Log in | Register

Glycemic control, mortality, and hypoglycemia in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials

Tomohide Yamada| Nobuhiro Shojima| Hisashi Noma| Toshimasa Yamauchi| Takashi Kadowaki
Original
Volume 43, Issue 1 / January , 2017

Pages 1 - 15

Abstract

Purpose

It is unclear whether tight glycemic control is warranted in all critically ill adults. We employed network meta-analysis to examine the risk of mortality and hypoglycemia associated with different glycemic control targets in critically ill adults.

Methods

Electronic databases were searched up to 2016 for randomized controlled trials comparing various insulin regimens in critically ill adults with hyperglycemia. Two reviewers independently extracted information and evaluated quality with the Cochrane risk-of-bias tool. Four glycemic control groups were compared: tight (blood glucose: 4.4 < 6.1 mmol/l), moderate (6.1 < 7.8 mmol/l), mild (7.8 < 10.0 mmol/l), and very mild (10.0 to < 12.2 mmol/l). Network meta-analysis was performed by a frequentist approach with multivariate random effects meta-analysis.

Results

Thirty-six randomized trials (17,996 patients) were identified. Compared with very mild control, tight control did not reduce the risk of short-term mortality [relative risk (RR) 0.94 (95 % CI 0.83–1.07, p = 0.36)], and neither did mild control [RR 0.88 (0.73–1.06), p = 0.18] or moderate control [RR 1.1 (0.66–1.84), p = 0.72]. However, severe hypoglycemia (<2.2 mmol/l) was more frequent with tight control than very mild control [RR 5.49 (3.22–9.38), p < 0.001] or mild control [RR 4.47 (2.5–8.03), p < 0.001]. Stratified analyses (cause of death, ICU type, time period, or diabetes) did not find significant between-group differences. Ranking analysis revealed the following hierarchy for avoiding death (highest to lowest rank): mild control, tight control, and very mild control.

Conclusions

Network meta-analysis showed no mortality benefit of tight glycemic control in critically ill patients, but fivefold more hypoglycemia versus mild or very mild control.

Keywords

References

  1. Norhammar AM, Rydén L, Malmberg K (1999) Admission plasma glucose. Independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients. Diabetes Care 22(11):1827–1831
    • View reference on PubMed
  2. Kosiborod M, Rathore SS, Inzucchi SE et al (2005) Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes. Circulation 111:3078–3086
    • View reference on PubMed
  3. Svensson AM, McGuire DK, Abrahamsson P et al (2005) Association between hyper- and hypoglycaemia and 2 year all-cause mortality risk in diabetic patients with acute coronary events. Eur Heart J 26:1255–1261
    • View reference on PubMed
  4. Van den Berghe G, Wouters P, Weekers F et al (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345(19):1359–1367
    • View reference on PubMed
  5. Van den Berghe G, Wilmer A, Hermans G et al (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354(5):449–461
    • View reference on PubMed
  6. NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY et al (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 360(13):1283–1297
  7. NICE-SUGAR Study Investigators, Finfer S, Liu B, Chittock DR et al (2012) Hypoglycemia and risk of death in critically ill patients. N Engl J Med 367(12):1108–1118
  8. Krinsley JS, Grover A (2007) Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med 35(10):2262–2267
    • View reference on PubMed
  9. Griesdale DE, de Souza RJ, van Dam RM et al (2009) Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 180(8):821–827
    • View reference on PubMed
  10. Kramer AH, Roberts DJ, Zygun DA (2012) Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis. Crit Care 16(5):R203
    • View reference on PubMed
  11. Friedrich JO, Chant C, Adhikari NK (2010) Does intensive insulin therapy really reduce mortality in critically ill surgical patients? A reanalysis of meta-analytic data. Crit Care 14(5):324
    • View reference on PubMed
  12. Wiener RS, Wiener DC, Larson RJ (2008) Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 300(8):933–944
    • View reference on PubMed
  13. American Diabetes Association (2015) Standards of medical care in diabetes-2015. Diabetes Care 38(suppl 1):S80–S85
  14. Higgins J, Green S (2011) Cochrane handbook for systematic reviews of interventions. Version 5.1.0. Cochrane Collaboration. http://handbook.cochrane.org/. Accessed 1 Sep 2015
  15. Bangalore S, Toklu B, Kotwal A et al (2014) Anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction: a meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors. BMJ 11(349):g6419
  16. Higgins JPT, Jackson D, Barrett JK et al (2012) Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods 3:98–110
    • View reference on PubMed
  17. White IR, Barrett JK, Jackson D et al (2012) Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Res Synth Methods 3:111–125
    • View reference on PubMed
  18. White IR (2009) Multivariate random-effects meta-analysis. Stata J 9:40–56
  19. Chaimani A, Higgins JP, Mavridis D et al (2013) Graphical tools for network meta-analysis in STATA. PLoS ONE 8(10):e76654
    • View reference on PubMed
  20. Salanti G, Ades AE, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64(2):163–171
    • View reference on PubMed
  21. Giakoumidakis K, Eltheni R, Patelarou E et al (2013) Effects of intensive glycemic control on outcomes of cardiac surgery. Heart Lung 42(2):146–151
    • View reference on PubMed
  22. Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6(7):e1000100
    • View reference on PubMed
  23. Puhan MA, Schünemann HJ, Murad MH et al (2014) GRADE Working Group. A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ 24(349):g5630
  24. Higgins JP, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560
    • View reference on PubMed
  25. Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219
    • View reference on PubMed
  26. Iapichino G, Albicini M, Umbrello M et al (2008) Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients. Intensiv Care Med 34(10):1843–1850
  27. Farah R, Samokhvalov A, Zviebel F et al (2007) Insulin therapy of hyperglycemia in intensive care. Isr Med Assoc J 9(3):140–142
    • View reference on PubMed
  28. Bilotta F, Spinelli A, Giovannini F et al (2007) The effect of intensive insulin therapy on infection rate, vasospasm, neurologic outcome, and mortality in neurointensive care unit after intracranial aneurysm clipping in patients with acute subarachnoid hemorrhage: a randomized prospective pilot trial. J Neurosurg Anesthesiol 19(3):156–160
    • View reference on PubMed
  29. Savioli M, Cugno M, Polli F et al (2009) Tight glycemic control may favor fibrinolysis in patients with sepsis. Crit Care Med 37(2):424–431
    • View reference on PubMed
  30. Lazar HL, McDonnell MM, Chipkin S et al (2011) Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients. Ann Surg 254(3):458–463
    • View reference on PubMed
  31. Mitchell I, Knight E, Gissane J, Australian and New Zealand Intensive Care Society Clinical Trials Group et al (2006) A phase II randomised controlled trial of intensive insulin therapy in general intensive care patients. Crit Care Resusc 8(4):289–293
    • View reference on PubMed
  32. McMullin J, Brozek J, McDonald E et al (2007) Lowering of glucose in critical care: a randomized pilot trial. J Crit Care 22(2):112–118
    • View reference on PubMed
  33. Brunkhorst FM, Engel C, Bloos F et al (2008) German competence network sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358(2):125–139
    • View reference on PubMed
  34. De La Gdel C, Donado JH, Grupo de Investigacion en Cuidado intensivo: GICI-HPTU 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(5):R120
  35. Arabi YM, Dabbagh OC, Tamim HM et al (2008) Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med 36(12):3190–3197
    • View reference on PubMed
  36. Oksanen T, Skrifvars MB, Varpula T et al (2007) Strict versus moderate glucose control after resuscitation from ventricular fibrillation. Intensiv Care Med 33(12):2093–2100
  37. Bruno A, Kent TA, Coull BM et al (2008) Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke 39(2):384–389
    • View reference on PubMed
  38. Grey NJ, Perdrizet GA (2004) Reduction of nosocomial infections in the surgical intensive-care unit by strict glycemic control. Endocr Pract 10(Suppl 2):46–52
    • View reference on PubMed
  39. Preiser JC, Devos P, Ruiz-Santana S 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. Intensiv Care Med 35(10):1738–1748
  40. Staszewski J, Brodacki B, Kotowicz J et al (2011) Intravenous insulin therapy in the maintenance of strict glycemic control in nondiabetic acute stroke patients with mild hyperglycemia. J Stroke Cerebrovasc Dis 20(2):150–154
    • View reference on PubMed
  41. Green DM, O’Phelan KH, Bassin SL et al (2010) Intensive versus conventional insulin therapy in critically ill neurologic patients. Neurocrit Care 13(3):299–306
    • View reference on PubMed
  42. Coester A, Neumann CR, Schmidt MI (2010) Intensive insulin therapy in severe traumatic brain injury: a randomized trial. J Trauma 68(4):904–911
    • View reference on PubMed
  43. Johnston KC, Hall CE, Kissela BM, GRASP Investigators et al (2009) Glucose regulation in acute stroke patients (GRASP) trial: a randomized pilot trial. Stroke 40(12):3804–3809
    • View reference on PubMed
  44. Yang M, Guo Q, Zhang X et al (2009) Intensive insulin therapy on infection rate, days in NICU, in-hospital mortality and neurological outcome in severe traumatic brain injury patients: a randomized controlled trial. Int J Nurs Stud 46(6):753–758
    • View reference on PubMed
  45. Kreisel SH, Berschin UM, Hammes HP et al (2009) Pragmatic management of hyperglycaemia in acute ischaemic stroke: safety and feasibility of intensive intravenous insulin treatment. Cerebrovasc Dis 27(2):167–175
    • View reference on PubMed
  46. Azevedo JR, Lima ER, Cossetti RJ et al (2007) Intensive insulin therapy versus conventional glycemic control in patients with acute neurological injury: a prospective controlled trial. Arq Neuropsiquiatr 65(3B):733–738
    • View reference on PubMed
  47. Cappi SB, Noritomi DT, Velasco IT et al (2012) Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis. Intensiv Care Med 38(4):634–641
  48. COIITSS Study Investigator, Annane D, Maxime A, Cariou V (2010) Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 303(4):341–348
  49. Rosso C, Corvol JC, Pires C et al (2012) Intensive versus subcutaneous insulin in patients with hyperacute stroke: results from the randomized INSULINFARCT trial. Stroke 43(9):2343–2349
    • View reference on PubMed
  50. Gandhi GY, Nuttall GA, Abel MD et al (2007) Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Ann Intern Med 146(4):233–243
    • View reference on PubMed
  51. Bilotta F, Caramia R, Paoloni FP et al (2009) Safety and efficacy of intensive insulin therapy in critical neurosurgical patients. Anesthesiology 110(3):611–619
    • View reference on PubMed
  52. Cao SG, Ren JA, Shen B et al (2011) Intensive versus conventional insulin therapy in type 2 diabetes patients undergoing D2 gastrectomy for gastric cancer: a randomized controlled trial. World J Surg 35(1):85–92
    • View reference on PubMed
  53. Arabi YM, Tamim HM, Dhar GS et al (2011) Permissive underfeeding and intensive insulin therapy in critically ill patients: a randomized controlled trial. Am J Clin Nutr 93(3):569–577
    • View reference on PubMed
  54. Desai SP, Henry LL, Holmes SD et al (2012) Strict versus liberal target range for perioperative glucose in patients undergoing coronary artery bypass grafting: a prospective randomized controlled trial. J Thorac Cardiovasc Surg 143(2):318–325
    • View reference on PubMed
  55. Chan RP, Galas FR, Hajjar LA et al (2009) Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial. Clinics (Sao Paulo) 64(1):51–60
  56. Kalfon P, Giraudeau B, Ichai C, CGAO-REA Study Group et al (2014) Tight computerized versus conventional glucose control in the ICU: a randomized controlled trial. Intensiv Care Med 40(2):171–181
  57. Henderson WR, Dhingra V, Chittock D, Canadian Critical Trials Group et al (2009) The efficacy and safety of glucose control algorithms in intensive care: a pilot study of the Survival Using Glucose Algorithm Regulation (SUGAR) trial. Pol Arch Med Wewn 119(7–8):439–446
    • View reference on PubMed
  58. Whitmer RA, Karter AJ, Yaffe K et al (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301(15):1565–1572
    • View reference on PubMed
  59. Khan MI, Barlow RB, Weinstock RS (2011) Acute hypoglycemia decreases central retinal function in the human eye. Vision Res 51(14):1623–1626
    • View reference on PubMed
  60. Moghissi ES, Korytkowski MT, DiNardo M, American Association of Clinical Endocrinologists et al (2009) American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract 15(4):353–369
    • View reference on PubMed
  61. Mills EJ, Thorlund K, Ioannidis JP (2013) Demystifying trial networks and network meta-analysis. BMJ 14(346):f2914
  62. Stewart LA, Tierney JF (2002) To IPD or not to IPD? Advantages and disadvantages of systematic reviews using individual patient data. Eval Health Prof 25(1):76–97
    • View reference on PubMed
  63. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(6):e1000097. doi:10.1371/journal.pmed1000097
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement