Published online before print April 3, 2003, doi: 10.1161/01.STR.0000068407.77577.C6
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(Stroke. 2003;34:1240.)
© 2003 American Heart Association, Inc.
Original Contributions |
Editorial Comment—Hyperglycemia and Early Reperfusion Therapy
Stroke Unit, Department of Neurology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Clinical studies of acute ischemic stroke support the conclusions of most experimental studies of focal cerebral ischemia in suggesting that admission hyperglycemia is associated with a worse clinical outcome.1 This association is more consistent in nonlacunar strokes2 and in experimental models of reversible focal cerebral ischemia.3 The acute ischemic penumbra might be preferentially susceptible to injury in hyperglycemic ischemia. Indeed, by use of MR methods, hyperglycemia in acute ischemic stroke was shown to promote the evolution of hypoperfused tissue to infarction and to do so by increased brain lactate production.4
This role of hyperglycemia may be of particular importance in patients treated with early reperfusion therapy. Elevated admission blood glucose has emerged as a probable risk factor for thrombolysis-related ICH and for poor outcome in patients with acute ischemic stroke.5–7 A recent post hoc analysis from the NINDS rtPA Stroke Trial has shown that in patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of whether recombinant tPA (rtPA) treatment is given.8
In the accompanying article, Alvarez-Sabín et al demonstrate, in a case series of patients with acute ischemic stroke treated with rtPA and assessed serially by TCD, that admission hyperglycemia independently predicts poor outcome in reperfused but not in nonreperfused rtPA-treated patients. These intriguing findings suggest that the deleterious effect of hyperglycemia on infarct growth may be related to whether or not reperfusion occurs. While the study provides useful data that extend previous observations, there are also apparent inherent caveats from the retrospective and uncontrolled nature of these analyses, which are based on a relatively small series of patients from a single center.
Hyperglycemia can be rapidly and relatively easily corrected and controlled. Better glycemic control by intravenous insulin and glucose infusion has been shown to improve clinical outcomes from acute myocardial infarction, in particular when it was added to acute reperfusion therapy.9,10 Randomized controlled trials are currently under way, designed to determine whether insulin-induced and -maintained euglycemia in acute stroke patients is effective.11 On the basis of the current state of knowledge, including the accompanying article, it is reasonable to hypothesize that metabolic support may be of particular value, in combination with reperfusion therapy for acute ischemic stroke, in minimizing reperfusion injury related to hyperglycemia. This possibility is especially important in light of the growing use of new strategies for early reperfusion therapy in acute ischemic stroke. Aggressive insulin treatment may exert important metabolic effects beyond maintaining euglycemia, but such treatment is not without potential risks.12 Therefore, the optimal and safe protocol of administering insulin should be sought and rigorously tested in carefully designed prospective clinical trials utilizing reperfusion therapy.
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2. Bruno A, Biller J, Adams HP Jr, Clarke WR, Woolson RF, Williams LS, Hansen MD, for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Acute blood glucose level and outcome from ischemic stroke. Neurology. 1999;52:280–284.
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11. Scott JF, Robinson GM, French JM, O’Connell JE, Alberti KG, Gray CS. Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia: the Glucose Insulin in Stroke Trial (GIST). Stroke. 1999; 30: 793–799.
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