Frequency and Clinical Significance of Negative Anion Gap Values in an Academic Medical Center Population

Anion gap is a value calculated by determining the difference between major plasma cations (sodium, sometimes additionally potassium) and anions (namely bicarbonate and chloride), with “normal” levels falling somewhere between 8 and 16 mEq/L. Elevations in anion gap are classically described in a variety of different clinical disease states, including but not limited to uremia, ketoacidoses, lactic acidosis, and a number of drug toxicities. Comparatively little is understood about the etiology of low and negative (<0) anion gap measurements; however, certain patient populations and pathologic states have been associated with negative anion gap measurements, such as multiple myeloma and hypertriglyceridemia (Kraut, 2007). We reviewed laboratory chemistries for 340,354 pediatric and adult patients over a ten-year period (2009-2018). Laboratory testing included values from basic and comprehensive metabolic panels and blood gas analyses. Chart review was performed on adult patients with anion gaps measuring less than 0 mEq/L to assess for medical trends or other explanations such as analytical interference or data errors. Additionally, blood gas analyses from patients being cared for in the neonatal intensive care unit (NICU) over the same ten-year period were also reviewed. Of the adult patients, 0.046% (157 samples) had an anion gap measuring below 0 mEq/L. Samples obtained as part of a blood gas analysis made up 52% of all negative gaps. While no definitive trends were noted, 23 samples were noted to be from patients with history of malignancy (solid tumor and hematopoietic), including multiple myeloma (4 patients).[mkrasows1] In addition to malignancy, 17 patients with hypertriglyceridemia were also found to have negative anion gaps. Negative anion gaps were rare in outpatient populations. Negative anion gaps as a result of a laboratory error were also rare, constituting only 1.3% of cases (2 patients). Negative anion gaps were comparatively more common in the NICU population, with 983 patients having a negative anion gap[mkrasows2] (0.289 %). NICU patients constituted 91% of all blood gas analyses with a negative anion gap, demonstrating that negative anion gaps are much more prevalent in this patient population than they are in other pediatric and adult populations. Negative anion gaps are relatively rare occurrences in the adult outpatient population; however, they can be seen in association with certain underlying disease states such as malignancy. By comparison, negative anion gaps are much more common in critically-ill populations, most notably NICU patients.

Spurious Hyperchloremia and Negative Anion Gap in a Child with Refractory Epilepsy

We report a case with spurious hyperchloremia with negative anion gap in a child who was taking potassium bromide for refractory epilepsy. Blood chemistry showed a high chloride level (171 mEq/L) and a negative anion gap (−52 mEq/L). Plasma chloride concentration is measured by an ion-selective electrode method; however the presence of other anions like bromide and iodides can interfere with chloride level and largely overestimates the chloride concentration. Thus hyperchloremia with a negative anion gap is a clue to the diagnosis of halides like bromide and iodide ingestion.