Research Priorities for Diabetic Ketoacidosis: An Evidence and Gap Mapping Review

Background/Objectives: Diabetic ketoacidosis (DKA) is a common acute complication of diabetes with treatment consisting of reversal of cause, insulin administration, fluid resuscitation and electrolyte repletion. Yet, many aspects of DKA management are currently based on low-quality evidence or physiological rationale. This evidence and gap map review presents an overview of the current body of literature and identifies evidence gaps in relation to therapeutic interventions for DKA. Methods: Interventions and outcomes relevant to DKA were identified and iteratively developed to produce a coding model for the proposed evidence and gap map. PubMed was searched with Me SH terms relevant to the identified interventions and outcomes. Studies identified were screened and assigned interventions and outcomes. Interventional research was uploaded to EPPI-Reviewer and EPPI-Mapper to produce the evidence and gap map. Results: The search identified 1131 studies, of which 18 were non-human and 345 were duplicates. A total of 768 unique studies were screened, and 118 were identified as interventions (52 pediatric and 66 adult studies). A total of 26 high-quality studies, 88 medium-quality studies and 4 low-quality studies were identified. These 118 studies were coded into the proposed DKA evidence and gap map. The intervention domains were fluid therapy, insulin therapy, electrolyte replacement, adjunct therapies and admission type. The outcome domains were DKA resolution, insulin duration, length of stay, morbidity and mortality, complications, and biochemical parameters. Conclusions: Fluid type and insulin infusion administration were prominent in the current literature. These studies frequently used DKA resolution and complications associated with DKA such as electrolyte disturbances and cerebral edema as the primary outcomes. Substantial gaps were identified with scant evidence to guide prophylactic electrolyte administration, enteral intake and adjunctive therapy (thiamine, bicarbonate). Even for well-investigated interventions such as fluids and insulin, substantial gaps existed, particularly for patient-centered and healthcare service outcomes.