Worsening Acidosis During Continuous Kidney Replacement Therapy: A Case for Caution

Introduction: Continuous renal replacement therapy (CRRT) is frequently used in the intensive care unit for management of acute kidney injury (AKI) in patients with hemodynamic instability. A variety of CRRT solutions are available with distinct biochemical properties. Electrolyte-enriched solutions have been developed to help prevent metabolic derangements (e.g. hypophosphatemia) during CRRT. Case Description: A 44-year-old man presented with acute respiratory failure, septic shock, and oligoanuric AKI. CRRT (continuous hemodialfiltration) was initiated with a phosphate-containing solution (Phoxillum, Baxter, Chicago, Illinois) at a rate of 3400 ml/h, which was followed by a gradual improvement in the biochemical profile. Nutrition was provided with a high-protein formula (Osmolite 1.5 cal, Abbott, Abbott Park, Illinois). Four days later, he was noted to have anion-gap metabolic acidosis (bicarbonate 12 mmol/L, anion gap 22). He had normal serum lactate, glucose, beta-hydroxybutyrate levels, and negative ketones 3 times. However, repeat testing on day 7 revealed serum beta-hydroxybutyrate of 8.6 mmol/L (N: 0.02-0.27), confirming the diagnosis of euglycemic ketoacidosis (EKA). The CRRT solution was changed to a glucose-containing solution (100 mg/dL), which was followed by a gradual improvement in serum bicarbonate concentration and anion gap. Discussion: EKA typically develops in the setting of low-calorie intake, insulin resistance, and an excess of counter-regulatory hormones. Since a substantial amount of glucose is removed during CRRT, using glucose-free solutions could result in rapid depletion of the glycogen stores, and activation of lipolysis-releasing ketogenesis substrates in the critically ill. This will shift the carbohydrate metabolism towards gluconeogenesis and ketogenesis, resulting in EKA. This case highlights the importance of keeping EKA on the list of differential diagnoses in critically ill patients who are receiving CRRT and develop high anion gap metabolic acidosis with glucose-free solutions. It is also unique in that the rise in serum levels of the ketones was significantly delayed, leading to a diagnostic dilemma, highlighting the need to re-check the levels of ketones in the face of unexplained worsening acidosis.