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Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: long-term follow-up of a subgroup of patients from the NICE-SUGAR study

Abstract

Purpose

To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury.

Methods

In a large international randomized trial patients were randomly assigned to a target blood glucose (BG) range of either 4.5–6.0 mmol/L (intensive control) or <10 mmol/L (conventional control). Patients with traumatic brain injury (TBI) were identified at randomization and data were collected to examine the extended Glasgow outcome score (includes mortality) at 24 months.

Results

Of the 6104 randomized patients, 391 satisfied diagnostic criteria for TBI; 203 (51.9 %) were assigned to intensive and 188 (48.1 %) to conventional control; the primary outcome was available for 166 (81.8 %) and 149 (79.3 %) patients, respectively. The two groups had

similar baseline characteristics. At 2 years 98 (58.7 %) patients in the intensive group and 79 (53.0 %) in the conventional group had a favorable neurological outcome (odds ratio [OR] 1.26, 95 % CI 0.81–1.97; P = 0.3); 35 patients (20.9 %) in the intensive group and 34 (22.8 %) in the conventional group had died (OR 0.90, 95 % CI 0.53–1.53; P = 0.7); moderate hypoglycemia (BG 2.3–3.9 mmol/L; 41–70 mg/dL) occurred in 160/202 (79.2 %) and 17/188 (9.0 %), respectively (OR 38.3, 95 % CI 21.0–70.1; P < 0.0001); severe hypoglycemia (BG ≤ 2.2 mmol/L; ≤40 mg/dL) in 10 (4.9 %) and 0 (0.0 %), respectively (OR 20.5 95 % CI 1.2–351.6, P = 0.003).

Conclusion

Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, we found no significant difference in clinically important outcomes.

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Acknowledgments

Australian National Health and Medical Research Council; Health Research Council of New Zealand; Canadian Institutes for Health Research; Victorian Neurotrauma Initiative.

Conflicts of interest

None of the members of the writing committee have conflicts of interest in respect of this manuscript.

Author information

Authors and Affiliations

Consortia

Additional information

The NICE-SUGAR study is a collaboration of the Australia and New Zealand Intensive Care Society Clinical Trials Group, The George Institute for Global Health (University of Sydney), the Canadian Critical Care Trials Group and Vancouver Coastal Health Research Institute (University of British Columbia). The NICE-SUGAR study investigators are listed in the appendix.

Take-home message: Patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently. Mortality and neurological recovery assessed using the extended Glasgow outcome score did not differ between groups.

Please address correspondence to Prof. Simon Finfer at The George Institute for Global Health, GPO Box 5389, Sydney, NSW 2001, Australia (e-mail: sfinfer@georgeinstitute.org.au; Tel.: +61-2-94632633).

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Appendix

Appendix

NICE-SUGAR Study Investigators

Writing Committee: Simon Finfer (Chair, PI NICE Study), Dean Chittock (PI SUGAR Trial), Yang Li, Denise Foster, Vinay Dhingra, Rinaldo Bellomo, Deborah Cook, Peter Dodek, Paul Hebert, William Henderson, Daren Heyland, Alisa Higgins, Colin McArthur, Imogen Mitchell, John Myburgh, Bruce Robinson, Juan Ronco.

NICE (ANZ) Management Committee: Simon Finfer, (Chair), Deborah Blair, (Project Manager), Rinaldo Bellomo, Colin McArthur (Lead Investigator, New Zealand), Imogen Mitchell, John Myburgh, Robyn Norton, Julie Potter.

SUGAR (North American) Management Committee: Dean Chittock (Chair), Vinay Dhingra (Past Chair), Denise Foster (Senior Project Manager), Deborah Cook, Peter Dodek, Paul Hébert, William Henderson, Daren Heyland, Ellen McDonald, Juan Ronco. (Ex officio Member: Irwin Schweitzer, Canadian Institutes for Health Research.)

Independent Data Monitoring Committee: Richard Peto (Chair), Peter Sandercock, Charles Sprung, J. Duncan Young.

Statistical Analysis (The George Institute for International Health, University of Sydney, NSW, Australia) Yang Li, Qiang Li, Severine Bompoint, Laurent Billot.

Study Coordinating Centre (The George Institute for International Health, University of Sydney, NSW, Australia) Yang Li, Leonie Crampton, Fotios Darcy, Kathy Jayne, Viraji Kumarasinghe, Lorraine Little, Suzanne McEvoy, Stephen MacMahon, Sameer Pandey, Suzanne Ryan, Ravi Shukla, Bala Vijayan.

University of Sydney (Faculty of Medicine), Kolling Institute and Department of Endocrinology, Royal North Shore Hospital: Bruce Robinson (Dean).

ANZ Site investigators: (Alphabetically by institution, Australia unless stated, NZ = New Zealand. NSW = New South Wales, WA = Western Australia).

Auckland City Hospital (DCCM), Auckland, NZ: Susan Atherton, Jeanette Bell, Louise Hadfield, Craig Hourigan, Colin McArthur, Lynette Newby, Catherine Simmonds.

Auckland City Hospital (CVICU), Auckland, NZ: Heidi Buhr, Michelle Eccleston, Shay McGuinness, Rachael Parke.

The Austin Hospital, Melbourne, Victoria: Rinaldo Bellomo, Samantha Bates, Donna Goldsmith, Inga Mercer, Kim O’Sullivan.

Ballarat Base Hospital, Ballarat, Victoria: Robert Gazzard, Dianne Hill, Christine Tauschke.

Blacktown Hospital, Blacktown, NSW: Dhawal Ghelani, Kiran Nand, Graham Reece, Treena Sara.

Box Hill Hospital, Box Hill, Victoria: Suzanne Elliott, David Ernest, Angela Hamilton.

The Canberra Hospital, Canberra, Australian Capital Territory: Rebecca Ashley, Andrew Bailey, Elise Crowfoot, Jelena Gissane, Imogen Mitchell, Jamie Ranse, Joy Whiting.

Concord Repatriation Hospital, Concord, NSW: Kristina Douglas, David Milliss, Jeff Tan, Helen Wong.

Fremantle Hospital, Fremantle, WA: David Blythe, Annemarie Palermo.

John Hunter Hospital, Newcastle, NSW: Miranda Hardie, Peter Harrigan, Brett McFadyen.

Liverpool Hospital, Liverpool, NSW: Sharon Micallef, Michael Parr.

Middlemore Hospital, Auckland, NZ: Anna Boase, Judi Tai, Anthony Williams.

Nepean Hospital, Nepean, NSW: Louise Cole, Ian Seppelt, Leonie Weisbrodt, Sarah Whereat.

North Shore Hospital, Auckland, NZ: Annette Flanagan, Janet Liang.

Prince of Wales Hospital, Sydney, NSW: Frances Bass, Michelle Campbell, Naomi Hammond, Lisa Nicholson, Yahya Shehabi.

Queen Elizabeth Hospital, Adelaide, South Australia: Jonathan Foote, Sandra Peake, Patricia Williams.

Royal Brisbane Hospital, Brisbane, Queensland: Renae Deans, Cheryl Fourie, Melissa Lassig-Smith, Jeffrey Lipman, Janine Stuart.

Royal Hobart Hospital, Hobart, Tasmania: Anthony Bell, Tanya Field, Richard McAllister, Kathryn Marsden, Andrew Turner.

Royal North Shore Hospital, Sydney, NSW: Susan Ankers, Simon Bird, Simon Finfer, Richard Lee, Anne O’Connor, Julie Potter, Naresh Ramakrishnan, Ray Raper.

St. George Hospital, Sydney, NSW: Vanessa Dhiacou, Kathryn Girling, Alina Jovanovska, John Myburgh.

St. Vincent’s Hospital, Melbourne, Victoria: Nicole Groves, Jenny Holmes, John Santamaria, Roger Smith.

Sir Charles Gairdner Hospital, Perth, WA: Stuart Baker, Brigit Roberts.

Wellington Hospital, Wellington, NZ: Lynne Andrews, Richard Dinsdale, Rosemary Fenton, Diane Mackle, Sarah Mortimer.

Western Hospital, Melbourne, Victoria: Craig French, Lorraine Little, Heike Raunow.

Wollongong Hospital, Wollongong, NSW: Michelle Gales, Francisco Hill, Sundaram Rachakonda, Darren Rogan.

NSW Institute of Trauma and Injury Management, Sydney, NSW, Australia: Christine Allsop.

Australian and New Zealand Intensive Care Research Centre, Melbourne, Victoria, Australia: Alisa Higgins.

The Alfred Health and Monash University, Melbourne, Victoria, Australia: Dinesh Varma

North American Site investigators (Canada unless stated):

Calgary Health Region, Calgary, Alberta—Kevin Champagne, Christopher Doig, Linda Knox, Pauline Taylor, Crystal Wilson.

Kingston General Hospital, Kingston, Ontario—John Drover, Sharlene Hammond, Elizabeth Mann, Monica Myers, Amber Robinson.

Maisonneuve Rosemont Hospital, Montreal, Quebec—Johanne Harvey, Yoanna Skrobik.

Mayo Clinic, Rochester, Minnesota, USA—Anita Baumgartner, Laurie Meade, Nicholas Vlahakis.

Mount Sinai Hospital, Toronto, Ontario—Cheryl Ethier, Marnie Kramer-Kile, Sangeeta Mehta.

Ottawa General Hospital, Ottawa, Ontario—Claude Gaudert, Salmaan Kanji, Tracy McArdle, Irene Watpool.

St Joseph’s Healthcare, Hamilton, Ontario—France Clark, Deborah Cook, Ellen McDonald, Andrea Tkaczyk.

St Michael’s Hospital, Toronto, Ontario—John Marshall, Jeanna Morrissey, Orla Smith, Kerri Porretta, Victoria Wen.

St Paul’s Hospital, Vancouver, British Columbia—Betty Jean Ashley, Peter Dodek, Sheilagh Mans.

Sunnybrook Health Sciences Centre, Toronto, Ontario—Boris Bojilov, Karen Code, Robert Fowler, Nicole Marinoff.

Toronto General Hospital, Toronto, Ontario—Leslie Chu, John Granton, Margaret McGrath-Chong, Marilyn Steinberg.

Toronto Western Hospital, Toronto, Ontario—Niall Ferguson, Stephanie Go, Andrea Matte, Jonathan Rosenberg, James Stevenson.

University of Alberta Hospital, Edmonton, Alberta—Michael Jacka, Leeca Sonnema.

Vancouver General Hospital, Vancouver, British Columbia—Roger Autio, Angela Brevner, Dean Chittock, Dara Davies, Pia Ganz, Maureen Gardner, Susan Logie, Laurie Smith.

Vancouver Island Health Authority, Victoria, British Columbia—Leslie Atkins, Fiona Auld, Marni Stewart, Gordon Wood.

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The NICE-SUGAR Study Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group and the Canadian Critical Care Trials Group. Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: long-term follow-up of a subgroup of patients from the NICE-SUGAR study. Intensive Care Med 41, 1037–1047 (2015). https://doi.org/10.1007/s00134-015-3757-6

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Keywords

  • Brain injury
  • Blood glucose
  • Hypoglycemia
  • Treatment outcome
  • Randomized trial