An intravenous insulin protocol for strict glycemic control in acute ischaemic stroke G. Ntaios a , M. Egli b , A. Arsovska a , D. Joye a , Y. Bettex a , E. Lauber a , A. Eskandari a , S. D‘Ambrogio a , B. Richoz a , J. Ruiz b and P. Michel a a Neurology Service; and b Service of Endocrinology, Diabetes and Metabolism, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Keywords: intravenous insulin, ischaemic stroke, post- stroke hyperglycemia Received 18 April 2011 Accepted 16 August 2011 Background and purpose: There is a J-shaped association between admission glycemia and outcome. We designed an intravenous insulin protocol aiming at rapid and strict glucose control in hyperglycemic ischaemic stroke patients. Here, we describe the initial experience, safety, and efficacy of this protocol to achieve and maintain euglycemia in the first 48 h. Methods: The protocol is based on parallel scales for adjustment of insulin infusion rate according to current glycemia and the rate of change of glycemia, which was recommended in our stroke unit in 4/2007 in acute ischaemic stroke patients with glycemia > 6 mM. Data were registered in the Acute Stroke Registry and Analysis of Lausanne (ASTRAL). Capillary blood glycemia was measured hourly with fingerprick test at onset of treatment and after each scale change. Target glycemia was 4.0– 6.0 mM pre-prandially (5.5–8.0 mM post-prandially). Hypokalemia was defined as serum potassium < 3.5 mM and measured every 12 h. Specific algorithms were employed during meals and for patients leaving temporarily the stroke unit for diagnostic or therapeutic workup. Results: In the 90 protocol patients, the first normoglycemia was achieved within 8 h of treatment in 91.1% of patients (median interval 4 h (interquartile range (IQR): 3–6). During the median treatment duration of 25.5 h (IQR: 19.7–37.7), median glucose reduction was 2.5 mM (IQR: 1.3–4.3 mM). The overall rate of hypoglycemias was 4.5% and hypokalemias 18.5%. There was a significant increase in the proportion of hypokalemias on the first on-treatment measurement compared to admission (24.4% vs. 8.9%, P = 0.002). Conclusions: The proposed intravenous insulin protocol controls acute post-stroke hyperglycemia but frequently leads to hypokalemia. This issue needs to be addressed for the protocol to be suitable for use in larger, randomized controlled trial to explore its clinical effect. Introduction Patients with acute stroke frequently present with hyperglycemia, with its incidence estimates varying and depending on the frequency of glucose measurements and the criteria used to define hyperglycemia [1]. The incidence of post-stroke hyperglycemia was approxi- mately 45% in studies with frequent glucose measure- ments and a cut-off of 7 mM to define hyperglycemia [2]. Recently, it was shown that the association between post-stroke glycemia and functional outcome follows a J-shaped curve, with both hypoglycemia (< 3.7 mM) and hyperglycemia (> 7.3 mM) related to unfavorable prognosis [3]. Possible mechanisms for the deleterious effect of hyperglycemia on stroke outcome include impaired recanalization, decreased reperfusion, increased reperfusion injury, accumulation of lactic acid and dysfunctional pH homeostasis, mitochondrial dysfunction at the ischaemic tissue, and increased rate of hemorrhagic complications after thrombolytic treatment [4]. There is growing debate over the value of aggressive glucose reduction with insulin infusion during the acute phase of stroke [5,6]. The largest randomized Correspondence: G. Ntaios MD, Neurology Service, CHUV CH- 1011, Lausanne, Switzerland (tel.: +306972770288; fax: +41213141244; e-mail: ntaiosgeorge@yahoo.gr). Ó 2011 The Author(s) European Journal of Neurology Ó 2011 EFNS 443 European Journal of Neurology 2012, 19: 443–451 doi:10.1111/j.1468-1331.2011.03537.x