Unexplained metabolic acidosis in critically ill patients: the role of pyroglutamic acid

Objective: To determine the role of pyroglutamic acid (PGA) in the pathogenesis of unexplained metabolic acidosis in critically ill patients. Design and setting: Case series in the medical ICU of an urban hospital. Patients: 23 patients admitted to the medical ICU with acidemia (PH <7.35 or HCO3 <= 16 mEq/l) not explained by the presence of ketoacidosis, lactic acidosis, renal failure or ingestion of drugs or toxins and who had an increase in the strong ion gap (SIG) greater than 5. Measurements and results: Plasma levels of sodium, potassium, chloride, bicarbonate, calcium (ionized), magnesium, lactate, phosphate, albumin, blood urea nitrogen, and creatinine were measured. Arterial blood gases and urine dipstick for ketones were also analyzed. Plasma was assayed for PGA using gas chromatography. The patient's history and Kardex were reviewed for evidence of acetaminophen administration. The plasma PGA level was found to be very low in all patients studied. The correlation between SIG and PGA (r) was -0.01 (95% CI: -0.42 to 0.40). PGA therefore did not account for the observed increase in the SIG. There appeared to be no obvious influence of acetaminophen intake on levels of PGA in the plasma. Conclusions: We were unable to confirm the importance of PGA as a cause of unexplained metabolic acidosis and increased SIG in our critically ill patients.