title: Tight Glycemic Control in Critically Ill Children.
abstract: In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking.
  
  
  
  In a 35-center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower-target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher-target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)-free days to day 28.
  
  
  
  The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower-target group and 353 to the higher-target group. In the intention-to-treat analysis, the median number of ICU-free days did not differ significantly between the lower-target group and the higher-target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per-protocol analyses, the median time-weighted average glucose level was significantly lower in the lower-target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher-target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower-target group also had higher rates of health care-associated infections than those in the higher-target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator-free days.
  
  
  
  Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF-PINT ClinicalTrials.gov number, NCT01565941 .).
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Michael S D
authors.initials: MS
authors.lastname: Agus
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: David
authors.initials: D
authors.lastname: Wypij
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Eliotte L
authors.initials: EL
authors.lastname: Hirshberg
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Vijay
authors.initials: V
authors.lastname: Srinivasan
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: E Vincent
authors.initials: EV
authors.lastname: Faustino
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Peter M
authors.initials: PM
authors.lastname: Luckett
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Jamin L
authors.initials: JL
authors.lastname: Alexander
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Asaro
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Martha A Q
authors.initials: MA
authors.lastname: Curley
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Garry M
authors.initials: GM
authors.lastname: Steil
authors.affiliation: From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children's Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children's Hospital, Salt Lake City, and Intermountain Medical Center, Murray - both in Utah (E.L.H.); Children's Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania - all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children's Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.).
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Nadkarni
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis*; D013504:Cardiovascular Surgical Procedures; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D017052:Hospital Mortality; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage*; D015278:Intensive Care Units, Pediatric; D057194:Intention to Treat Analysis; D007902:Length of Stay; D008297:Male; D011184:Postoperative Period
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose