Intensive Care Medicine

, Volume 40, Issue 2, pp 171–181 | Cite as

Tight computerized versus conventional glucose control in the ICU: a randomized controlled trial

  • Pierre KalfonEmail author
  • Bruno Giraudeau
  • Carole Ichai
  • Alexandre Guerrini
  • Nicolas Brechot
  • Raphaël Cinotti
  • Pierre-François Dequin
  • Béatrice Riu-Poulenc
  • Philippe Montravers
  • Djilalli Annane
  • Hervé Dupont
  • Michel Sorine
  • Bruno Riou
  • On behalf of the CGAO–REA Study Group
Seven-Day Profile Publication



The blood glucose target range and optimal method to reach this range remain a matter of debate in the intensive care unit (ICU). A computer decision support system (CDSS) might improve the outcome of ICU patients through facilitation of a tighter blood glucose control.


We conducted a multi-center randomized trial in 34 French ICU. Adult patients expected to require treatment in the ICU for at least 3 days were randomly assigned without blinding to undergo tight computerized glucose control with the CDSS (TGC) or conventional glucose control (CGC), with blood glucose targets of 4.4–6.1 and <10.0 mmol/L, respectively. The primary outcome was all-cause death within 90 days after ICU admission.


Of the 2,684 patients who underwent randomization to the TGC and CGC treatment groups, primary outcome was available for 1,335 and 1,311 patients, respectively. The baseline characteristics of these treatment groups were similar in terms of age (61 ± 16 years), SAPS II (51 ± 19), percentage of surgical admissions (40.0 %) and proportion of diabetic patients (20.3 %). A total of 431 (32.3 %) patients in the TGC group and 447 (34.1 %) in the CGC group had died by day 90 (odds ratio for death in the TGC 0.92; 95 % confidence interval 0.78–1.78; p = 0.32). Severe hypoglycemia (<2.2 mmol/L) occurred in 174 of 1,317 patients (13.2 %) in the TGC group and 79 of 1,284 patients (6.2 %) in the CGC group (p < 0.001).


Tight computerized glucose control with the CDSS did not significantly change 90-day mortality and was associated with more frequent severe hypoglycemia episodes in comparison with conventional glucose control.


Critical care Glucose control Computerized decision-support systems ICU Mortality Randomized controlled trials 



The CGAO–REA study was supported, in part, by the Société Francaise d’Anesthésie et de Réanimation (SFAR) and Baxter Healthcare Corporation. The study sponsor was Centre Hospitalier de Chartres, France. Dr. Kalfon is honored to have received the “Grand prix pour la Recherche 2008” from the Société Francaise d’Anesthésie et de Réanimation (SFAR) supporting the CGAO–REA study. We gratefully thank all members of the nursing staff of each participating ICU for their strong involvement and motivation in the study. We gratefully thank Amélie Le Gouge, and Mathieu Lemaire (INSERM Centre d’investigation clinique 202, Centre Hospitalier Universitaire de Tours), for participating in the statistical analysis; Gaëtan Roudillon and Gilles Rafalli (LK2, Saint-Avertin, France) for their major and invaluable role during the deployment of the software CGAO in 34 centers and for participating under the supervision of the lead investigator in training of clinical staffs and providing technical and educational support; Bérangère Bonnel, Cécile Jourdain, Dr Caroline Touboul, Patrick Piesvaux, Sylvie Aprelon, Emilie Breton, Isabelle Tessier and Leslie Leshayes (Hôpital Louis Pasteur, Centre Hospitalier de Chartres, Chartres) for their invaluable help in collecting data; Dr David Baker, DM, FRCA, (Department of Anesthesiology and Critical Care, Hôpital Necker-Enfants Malades, Paris) for reviewing the manuscript. Dr. Kalfon, and Mr. Giraudeau had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Kalfon, Ichai, Riou and Mr. Giraudeau participated in the study concept and design. Drs. Kalfon, Ichai, Brechot, Cinotti, Dequin, Riu-Poulenc, Montravers, Annane and Dupont participated in the acquisition of data. Drs. Kalfon, Riou, Ichai, Chastre (see ESM), Dequin, Montravers, Annane, Dupont, Mr. Giraudeau, Mr. Guerrini and Mr. Sorine participated in the analysis and interpretation of data. Drs. Kalfon, Ichai, Riou, Chastre (see ESM) and Mr. Giraudeau participated in the drafting of the manuscript and the critical revision of the manuscript for important intellectual content. Mr. Giraudeau performed the statistical analysis. Dr. Kalfon obtained funding. Drs. Kalfon, Ichai, Dequin, Montravers, Annane, Dupont, Riou, Mr. Giraudeau, Mr. Guerrini, and Mr. Sorine participated in the administrative, technical, or material support. The study supervision was performed by Dr. Kalfon.

Conflicts of interest

Dr. Kalfon is a board member of LK2 (Saint-Avertin, France) and has shares in LK2. On behalf of all remaining authors, the corresponding author states that the remaining authors have no conflict of interest.

Supplementary material

134_2013_3189_MOESM1_ESM.doc (24 kb)
Supplementary material 1 (DOC 23 kb)
134_2013_3189_MOESM2_ESM.doc (700 kb)
Supplementary material 2 (DOC 700 kb)
134_2013_3189_MOESM3_ESM.doc (24 kb)
Supplementary material 3 (DOC 24 kb)
134_2013_3189_MOESM4_ESM.doc (30 kb)
Supplementary material 4 (DOC 30 kb)


  1. 1.
    Dungan KM, Braithwaite SS, Preiser JC (2009) Stress hyperglycaemia. Lancet 373:1798–1807PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Kavanagh BP, McCowen KC (2010) Clinical practice: glycemic control in the ICU. N Engl J Med 363:2540–2546PubMedCrossRefGoogle Scholar
  3. 3.
    Lena D, Kalfon P, Preiser JC, Ichai C (2011) Glycemic control in the intensive care unit and during the postoperative period. Anesthesiology 114:438–444PubMedCrossRefGoogle Scholar
  4. 4.
    van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367PubMedCrossRefGoogle Scholar
  5. 5.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R et al (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, Dhaliwal R, Henderson WR, Chittock DR, Finfer S et al (2009) Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 180:821–827PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Wiener RS, Wiener DC, Larson RJ (2008) Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 300:933–944PubMedCrossRefGoogle Scholar
  8. 8.
    Aragon D (2006) Evaluation of nursing work effort and perceptions about blood glucose testing in tight glycemic control. Am J Crit Care 15:370–377PubMedGoogle Scholar
  9. 9.
    Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354:449–461PubMedCrossRefGoogle Scholar
  10. 10.
    Arabi YM, Dabbagh OC, Tamim HM, Al-Shimemeri AA, Memish ZA, Haddad SH, Syed SJ, Giridhar HR, Rishu AH, Al-Daker MO et al (2008) Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med 36:3190–3197PubMedCrossRefGoogle Scholar
  11. 11.
    Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S et al (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139PubMedCrossRefGoogle Scholar
  12. 12.
    De La Rosa Gdel C, Donado JH, Restrepo AH, Quintero AM, Gonzalez LG, Saldarriaga NE, Bedoya M, Toro JM, Velasquez JB, Valencia JC et al (2008) Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial. Crit Care 12:R120CrossRefGoogle Scholar
  13. 13.
    Preiser JC, Devos P, Ruiz-Santana S, Melot C, Annane D, Groeneveld J, Iapichino G, Leverve X, Nitenberg G, Singer P et al (2009) A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 35:1738–1748PubMedCrossRefGoogle Scholar
  14. 14.
    Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR et al (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297PubMedCrossRefGoogle Scholar
  15. 15.
    Marik PE, Preiser JC (2010) Toward understanding tight glycemic control in the ICU: a systematic review and meta analysis. Chest 137:544–551PubMedCrossRefGoogle Scholar
  16. 16.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R et al (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 41:580–637PubMedCrossRefGoogle Scholar
  17. 17.
    Ichai C, Preiser JC (2010) International recommendations for glucose control in adult non diabetic critically ill patients. Crit Care 14:R166PubMedGoogle Scholar
  18. 18.
    Jacobi J, Bircher N, Krinsley J, Agus M, Braithwaite SS, Deutschman C, Freire AX, Geehan D, Kohl B, Nasraway SA et al (2012) Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med 40:3251–3276PubMedCrossRefGoogle Scholar
  19. 19.
    Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P (2011) Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med 154:260–267PubMedCrossRefGoogle Scholar
  20. 20.
    Chase JG, LeCompte A, Shaw GM, Blakemore A, Wong J, Lin J, Hann CE (2008) A benchmark data set for model-based glycemic control in critical care. J Diabetes Sci Technol 2:584–594PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Cordingley JJ, Vlasselaers D, Dormand NC, Wouters PJ, Squire SD, Chassin LJ, Wilinska ME, Morgan CJ, Hovorka R, Van den Berghe G (2009) Intensive insulin therapy: enhanced model predictive control algorithm versus standard care. Intensive Care Med 35:123–128PubMedCrossRefGoogle Scholar
  22. 22.
    Meynaar IA, Dawson L, Tangkau PL, Salm EF, Rijks L (2007) Introduction and evaluation of a computerised insulin protocol. Intensive Care Med 33:591–596PubMedCrossRefGoogle Scholar
  23. 23.
    Vogelzang M, Zijlstra F, Nijsten MW (2005) Design and implementation of GRIP: a computerized glucose control system at a surgical intensive care unit. BMC Med Inform Decis Mak 5:38PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Eslami S, Abu-Hanna A, de Jonge E, de Keizer NF (2009) Tight glycemic control and computerized decision-support systems: a systematic review. Intensive Care Med 35:1505–1517PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P (2008) Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med 148:295–309PubMedCrossRefGoogle Scholar
  26. 26.
    Kreymann KG, Berger MM, Deutz NE, Hiesmayr M, Jolliet P, Kazandjiev G, Nitenberg G, van den Berghe G, Wernerman J, Ebner C et al (2006) ESPEN guidelines on enteral nutrition: intensive care. Clin Nutr 25:210–223PubMedCrossRefGoogle Scholar
  27. 27.
    Bequette BW (2007) Analysis of algorithms for intensive care unit blood glucose control. J Diabetes Sci Technol 1:813–824PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710PubMedCrossRefGoogle Scholar
  29. 29.
    O’Brien PC, Fleming TR (1979) A multiple testing procedure for clinical trials. Biometrics 35:549–556PubMedCrossRefGoogle Scholar
  30. 30.
    Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963PubMedCrossRefGoogle Scholar
  31. 31.
    Finfer S, Liu B, Chittock DR, Norton R, Myburgh JA, McArthur C, Mitchell I, Foster D, Dhingra V, Henderson WR et al (2012) Hypoglycemia and risk of death in critically ill patients. N Engl J Med 367:1108–1118PubMedCrossRefGoogle Scholar
  32. 32.
    Egi M, Bellomo R, Stachowski E, French CJ, Hart G (2006) Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 105:244–252PubMedCrossRefGoogle Scholar
  33. 33.
    Eslami S, Taherzadeh Z, Schultz MJ, Abu-Hanna A (2011) Glucose variability measures and their effect on mortality: a systematic review. Intensive Care Med 37:583–593PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Hermanides J, Vriesendorp TM, Bosman RJ, Zandstra DF, Hoekstra JB, Devries JH (2010) Glucose variability is associated with intensive care unit mortality. Crit Care Med 38:838–842PubMedCrossRefGoogle Scholar
  35. 35.
    Mackenzie IM, Whitehouse T, Nightingale PG (2011) The metrics of glycaemic control in critical care. Intensive Care Med 37:435–443PubMedCrossRefGoogle Scholar
  36. 36.
    Finfer S, Wernerman J, Preiser JC, Cass T, Desaive T, Hovorka R, Joseph JI, Kosiborod M, Krinsley J, Mackenzie I et al (2013) Clinical review: consensus recommendations on measurement of blood glucose and reporting glycemic control in critically ill adults. Crit Care 17:229PubMedCrossRefGoogle Scholar
  37. 37.
    Morris AH, Orme J Jr, Truwit JD, Steingrub J, Grissom C, Lee KH, Li GL, Thompson BT, Brower R, Tidswell M et al (2008) A replicable method for blood glucose control in critically Ill patients. Crit Care Med 36:1787–1795PubMedCrossRefGoogle Scholar
  38. 38.
    Antonelli M, Bonten M, Cecconi M, Chastre J, Citerio G, Conti G, Curtis JR, Hedenstierna G, Joannidis M, Macrae D et al (2013) Year in review in Intensive Care Medicine 2012: I. Neurology and neurointensive care, epidemiology and nephrology, biomarkers and inflammation, nutrition, experimentals. Intensive Care Med 39:232–246PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Krinsley JS, Egi M, Kiss A, Devendra AN, Schuetz P, Maurer PM, Schultz MJ, van Hooijdonk RT, Kiyoshi M, Mackenzie IM et al (2013) Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study. Crit Care 17:R37PubMedCrossRefGoogle Scholar
  40. 40.
    Van den Berghe G (2013) What’s new in glucose control in the ICU? Intensive Care Med 39:823–825PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  • Pierre Kalfon
    • 1
    • 2
    Email author
  • Bruno Giraudeau
    • 3
  • Carole Ichai
    • 4
  • Alexandre Guerrini
    • 5
    • 6
  • Nicolas Brechot
    • 7
  • Raphaël Cinotti
    • 8
  • Pierre-François Dequin
    • 9
  • Béatrice Riu-Poulenc
    • 10
  • Philippe Montravers
    • 11
  • Djilalli Annane
    • 12
  • Hervé Dupont
    • 13
  • Michel Sorine
    • 6
  • Bruno Riou
    • 2
    • 14
  • On behalf of the CGAO–REA Study Group
  1. 1.Service de Réanimation polyvalente, Hôpital Louis Pasteur Hôpitaux de ChartresChartres CedexFrance
  2. 2.UMR INSERM 956Université Pierre et Marie CurieParisFrance
  3. 3.INSERM CIC (Centre d’investigation clinique) 202Centre Hospitalier Universitaire (CHU) de ToursToursFrance
  4. 4.Service de Réanimation médico-chirurgicale, Hôpital Saint-RochCHU de NiceNiceFrance
  5. 5.LK2Saint-AvertinFrance
  6. 6.Institut National de Recherche en Informatique et en Automatique (INRIA)RocquencourtFrance
  7. 7.Service de Réanimation médicale, Institut de Cardiologie, CHU Pitié-SalpêtrièreAssistance Publique-Hôpitaux de Paris (AP-HP)ParisFrance
  8. 8.Service de Réanimation chirurgicale cardio-thoracique et vasculaire, Hôpital LaennecCHU de NantesNantesFrance
  9. 9.Service de Réanimation médicale, Hôpital BretonneauCHRU de ToursToursFrance
  10. 10.Service de Réanimation polyvalente, Hôpital PurpanCHU de ToulouseToulouseFrance
  11. 11.Département d’Anesthésie et Réanimation chirurgicale, CHU Bichat-Claude Bernard AP-HPParisFrance
  12. 12.Service de RéanimationCHU Raymond Poincaré, AP-HPGarchesFrance
  13. 13.Service d’Anesthésie Réanimation, Hôpital NordCHRU AmiensAmiensFrance
  14. 14.Service d’accueil des Urgences, CHU Pitié-Salpêtrière AP-HPParisFrance

Personalised recommendations