Hypophosphatemia in Diabetic Ketoacidosis During Intensive Care Admission

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Abstract
Introduction: Diabetic ketoacidosis (DKA) is a common complication of diabetes mellitus characterized by metabolic acidosis, ketogenesis, hypovolemia, hyperglycemia, and electrolyte depletion. During treatment of DKA with intravenous fluids and insulin, some electrolyte disturbances can worsen. Hypophosphatemia is one such electrolyte disturbance that has not been well characterized in patients with severe DKA requiring Intensive Care Unit (ICU) admissions. This study sought to evaluate the incidence, severity, associations, and outcomes of hypophosphatemia in DKA. Methods: This retrospective multicenter study was conducted across DKA admissions to Queensland ICUs from 2016 to 2021. Adult patients (>18 years) requiring ICU admission for management of DKA were included in this study. Patients with DKA were stratified by lowest recorded phosphate level as: normal ≥ 0.80 mmol/L, mild 0.50–0.79 mmol/L, moderate 0.30–0.49 mmol/L and severe < 0.3 mmol/L. Patient demographics, comorbidities, ICU-related supports, and medications (including fluid, insulin administration, phosphate, and other electrolyte replacement) were collected. Univariate analysis was performed between hypophosphatemia severity and normophosphatemia subgroups to determine risk factors, outcomes, replacement, and progression of hypophosphatemia in the ICU. Phosphate replacement and administered insulin was compared to nadir serum phosphate level. Multivariate analysis and linear regression were performed to identify risk factors for the development of hypophosphatemia. Results: A total of 842 admissions of 669 unique patients due to DKA were included; 436 of 842 (51.8%) admissions maintained normophosphatemia in the ICU, while 220 (26.1%, n = 220/842) had mild hypophosphatemia, 124 (14.7%, n = 124/842) had moderate hypophosphatemia and 62 (7.4%, n = 62/842) had severe hypophosphatemia. Patients with higher BMI, higher APACHE II/III score, cerebrovascular disease and all blood gas parameters (excluding PaO2) were found to have more severe hypophosphatemia. Lower serum phosphate was associated with greater replacement and greater insulin administration per kilogram body weight. ICU length of stay, hospital length of stay and mortality were not affected by degree of hypophosphatemia (p > 0.05). Linear regression revealed that standard base excess was strongly associated with the development of hypophosphatemia (β = 0.02, 95% CI 0.01–0.02, p < 0.001). Conclusions: Increasing severity of hypophosphatemia was associated with increasing severity of DKA. Increased ICU length of stay was related to increased severity of hypophosphatemia.

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