Review: tight glucose control increases risk of hypoglycaemia but not short-term mortality in critically ill adults
Dr R Wiener, Department of Veterans Affairs Medical Center, White River Junction, VT, USA;
What are the benefits and risks of tight glucose control in critically ill adults?
Included studies compared tight glucose control (glucose goal <150 mg/dl [8.3 mmol/l] using an insulin infusion) with usual care in patients in adult intensive care units (ICUs) and had one of the outcomes of interest as a primary or secondary end point. Studies of primarily intraoperative interventions or that could not provide adequate outcome or methodological data were excluded. Outcomes of interest were hospital or 30-day mortality, septicaemia (sepsis, septicaemia, bacteraemia, or positive blood cultures), need for dialysis in patients without a pre-existing need, and hypoglycaemia (⩾1 blood glucose measurement ⩽40 mg/dl [2.2 mmol/l]).
Medline (1950 to Jun 2008), Cochrane Library (Issue 1, 2008), trial registries (Aug 2007), conference abstracts of American Thoracic Society (2001–8) and Society of Critical Care Medicine (2004–8), and reference lists were searched for randomised controlled trials (RCTs). Trial investigators were contacted for missing data. 34 RCTs met the selection criteria (9 published only as abstracts and 2 unpublished). 29 RCTs (n = 8432, mean age 46–75 y) that provided full study details and reported ⩾1 event were included in the meta-analysis. Study quality was modest (Jadad scores ⩽3 out of 5) because no trials used blinding. All trials had ⩾80% follow-up (28 d to 6 mo or end of hospital stay), and 2 trials had group differences in baseline patient characteristics.
Meta-analysis showed that tight glucose control and usual care did not differ for short-term mortality or new need for dialysis (table). Tight glucose control reduced risk of septicaemia but increased risk of hypoglycaemia more than usual care (table).
In critically ill adults, tight glucose control increases risk of hypoglycaemia but not short-term mortality.
A modified version of this abstract appears in ACP Journal Club.
Soylemez Wiener R, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 2008;300:933–44.
Source of funding: Dartmouth Medical School; Dartmouth-Hitchcock Medical Center; US Department of Veterans Affairs.
The use of tight glucose control in ICUs has been recommended in clinical guidelines since 2001 when van den Berghe et al1 showed that it reduced mortality in ICU patients by 40%. Tight glucose control means maintaining blood glucose concentrations at <150 mg/dl with insulin infusions during ICU stays. However, the benefits of normoglycaemia in critically ill patients have been questioned because subsequent RCTs found that tight glucose control did not reduce hospital mortality.2 The meta-analysis by Wiener et al supports the results of these RCTs: overall mortality was 21.6% for patients receiving tight glucose control and 23.3% for those receiving usual care, a non-significant difference. Furthermore, subgroup analyses showed no differences in mortality in studies using very tight glucose control goals (⩽110 mg/dl [6.1 mmol/l]) and those using moderately tight goals (111–150 mg/dl [6.2–8.3 mmol/l]), or by setting (surgical, medical, or both). However, tight glucose control was associated with increased risk of hypoglycaemia, and this was also consistent across ICU settings. Hypoglycaemia can increase risk of death and, therefore, has important implications for nursing. Glucose concentrations and insulin titration should be closely monitored because inappropriate increases in insulin administration are associated with death in the ICU.3
Although it is critical to have evidence-based clinical guidelines, general recommendations formulated from validated clinical research should be tailored to the needs of individual patients.4