Pragmatic Management of Hyperglycaemia in Acute Ischaemic Stroke: Safety and Feasibility of Intensive Intravenous Insulin Treatment

Department of Neurology, Universitatsklinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, Mannheim, Germany.
Cerebrovascular Diseases (Impact Factor: 3.75). 12/2008; 27(2):167-75. DOI: 10.1159/000185608
Source: PubMed


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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    • "TG: 4.0–6.0 Median BG CG: 6.4 TG: 5.0 Mortality, hypoglycemia Cavalcanti et al. [26] 112 Respiratory, 32; sepsis, cardiovascular, neurologic, 44 59.9 46 30 20.5 (median) 90 days CG: subcutaneous insulin injection TG: insulin infusion NA CG: b8.3 TG: 4.4–6.1 Median BG CG: 8.8 TG: 7.1 Hypoglycemia Kreisel et al. [27] 40 Acute ischemic stroke, 100 71.6 60 33 NA 120 days CG: subcutaneous insulin injection TG: insulin infusion CG: 5.4 TG: 13.3 CG:b11.1 TG: 4.44–6.11 Mean BG CG: 8.01 TG: 6.49 Mortality Green et al. [28] 81 Ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, 35; traumatic brain injury, 49 51 69 NA NA 90 days CG: subcutaneous insulin injection or insulin infusion TG: insulin infusion Mean insulin infusion rate CG: 1.4 IU/h TG: 2.39 IU/h CG: ≤8.3 TG: 4.4–6.1 Mean BG CG: 7.9 TG: 6.2 Mortality, hypoglycemia, sepsis Mixed ICU Mitchell et al. [30] 70 Medical: 61 Surgical: 3 9 65.4 60 14 20.5 (median) Hospital stay Both groups: insulin infusion CG: 0 TG: 35.7 (median) CG: 10–11.1 TG: 4.4–6.1 Median BG CG: 7.9 TG: 5.4 Mortality, hypoglycemia Arabi et al. [9] 523 Medical: 83 Surgical: 17 52.4 "
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    ABSTRACT: Critically ill patients commonly develop hyperglycemia. It remains unclear, however, to what extent correcting hyperglycemia will benefit these patients. We performed this meta-analysis to evaluate the benefits and risks of intensive glucose control versus conventional glucose control in critically ill adult patients. A systematic literature search of MEDLINE, PubMed, and Cochrane databases (until June 2011) was conducted using specific search terms. Randomized controlled trials that compared intensive glucose control with a target glucose goal <6.1 mmol/l (110 mg/dl) to conventional glucose control in adult intensive care patients were included. The random-effect model was used to estimate the pooled risk ratio of the two treatment arms. Twenty two studies that randomized 13,978 participants were included in the meta-analysis. Overall, intensive glucose control did not reduce the short-term mortality (RR=1.02, 95% CI: 0.95-1.10, p=0.51), 90 day or 180 day mortality (RR=1.06, 95% CI: 0.99-1.13, p=0.08), sepsis (RR=0.96, 95% CI: 0.83-1.12, p=0.59) or new need for dialysis (RR=0.96, 95% CI: 0.83-1.11, p=0.57). The incidence of hypoglycemia was significantly higher in intensive glucose control group compared with conventional glucose control group (RR=5.01, 95% CI: 3.45-7.28, p<0.00001). This meta-analysis found that intensive glucose control in critically ill adults did not reduce mortality but is associated with a significantly increased risk of hypoglycemia.
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    • "Single values have less prognostic value than sustained hyperglycaemia, and hyperglycaemia at any time within 48 h following admission may be more relevant than single recordings [6]. This insight has potentially major implications for stroke management, given the major staffing requirements for insulin infusion management and high incidence of hypoglycaemia in stroke unit settings [30]. In this context, further information on the predictors and natural history of PSH is necessary. "
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