title: Prevalence of ketosis, ketonuria, and ketoacidosis during liberal glycemic control in critically ill patients with diabetes: an observational study.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  Australian New Zealand Clinical Trials Registry ( ACTRN12615000216516 ; trial registration date 5 March 2015).
authors.affiliation: Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, 3084, VIC, Australia.
authors.forename: Nora
authors.initials: N
authors.lastname: Luethi
authors.affiliation: Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, 3084, VIC, Australia.|Department of Intensive Care Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Cioccari
authors.affiliation: Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, 3084, VIC, Australia.|Department of Perioperative Medicine, Intensive Care and Emergency, Cattinara Hospital, Trieste University School of Medicine, Trieste, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Crisman
authors.affiliation: Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, 3084, VIC, Australia.|Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.affiliation: Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, 3084, VIC, Australia.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Eastwood
authors.affiliation: Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, 3084, VIC, Australia. johan.martensson@austin.org.au.|Department of Anaesthesia and Intensive Care Medicine, Karolinska University Hospital, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden. johan.martensson@austin.org.au.
authors.forename: Johan
authors.initials: J
authors.lastname: Mårtensson
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000032:analysis / Q000097:blood; D018806:APACHE; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D016883:Diabetic Ketoacidosis / Q000453:epidemiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D007362:Intensive Care Units / Q000458:organization & administration / Q000706:statistics & numerical data; D007657:Ketone Bodies / Q000032:analysis / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D051297:Sodium-Glucose Transporter 2 / Q000494:pharmacology / Q000627:therapeutic use; D018709:Statistics, Nonparametric
chemical_list: D020155:3-Hydroxybutyric Acid; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D007657:Ketone Bodies; D051297:Sodium-Glucose Transporter 2; C089180:SLC5A2 protein, human; C517652:hemoglobin A1c protein, human
keywords: 3-beta-hydroxybutyrate; Adults; Critical illness; Diabetes mellitus; Ketone bodies; Permissive hyperglycemia