On his fourth day in the surgical intensive care unit, a 48-year-old man requires reassess… — USMLE Step 2 CK

On his fourth day in the surgical intensive care unit, a 48-year-old man requires reassessment due to declining urine output and worsening laboratory parameters. He originally underwent an emergent exploratory laparotomy and bowel resection for blunt abdominal trauma. On postoperative day 1, he developed severe alcohol withdrawal delirium, which has been continuously managed with a high-dose intravenous lorazepam infusion.

His temperature is $37.7^\circ\text{C}$ ( $99.9^\circ\text{F}$ ), blood pressure is $118/76\text{ mm Hg}$ , pulse is $102/\text{min}$ , and respiratory rate is $22/\text{min}$ . The abdomen is non-distended and appropriately tender at the incision site, with no rebound or guarding.

Laboratory results are as follows:

Laboratory Test	Result
Sodium ( $Na^+$ )	$140 \text{ mEq/L}$
Potassium ( $K^+$ )	$4.5 \text{ mEq/L}$
Chloride ( $Cl^-$ )	$100 \text{ mEq/L}$
Bicarbonate ( $HCO_3^-$ )	$14 \text{ mEq/L}$
Blood urea nitrogen (BUN)	$56 \text{ mg/dL}$
Creatinine	$2.8 \text{ mg/dL}$ (Baseline $0.9 \text{ mg/dL}$ )
Glucose	$180 \text{ mg/dL}$
Serum osmolality (measured)	$345 \text{ mOsm/kg H}_2\text{O}$

Arterial blood gas analysis on room air reveals:
pH: $7.28$
$PaCO_2$ : $30 \text{ mm Hg}$
$PaO_2$ : $92 \text{ mm Hg}$

Based on the provided information, which of the following is the most appropriate next step in management?

Discontinue the current sedative infusion and initiate dexmedetomidineAnswer
B
Administer intravenous fomepizole and prepare for hemodialysis
C
Obtain blood cultures and escalate to empiric broad-spectrum antibiotics
D
Administer a continuous intravenous sodium bicarbonate infusion
E
Obtain a computed tomography scan of the abdomen and pelvis with contrast

Answer

Discontinue the current sedative infusion and initiate dexmedetomidine

The correct answer directly addresses the root iatrogenic cause of this patient's severe metabolic derangement. He is experiencing a high anion gap metabolic acidosis (Anion Gap = 26) coupled with a significantly elevated osmolar gap of 35 (Calculated osmolality = 310; Measured = 345). In a patient who has been hospitalized for four days, an elevated osmolar gap is virtually impossible to attribute to acute toxic alcohol ingestion (such as methanol or ethylene glycol) prior to admission, as these compounds would have long been metabolized. Instead, the continuous high-dose lorazepam infusion is the culprit. Intravenous formulations of lorazepam and diazepam utilize propylene glycol as a solvent diluent. Prolonged or high-dose infusions lead to propylene glycol accumulation, which is sequentially metabolized by alcohol dehydrogenase into lactic acid and pyruvic acid. This accumulation causes a high anion gap metabolic acidosis, hyperosmolarity, and acute tubular necrosis (evidenced by his elevated creatinine). The most critical and appropriate next step is to discontinue the offending agent (lorazepam) and switch to an alternative sedative that does not contain propylene glycol, such as dexmedetomidine, midazolam, or propofol.

Step-by-Step Solution

Calculate the anion gap:

Na^+ - (Cl^- + HCO_3^-)

140 - (100 + 14) = 26 \text{ mEq/L}

To identify the primary metabolic acid-base disorder as a High Anion Gap Metabolic Acidosis (HAGMA).

Evaluate respiratory compensation using Winter's formula:

PaCO_2 = 1.5 \times HCO_3^- + 8 \pm 2

1.5 \times 14 + 8 = 29 \pm 2

. The measured

PaCO_2

30 \text{ mm Hg}

, representing appropriate compensation.

To rule out a superimposed primary respiratory disorder.

Calculate the expected serum osmolality:

2 \times Na^+ + BUN/2.8 + Glucose/18

2(140) + 56/2.8 + 180/18 = 280 + 20 + 10 = 310 \text{ mOsm/kg H}_2\text{O}

To determine the expected osmolality for comparison against the measured laboratory value.

Calculate the osmolar gap: Measured Osmolality - Calculated Osmolality

345 - 310 = 35 \text{ mOsm/kg H}_2\text{O}

(Normal < 10).

A significant osmolar gap in the presence of HAGMA narrows the differential primarily to toxic alcohols or propylene glycol.

Synthesize the timeline and medication history

The onset of this derangement on Hospital Day 4 rules out community ingestion of toxic alcohols. The high-dose lorazepam infusion is identified as the source of propylene glycol.

To determine the iatrogenic etiology and select the most appropriate corrective intervention.

Key Concept

Propylene glycol toxicity from continuous intravenous benzodiazepine infusions (lorazepam or diazepam) presents with an acute high anion gap metabolic acidosis, a significantly elevated osmolar gap, and acute tubular necrosis.

Estimated Time:2m 30s

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