylate concentration.
The correct answer is measurement of serum salicylate concentration. This patient's laboratory results demonstrate a mixed acid-base disorder characterized by a primary high anion gap metabolic acidosis and a concurrent primary respiratory alkalosis. The anion gap is elevated at 24 mEq/L (142−(106+12)142 - (106 + 12)). According to Winter's formula, the expected PaCO 2_2 for a bicarbonate of 12 mEq/L is (1.5×12)+8±2=26±2(1.5 \times 12) + 8 \pm 2 = 26 \pm 2 mmHg. Because the patient's measured PaCO 2_2 (18 mmHg) is significantly lower than the expected range, a concurrent primary respiratory alkalosis is present. The combination of a high anion gap metabolic acidosis and a primary respiratory alkalosis is the classic hallmark of salicylate toxicity. Salicylates directly stimulate the medullary respiratory center (causing hyperventilation and respiratory alkalosis) and uncouple oxidative phosphorylation in mitochondria (causing lactic acidosis and ketoacidosis). Given the patient's history of major depressive disorder and access to over-the-counter pain relievers, an intentional overdose is highly likely.

Step-by-Step Solution

1
Calculate the serum anion gap to identify the primary metabolic disturbance.
Anion Gap = 142−(106+12)=24142 - (106 + 12) = 24 mEq/L.
An elevated anion gap (>12 mEq/L) confirms the presence of a high anion gap metabolic acidosis (HAGMA).
2
Apply Winter's formula to determine if respiratory compensation is appropriate.
Expected PaCO 2_2 = (1.5×12)+8±2=26±2(1.5 \times 12) + 8 \pm 2 = 26 \pm 2 mmHg. The measured PaCO 2_2 is 18 mmHg.
Comparing the measured PaCO 2_2 to the expected PaCO 2_2 detects concurrent respiratory acid-base disorders.
3
Synthesize the findings of HAGMA and the lower-than-expected PaCO 2_2.
The patient has a primary high anion gap metabolic acidosis AND a primary respiratory alkalosis.
Because the measured PaCO 2_2 (18 mmHg) is significantly lower than the expected range (24-28 mmHg), there is an independent process driving hyperventilation.
4
Select the diagnostic test that corresponds to this specific mixed disorder.
Measurement of serum salicylate concentration is indicated.
Salicylate toxicity uniquely uncouples oxidative phosphorylation (causing lactic/ketoacidosis) and directly stimulates the medullary respiratory center (causing respiratory alkalosis).

Key Concept

Mixed Acid-Base Disorders and Salicylate Toxicity

Alternative Method

In addition to assessing the respiratory compensation, the Delta Ratio (ΔAG/ΔHCO3−\Delta AG / \Delta HCO_3^-) can be calculated to evaluate for a third concurrent metabolic disorder. Here, the ΔAG\Delta AG is 24−12=1224 - 12 = 12, and the ΔHCO3−\Delta HCO_3^- is 24−12=1224 - 12 = 12. The ratio is 12/12=1.012/12 = 1.0, which confirms a pure high anion gap metabolic acidosis without an additional secondary metabolic alkalosis or normal gap acidosis. This allows the clinician to focus exclusively on the respiratory derangement.
Estimated Time:2m 0s
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General Internal Medicine

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