Propylene Glycol Toxicity from Pentobarbital Infusion
The most likely cause of this patient's high-anion-gap metabolic acidosis is propylene glycol toxicity from the pentobarbital infusion. 1
Clinical Reasoning
This patient presents with classic laboratory findings of propylene glycol toxicity:
- High anion gap metabolic acidosis (anion gap = 132 - [91 + 13] = 28 mEq/L)
- Elevated osmolar gap (14 mOsm/L, above the threshold of 10-12 mOsm/L)
- Severe acidosis (pH 7.15, bicarbonate 13)
- Acute kidney injury (creatinine 3.1, worsened from baseline stage IIIa CKD)
The pentobarbital formulation contains propylene glycol as a diluent 2, and this patient received substantial doses: a 20 mg/kg loading dose followed by continuous infusion at 4 mg/kg/h for 2+ days, plus additional 5 mg/kg boluses. Propylene glycol toxicity manifests as metabolic acidosis and acute kidney injury 1, and an osmolar gap >10-12 mOsm/L reliably identifies patients with significant propylene glycol accumulation 1.
Why Not the Other Options?
Alcohol-induced ketoacidosis is unlikely because:
- Serum ketones are only 0.5 (minimally elevated)
- While the patient has alcohol use disorder, alcoholic ketoacidosis typically presents with serum bicarbonate usually not lower than 18 mEq/L in starvation ketosis 3
- This patient's bicarbonate is 13 mEq/L with profound acidosis (pH 7.15)
- The osmolar gap and clinical context point elsewhere
Renal tubular acidosis (RTA) is excluded because:
- RTA causes hyperchloremic (normal anion gap) metabolic acidosis, not high anion gap acidosis 3
- This patient has a clearly elevated anion gap of 28 mEq/L
- The acute presentation and osmolar gap are inconsistent with RTA
Isotonic saline infusion does not cause this picture because:
- Normal saline can cause hyperchloremic (non-anion gap) metabolic acidosis 4
- The patient has a high anion gap, not hyperchloremic acidosis
- While saline was administered at 125 mL/h, this rate and duration would not produce this degree of acidosis
- The osmolar gap elevation cannot be explained by saline
Supporting Evidence for Propylene Glycol Toxicity
The guideline explicitly warns that propylene glycol toxicity can occur with total daily IV doses as low as 1 mg/kg 1, far below what this patient received. The patient's pre-existing stage IIIa chronic kidney disease significantly increases risk 5, as propylene glycol is partially renally excreted and accumulates in renal dysfunction.
Critical diagnostic features present:
- Osmolar gap >10-12 mOsm/L (this patient: 14 mOsm/L) 1
- High anion gap metabolic acidosis
- Acute kidney injury superimposed on CKD
- Recent high-dose pentobarbital infusion containing propylene glycol 2
Propylene glycol is metabolized by alcohol dehydrogenase to lactic acid 6, 7, which explains the severe metabolic acidosis. The combination of impaired renal clearance, high drug doses, and prolonged infusion duration creates the perfect storm for toxicity 1, 5.
Clinical Pitfall
Propylene glycol toxicity symptoms can mimic sepsis 5, which is common in ICU patients, making this diagnosis easily missed. The key is recognizing the osmolar gap elevation in the context of medications containing propylene glycol as a solvent—not just lorazepam (which this patient also received for alcohol withdrawal), but also pentobarbital, phenytoin, and diazepam 5, 2.