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Cited by 1,096Hyperglycemia and glycemic control in critically ill and hospitalized patientsDiabetes Management and ResearchIntensive Care Unit Cognitive Disorders

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

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Griesdale, D. E. G., de Souza, R. J., van Dam, R. M., Heyland, D. K., Cook, D. J., Malhotra, A., Dhaliwal, R., Henderson, W. R. +3 more·2009·Canadian Medical Association Journal
DOI 10.1503/cmaj.090206PMC PMC2665940
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Abstract

BACKGROUND: Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). METHODS: We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation - Survival Using Glucose Algorithm Regulation) study. RESULTS: We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level < or = 6.1 mmol/L v. < or = 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. INTERPRETATION: Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.

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  • Aggressive lowering of glycemia in the ICU is not uniformly beneficial.

    “However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”

    From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [72]

    Experimental — accuracy not yet measured

  • Aggressive lowering of glycemia in the ICU markedly increases the risk of severe hypoglycemia.

    “However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”

    From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [72]

  • Aggressive lowering of glycemia in the ICU may be associated with increased mortality.

    “However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”

    From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [72]

    Experimental — accuracy not yet measured

  • A retrospective study suggested that tidal volumes should be lowered even with plateau pressures ≤ 30 cm H2O because lower plateau pressures were associated with reduced hospital mortality.

    “A retrospective study suggested that tidal volumes should be lowered even with plateau pressures ≤ 30 cm H 2 O (431) because lower plateau pressures were associated with reduced hospital mortality (432).”

    From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [432]

    The Mortality section reports outcomes for intensive insulin therapy, not an association between plateau pressure and hospital mortality. Searches for lower plateau pressures, tidal volumes, and the 30 cm H2O threshold found no passage addressing the claim. In the citing sentence, this source is attached to the plateau-pressure and mortality association (432), not the preceding recommendation (431). (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Meta-analyses report a higher incidence of hypoglycemia (glucose < 40 mg/dL) in critically ill patients where blood glucose was targeted to 80-110 mg/dL.

    “Meta-analyses also report a higher incidence of hypoglycemia (glucose < 40 mg/dL) in critically patients where blood glucose was targeted to 80–110 mg/dL [516, 517].”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [516]

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Research works printed but not linked: 4

  1. [8]8. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in criti- cally ill patients. N Engl J Med 2001;345:1359-67.
  2. [13]13. Devos P, Preiser J, Mélot C. Impact of tight glucose control by intensive insulin therapy on ICU mortality and the rate of hypoglycaemia: final results of the glu- control study [abstract]. Intensive Care Med 2007;33:S189.
  3. [17]17. Institute for Healthcare Improvement. Implement effective glucose control: establish a glycemic control policy in your ICU. Cambridge (MA): The Institute; Available: www.ihi.org/IHI/Topics/CriticalCare/IntensiveCare/Changes/IndividualChanges /EstablishaGlycemicControlPolicyinYourICU.htm (accessed 2009 Jan. 27).
  4. [33]33. Mackenzie IM, Ercole A, Ingle S, et al. Glycaemic control and outcome in general intensive care: The east anglian GLYCOGENIC study. Br J Intensive Care 2008; 18:121-6.

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Authors
Griesdale, D. E. G., de Souza, R. J., van Dam, R. M., Heyland, D. K., Cook, D. J., Malhotra, A., Dhaliwal, R., Henderson, W. R., Chittock, D. R., Finfer, S., & Talmor, D.
Affiliations
Brigham and Women's Hospital (US)
ORCID
Venue
Canadian Medical Association Journal
Publisher
CMA Joule Inc.
Published
2009-03-24
Volume
180
Issue
8
Pages
821-827
ISSN
  • 0820-3946 (ISSN-L)
  • 1488-2329
DOI
10.1503/cmaj.090206
PMC
PMC2665940
OpenAlex
W2157775267
Cited by
1,096
References
56
Citations by year
2026: 5 · 2025: 9 · 2024: 21 · 2023: 25 · 2022: 18 · 2021: 31 · 2020: 40 · 2019: 36 · 2018: 38 · 2017: 54 · 2016: 59 · 2015: 67 · 2014: 98 · 2013: 102 · 2012: 120
FWCI
21.45
Type
journal article
Language
en
Open access
Locations
  • Canadian Medical Association Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
Keywords
intensive insulin therapy, critically ill patients, mortality, severe hypoglycemia, hyperglycemia, surgical intensive care unit, glycemic targets, intensive care unit
MeSH terms
Cause of Death, Dose-Response Relationship, Drug, Female, Humans, Hypoglycemia, Insulin, Intensive Care Units, Male, Risk Management, Survival Analysis, Randomized Controlled Trials as Topic, Critical Illness, Hospital Mortality, Risk Assessment, Maximum Tolerated Dose

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