Pragmatic Management of Hyperglycaemia in Acute Ischaemic Stroke: Safety and Feasibility of Intensive Intravenous Insulin Treatment
ABSTRACT In patients with acute ischaemic stroke, hyperglycaemia has been retrospectively associated with negative outcome. There is an ongoing discussion as to which treatment algorithm, if any, provides the most effective prospective intervention. Here we test the safety and feasibility of an intravenous insulin-only infusion protocol designed for pragmatic routine clinical use.
40 ischaemic stroke patients with onset <24 h ago, admitted to our stroke unit, were randomized either to the study regimen (50 IU insulin in 50 ml 0.9% saline solution applied intravenously via a perfusor pump), with the aim of reaching and maintaining blood glucose levels between 4.44 mmol/l (80 mg/dl) and 6.11 mmol/l (110 mg/dl), or were treated with insulin subcutaneously if concentrations were above 11.10 mmol/l (200 mg/dl). Treatment was continued for 5 days. Primary outcome was the number of hypoglycaemic (<3.33 mmol/l; <60 mg/dl) and severe hyperglycaemic (>16.65 mmol/l; >300 mg/dl) events.
Hypoglycaemic events were significantly more common in patients treated intensively (total n = 25; incidence rate ratio, IRR = 5.3; 95% CI = 1.2-22.4; p < 0.05). Symptomatic events were rare (total n = 5). Severe hyperglycaemia was associated with conventional treatment (IRR = 4.9; 95% CI = 1.5-15.9; p < 0.05). Though those treated intensively attained near-normoglycaemic levels quicker and had significantly lower blood glucose levels over the study period (6.49 +/- 2.19 mmol/l vs. 8.01 +/- 3.06 mmol/l; 95% CI = -1.78 to -1.28, p < 0.0005), treatment imposes considerable strain on both patients and caregivers.
The intensive intravenous insulin infusion protocol effectively lowers blood glucose levels with an increased risk of manageable hypoglycaemic events. However, a highly motivated and trained staff seems essential, limiting feasibility outside of specialty care settings.
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ABSTRACT: Hyperglycemia is commonly encountered in both diabetic and non-diabetic patients in acute ischemic stroke. Hyperglycemia in stroke has been associated with poor clinical outcome, a phenomenon that has been studied in experimental models, where hyperglycemia was shown to enhance cortical toxicity, increase infarct volumes, promote inflammation, and affect the cerebral vasculature. This has led to many trials attempting to modulate the hyperglycemic response as a therapeutic and neuroprotective strategy. Intensive glycemic control has been evaluated in stroke patients, with conflicting results. The evidence linking hyperglycemia with neurotoxicity coupled with the failure of intensive glucose control regimens to improve functional outcomes in stroke suggests that novel approaches should be devised. Recent attention has been paid to another related phenomenon, that of glycemic variability, which has been proven to be a predictor of outcome in critically ill patients; however, its the impact in stroke has not been evaluated.Translational Stroke Research 08/2014; 5(6). DOI:10.1007/s12975-014-0365-7
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ABSTRACT: Brain has a continuous demand for energy that is met by oxidative metabolism of oxygen and glucose. This demand is compromised in the injured brain and if the inadequate supply persists it will lead to permanent tissue damage. Zero values of cerebral glucose have been associated with infarction and poor neurological outcome. Furthermore, hyperglycemia is common in patients with neurological insults and associated with poor outcome. Intensive insulin therapy (IIT) to control blood glucose has been suggested and used in neurointensive care with conflicting results. This review covers the studies reporting on monitoring of cerebral glucose with microdialysis in patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and ischemic stroke. Studies investigating IIT are also discussed. Available data suggest that low cerebral glucose in patients with TBI and SAH provides valuable information on development of secondary ischemia and has been correlated with worse outcome. There is also indication that the location of the catheter is important for correlation between plasma and brain glucose. In conclusion considering catheter location, monitoring of brain glucose in the neurointensive care not only provides information on imminent secondary ischemia it also reveals the effect of peripheral treatment on the injured brain.Frontiers in Neurology 06/2014; 5:91. DOI:10.3389/fneur.2014.00091
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ABSTRACT: Poststroke hyperglycemia has been associated with unfavorable outcome. Several trials investigated the use of intravenous insulin to control hyperglycemia in acute stroke. This meta-analysis summarizes all available evidence from randomized controlled trials in order to assess its efficacy and safety. We searched PubMed until 15/02/2013 for randomized clinical trials using the following search items: 'intravenous insulin' or 'hyperglycemia', and 'stroke'. Eligible studies had to be randomized controlled trials of intravenous insulin in hyperglycemic patients with acute stroke. Analysis was performed on intention-to-treat basis using the Peto fixed-effects method. The efficacy outcomes were mortality and favorable functional outcome. The safety outcomes were mortality, any hypoglycemia (symptomatic or asymptomatic), and symptomatic hypoglycemia. Among 462 potentially eligible articles, nine studies with 1491 patients were included in the meta-analysis. There was no statistically significant difference in mortality between patients who were treated with intravenous insulin and controls (odds ratio: 1·16, 95% confidence interval: 0·89-1·49). Similarly, the rate of favorable functional outcome was not statistically different (odds ratio: 1·01, 95% confidence interval: 0·81-1·26). The rates of any hypoglycemia (odds ratio: 8·19, 95% confidence interval: 5·60-11·98) and of symptomatic hypoglycemia (odds ratio: 6·15, 95% confidence interval: 1·88-20·15) were higher in patients treated with intravenous insulin. There was no heterogeneity across the included trials in any of the outcomes studied. This meta-analysis of randomized controlled trials does not support the use of intravenous insulin in hyperglycemic stroke patients to improve mortality or functional outcome. The risk of hypoglycemia is increased, however.International Journal of Stroke 12/2013; 9(4). DOI:10.1111/ijs.12225 · 4.03 Impact Factor