title: Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial.
abstract: BACKGROUND
  Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol.
  
  
  METHODS
  Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM.
  
  
  RESULTS
  The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without hypoglycemia (<4 mM) during either therapy.
  
  
  CONCLUSIONS
  Fully automated closed-loop control based on subcutaneous glucose measurements is feasible and may provide efficacious and hypoglycemia-free glucose control in critically ill adults.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier, NCT01440842.
authors.forename: Lalantha
authors.initials: L
authors.lastname: Leelarathna
authors.forename: Shane W
authors.initials: SW
authors.lastname: English
authors.forename: Hood
authors.initials: H
authors.lastname: Thabit
authors.forename: Karen
authors.initials: K
authors.lastname: Caldwell
authors.forename: Janet M
authors.initials: JM
authors.lastname: Allen
authors.forename: Kavita
authors.initials: K
authors.lastname: Kumareswaran
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
authors.forename: Marianna
authors.initials: M
authors.lastname: Nodale
authors.forename: Jasdip
authors.initials: J
authors.lastname: Mangat
authors.forename: Mark L
authors.initials: ML
authors.lastname: Evans
authors.forename: Rowan
authors.initials: R
authors.lastname: Burnstein
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D016638:Critical Illness / Q000628:therapy; D018592:Cross-Over Studies; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000295:instrumentation / Q000379:methods*; D011446:Prospective Studies; D040521:Subcutaneous Tissue / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin