Intensive insulin therapy for critically ill patients

OBJECTIVE: To evaluate the clinical outcomes of glycemic control of intensive insulin therapy and recommend its place in the management of critically ill patients. DATA SOURCES: Searches of MEDLINE (1966-March 2004) and Cochrane Library, as well as an extensive manual review of abstracts were performed using the key search terms hyperglycemia, insulin, intensive care unit, critically ill, outcomes, and guidelines and algorithms. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and deemed relevant if they included and assessed clinical outcomes. DATA SYNTHESIS: Mortality among patients with prolonged critical illness exceeds 20%, and most deaths are attributable to sepsis and multisystem organ failure. Hyperglycemia is common in critically ill patients, even in those with no history of diabetes mellitus. Maintaining normoglycemia with insulin in critically ill patients has been shown to improve neurologic, cardiovascular, and infectious outcomes. Most importantly, morbidity and mortality are reduced with aggressive insulin therapy. This information can be implemented into protocols to maintain strict control of glucose. CONCLUSIONS: Use of insulin protocols in critically ill patients improves blood glucose control and reduces morbidity and mortality in critically ill populations. Glucose levels in critically ill patients should be controlled through implementation of insulin protocols with the goal to achieve normoglycemia, regardless of a history of diabetes. Frequent monitoring is imperative to avoid hypoglycemia.     

Pros and cons of continuous glucose monitoring in the intensive care unit

Diabetes mellitus affects people worldwide, and management of its acute complications or treatment-related adverse events is particularly important in critically ill patients. Previous reports have confirmed that hyperglycemia can increase the risk of mortality in patients cared in the intensive care unit (ICU). In addition, severe and multiple hypoglycemia increases the risk of mortality when using insulin or intensive antidiabetic therapy. The innovation of continuous glucose monitoring (CGM) may help to alert medical caregivers with regard to the development of hyperglycemia and hypoglycemia, which may decrease the potential complications in patients in the ICU. The major limitation of CGM is the measurement of interstitial glucose levels rather than real-time blood glucose levels; thus, there will be a delay in the treatment of hyperglycemia and hypoglycemia in patients. Recently, the European Union approved a state-of-art artificial intelligence directed loop system coordinated by CGM and a continuous insulin pump for diabetes control, which may provide a practical way to prevent acute adverse glycemic events related to antidiabetic therapy in critically ill patients. In this mini-review paper, we describe the application of CGM to patients in the ICU and summarize the pros and cons of CGM.     

50% dextrose: antidote or toxin?

The empiric administration of 50% dextrose to all patients presenting to the ED with altered mental status is a standard of care predicated on the assumption that glucose administration is harmless to nonhypoglycemic patients. Considerable evidence now disputes this assumption. Glucose administration before complete cerebral ischemia in experimental animals worsens neurologic and histologic outcome. Administration of glucose during severe incomplete ischemia has a similar detrimental effect. The translation of these experimental findings into clinical practice has been slow, perhaps hindered by the frequent use of rodent models and large bolus doses of glucose. However, evidence is now provided by primate and human studies and by experimental designs using clinically relevant doses of glucose. These clinical and experimental findings in conjunction with the wide availability of a rapid bedside screen for hypoglycemia provide the rationale for an alteration in the standard of care. The empiric administration of glucose should be avoided in patients at risk of cerebral ischemia, such as those with acute stroke, impending cardiac arrest, or severe hypotension or receiving CPR. A bedside fingerstick blood glucose estimation should be performed immediately on all patients presenting with altered mental status. The administration of 50% dextrose should be reserved for those patients in whom hypoglycemia is demonstrated; this practice will uphold Hippocrates' most basic principle of clinical medicine, "The physician must...do no harm."     

Effects of hyperglycemia on neurologic outcome in stroke patients.

Hyperglycemia in acute stroke patients increases cerebral infarct size and worsens neurologic outcome with and without preexisting diabetes mellitus. Hyperglycemia results from metabolic alterations in glucose metabolism, and is most common in patients with acute illness such as stroke. Strict control of hyperglycemia with intensive insulin therapy has been shown to dramatically decrease hospital morbidity and mortality, inpatient stays, hospital costs, and, most importantly, neurologic injury. Insulin treatment protocols developed and implemented by multidisciplinary teams allow for rapid and effective control of hyperglycemia. Nurses who know about hyperglycemia's often-neglected and detrimental effects can play a vital role in influencing outcomes in stroke patients.     

Blood glucose control in the intensive care unit: discrepancy between belief and practice

A survey among pediatric intensive care physicians showed that a great disparity exists between physicians' beliefs regarding hyperglycemia in critically ill patients and their daily practices to screen and treat hyperglycemia. One of the most prominent reasons for hesitating to implement tight glycemic control is the fear of evoking iatrogenic hypoglycemia. Results from ongoing and future studies focusing on both short- and long-term effects of tight glycemic control in broad populations of critically ill children can provide further strong evidence for implementing tight glycemic control. Improving the accuracy of bedside blood glucose measurements and developing reliable computer algorithms to steer insulin infusions can help to overcome the fear of evoking iatrogenic hypoglycemia.     

Intensive insulin treatment improves forearm blood flow in critically ill patients: a randomized parallel design clinical trial

Introduction  

Intensive insulin treatment of critically ill patients was seen as a promising method of treatment, though recent studies showed that reducing the blood glucose level below 6 mmol/l had a detrimental outcome. The mechanisms of the effects of insulin in the critically ill are not completely understood. The purpose of the study was to test the hypothesis that intensive insulin treatment may influence forearm blood flow independently of global hemodynamic indicators.     

Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring

OBJECTIVE: In some studies intensive diabetes treatment in patients with type 2 diabetes may be associated with increased cardiovascular events. It is not clear whether these events are related to hypoglycemic episodes. To determine whether episodes of hypoglycemia were more likely to be associated with cardiac ischemia than normoglycemia or hyperglycemia, we carried out a study in 21 patients with coronary artery disease (CAD) and type 2 diabetes treated with insulin who had good glycemic control. RESEARCH DESIGN AND METHODS: We carried out 72-h continuous glucose monitoring along with simultaneous cardiac Holter monitoring for ischemia. Patients also recorded symptoms of cardiac ischemia (chest pain) and symptoms of hypoglycemia. RESULTS: Satisfactory continuous glucose monitoring system recordings were obtained in 19 patients. We recorded 54 episodes of hypoglycemia (blood glucose <70 mg/dl; 26 of these were symptomatic) and 59 episodes of hyperglycemia (blood glucose >200 mg/dl; none symptomatic). Of the 54 episodes of hypoglycemia, 10 were associated with symptoms of chest pain, during 4 of which electrocardiographic abnormalities were documented. In contrast, only 1 episode of chest pain occurred during 59 episodes of hyperglycemia. No chest pain or electrocardiographic abnormalities occurred when the blood glucose was within the normal range. The difference between the frequency of ischemia during hypoglycemia and the frequency during both hyperglycemia and normoglycemia was statistically significant (P < 0.01). There were 50 episodes during which the blood glucose changed by >100 mg over a 60-min period, and ischemic symptoms occurred during 9 of these episodes (P < 0.01 compared with stable normoglycemia or hyperglycemia). CONCLUSIONS: Hypoglycemia is more likely to be associated with cardiac ischemia and symptoms than normoglycemia and hyperglycemia, and it is particularly common in patients who experience considerable swings in blood glucose. These data may be important in the institution of insulin treatment and attempting near-normal glycemia in patients with known CAD. Further research is needed to determine strategies to prevent ischemia associated with hypoglycemia.     

Circadian rhythm of blood glucose values in critically ill patients

OBJECTIVE: To test whether there is a circadian rhythm of blood glucose control in critically ill patients and whether morning blood glucose is an accurate surrogate of overall blood glucose control. DESIGN: Retrospective multiple-center observational study. SETTING: Intensive care units of three tertiary hospitals and one affiliated private hospital. PATIENTS: Cohort of 8,307 consecutive critically ill patients. INTERVENTIONS: Extraction of blood glucose values from electronically stored measurements. Extraction of demographic and outcome data from unit and hospital databases. Statistical assessment of variations in blood glucose control over each 24-hr cycle. MEASUREMENTS AND MAIN RESULTS: We studied 208,362 blood glucose measurements in 8,307 patients (5.5 measurements/day/person). In each hospital, there was a circadian rhythm of blood glucose control (p<.0001). The differences between highest and lowest blood glucose concentration in different time periods in each hospital were 0.27, 0.28, 0.95, and 0.22 mmol/L. There was also significant variation in the incidence and notional duration of hyperglycemia. The differences between the lowest and highest incidence of hyperglycemia in different time periods were 3.3, 2.7, 9.9, and 2.6% in each hospital. In all four hospitals, the average blood glucose value from 5:30 am to 6:30 am was significantly lower than the 24-hr average. CONCLUSIONS: Blood glucose values and the incidence of hyperglycemia have a circadian rhythm in critically ill patients. Morning blood glucose may not be an accurate surrogate of blood glucose control over the daily cycle.     

Physiology and pharmacology of cerebral blood flow and metabolism

In many critically ill patients, long-term neurologic outcome may depend on the adequacy of regional or global CBF. Despite this possibility, clinical protocols for the management of the cerebral circulation in acute neurologic disease have developed slowly. Perhaps progress in central nervous system monitoring, coupled with recent advances in cerebrovascular pharmacology, will alter the management and prognosis of patients with critical neurologic illness.     

The value of point-of-care testing when instituting an insulin drip protocol

The critically ill patient's response to stress is to increase production of glucose; his can lead to hyperglycemia as insulin releasing factors become overloaded. Although parenteral insulin can aid in preventing complications of hyperglycemia by maintaining a euglycemic state, care must be taken to prevent hypoglycemia. The safest way to prevent large fluctuations in blood glucose levels is frequent monitoring of blood glucose levels via bedside glucose testing. As blood glucose levels fluctuate, the critical care nurse may titrate an insulin drip without specific orders for how much to increase or decrease the amount of insulin infusing. By developing a protocol, including a formula to calculate the amount of insulin to infuse, based on blood glucose levels, the critical care nurse can safely, competently, and accurately maintain blood glucose levels under 250 mg/dL.     

Glycemic control in critically ill patients

Hyperglycemia is common in critically ill patients and can be caused by various mechanisms, including nutrition, medications, and insufficient insulin. In the past, hyperglycemia was thought to be an adaptive response to stress, but hyperglycemia is no longer considered a benign condition in patients with critical illnesses. Indeed, hyperglycemia can increase morbidity and mortality in critically ill patients. Correction of hyperglycemia may improve clinical outcomes. To date, a definite answer with regard to glucose management in general intensive care unit patients, including treatment thresholds and glucose target is undetermined. Meta-analyses of randomized controlled trials suggested no survival benefit of tight glycemic control and a significantly increased incidence of hypoglycemia. Studies have shown a J- or U-shaped relationship between average glucose values and mortality; maintaining glucose levels between 100 and 150 mg/dL was likely to be associated with the lowest mortality rates. Recent studies have shown glycemic control < 180 mg/dL is not inferior to near-normal glycemia in critically ill patients and is clearly safer. Glycemic variability is also an important aspect of glucose management in the critically ill patients. Higher glycemic variability may increase the mortality rate, even in patients with the same mean glucose level. Decreasing glucose variability is an important issue for glycemic control in critically ill patients. Continuous measurements with automatic closed-loop systems could be considered to ensure that blood glucose levels are controlled within a specific range and with minimal variability.     

危重症病人应激性高血糖短期胰岛素强化治疗的临床护理

目的:探讨短期胰岛素强化治疗对危重病人预后的影响,并分析相关护理问题。方法:选择入住ICU、既往无糖尿病史的危重病人108例,随机分为治疗组和对照组各54例。治疗组给予7 d的短期强化胰岛素治疗,随后给予常规的血糖控制;对照组则一直给予常规的血糖控制。强化胰岛素治疗控制血糖在4.4～8.3 mmol/L,常规血糖控制在4.4～11.1 mmol/L。结果:治疗组ICU住院时间、机械通气天数、院内感染发生率、多器官功能障碍综合征(MODS)发生率及病死率均明显低于对照组(P<0.05),两组低血糖的发生率差异比较无统计学意义(P>0.05)。结论:短期胰岛素强化治疗能有效控制重症病人的应激性高血糖,改善预后,实施过程中要做好病人血糖动态监测工作,减少低血糖的发生率。     

Elevated brain lactate accumulation and increased neurologic deficit are associated with modest hyperglycemia in global brain ischemia

This study determined if hyperglycemia: (1) augments ischemic cerebral cortical lactate accumulation during complete cerebral ischemia; and (2) exacerbates subsequent neurologic morbidity and mortality. Dextrose (D5W, n = 8) or normal saline (n = 6) was administered i.v. prior to 10 min of global cerebral ischemia induced by normothermic cardiac arrest in dogs. Before arrest plasma glucose was significantly higher in the D5W-treated group than saline-infused (407 +/- 31 vs. 11 9 +/- 20 mg/dl, P less than 0.05). By 6 h post-arrest, seven of eight D5W-infused dogs died, compared to one of six saline-infused dogs (P = 0.002). D5W-infused dogs showed significantly greater neurologic deficit at 2, 6, and 12 h post-arrest. In a complementary protocol, dogs were pretreated in the same manner, however, six cerebral cortical brain biopsies were taken before, during, and immediately after cardiac arrest. Plasma glucose was 320 +/- 17 mg/dl in the D5W-infused dogs and lower (P less than 0.001), 140 +/- 5 mg/dl, in the saline-infused group. Cerebral cortical lactate accumulation was slightly but significantly greater during ischemia and early reperfusion in animals receiving dextrose. Neither plasma nor cerebrospinal fluid (CSF) creatine kinase isoenzymes nor plasma or CSF lactate concentrations, measured during and for 25 min after cardiac arrest, served as a good prognostic indicator of 24 h neurologic morbidity or mortality. Therefore, induction of complete cerebral ischemia in the presence of moderate hyperglycemia is associated with profound neurologic dysfunction and striking mortality. A qualitative but not quantitative increase in brain lactate accumulation is consistent with the hypothesis that lactate may contribute to the increased severity of neurologic dysfunction with hyperglycemia.     

193例危重病患儿血糖变化分析

目的：通过分析193例危重患儿的血糖变化,探讨应激性高血糖对病情进展和预后的影响。方法：对2002年1月-2007年12月在我院PICU住院的193例危重患儿的资料进行回顾性分析,运用t检验、x^2检验、方差分析和相关分析的统计学方法进行比较。结果：①193例危重病患儿中高血糖组有123例,高血糖的发生率为63．7％;血糖最小值为0．9mmol／L,最大值为30．5mmol／L,均值为8．2mmol／L;②123例高血糖患儿中,G3岁组87例（63．0％）,3～7岁组17例（60．7％）,7～10岁组9例（64．3％）,〉10岁组10例（76．9％）,各年龄组高血糖发生率接近（P〉0．05）,均高于正常血糖发生率。③肺炎组发生高血糖有46例,颅内感染组24例,腹泻组11例,心肌炎组2例,感染性休克组11例,非感染性疾病组11例,其他组5例,意外组13例,不同原发病的血糖均数：肺炎为（7．075±2．900）mmol／L,颅内感染（8．259±3．840）mmol／L,腹泻（8．545±5．600）mmol／L,心肌炎（9．052±9．100）mmol／L,感染性休克（11．154±8．000）mmol／L,非感染性疾病（7．358±3．930）mmol／L,其他为（7．246±2．940）mmol／L,意外（12．329±7．890）mmol／L,经方差分析,不同的原发病其血糖升高的水平存在差异（PG0．05）;④正常血糖患儿平均住院时问14．94d,平均住PICU时间9．5d,平均机械通气时间6．472d,而高血糖患儿的平均住院时间18．32d,平均住PICU时间12d,平均机械通气时间10．1901d,经t检验,高血糖组机械通气时间和住PICU时间长于正常血糖组（均P〈0．05）;⑤正常血糖组发生单个脏器损害的有31例,2个脏器损害的14例,3个以上脏器损害的18例,而高血糖组分别为27、41、55例（P〈0．05）,提示高血糖组脏器损害更严重;⑥高血糖组患儿住院7d内死亡人数31例,高于血糖正常组的8例（P〈0．05）,说明高血糖组患儿住院7d内的死亡率高于正常血糖组。结论：危重病患儿常出现高血糖,血糖升高与疾病严重程度有密切联系,血糖水平升高会导致预后不良,是导致死亡率增加和住院时间延长的重要因素,在治疗过程中应严格检测血糖的变化,尽可能将其控制在正常范围内。     

Differential early mitogen-activated protein kinase activation in hyperglycemic ischemic brain injury in the rat

BACKGROUND: Hyperglycemia aggravates brain injury induced by focal ischemia-reperfusion. The mitogen-activated protein kinase (MAPK) members extracellular-signal regulated kinase (Erk) and c-Jun N-terminal kinase (JNK) have been proposed as mediators of ischemic brain injury, and Erk is strongly activated by combined hyperglycemia and transient global ischemia. It is unclear whether similar MAPK activation appears in focal brain ischemia with concomitant hyperglycemia. DESIGN: Hyperglycemia was induced in rats by an intraperitoneal bolus of glucose (2 g kg(-1)). The rats were then subjected to 90 min of transient middle cerebral artery occlusion (MCAO). Erk and JNK activation were investigated with immunofluorescence and Western blot along with infarct size measurement based on tetrazolium staining and neurological score. RESULTS: The hyperglycemic rats showed increased tissue damage and impaired neurological performance after 1 day compared with controls. The hyperglycemia was generally moderate (< 15 mM). Erk activation was increased after 30 min of reperfusion in the ischemic cortex of the hyperglycemic rats, while JNK activation was present on the contralateral side. Phospho-Erk immunofluorescence revealed marked neuronal activation of Erk in the ischemic cortex of hyperglycemic rats compared with controls. CONCLUSION: Besides confirming the detrimental effects of hyperglycemia on focal ischemia-reperfusion, this study shows that hyperglycemia strongly activates the pathogenic mediator Erk in the ischemic brain in the early phase of reperfusion. JNK activation at this stage is present in the nonischemic hemisphere. The functional relevance of these findings needs further investigation.     

危重患者早期血糖波动与预后的相关性研究

目的 探讨危重患者早期血糖波动与预后的相关性.方法 回顾性分析95例危重患者的临床资料,根据入重症监护病房( ICU )28 d预后分为死亡组(43例)和存活组(52例),监测住ICU 72 h内的血糖,比较两组入ICU时血糖(BGadm)、平均血糖(MBG)、高血糖指数(HGI)、血糖不稳定指数(GLI)、低血糖发生率、胰岛素总用量;通过多因素logistic回归分析确定独立危险因素,并应用受试者工作特征曲线(ROC曲线)下面积(AUC)比较预测价值.结果 死亡组BGadm(mmol/L)、MBG(mmol/L)、HGI、低血糖发生率与存活组比较差异均无统计学意义(BGadm:9.87±4.48比9.26±3.07,MBG:8.59±1.23比847±1.01,HGI6.0:2.45±0.94比1.68±1.05,HGI83:0.84±0.70比0.68±0.51,低血糖发生率:9.30％比5.77％,均P＞0.05);急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分(分)、GLI、胰岛素72 h总用量(U)均显著高于存活组[APACHEⅡ评分:23 +6比19±6,GLI:56.96(65.43)比23.87(41.62),胰岛素72 h总用量:65.5( 130.5)比12.5(90.0),均P＜0.05].多因素logistic回归分析显示,APACHEⅡ评分与GLI为死亡独立危险因素[APACHEⅡ评分:优势比(OR)=1.09,95％可信区间(95％CI) 1.01～ 1.17; GLI:OR=1.03,95％口1.01～1.06,均P＜0.05];APACHEⅡ评分与GLI的AUC分别为0.69、0.71,二者无显著差异(P＞0.05).结论 危重患者早期血糖波动是患者入ICU 28 d死亡的独立危险因素,控制早期血糖波动可能有利于改善预后.     

Clinical challenges of glycemic control in the intensive care unit: A narrative review

Glucose control in patient admitted to the intensive care unit has been a topic of much debate over the past 20 years. The harmful effects of uncontrolled hyperglycemia and hypoglycemia in critically ill patients is well established. Although a large clinical trial in 2001 demonstrated significant mortality and morbidity benefits with tight glucose control in this patient population, the results could not be replicated by other investigators. The “Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation” trial in 2009 established that tight glucose control was not only of no benefit, but in fact harmful due to the significant risk of hypoglycemia. The current guidelines suggest a moderate approach with the initiation of intravenous insulin therapy in critically ill patients when the blood glucose level is above 180 mg/dL. The most important factor that underpins glycemic management in intensive care unit patients is the consequent prevention of hypoglycemia. Robust glucose monitoring strategies and insulin protocols need to be implemented in order to achieve this goal.     

An insulin infusion protocol in critically ill cardiothoracic surgery patients

BACKGROUND: Critically ill cardiothoracic patients are prone to hyperglycemia and an increased risk of surgical site infections postoperatively. Aggressive insulin treatment is required to achieve tight glycemic control (TGC) and improve outcomes. OBJECTIVE: To examine and report on the performance of an insulin infusion protocol to maintain TGC, defined as a blood glucose level of 80-150 mg/dL, in critically ill cardiothoracic surgical patients. METHODS: A nurse-driven insulin infusion protocol was developed and initiated in postoperative cardiothoracic surgical intensive care patients with or without diabetes. In this before-after cohort study, 2 periods of measurement were performed: a 6-month baseline period prior to the initiation of the insulin infusion protocol (control group, n = 174) followed by a 6-month intervention period in which the protocol was used (TGC group, n = 168). RESULTS: Findings showed percent and time of blood glucose measurements within the TGC range (control 47% vs TGC 61%; p = 0.001), AUC of glucose exposure >150 mg/dL versus time for the first 24 hours of the insulin infusion (control 28.4 vs TGC 14.8; p < 0.001), median time to blood glucose <150 mg/dL (control 9.4 h vs TGC 2.1 h; p < 0.001), and percent blood glucose <65 mg/dL as a marker for hypoglycemia (control 9.8% vs TGC 16.7%; NS). CONCLUSIONS: An insulin infusion protocol designed to achieve a goal blood glucose range of 80-150 mg/dL efficiently and significantly improved TGC in critically ill postoperative cardiothoracic surgery patients without significantly increasing the incidence of hypoglycemia.     

预防性应用盐酸氟桂利嗪对高血糖SD大鼠局部脑缺血再灌注损伤保护作用的研究

目的 采用高血糖条件下Sprague-Dawley（SD）大鼠局灶性脑缺血再灌注模型,观察神经功能缺损评分、脑梗死体积、脑组织病理形态改变及抑凋亡基因bcl-2的表达情况,探讨预防性应用盐酸氟桂利嗪对高血糖条件下SD大鼠局灶性脑缺血再灌注损伤是否有保护作用。方法36只雄性健康SD大鼠,建立高血糖模型后随机分为2组：高血糖组（n=18）、盐酸氟桂利嗪＋高血糖组（简称氟桂利嗪组n=18）,各组按脑缺血90min再灌注3h（n=6）、6h（n=6）、24h（n=6）分为3个亚组。比较氟桂利嗪组与高血糖组各再灌注时间点神经功能缺损评分、脑梗死体积和脑组织病理形态的改变。结果相同再灌注时间点,氟桂利嗪组比高血糖组神经功能缺损程度减轻,P〈0．05;相同时间点氟桂利嗪组较高血糖组梗死体积缩小,其中再灌注3、6h组间比较P〈0．05,再灌注24h组间比较P〈0．01;脑组织病理形态观察：氟桂利嗪组与高血糖组各再灌注时间点比较,变性、坏死的神经元减少,空泡化改变减轻,组织间水肿减轻。结论预防性应用盐酸氟桂利嗪能减轻高血糖条件下的局灶性脑缺血再灌注损伤,减轻神经功能缺损症状,缩小梗死体积,减轻神经细胞变性、坏死及组织水肿。     

Bench-to-bedside review: a possible resolution of the glucose paradox of cerebral ischemia

The glucose paradox of cerebral ischemia (namely, the aggravation of delayed ischemic neuronal damage by preischemic hyperglycemia) has been promoted as proof that lactic acidosis is a detrimental factor in this brain disorder. Recent studies, both in vitro and in vivo, have demonstrated lactate as an excellent aerobic energy substrate in the brain, and possibly a crucial one immediately postischemia. Moreover, evidence has been presented that refutes the lactic acidosis hypothesis of cerebral ischemia and thus has questioned the traditional explanation given for the glucose paradox. An alternative explanation for the aggravating effect of preischemic hyperglycemia on the postischemic outcome has consequently been offered, according to which glucose loading induces a short-lived elevation in the release of glucocorticoids. When an episode of cerebral ischemia in the rat coincided with glucose-induced elevated levels of corticosterone (CT), the main rodent glucocorticoid, an aggravation of the ischemic outcome was observed. Both the blockade of CT elevation by chemical adrenalectomy with metyrapone or the blockade of CT receptors in the brain with mifepristone (RU486) negated the aggravating effect of preischemic hyperglycemia on the postischemic outcome.