JAMA. 2008 Aug 27;300(8):933-44.
Wiener RS, Wiener DC, Larson RJ.
VA Outcomes Group, 111 B, Department of Veterans Affairs Medical Center, White
River Junction, VT 05009, USA. renda.s.wiener@dartmouth.edu
CONTEXT: The American Diabetes Association and Surviving Sepsis Campaign
recommend tight glucose control in critically ill patients based largely on 1
trial that shows decreased mortality in a surgical intensive care unit. Because
similar studies report conflicting results and tight glucose control can cause
dangerous hypoglycemia, the data underlying this recommendation should be
critically evaluated. OBJECTIVE: To evaluate benefits and risks of tight glucose
control vs usual care in critically ill adult patients. DATA SOURCES: MEDLINE
(1950-2008), the Cochrane Library, clinical trial registries, reference lists,
and abstracts from conferences from both the American Thoracic Society
(2001-2008) and the Society of Critical Care Medicine (2004-2008). STUDY
SELECTION: We searched for studies in any language in which adult intensive care
patients were randomly assigned to tight vs usual glucose control. Of 1358
identified studies, 34 randomized trials (23 full publications, 9 abstracts, 2
unpublished studies) met inclusion criteria. DATA EXTRACTION AND ANALYSIS: Two
reviewers independently extracted information using a prespecified protocol and
evaluated methodological quality with a standardized scale. Study investigators
were contacted for missing details. We used both random- and fixed-effects models
to estimate relative risks (RRs). RESULTS: Twenty-nine randomized controlled
trials totaling 8432 patients contributed data for this meta-analysis. Hospital
mortality did not differ between tight glucose control and usual care overall
(21.6% vs 23.3%; RR, 0.93; 95% confidence interval [CI], 0.85-1.03). There was
also no significant difference in mortality when stratified by glucose goal ([1]
very tight: < or = 110 mg/dL; 23% vs 25.2%; RR, 0.90; 95% CI, 0.77-1.04; or [2]
moderately tight: < 150 mg/dL; 17.3% vs 18.0%; RR, 0.99; 95% CI, 0.83-1.18) or
intensive care unit setting ([1] surgical: 8.8% vs 10.8%; RR, 0.88; 95% CI,
0.63-1.22; [2] medical: 26.9% vs 29.7%; RR, 0.92; 95% CI, 0.82-1.04; or [3]
medical-surgical: 26.1% vs 27.0%; RR, 0.95; 95% CI, 0.80-1.13). Tight glucose
control was not associated with significantly decreased risk for new need for
dialysis (11.2% vs 12.1%; RR, 0.96; 95% CI, 0.76-1.20), but was associated with
significantly decreased risk of septicemia (10.9% vs 13.4%; RR, 0.76; 95% CI,
0.59-0.97), and significantly increased risk of hypoglycemia (glucose < or= 40
mg/dL; 13.7% vs 2.5%; RR, 5.13; 95% CI, 4.09-6.43). CONCLUSION: In critically ill
adult patients, tight glucose control is not associated with significantly
reduced hospital mortality but is associated with an increased risk of
hypoglycemia.