8/14/2019 Journal Club : Benefits and risks of tight glucose control in critically ill adults: a meta-analysis

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Benefits and risks of tight glucose control in critically ill adults: a meta-analysis1

Wiener RS, Wiener DC, Larson RJ.JAMA. August 27, 2008; 300 (8): 933-944

Journal Club Presentation by Quang Bui, Pharm D. candidate 2010. Touro University. 9/22/08

Background

- An RCT by Van den Berghe et al shows that tight glucose control may reduce hospital mortality

by one third.2

- Recommendations were incorporated into the Surviving Sepsis Campaign and many other

guidelines worldwide.3

- Later RCT studies have not shown the same benefits. Eg. the same investigator find no benefits

for critically ill patients in ICU.4

Methods

- Search strategy : MEDLINE (1950-June 6, 2008) with MeSH, Cochrane Library (issue 1, 2008)

and multiple trial registries such as clinicaltrials.gov (August 2007).

- Study selection contact investigators of unpublished data to confirm eligibility.

Inclusion criteria of RCTs Exclusion criteria of RCTs- adult ICU setting

- intervention grp received tight Glc control (Glc goal

500 patients (21 with 100 patients, 7 with >500

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patients), ages 46-75, 31-95% males, 0-100% diabetics, and APACHE II scores 9-32; 2 studies

have discrepant baseline between intervention vs control; all have follow-up rate 80% or higher

& no double-blind, none has Jadad quality score higher than 3 of 5; target vs achieved Glc levels

varied.

Primary outcome Hospital mortality 27/29 trials show no differences.

No differences in both stratifications.Funnel plot shows no publication bias.

Secondary outcome Septicemia

(9 trials)

Tight Glc control assoc with significant reduced

risk of septicemia; stratified favor ICU patients &

moderately tight Glc control.

Van den Berghe et al study as outlier.

New dialysis need

(9 trials)

No significant association; no in stratification.

Van den Berghe et al study as outlier.

Hypoglycemia(15 trials)

Tight Glc control assoc with increased risk ofhypoglycemia by 5 fold; fairly consistent across

ICU settings & 2 outliers in medical ICU.

Conclusion- Tight Glc control was not associated with significant reduction in hospital mortality or new

dialysis need, but had increased hypoglycemia risk.

- In stratified group: reduced septicemia in surgical ICU.

- Therefore, recommend re-evaluation of guidelines.

- 3 reasons why the van der Berghe et al study is an outlier: bias, chance, and atypical clinical

practices.

Discussion

- Weaknesses

o Meta-analysis: are all the studies comparable? Jadad quality scores of 3 or less.

o Only 2 un-blinded reviewers (RSW & DCW) with disputes resolved via discussions.

o Most studies in the study were low powered and single-centered. Cant get anything that

the studies dont report.

o External validity: can not apply this findings to larger population

- Strengths

o 1358 relevant studies from MEDLINE, Cochrane, clinical trial registries, and conferences

from different countries.

o High internal validity: meta-analysis is easier to replicate than the van der Berghe et al

study with selective criteria.

o Articles gathered are mostly from 2006. The oldest from 1991.

- Recommendations

o This analysis is a fine example of why guidelines are changing constantly.

o Tight glucose control may be too critical in severely ill patients who are at high risks ofhypoglycemia. A high powered RCT is needed to solidify these results.

Resources1. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis.

JAMA. 2008; 300 (8): 933-944.

2. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients.NEJM. 2001;345 (19): 1359-1367.

3. Dellinger RP, Levy M, Carlet J, et al. Surviving sepsis campaign: international guidelines for management of severesepsis and septic shock: 2008.Intensive Care Med. 2008; 34 (1): 17-60.

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4. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU.NEJM. 2006; 354

(5):449-461.