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N Engl J Med. 2014 Jan 9;370(2):107-18. doi: 10.1056/NEJMoa1302564.

A randomized trial of hyperglycemic control in pediatric intensive care.

Collaborators (221)

Allen E, Betts H, Elbourne D, Grieve R, Guerriero C, Loverage M, Macrae D, Morris K, Pappachan J, Parslow R, Piercy D, Sadique Z, Van Dyck L, Smith-Wilson N, Tasker RC, Barnes P, Edwards S, Field D, Hooper J, Preece M, Quick T, Snowdon C, Tume L, Vlasselaers D, Williamson P, Allen E, Brooks L, Diallo K, Elbourne D, Frost C, Gadhiya A, Henley P, Morris E, Piercy D, Ramos P, Sturgess J, Truesdale A, Betts H, Bacon S, Betts H, Macrae D, Baines P, Morlidge C, Christopherson M, Guhadasan R, Haigh F, Hawcutt D, Hill H, Holmes P, Horan M, Jennings R, Kerr S, Potter F, Ratcliffe J, Scott E, Selby A, Sellers C, Shetty N, Sidaras D, Simpson E, Siner S, Thorburn K, Morris K, Laker S, Benson E, Duncan H, Ewing K, Faulkner J, Holdback N, Hydes L, Martin J, Menzies J, Sebastian S, Smith M, Spry J, Winmill H, Schindler M, Robinson N, Allen M, Davis P, Dean S, Fineman N, Fraser J, Goodwin S, Grant D, Jenkins I, Marriage S, Talmud J, Weir P, White M, Wolf A, Zafurallah I, Duthie M, Brunskill C, Patel R, Barry P, Pooboni S, Ramaiah R, Vora A, Westrope C, Whitelaw J, Peters M, Broadhead M, Riordan S, Blatcher T, Brierley J, Durkan L, Jones A, Krukenburg U, Lister P, Mok Q, Petros A, Pierce C, Sharma S, Darowski M, Atwal P, Cooper L, Macrae D, Bacon S, Adamovic T, Burmester M, Desai A, Furck A, Gala S, Harrison E, Lammers A, LaRovere J, Mittal A, Montgomery M, Pallawela J, Pathan N, Rodrigues W, Samad T, Toohey P, Fortune PM, MacDonald M, Rishton C, Barber R, Gnanalingham M, Hawkins K, Playfor S, Samuels M, Stewart D, Yates R, Gray M, Wall E, Smith S, Inwald D, Abdulla A, Brewer A, Cooper M, Habibi P, de Munter C, Nadel S, Qureshi S, Ramnarayan P, Smale A, Wolverson M, Mayer A, Wall K, Bevan C, Fernando L, Hancock S, Perring J, Pappachan J, Gale H, Grace L, Hyde P, Jones G, Macintosh I, McCorkell J, Mitchell R, Morton K, Ramakrishnan K, Rees S, Stanley V, Sykes K, Wilson P, McMaster P, Ramesh P, Lownds S, Alexander J, Beaumond K, Bebbington M, Dodd S, Lightfoot S, Newman E, Percival P, Proctor T, Robinson K, Shepley H, Sidley C, Wilson T, Dunger D, Harrison D, Hatch D, Peek G, Smith J, Grieve R, Guerriero C, Sadique Z, Bennett M, Flemming T, Strachan J, Fleming T, Parslow R, Moncrieff S, Kirby A, Tasker RC, Butcher W, Cooper A, Henderson L, Fatukasi J, Davies R, Dodd L, Gregory C, Poustie V, Smyth R, Van't Hoff W, Slavik Z, Tasker RC.

Author information

From Royal Brompton and Harefield NHS Foundation Trust (D.M.) and the Departments of Health Services Research and Policy (R.G., Z.S.) and Medical Statistics (E.A., D.E.) and the Clinical Trials Unit (E.A., D.E.), London School of Hygiene and Tropical Medicine, London, Birmingham Children's Hospital, Birmingham (K.M.), University Hospital Southampton NHS Foundation Trust, Southampton (J.P.), and the Division of Epidemiology, Leeds Institute of Genetics and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds (R.P.) - all in the United Kingdom; and the Departments of Neurology and Anesthesia, Boston Children's Hospital and Harvard Medical School, Boston (R.C.T.).

Erratum in

  • N Engl J Med. 2014 Apr 10;370(15):1469.



Whether an insulin infusion should be used for tight control of hyperglycemia in critically ill children remains unclear.


We randomly assigned children (≤16 years of age) who were admitted to the pediatric intensive care unit (ICU) and were expected to require mechanical ventilation and vasoactive drugs for at least 12 hours to either tight glycemic control, with a target blood glucose range of 72 to 126 mg per deciliter (4.0 to 7.0 mmol per liter), or conventional glycemic control, with a target level below 216 mg per deciliter (12.0 mmol per liter). The primary outcome was the number of days alive and free from mechanical ventilation at 30 days after randomization. The main prespecified subgroup analysis compared children who had undergone cardiac surgery with those who had not. We also assessed costs of hospital and community health services.


A total of 1369 patients at 13 centers in England underwent randomization: 694 to tight glycemic control and 675 to conventional glycemic control; 60% had undergone cardiac surgery. The mean between-group difference in the number of days alive and free from mechanical ventilation at 30 days was 0.36 days (95% confidence interval [CI], -0.42 to 1.14); the effects did not differ according to subgroup. Severe hypoglycemia (blood glucose, <36 mg per deciliter [2.0 mmol per liter]) occurred in a higher proportion of children in the tight-glycemic-control group than in the conventional-glycemic-control group (7.3% vs. 1.5%, P<0.001). Overall, the mean 12-month costs were lower in the tight-glycemic-control group than in the conventional-glycemic-control group. The mean 12-month costs were similar in the two groups in the cardiac-surgery subgroup, but in the subgroup that had not undergone cardiac surgery, the mean cost was significantly lower in the tight-glycemic-control group than in the conventional-glycemic-control group: -$13,120 (95% CI, -$24,682 to -$1,559).


This multicenter, randomized trial showed that tight glycemic control in critically ill children had no significant effect on major clinical outcomes, although the incidence of hypoglycemia was higher with tight glucose control than with conventional glucose control. (Funded by the National Institute for Health Research, Health Technology Assessment Program, U.K. National Health Service; CHiP Current Controlled Trials number, ISRCTN61735247.).

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