Mind the gap: Measured and Calculated Osmolarity are not interchangeable in Diabetic Hyperglycemic Emergencies.

INTRODUCTION Small case series have reported that diabetic ketoacidosis is associated with elevated osmolar gap, while no previous studies have assessed the accuracy of calculated osmolarity in the hyperosmolar hyperglycemic state. The aim of this study was to characterize the magnitude of the osmolar gap in these conditions and assess whether this changes over time. METHODS Retrospective cohort study using two publicly available intensive care datasets: Medical Information Mart of Intensive Care (MIMIC) IV and the eICU Collaborative Research Database. We identified adult admissions with diabetic ketoacidosis and the hyperosmolar hyperglycemic state who had measured osmolality results available contemporaneously with sodium, urea and glucose values. Calculated osmolarity was derived using the formula 2Na + glucose + urea (all values in mmol/L). RESULTS We identified 995 paired values for measured and calculated osmolarity, originating from 547 admissions (321 diabetic ketoacidosis, 103 hyperosmolar hyperglycemic state and 123 mixed presentations). A wide variation in osmolar gap was seen, including substantial elevations as well as low and negative values. There was a greater frequency of raised osmolar gaps at the start of the admission which tends to normalize by around 12-24hr. Similar results were seen regardless of the admission diagnosis. CONCLUSIONS Osmolar gap varies widely in diabetic ketoacidosis and the hyperosmolar hyperglycemic state and may be highly elevated especially at the time of admission. Clinicians should be aware that measured and calculated osmolarity values are not interchangeable in this population. These findings should be confirmed in a prospective study.