Anion Gap Remains Pragmatic Target for DKA Resolution

ALISO VIEJO, Calif. – July 1, 2026 – Patients experiencing life-threatening diabetic ketoacidosis (DKA) require quick action, diligent care and close monitoring as they receive insulin infusions and other medical interventions to bring their blood glucose and ketone levels back into balance.

Diabetic ketoacidosis is a serious complication of diabetes that occurs when there’s too little insulin in the blood to facilitate glucose transport into cells, leading to elevations in blood glucose and breakdown of fats into ketoacid byproducts. It can develop quickly and requires immediate medical attention.

Many hospital care teams refer to a specific measurement called the anion gap that is commonly included in routine bloodwork tests as one of the criteria for assessing the patient’s progress. However, leading diabetes organizations have recently issued updated guidelines that shift away from the anion gap to recommend measuring β-hydroxybutyrate levels as a primary laboratory criterion for determining when the medical emergency is resolved.

A team of critical care pharmacy specialists and intensive care physicians on the medical staff at Texas Health conducted a retrospective chart review comparing the clinical outcomes of adult patients admitted with DKA and treated with continuous intravenous insulin infusions at two hospitals in the system. At one facility, DKA resolution was defined using β-hydroxybutyrate levels and other criteria, while the other facility determined DKA resolution using the anion gap and corresponding clinical parameters.

They found that patients managed using the anion gap were transitioned to a long-acting insulin regimen (a key step in DKA resolution) a median of 10.2 hours sooner than those in the β-hydroxybutyrate–managed group, with no significant difference in rates of DKA recurrence or hospital length of stay. Those in the β-hydroxybutyrate-managed group had a median of 23.5 hours (17.9-31.0) before resolution while those in the anion gap-managed group had a median of 13.3 hours (10.0-18.2) before resolution.

“Clinical Utility of β-Hydroxybutyrate vs Anion Gap to Define Resolution of Diabetic Ketoacidosis” is published in American Journal of Critical Care (AJCC).

Co-author Andrew Faust, PharmD, BCCCP, is a critical care pharmacy specialist at Texas Health Presbyterian Hospital Dallas. He discussed takeaways from the study in a video interview that accompanies the journal article.

“Although recent guidelines favor β-hydroxybutyrate as a marker for DKA resolution, few clinical studies have directly compared its use with that of anion gap,” he said. “Our findings suggest a disconnect between the physiological rationale and clinical outcomes as β-hydroxybutyrate-based resolution criteria extended treatment duration without improving recurrence rates or length of the hospital stay.”

A total of 178 patients were included in the final analysis, with 89 individuals in each group. Baseline characteristics and incidence of severe DKA were similar between the two groups. While all included patients had a β-hydroxybutyrate value greater than 3 mmol/L at baseline, only three-quarters (73%) of patients in the anion gap-managed group had repeat β-hydroxybutyrate values measured during treatment.

In addition to the time to DKA resolution, the team looked at insulin rates and medication administration. Although the median hourly intravenous insulin rate at the time of transition to subcutaneous insulin was similar between the two groups, the median dose of subcutaneous long-acting insulin administered was 20 (15-30) units in the β-hydroxybutyrate-managed group and 15 (10-21) units in the anion gap-managed group. This may have been a factor in hypoglycemia warranting 50% dextrose administration, which was more common in patients managed by monitoring the β-hydroxybutyrate thresholds than in those managed with anion gap (18% vs 8%, respectively).

The researchers recommend prospective studies be conducted to compare clinical outcomes and determine whether the β-hydroxybutyrate target as recommended by the newest guidelines improves patient care. Specifically, measuring the trend of β-hydroxybutyrate concentration over the initial hours of treatment, as alluded to in some guidelines, is a potential, yet unstudied, approach to managing DKA.

To access the article and full-text PDF, visit the AJCC website at www.ajcconline.org.

About the American Journal of Critical Care:: The American Journal of Critical Care (AJCC), a bimonthly scientific journal published by the American Association of Critical-Care Nurses, provides leading-edge clinical research, with features that highlight bedside applications of select research articles. Established in 1992, the award-winning journal includes clinical and research studies, brief reports, editorials and commentaries that address questions relevant to critical care nursing, interprofessional practice and critical care delivery. AJCC enjoys a circulation of more than 136,000 acute and critical care nurses and can be accessed at https://www.ajcconline.org.

About the American Association of Critical-Care Nurses: For more than 55 years, the American Association of Critical-Care Nurses (AACN) has been dedicated to acute and critical care nursing excellence. The organization’s vision is to create a healthcare system driven by the needs of patients and their families in which acute and critical care nurses make their optimal contribution. AACN is the world’s largest specialty nursing organization, with more than 134,000 members and over 170 chapters in the United States.

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