Prevalence of ketosis, ketonuria, and ketoacidosis during liberal glycemic control in critically ill patients with diabetes: an observational study

Crit Care. 2016 Sep 15;20:297. doi: 10.1186/s13054-016-1462-7.


Background: It is uncertain whether liberal glucose control in critically ill diabetic patients leads to increased ketone production and ketoacidosis. Therefore, we aimed to assess the prevalence of ketosis, ketonuria and ketoacidosis in critically ill diabetic patients treated in accordance with a liberal glycemic control protocol.

Methods: We performed a prospective observational cohort study of 60 critically ill diabetic patients with blood and/or urine ketone bodies tested in ICU. All patients were treated according to a liberal glucose protocol targeting a blood glucose level (BGL) between 10 and 14 mmol/l in a single tertiary intensive care unit in Australia. We measured quantitative bedside blood 3-beta-hydroxybutyrate (β-OHB) and semi-quantitative urine ketones on ICU admission and daily during ICU stay, for a maximum of 10 consecutive days.

Results: Median blood β-OHB level on admission was 0.3 (0.1, 0.8) mmol/l. Ketoacidosis was rare (3 %), but some level of ketosis (β-OHB ≥0.6 mmol/l) was found in 38 patients (63 %) early during their ICU stay. However, there was no significant difference in prevalence or severity of ketonemia and ketonuria among patients with BGL above (permissive hyperglycemia) or below 10 mmol/l. On multivariable linear regression analysis there was no association between blood ketone levels and BGL, HbA1c, lactate levels, hematocrit, catecholamine infusion or APACHE III score. In contrast, blood ketone levels tended to be higher after cardiopulmonary bypass surgery (P = 0.06).

Conclusions: Liberal glycemic control in critically ill diabetic patients does not appear to be associated with a high prevalence of ketoacidosis or ketonemia. Moreover, ketosis is typically present on admission and resolves rapidly. Finally, cardiopulmonary bypass surgery may be an important trigger of ketone body production.

Trial registration: Australian New Zealand Clinical Trials Registry ( ACTRN12615000216516 ; trial registration date 5 March 2015).

Keywords: 3-beta-hydroxybutyrate; Adults; Critical illness; Diabetes mellitus; Ketone bodies; Permissive hyperglycemia.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / analysis
  • 3-Hydroxybutyric Acid / blood
  • Aged
  • Aged, 80 and over
  • Australia
  • Blood Glucose / analysis
  • Cohort Studies
  • Diabetic Ketoacidosis / epidemiology*
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hyperglycemia / drug therapy
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Intensive Care Units / organization & administration
  • Intensive Care Units / statistics & numerical data
  • Ketone Bodies / analysis
  • Ketone Bodies / blood
  • Ketone Bodies / urine
  • Male
  • Middle Aged
  • Prevalence*
  • Prospective Studies
  • Sodium-Glucose Transporter 2 / pharmacology
  • Sodium-Glucose Transporter 2 / therapeutic use
  • Statistics, Nonparametric


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Ketone Bodies
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • hemoglobin A1c protein, human
  • 3-Hydroxybutyric Acid

Associated data

  • ANZCTR/ACTRN12615000216516