Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols

Abstract

BackgroundDiabetic ketoacidosis (DKA) is an endocrine emergency with associated risk of morbidity and mortality. Despite this, DKA management lacks strong evidence due to the absence of large randomised controlled trials (RCTs).ObjectiveTo review existing studies investigating inpatient DKA management in adults, focusing on intravenous (IV) fluids; insulin administration; potassium, bicarbonate, and phosphate replacement; and DKA management protocols and impact of DKA resolution rates on outcomes.MethodsOvid Medline searches were conducted with limits “all adult” and published between “1973 to current” applied. National consensus statements were also reviewed. Eligibility was determined by two reviewers’ assessment of title, abstract, and availability.ResultsA total of 85 eligible articles published between 1973 and 2016 were reviewed. The salient findings were (i) Crystalloids are favoured over colloids though evidence is lacking. The preferred crystalloid and hydration rates remain contentious. (ii) IV infusion of regular human insulin is preferred over the subcutaneous route or rapid acting insulin analogues. Administering an initial IV insulin bolus before low-dose insulin infusions obviates the need for supplemental insulin. Consensus-statements recommend fixed weight-based over “sliding scale” insulin infusions although evidence is weak. (iii) Potassium replacement is imperative although no trials compare replacement rates. (iv) Bicarbonate replacement offers no benefit in DKA with pH > 6.9. In severe metabolic acidosis with pH < 6.9, there is lack of both data and consensus regarding bicarbonate administration. (v) There is no evidence that phosphate replacement offers outcome benefits. Guidelines consider replacement appropriate in patients with cardiac dysfunction, anaemia, respiratory depression, or phosphate levels <0.32 mmol/L. (vi) Upon resolution of DKA, subcutaneous insulin is recommended with IV insulin infusions ceased with an overlap of 1–2 h. (vii) DKA resolution rates are often used as end points in studies, despite a lack of evidence that rapid resolution improves outcome. (viii) Implementation of DKA protocols lacks strong evidence for adherence but may lead to improved clinical outcomes.ConclusionThere are major deficiencies in evidence for optimal management of DKA. Current practice is guided by weak evidence and consensus opinion. All aspects of DKA management require RCTs to affirm or redirect management and formulate consensus evidence-based practice to improve patient outcomes.

Diabetic ketoacidosis in adult patients: an audit of factors influencing time to normalisation of metabolic parameters

“…The optimal choice of intravenous resuscitation fluid in the management of DKA still remains to be determined. Crystalloids are favoured over colloids however evidence is lacking . Traditionally, 0.9% sodium chloride is first‐line treatment due to its efficacy, safety, cost and availability; and its ability to be readily mixed with potassium.…”

Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients

“…Specifically, the ADA recommends 1000-1500 mL and the UK guideline recommends 1000 mL of normal saline during the first hour. Although normal saline contains a supraphysiologic concentration of chloride potentially leading to hyperchloremic metabolic acidosis, as discussed in the complications section of this review, insufficient evidence exists to support the hypothesis that balanced electrolyte solutions improve time to resolution of diabetic ketoacidosis or prevent major adverse kidney events in this population 60. The UK guideline acknowledges this and includes a statement that balanced electrolyte solutions can be used, but as they are not commercially available with premixed potassium chloride, they must be used in conjunction with additional potassium replacement 2…”

“…By contrast, the UK guideline recommends 40 mmol/L in each liter of normal saline when serum potassium is below 5.5 mmol/L and the patient is passing urine 2. As existing published trials evaluating potassium replacement rates were not designed to determine optimal potassium replacement rates in patients with diabetic ketoacidosis, evidence is lacking to support either recommendation over the other 60. Because insulin therapy promotes an intracellular shift of potassium, it is recommended that insulin should not be started if the serum potassium is below 3 mmol/L to avoid worsening of hypokalemia.…”

“…This is not considered to be a serious complication and usually resolves spontaneously in a few days 198. No evidence supports the use of colloid solutions, balanced electrolyte solutions (such as Plasma-Lyte), or Ringer’s lactate in place of 0.9% sodium chloride solution in the management of diabetic ketoacidosis 60. In one RCT conducted at two institutions, 57 patients admitted with diabetic ketoacidosis were randomly assigned to receive fluid resuscitation with 0.9% sodium chloride or Ringer’s lactate.…”

“…Although not specifically designated as a guideline, it has been used for this purpose with several more recent reviews and commentaries that outline both the strengths and weaknesses of this widely followed report, as well as areas that are in need of revision or future study 7106063. The most recent 2019 ADA clinical practice recommendations for management of diabetic ketoacidosis include several updates to the 2009 consensus statement, as pointed out in table 1 and table 2 6.…”