Aim Diabetic ketoacidosis is a hyperglycaemic emergency that is often treated in intensive care units (ICUs) despite having a low mortality and good prognosis. Current risk stratification is based primarily on acidosis, but it has been suggested that hyperosmolarity may also be an important marker of increased severity. Our aim was to evaluate the relationship between raised serum osmolarity and adverse clinical outcomes in ICU admissions for ketoacidosis. Methods Retrospective review of prospectively collected data for adult admissions with ketoacidosis in the Australian and New Zealand Intensive Care Society Adult Patient Database over a 15-year period (2004-2018). Exclusions were readmissions and records with critical missing data. Serum hyperosmolarity was defined as > 320 mosm/l. The primary outcome was hospital mortality; secondary outcomes were ICU mortality and other adverse clinical events. Results Some 17 379 admissions were included in the study population. People with hyperosmolarity had fourfold increased mortality, a higher incidence of renal failure and need for mechanical ventilation, and prolonged ICU and hospital length of stay. The relationship with mortality remained highly significant even after adjusting for severity of acidosis, hospital type, year of admission, time to ICU, and a modified Australia and New Zealand Risk of Death propensity score. Conclusions Although adults with ketoacidosis have a good prognosis overall, hyperosmolarity was independently associated with a significantly higher incidence of multiple adverse outcomes including mortality. Whether or not this is directly causal, it may have practical applications to improve risk stratification and identify individuals at risk of adverse outcomes.

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.

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