Skip to main content

Advertisement

SpringerLink
Log in

The metrics of glycaemic control in critical care

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Introduction

Trials of tight glucose control have compared measures of central tendency, such as average blood glucose, and yielded conflicting results. Other metrics, such as standard deviation, reflect different properties of glucose control and are also associated with changes in outcome. It is possible, therefore, that the conflicting results from interventional studies arise from effects on glycaemic control that have not been reported.

Methods

Using glucose measurements from patients admitted to four adult intensive care units in one UK hospital, we sought to identify metrics of glycaemic control, examine the relationship between them and identify the metrics that are both independently and most strongly associated with outcome.

Results

We examined nine previously described metrics and identified a further four. Cluster analysis classified these metrics into two families, namely, those reflecting measures of central tendency and those reflecting measures of dispersion. A measure of minimum glucose was also identified but related to neither family. Plots of the quintiles of these metrics against hospital mortality revealed population-specific relationships. Areas under receiver-operating characteristic curves could not identify an optimum metric of central tendency or dispersion. Using odds ratios, we were able to show that the effect of these metrics is independent of one another.

Conclusion

Our results suggest that glycaemic control is associated with outcome on the basis of three independent metrics, reflecting measures of central tendency, measures of dispersion and a measure of minimum glucose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  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 355:773–778

    Article  CAS  PubMed  Google Scholar 

  2. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress hyperglycaemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 32:2426–2432

    Article  CAS  PubMed  Google Scholar 

  3. Ali NA, O’Brien JM Jr, Blum W, Byrd JC, Klisovic RB, Marcucci G, Phillips G, Marsh CB, Lemeshow S, Grever MR (2007) Hyperglycemia in patients with acute myeloid leukemia is associated with increased hospital mortality. Cancer 110:96–102

    Article  PubMed  Google Scholar 

  4. Bochicchio GV, Joshi M, Bochicchio KM, Pyle A, Johnson SB, Meyer W, Lumpkins K, Scalea TM (2007) Early hyperglycemic control is important in critically injured trauma patients. J Trauma 63:1353–1358; discussion 1358–1359

    Google Scholar 

  5. Baker EH, Janaway CH, Philips BJ, Brennan AL, Baines DL, Wood DM, Jones PW (2006) Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax 61:284–289

    Article  CAS  PubMed  Google Scholar 

  6. Krinsley JS (2003) Association between hyperglycaemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc 78:1471–1478

    Article  PubMed  Google Scholar 

  7. 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 345:1359–1367

    Article  PubMed  Google Scholar 

  8. 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 354:449–461

    Article  PubMed  Google Scholar 

  9. Krinsley JS (2004) Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 79:992–1000

    Article  PubMed  Google Scholar 

  10. Scalea TM, Bochicchio GV, Bochicchio KM, Johnson SB, Joshi M, Pyle A (2007) Tight glycemic control in critically injured trauma patients. Ann Surg 246:605–610; discussion 610–602

    Google Scholar 

  11. Arabi YM, Dabbagh OC, Tamim HM, Al-Shimemeri AA, Memish ZA, Haddad SH, Syed SJ, Giridhar HR, Rishu AH, Al-Daker MO, Kahoul SH, Britts RJ, Sakkijha MH (2008) Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med 36:3190–3197

    Article  CAS  PubMed  Google Scholar 

  12. De La Rosa G, Donado JH, Restrepo AH, Quintero AM, Gonzalez LG, Saldarriaga NE, Bedoya M, Toro JM, Velasquez JB, Valencia JC, Arango CM, Aleman PH, Vasquez EM, Chavarriaga JC, Yepes A, Pulido W, Cadavid CA (2008) Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial. Crit Care 12:R120

    Article  Google Scholar 

  13. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297

    Article  PubMed  Google Scholar 

  14. Fischer KF, Lees JA, Newman JH (1986) Hypoglycemia in hospitalized patients. Causes and outcomes. N Engl J Med 315:1245–1250

    Article  CAS  PubMed  Google Scholar 

  15. Krinsley JS, Grover A (2007) Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med 35:2262–2267

    Article  PubMed  Google Scholar 

  16. Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Taori G, Hegarty C, Bailey M (2010) Hypoglycemia and outcome in critically ill patients. Mayo Clin Proc 85:217–224

    Article  PubMed  Google Scholar 

  17. 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 38:838–842

    Article  CAS  PubMed  Google Scholar 

  18. Meyfroidt G, Keenan DM, Wang X, Wouters PJ, Veldhuis JD, Van den Berghe G (2010) Dynamic characteristics of blood glucose time series during the course of critical illness: effects of intensive insulin therapy and relative association with mortality. Crit Care Med 38:1021–1029

    Article  CAS  PubMed  Google Scholar 

  19. Campbell M, Fitzpatrick R, Haines A, Kinmonth AL, Sandercock P, Spiegelhalter D, Tyrer P (2000) Framework for design and evaluation of complex interventions to improve health. Br Med J 321:694–696

    Article  CAS  Google Scholar 

  20. 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 105:244–252

    Article  CAS  PubMed  Google Scholar 

  21. Ali NA, O’Brien JM Jr, Dungan K, Phillips G, Marsh CB, Lemeshow S, Connors AF Jr, Preiser JC (2008) Glucose variability and mortality in patients with sepsis. Crit Care Med 36:2316–2321

    Article  PubMed  Google Scholar 

  22. Krinsley JS (2008) Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med 36:3008–3013

    Article  CAS  PubMed  Google Scholar 

  23. Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Hegarty C, Bailey M (2008) Blood glucose concentration and outcome of critical illness: the impact of diabetes. Crit Care Med 36:2249–2255

    Article  CAS  PubMed  Google Scholar 

  24. Kosiborod M, Inzucchi SE, Krumholz HM, Xiao L, Jones PG, Fiske S, Masoudi FA, Marso SP, Spertus JA (2008) Glucometrics in patients hospitalized with acute myocardial infarction: defining the optimal outcomes-based measure of risk. Circulation 117:1018–1027

    Article  CAS  PubMed  Google Scholar 

  25. Oksanen T, Skrifvars MB, Varpula T, Kuitunen A, Pettila V, Nurmi J, Castren M (2007) Strict versus moderate glucose control after resuscitation from ventricular fibrillation. Intensive Care Med 33:2093–2100

    Article  CAS  PubMed  Google Scholar 

  26. Meynaar IA, Dawson L, Tangkau PL, Salm EF, Rijks L (2007) Introduction and evaluation of a computerised insulin protocol. Intensive Care Med 33:591–596

    Article  CAS  PubMed  Google Scholar 

  27. Mitchell I, Knight E, Gissane J, Tamhane R, Kolli R, Leditschke IA, Bellomo R, Finfer S (2006) A phase II randomised controlled trial of intensive insulin therapy in general intensive care patients. Crit Care Resusc 8:289–293

    PubMed  Google Scholar 

  28. Wittenberg MD, Gattas DJ, Ryan A, Totaro R (2008) Introduction of intensive glycaemic control into a neurosurgical intensive care unit: a retrospective cohort study. Crit Care Resusc 10:203–208

    PubMed  Google Scholar 

  29. Krinsley JS (2009) Glycemic variability and mortality in critically ill patients: the impact of diabetes. J Diabetes Sci Technol 3:1292–1301

    PubMed  Google Scholar 

  30. Murata GH, Duckworth WC, Shah JH, Wendel CS, Hoffman RM (2004) Sources of glucose variability in insulin-treated type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES). Clin Endocrinol (Oxf) 60:451–456

    Article  Google Scholar 

  31. Christiansen C, Toft P, Jorgensen HS, Andersen SK, Tonnesen E (2004) Hyperglycaemia and mortality in critically ill patients. A prospective study. Intensive Care Med 30:1685–1688

    Article  PubMed  Google Scholar 

  32. Ligtenberg JJ, Meijering S, Stienstra Y, van der Horst IC, Vogelzang M, Nijsten MW, Tulleken JE, Zijlstra JG (2006) Mean glucose level is not an independent risk factor for mortality in mixed ICU patients. Intensive Care Med 32:435–438

    Article  CAS  PubMed  Google Scholar 

  33. Vogelzang M, van der Horst IC, Nijsten MW (2004) Hyperglycaemic index as a tool to assess glucose control: a retrospective study. Critical Care 8:R122–R127

    Article  PubMed  Google Scholar 

  34. Pachler C, Plank J, Weinhandl H, Chassin LJ, Wilinska ME, Kulnik R, Kaufmann P, Smolle KH, Pilger E, Pieber TR, Ellmerer M, Hovorka R (2008) Tight glycaemic control by an automated algorithm with time-variant sampling in medical ICU patients. Intensive Care Med 34:1224–1230

    Article  CAS  PubMed  Google Scholar 

  35. Vogelzang M, Nijboer JM, van der Horst IC, Zijlstra F, ten Duis HJ, Nijsten MW (2006) Hyperglycemia has a stronger relation with outcome in trauma patients than in other critically ill patients. J Trauma 60:873–877; discussion 878–879

    Google Scholar 

  36. Ryan EA, Shandro T, Green K, Paty BW, Senior PA, Bigam D, Shapiro AM, Vantyghem MC (2004) Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes 53:955–962

    Article  CAS  PubMed  Google Scholar 

  37. Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF (1970) Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 19:644–655

    CAS  PubMed  Google Scholar 

  38. Beckstead JW (2002) Using hierarchical cluster analysis in nursing research. West J Nurs Res 24:307–319

    Article  PubMed  Google Scholar 

  39. Hanley JA, McNeil BJ (1983) A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 148:839–843

    CAS  PubMed  Google Scholar 

  40. Mowery NT, Gunter OL, Guillamondegui O, Dossett LA, Dortch MJ, Morris JA Jr., May AK (2009) Stress insulin resistance is a marker for mortality in traumatic brain injury. J Trauma 66:145–151; discussion 151–143

    Google Scholar 

  41. Dossett LA, Cao H, Mowery NT, Dortch MJ, Morris JM Jr., May AK (2008) Blood glucose variability is associated with mortality in the surgical intensive care unit. Am Surg 74:679–685; discussion 685

    Google Scholar 

  42. Waeschle RM, Moerer O, Hilgers R, Herrmann P, Neumann P, Quintel M (2008) The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability. Crit Care 12:R129

    Article  PubMed  Google Scholar 

  43. Bagshaw SM, Bellomo R, Jacka MJ, Egi M, Hart GK, George C, ANZICS CORE Management Committee (2009) The impact of early hypoglycemia and blood glucose variability on outcome in critical illness. Critical Care 13:R91

    Article  PubMed  Google Scholar 

  44. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139

    Article  CAS  PubMed  Google Scholar 

  45. Preiser J-C, Devos P, Ruiz-Santana S, Mélot C, Annane D, Groeneveld J, Iapichino G, Leverve X, Nitenberg G, Singer P, Wernerman J, Joannidis M, Stecher A, Chioléro R (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 35:1738–1748

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Ian Young (Principal Analyst Programmer, Wolfson Computer Laboratory) for extracting the data which forms the basis of this paper. We would also like to thank our anonymous reviewers for their extraordinarily helpful and supportive input to this manuscript.

Author information

Authors and Affiliations

  1. Department of Anaesthesia and Critical Care Medicine, Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust , Edgbaston, Birmingham, B15 2TH, UK

    Iain M. J. Mackenzie & Tony Whitehouse

  2. Wellcome Trust Clinical Research Facility, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK

    Peter G. Nightingale

  3. Division of Medical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Iain M. J. Mackenzie & Tony Whitehouse

Authors
  1. Iain M. J. Mackenzie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tony Whitehouse
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter G. Nightingale
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iain M. J. Mackenzie.

Additional information

This article is discussed in the editorial available at: doi:10.1007/s00134-010-2110-3.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 1.06 MB)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mackenzie, I.M.J., Whitehouse, T. & Nightingale, P.G. The metrics of glycaemic control in critical care. Intensive Care Med 37, 435–443 (2011). https://doi.org/10.1007/s00134-010-2103-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-010-2103-2

Keywords

Search

Navigation