CI: Blood Glucose Control (2009)

Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: A meta-analysis. JAMA. 2008 Aug 27; 300(8): 933-944.
PubMed ID: 18728267
Study Design:
Meta-analysis or Systematic Review
M - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To evaluate the benefits and risks of tight glucose control vs. usual care in critically ill adult patients.

Inclusion Criteria:

Randomized controlled trials that met each of the following criteria:

  • The setting was an adult ICU
  • The intervention group received tight glucose control (glucose goal less than 150mg per dL) obtained using an insulin infusion during part of all of the ICU stay
  • The comparison group received usual care (glucose goal and method of insulin administration could vary between studies). The primary or secondary end points included hospital or short-term mortality (up to 30 days), septicemia, new need for dialysis or hypoglycemia.


Exclusion Criteria:

Studies were excluded:

  • If the intervention was conducted primarily during the intra-operative period rather than during the ICU stay
  • Unable to obtain adequate details of study methodology or results from the article or study investigators.


Description of Study Protocol:
  • Data Sources: MEDLINE (1950 to 2008), the Cochrane Library, clinical trial registries, reference lists, and abstracts from conferences from both the American Thoracic Society (2001 to 2008) and the Society of Critical Care Medicine (2004-2008)
  • Study Selection: Studies in any language in which adult intensive care patients were randomly assigned to tight vs. usual glucose control. Of 1,358 identified studies, 34 randomized trials (23 full publications, nine abstracts, two unpublished studies) met inclusion criteria.
  • Statistical Analysis: Two reviewers independently extracted information using a pre-specified protocol and evaluated methodological quality with a standardized scale. Both random- and fixed-effects models to estimate relatives risks (RRs) were used.
Data Collection Summary:

Type of Information Abstracted from Articles

  • Primary outcome measure: Hospital mortality. Hospital mortality was defined as death occurring during the hospital stay or within 30 days following admission.
  • Secondary outcome measures: Septicemia, new need for dialysis and hypoglycemia.

 How Information Was Combined

All outcome measures were calculated on a per-patient basis.

Analytic Methods Used

  • Subgroup analyses: Glucose control and ICU setting
  • Sensitivity analysis: Proportion of diabetics, use of insulin-only infusions and achieved mean glucose control
  • Quantitative Data Synthesis: Use of software provided by Cochrane Collaboration for all analyses version 4.2. This software calculates relative risks (RRs) for studies with at least one occurrence in either study group for each outcome. Trials with missing outcome data or zero occurrences in both groups were excluded from meta-analysis of the outcome. Calculation was made of a pooled RR and 95% confidence interval (CI) for each outcome and considered statistically significant if the test for overall effect had a P value of less than 0.05.




Description of Actual Data Sample:
  • Initial N: Twenty-nine randomized controlled trials totaling 8,432 patients contributed to this meta-analysis
  • Age: Adult, no mean age given.
Summary of Results:

NS difference in total hospital, ICU mortality or new need for dialysis. Rate of septicemia was significantly decreased with tight glucose control; however, incidence of hypoglycemia was much higher.



Tight Glucose Control

Usual Care

Statistical Significance of Group Difference

Total % hospital mortality




RR, 0.93

95% CI, 0.85 to 1.03

ICU, surgical (%)




RR, 0.88

95% CI, 0.63 to 1.22

ICU, medical (%)




RR, 0.92

95% CI, 0.82 to 1.04

ICU, medical surgical (%) 26.1% 27%

RR, 0.95

95% CI, 0.80 to 1.13

New need for dialysis 11.2% 12.1%

RR, 0.96

95% CI, 0.76 to 1.20

Rate of septicemia 10.9% 13.4%

RR, 0.76

95% CI, 0.59 to 0.97

Rate of hypoglycemia 13.7%  2.5%

RR, 5.13

95% CI, 4.09 to 6.43

Other Findings

NS difference in death rate when stratified by intensive care unit setting.

  • Surgical units had 8.8% (tight) vs. 10.8% (conventional); RR, 0.88; 95% Cl, 0.63 to 1.22
  • Medical unit: 26.9% (tight) vs. 29.7% (conventional); RR,0,92; 95% Cl, 0.82 to 1.04
  • Mixed medical-surgical units, mortality for tight glucose control 26.1 % vs. 27.0% for conventional control; RR, 0.95; 95% Cl, 0.80 to 1.13). 


Author Conclusion:
  • In critically ill adult patients, tight glucose control is not associated with significantly reduced mortality but is associated with an increased risk of hypoglycemia
  • Given the overall findings of this meta-analysis, it seems appropriate that the guidelines recommending tight glucose control in all critically ill patients should be re-evaluated until the results of larger, more definitive clinical trials are available.
Funding Source:
Government: US Department of Veterans Affairs
University/Hospital: Dartmouth Medical School; Dartmouth-Hitchcock Medical Center
Reviewer Comments:

Sixteen international professional societies endorse tight glucose control in all critically ill patients. This extensive meta-analysis highlights the controversy over whether this practice is warranted.

Studies Included in the Meta-analysis

  • Very tight control (less than 110mg per dL):
    • Surgical: van den Berghe et al, 2001; Hoedemaekers et al, 2005; van Wezel et al, 2006; He et al, 2007; Stecher et al, 2006
    • Medical: Bland et al, 2005; van den Berghe et al, 2006; Oksanen et al, 2007; Benito et al, 2008; Fernandez et al, 2005
    • Med-Surg: Yu et al, 2005; Mitchell et al, 2006; Brunkhorst et al, 2008; Iapichino et al, 2008; Mackenzie et al, 2005; Arabi et al, 2006; DelaRosa et al, 2006; Devos, 2007.
  • Moderately tight control (lLess than 150mg per dL)
    • Surgical: Grey and Perdrizet, 2004; Bilotta et al, 2007; Bilotta et al, 2008; Kia et al, 2005; Chan, unpublished, 2007
    • Medical: Davies et al, 1991; Stefanidis et al, 2002; Walters et al, 2006; Gray et al, 2007; Bruno et al, 2008
    • Med-Surg: Farah et al, 2007; McMullin et al, 2007; Saberi et al, 2004; Henderson et al, 2005; Azevedo, unpublished, 2008.


Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes