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
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.
Figures in this publication
Available from: sciencedirect.com
- "TG: 4.0–6.0 Median BG CG: 6.4 TG: 5.0 Mortality, hypoglycemia Cavalcanti et al.  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.  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.  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.  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.  523 Medical: 83 Surgical: 17 52.4 "
[Show abstract] [Hide abstract]
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.
Available from: Keith W Muir
- "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 . 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 . In this context, further information on the predictors and natural history of PSH is necessary. "
[Show abstract] [Hide abstract]
ABSTRACT: Post-stroke hyperglycaemia (PSH) is associated with higher mortality and dependence, but further data on predictors of PSH and its evolution over time are required. We examined the prevalence, predictors, and prognosis of acute PSH using data from well-characterised clinical trials in the VISTA database.
Data were extracted for individual participants enrolled <24 h after stroke with ≥1 blood glucose readings documented. PSH was defined as glucose >7.0 mmol/l. Outcome measures were: (1) prevalence of PSH; (2) predictors of PSH by binary logistic regression; (3) mortality, and (4) favourable functional outcome [modified Rankin Scale (mRS) score <2] at day 90.
For 2,649 subjects treated at a median 5.5 h after admission, PSH was present in 1,126 (42.6%, 95% CI 40.7-44.5) on admission and within the first 48 h in 1,421 (53.7%, 95% CI 51.8-55.6). PSH developed between 24 and 48 h in 19.4% (95% CI 17.5-21.4) of initially normoglycaemic subjects. Admission and 48-hour PSH were predicted predominantly by a history of diabetes (for admission PSH: OR 7.40, 95% CI 5.60-9.79) and less clearly by stroke severity. Favourable outcome (mRS <2) at day 90 was less likely with PSH within the first 48 h, advanced age, and higher NIHSS score, and more likely with recombinant tissue plasminogen activator treatment.
Over 40% of ischaemic stroke patients are hyperglycaemic on admission, and 20% of those who are initially normoglycaemic develop hyperglycaemia within 48 h. Diabetes is the strongest predictor of acute hyperglycaemia. Hyperglycaemia within the first 48 h is independently associated with higher mortality and poorer functional outcome, with an absolute increase of 12.9%.
Available from: psu.edu
[Show abstract] [Hide abstract]
ABSTRACT: The advent of portable and high-density devices has made power consumption a critical design concern. In this paper, we address the problem of reducing power consumption via gate-level voltage scaling for those designs that are not under the strictest timing budget. We first use a maximum-weighted independent set formulation for voltage reduction on non-critical parts of the circuit. Then, we use a minimum-weighted separator set formulation to do gate sizing and integrate the sizing procedure with a voltage scaling procedure to enhance power saving on the whole circuit. The proposed methods are evaluated using the MCNC benchmark circuits. An average of 19.12% power reduction over the circuits having only one supply voltage has been achieved
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.