Michael S D Agus1, David Wypij1, Eliotte L Hirshberg1, Vijay Srinivasan1, E Vincent Faustino1, Peter M Luckett1, Jamin L Alexander1, Lisa A Asaro1, Martha A Q Curley1, Garry M Steil1, Vinay M Nadkarni1. 1. 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.).
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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 .).
RCT Entities:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: Judith Jacobi; Nicholas Bircher; James Krinsley; Michael Agus; Susan S Braithwaite; Clifford Deutschman; Amado X Freire; Douglas Geehan; Benjamin Kohl; Stanley A Nasraway; Mark Rigby; Karen Sands; Lynn Schallom; Beth Taylor; Guillermo Umpierrez; John Mazuski; Holger Schunemann Journal: Crit Care Med Date: 2012-12 Impact factor: 7.598
Authors: Dirk Vlasselaers; Ilse Milants; Lars Desmet; Pieter J Wouters; Ilse Vanhorebeek; Ingeborg van den Heuvel; Dieter Mesotten; Michael P Casaer; Geert Meyfroidt; Catherine Ingels; Jan Muller; Sophie Van Cromphaut; Miet Schetz; Greet Van den Berghe Journal: Lancet Date: 2009-01-26 Impact factor: 79.321
Authors: Stéphane Leteurtre; Alain Martinot; Alain Duhamel; François Proulx; Bruno Grandbastien; Jacques Cotting; Ronald Gottesman; Ari Joffe; Jurg Pfenninger; Philippe Hubert; Jacques Lacroix; Francis Leclerc Journal: Lancet Date: 2003-07-19 Impact factor: 79.321
Authors: Yaseen M Arabi; Ousama C Dabbagh; Hani M Tamim; Abdullah A Al-Shimemeri; Ziad A Memish; Samir H Haddad; Sofia J Syed; Hema R Giridhar; Asgar H Rishu; Mouhamad O Al-Daker; Salim H Kahoul; Riette J Britts; Maram H Sakkijha Journal: Crit Care Med Date: 2008-12 Impact factor: 7.598
Authors: Michael G Gaies; James G Gurney; Alberta H Yen; Michelle L Napoli; Robert J Gajarski; Richard G Ohye; John R Charpie; Jennifer C Hirsch Journal: Pediatr Crit Care Med Date: 2010-03 Impact factor: 3.624
Authors: Vijay Srinivasan; Philip C Spinella; Henry R Drott; Carey L Roth; Mark A Helfaer; Vinay Nadkarni Journal: Pediatr Crit Care Med Date: 2004-07 Impact factor: 3.624
Authors: Mark J Peters; Andrew Argent; Marino Festa; Stéphane Leteurtre; Jefferson Piva; Ann Thompson; Douglas Willson; Pierre Tissières; Marisa Tucci; Jacques Lacroix Journal: Intensive Care Med Date: 2017-03-17 Impact factor: 17.440
Authors: Jenna Sopfe; Laura Pyle; Amy K Keating; Kristen Campbell; Arthur K Liu; R Paul Wadwa; Michael R Verneris; Roger H Giller; Gregory P Forlenza Journal: Blood Adv Date: 2019-02-12
Authors: Vijay Srinivasan; Natalie R Hasbani; Nilesh M Mehta; Sharon Y Irving; Sarah B Kandil; H Christine Allen; Katri V Typpo; Natalie Z Cvijanovich; E Vincent S Faustino; David Wypij; Michael S D Agus; Vinay M Nadkarni Journal: Pediatr Crit Care Med Date: 2020-03 Impact factor: 3.624