Intensive Care Medicine

, Volume 34, Issue 7, pp 1224–1230 | Cite as

Tight glycaemic control by an automated algorithm with time-variant sampling in medical ICU patients

  • Christoph PachlerEmail author
  • Johannes Plank
  • Heinz Weinhandl
  • Ludovic J. Chassin
  • Malgorzata E. Wilinska
  • Roman Kulnik
  • Peter Kaufmann
  • Karl-Heinz Smolle
  • Ernst Pilger
  • Thomas R. Pieber
  • Martin Ellmerer
  • Roman Hovorka



Tight glycaemic control (TGC) in critically ill patients improves clinical outcome, but is difficult to establish The primary objective of the present study was to compare glucose control in medical ICU patients applying a computer-based enhanced model predictive control algorithm (eMPC) extended to include time-variant sampling against an implemented glucose management protocol.


Open randomised controlled trial.


Nine-bed medical intensive care unit (ICU) in a tertiary teaching hospital.

Patients and participants

Fifty mechanically ventilated medical ICU patients.


Patients were included for a study period of up to 72 h. Patients were randomised to the control group (n = 25), treated by an implemented insulin algorithm, or to the eMPC group (n = 25), using the laptop-based algorithm. Target range for blood glucose (BG) was 4.4–6.1 mM. Efficacy was assessed by mean BG, hyperglycaemic index (HGI) and BG sampling interval. Safety was assessed by the number of hypoglycaemic-episodes < 2.2 mM. Each participating nurse filled-in a questionnaire regarding the usability of the algorithm.

Measurements and main results

BG and HGI were significantly lower in the eMPC group [BG 5.9 mM (5.5–6.3), median (IQR); HGI 0.4 mM (0.2–0.9)] than in control patients [BG 7.4 mM (6.9–8.6), p < 0.001; HGI 1.6 mM (1.1–2.4), p < 0.001]. One hypoglycaemic episode was detected in the eMPC group; no such episodes in the control group. Sampling interval was significantly shorter in the eMPC group [eMPC 117 min (± 34), mean (± SD), vs 174 min (± 27); p < 0.001]. Thirty-four nurses filled-in the questionnaire. Thirty answered the question of whether the algorithm could be applied in daily routine in the affirmative.


The eMPC algorithm was effective in maintaining tight glycaemic control in severely ill medical ICU patients.


Critically ill Insulin resistance Tight glycemic control Computer algorithm 



The authors want to express their special thanks to the nursing staff of the Intensive Care Unit of the Department of Internal Medicine (Medical University Graz), who performed all study-related activities in addition to their routine workload.

The study is part of CLINICIP, an IST (Information Society and Technology) project funded by the European Community under the Sixth Framework Programme, Action Line eHealth, Project Reference 506965.

Supplementary material

134_2008_1033_MOESM1_ESM.doc (2.3 mb)
Electronic Supplementary Material (DOC 2,3M)
134_2008_1033_MOESM2_ESM.doc (38 kb)
Electronic Supplementary Material (DOC 39K)
134_2008_1033_MOESM3_ESM.doc (4.9 mb)
Electronic Supplementary Material (DOC 4,9M)


  1. 1.
    Capes SE, Hunt D, Malmberg K, Gerstein HC (2000) Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 355:773–778PubMedCrossRefGoogle Scholar
  2. 2.
    Yendamuri S, Fulda GJ, Tinkoff GH (2003) Admission hyperglycemia as a prognostic indicator in trauma. J Trauma 55:33–38PubMedCrossRefGoogle Scholar
  3. 3.
    McCowen KC, Malhotra A, Bistrian BR (2001) Stress-induced hyperglycemia. Crit Care Clin 17:107–124PubMedCrossRefGoogle 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 the critically ill patients. N Engl J Med 345:1359–1367CrossRefGoogle Scholar
  5. 5.
    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 354:449–461CrossRefGoogle Scholar
  6. 6.
    McMullin J, Brozek J, Jaeschke R, Hamielec C, Dhingra V, Rocker G, Freitag A, Gibson J, Cook D (2004) Glycemic control in the ICU: a multicenter survey. Intensive Care Med 30:798–803PubMedCrossRefGoogle Scholar
  7. 7.
    Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM (2004) Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32:858–873PubMedCrossRefGoogle Scholar
  8. 8.
    Meijering S, Corstjens AM, Tulleken JE, Meertens JH, Zijlstra JG, Ligtenberg JJ (2006) Towards a feasible algorithm for tight glycaemic control in critically ill patients: a systematic review of the literature. Crit Care 10:R19PubMedCrossRefGoogle Scholar
  9. 9.
    Wilson M, Weinreb J, Hoo GW (2007) Intensive insulin therapy in critical care: a review of 12 protocols. Diabetes Care 30:1005–1011PubMedCrossRefGoogle Scholar
  10. 10.
    Pittas AG, Siegel RD, Lau J (2004) Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials. Arch Intern Med 164:2005–2011PubMedCrossRefGoogle Scholar
  11. 11.
    Vriesendorp TM, van Santen S, DeVries JH, de Jonge E, Rosendaal FR, Schultz MJ, Hoekstra JB (2006) Predisposing factors for hypoglycemia in the intensive care unit. Crit Care Med 34:96–101PubMedCrossRefGoogle Scholar
  12. 12.
    Mitchell I, Finfer S, Bellomo R, Higlett T (2006) Management of blood glucose in the critically ill in Australia and New Zealand: a practice survey and inception cohort study. Intensive Care Med 32:867–874PubMedCrossRefGoogle Scholar
  13. 13.
    Weber-Carstens S, Deja M, Bercker S, Dimroth A, Ahlers O, Kaisers U, Keh D (2007) Impact of bolus application of low-dose hydrocortisone on glycemic control in septic shock patients. Intensive Care Med 33:730–733PubMedCrossRefGoogle Scholar
  14. 14.
    Plank J, Blaha J, Cordingley J, Wilinska ME, Chassin LJ, Morgan C, Squire S, Haluzik M, Kremen J, Svacina S, Toller W, Plasnik A, Ellmerer M, Hovorka R, Pieber TR (2006) Multicentric, randomized, controlled trial to evaluate blood glucose control by the model predictive control algorithm versus routine glucose management protocols in intensive care unit patients. Diabetes Care 29:271–276PubMedCrossRefGoogle Scholar
  15. 15.
    Pachler C, Plank J, Weinhandl H, Chassin L, Hovorka R, Smolle K, Pieber TR, Ellmerer M (2007) Efficacy and user acceptance of a computer algorithm to establish tight glycemic control (abstract). Intensive Care Med 33[Suppl 2]:54Google Scholar
  16. 16.
    Kanji S, Buffie J, Hutton B, Bunting PS, Singh A, McDonald K, Fergusson D, McIntyre LA, Hebert PC (2005) Reliability of point-of-care testing for glucose measurement in critically ill adults. Crit Care Med 33:2778–2785PubMedCrossRefGoogle Scholar
  17. 17.
    Critchell CD, Savarese V, Callahan A, Aboud C, Jabbour S, Marik P (2007) Accuracy of bedside capillary blood glucose measurements in critically ill patients. Intensive Care Med 33:2079–2084PubMedCrossRefGoogle Scholar
  18. 18.
    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 5:38PubMedCrossRefGoogle Scholar
  19. 19.
    Hovorka R, Canonico V, Chassin LJ, Haueter U, Massi-Benedetti M, Orsini Federici M, Pieber TR, Schaller HC, Schaupp L, Vering T, Wilinska ME (2004) Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes. Physiol Meas 25:905–920PubMedCrossRefGoogle Scholar
  20. 20.
    Hovorka R, Chassin LJ, Wilinska ME, Canonico V, Akwi JA, Federici MO, Massi-Benedetti M, Hutzli I, Zaugg C, Kaufmann H, Both M, Vering T, Schaller HC, Schaupp L, Bodenlenz M, Pieber TR (2004) Closing the loop: the adicol experience. Diabetes Technol Ther 6:307–318PubMedCrossRefGoogle Scholar
  21. 21.
    Kanji S, Singh A, Tierney M, Meggison H, McIntyre L, Hebert PC (2004) Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults. Intensive Care Med 30:804–810PubMedCrossRefGoogle Scholar
  22. 22.
    Vogelzang M, van der Horst IC, Nijsten MW (2004) Hyperglycaemic index as a tool to assess glucose control: a retrospective study. Crit Care 8:R122–127PubMedCrossRefGoogle Scholar
  23. 23.
    Vlasselaers D, Notele G, Van den Berghe G, Wouters P, Chassin L, Wilinska G, Hovorka R (2006) Tight glycaemic control in ICU with model predictive control and time-variant sampling (abstract). Intensive Care Med 32[Suppl 1]:272Google Scholar
  24. 24.
    Mader J, Korsatko S, Ikeoka D, Plank J, Bodenlenz M, Suppan M, Sinner F, Smolle K, Pieber TR, Ellmerer M (2007) Subcutaneous glucose monitoring in patients with severe sepsis (abstract). Crit Care 11[Suppl 2]:58Google Scholar
  25. 25.
    Diabetes Control and Complications Trial Research Group (1997) Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes 46:271–286CrossRefGoogle Scholar
  26. 26.
    UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352:837–853CrossRefGoogle Scholar
  27. 27.
    Cryer PE (2006) Hypoglycaemia: the limiting factor in the glycaemic management of the critically ill? Diabetologia 49:1722–1725PubMedCrossRefGoogle Scholar
  28. 28.
    Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A (2003) Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 125:1007–1021PubMedCrossRefGoogle Scholar
  29. 29.
    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
  30. 30.
    Clayton SB, Mazur JE, Condren S, Hermayer KL, Strange C (2006) Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit. Crit Care Med 34:2974–2978PubMedGoogle Scholar
  31. 31.
    Lacherade JC, Jabre P, Bastuji-Garin S, Grimaldi D, Fangio P, Theron V, Outin H, De Jonghe B (2007) Failure to achieve glycemic control despite intensive insulin therapy in a medical ICU: incidence and influence on ICU mortality. Intensive Care Med 33:814–821PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Christoph Pachler
    • 1
    Email author
  • Johannes Plank
    • 1
  • Heinz Weinhandl
    • 1
  • Ludovic J. Chassin
    • 2
  • Malgorzata E. Wilinska
    • 2
  • Roman Kulnik
    • 1
  • Peter Kaufmann
    • 1
  • Karl-Heinz Smolle
    • 1
  • Ernst Pilger
    • 1
  • Thomas R. Pieber
    • 1
  • Martin Ellmerer
    • 1
  • Roman Hovorka
    • 2
  1. 1.Department of Internal MedicineMedical University GrazGrazAustria
  2. 2.Department of PaediatricsUniversity of CambridgeCambridgeUK

Personalised recommendations