Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis
1 Department of Critical Care Medicine, University of Calgary, ICU Administration - Ground Floor, McCaig Tower, 3134 Hospital Dr NW, Calgary, AB T2N 2T9, Canada
2 Department of Clinical Neurosciences, University of Calgary, Room 1995 - Foothills Hospital, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada
3 Department of Community Health Sciences, University of Calgary, Faculty of Medicine - 3rd Floor TRW Building, 3280 Hospital Dr NW, Calgary, AB T2N 2T9, Canada
4 Department of Surgery, University of Calgary, North Tower 10th Floor - Foothills Hospital, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada
Critical Care 2012, 16:R203 doi:10.1186/cc11812
See related commentary by Bilotta and Rosa, http://ccforum.com/content/16/5/163.Published: 22 October 2012
Hyper- and hypoglycemia are strongly associated with adverse outcomes in critical care. Neurologically injured patients are a unique subgroup, where optimal glycemic targets may differ, such that the findings of clinical trials involving heterogeneous critically ill patients may not apply.
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intensive insulin therapy with conventional glycemic control among patients with traumatic brain injury, ischemic or hemorrhagic stroke, anoxic encephalopathy, central nervous system infections or spinal cord injury.
Sixteen RCTs, involving 1248 neurocritical care patients, were included. Glycemic targets with intensive insulin ranged from 70-140 mg/dl (3.9-7.8 mmol/L), while conventional protocols aimed to keep glucose levels below 144-300 mg/dl (8.0-16.7 mmol/L). Tight glycemic control had no impact on mortality (RR 0.99; 95% CI 0.83-1.17; p = 0.88), but did result in fewer unfavorable neurological outcomes (RR 0.91; 95% CI 0.84-1.00; p = 0.04). However, improved outcomes were only observed when glucose levels in the conventional glycemic control group were permitted to be relatively high [threshold for insulin administration > 200 mg/dl (> 11.1 mmol/L)], but not with more intermediate glycemic targets [threshold for insulin administration 140-180 mg/dl (7.8-10.0 mmol/L)]. Hypoglycemia was far more common with intensive therapy (RR 3.10; 95% CI 1.54-6.23; p = 0.002), but there was a large degree of heterogeneity in the results of individual trials (Q = 47.9; p<0.0001; I2 = 75%). Mortality was non-significantly higher with intensive insulin in studies where the proportion of patients developing hypoglycemia was large (> 33%) (RR 1.17; 95% CI 0.79-1.75; p = 0.44).
Intensive insulin therapy significantly increases the risk of hypoglycemia and does not influence mortality among neurocritical care patients. Very loose glucose control is associated with worse neurological recovery and should be avoided. These results suggest that intermediate glycemic goals may be most appropriate.