Hyperglycemia after Acute Ischemic Stroke: Prediction, Significance and Immediate Control with Insulin-Potassium-Saline-Magnesium Infusions

Abstract

Introduction: It is well known that in the first 24 h after stroke onset, plasma glucose concentrations are elevated in 20–43% of patients, of whom more than half are not known to have diabetes mellitus. Glucose levels >8 mmol/l have been found to be predictive of a poor prognosis in ischemic stroke patients. It is thought that the clinical use of insulin infusions has a beneficial effect on hyperglycemia. Indeed, insulin therapy in critically ill patients, including acute stroke patients, is safe and results in lower mortality and complication rates. Unfortunately, the impact of intensive insulin therapy in non-critically ill patients with hyperglycemia is poorly understood. Objectives: It was the aim of this study to determine the clinical efficacy and safety of early-onset therapy with human recombinant insulin: glycemic control measured by reduction in plasma glucose concentrations, vital activity measured by the Barthel index (no significant disability was defined as ≤50, moderate disability was defined as 51–75, and severe disability was defined as ≧75), and neurological deficit measured by the National Institutes of Health Stroke Scale (NIHSS; values ranging from 0 = normal to 42 = worst case) in non-critically ill ischemic stroke diabetic and non-diabetic patients. Design: We used a randomized prospec- tive open trial of insulin-potassium-saline-magnesium (IPSM) infusions in patients after acute ischemic stroke presenting with mild to moderate hyperglycemia. Acute (<24 h) ischemic stroke patients (n = 128) with hyperglycemia on admission between 7.0 and 16 mmol/l with and without type 2 diabetes mellitus (T2DM) were randomly divided into four groups: (1) hyperglycemia associated with T2DM and treated with IPSM (n = 36), (2) hyperglycemia associated with T2DM without IPSM administration (n = 40), (3) hyperglycemia without confirmed T2DM and treated with IPSM (n = 25), and (4) hyperglycemia without confirmed T2DM and without IPSM administration (n = 27). Results: Treatment with the IPSM regimen permitted to normalize blood glucose levels. The neurological deficit according to the NIHSS in stroke patients with hyperglycemia treated with insulin did not worsen in the first 3 days. Results were expressed as means ± SD of NIHSS scores at admission and at day 30. At the same time, the clinical status of patients not treated with insulin worsened. Three weeks after admission, the neurological deficit improved in treated stroke patients (13.5 ± 1.5 and 8.6 ± 1.1, respectively; p < 0.05) and untreated patients with T2DM (13.2 ± 1.7 and 8.9 ± 1.3; p < 0.05). However, the neurological deficit in stroke patients without T2DM, but with hyperglycemia not treated with insulin did not improve significantly (14.4 ± 1.5 and 10.1 ± 1.0, respectively; p > 0.05). Administration of IPSM led to a significant improvement in the neurological status (14.6 ± 1.5 and 8.9 ± 1.3; p < 0.05). Conclusions: Insulin therapy (IPSM infusion) is a safe and effective approach to normalize blood glucose levels after ischemic stroke. Administrati...

Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis

“…Three RCTs involving patients with ischemic stroke used GKI regimens rather than only intensive insulin as their experimental treatment [65-67]. Another trial used an insulin-saline-potassium-magnesium infusion [68]. These four studies were excluded from the primary analysis, but their results were incorporated into a secondary analysis.…”

Intravenous Insulin Treatment in Acute Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Various intravenous insulin regimens were used in the included studies: (a) 400 ml of 0·9% NaCl, 40 ml of 3% KCl, 10 ml of 25% magnesium sulfate and Farmasulin (Farmak, Ukraine) ; (b) infusion of insulin (Human Actrapid, Novo Nordisk, Bagsværd, Denmark) with dosage adjustment according to a sliding scale ; (c) 500 ml glucose‐potasium‐insulin regimen of 10% dextrose and 20 mmol potassium chloride with an initial insulin dose of 16 units of soluble recombinant human insulin ; (d) 50 IU of actrapid insulin in 50 ml of 0·9% sodium chloride with an initial infusion dose of 2 IU/h ; (e) 25 IU in 500 ml normal saline ; (f) 50 IU normal insulin in 50 ml of 0·9% saline solution ; (g) Novolin brand insulin in normal saline (1 U/1 ml) as a continuous infusion ; (h) 500 ml of 10% dextrose, 20 mmol potassium chloride, and 16 units of soluble recombinant human insulin ; and (i) soluble human Actrapid insulin was administered in an intravenous continuous infusion with hourly dose adaptation . The control group was treated with normal saline in three studies or subcutaneous insulin in five studies .…”

“…The control group was treated with normal saline in three studies or subcutaneous insulin in five studies . Various target glycemia levels were used: 3·9–6·1 mmol/l , 4–7 mmol/l , 4·4–6·1 mmol/l , 4·4–7 mmol/l , 5–7·2 mmol/l , 5–7·9 mmol/l , and < 7 mmol/l .…”

“…Favorable outcome was defined with the modified Rankin score in six studies and the Barthel index in two studies . Favorable outcome and mortality were assessed at 1 , 3 , or 4 months after stroke.…”

“…Favorable outcome was defined with the modified Rankin score in six studies and the Barthel index in two studies . Favorable outcome and mortality were assessed at 1 , 3 , or 4 months after stroke. Hypoglycemia was defined as a glucose value <4 mmol/l in two studies , <3·3 mmol/l in three studies , and <3 mmol/l in two studies .…”