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Currently, the major issue in glycemic control in neurocritical care patients is that tight glycemic control (target range of 80 to 110 mg/dL) using intensive insulin therapy is associated with higher rates of hypoglycemia without an improvement in survival rate. The review by Kramer and colleagues in this issue of Critical Care confirms these data but provides solid evidence about the relationship between hyperglycemia and worsened neurological outcome after acute brain injury. In accordance with the conclusions of Kramer and colleagues, we recommend that a glucose control goal in neurocritical care patients be in the 'moderate' target range (110 to 180 mg/dL). In addition, we recommend adequate nutrition before and during insulin infusion, avoidance of insulin as a bolus, and the use of continuous insulin infusion, beginning with low doses with titration to individual sensitivity. Careful and accurate glycemic monitoring is especially important when insulin is infused.

Purpose of Review: This review focuses on recent findings in perioperative management of blood glucose control using intensive insulin therapy in neurosurgical and neurocritical care and in other intensive care unit patients. We also aim to address practical issues and make recommendations that may contribute to the safe clinical application of intensive insulin therapy targeted to optimize blood glucose control in these patients., Recent Findings: Intensive insulin therapy targeted to obtain tight blood glucose control induces a substantial increase in the number of hypoglycemic episodes and mortality rate. On the contrary, hyperglycemia--both isolated episodes and high mean glucose levels--is associated with worsened neurologic outcome and increased mortality., Summary: In neurosurgical and neurocritical care as well as other intensive care unit patients, both hypoglycemia and hyperglycemia have significant adverse effects. The optimal glucose level remains under debate but significant steps have evolved with the call for judicious control and elimination of the historical approach to glycemic management, which underestimated drawbacks associated with dysglycemia. The increased incidence of hypoglycemia and mortality as well as the impact of hyperglycemia on worsening neurologic function in patients with acute brain damage heightens the need for more clinical studies on perioperative glucose management in these patients.

Background: Intensive insulin therapy to maintain blood glucose at or below 6.11 mM reduces morbidity and mortality after cardiac surgery and morbidity in medical intensive care unit (ICU) patients. The authors investigated the clinical safety and outcome effects of intensive insulin therapy compared to conventional insulin therapy in patients receiving postoperative intensive care after neurosurgical procedures., Methods: In this prospective randomized controlled trial, 483 patients undergoing elective or emergency brain surgery were prospectively and randomly assigned either to intensive insulin therapy (241 patients), receiving insulin titrated to maintain blood glucose levels within the range of 4.44-6.11 mM, or to conventional insulin therapy (242 patients), receiving insulin to maintain blood glucose levels below 11.94 mM. Primary endpoint was incidence of hypoglycemia (defined as blood glucose < 2.78 mM). Efficacy measures included the length of ICU stay, infection rate, and 6 months follow-up Glasgow outcome scale score and overall survival., Results: Hypoglycemia episodes were more frequent in patients receiving intensive insulin therapy, median (min-max): 8 (0-23) versus 3 (0-4); P < 0.0001. The length of stay in the ICU was shorter (6 vs. 8 days; P = 0.0001), and the infection rate was lower (25.7% vs. 39.3%; P = 0.0018). Glasgow outcome scale score and overall survival at 6 months were similar in the two groups., Conclusions: Intensive insulin therapy in patients admitted to a postoperative neurosurgical ICU after brain surgery is associated with iatrogenic hypoglycemia, but it can also reduce the infection rate and shorten the ICU stay.

Introduction: To investigate the risks and possible benefits of routine versus intensive insulin therapy, assessed by the frequency of hypoglycemic events defined as a glucose concentration less than 80 mg/dl (<4.44 mmol/l) in patients admitted to the intensive care unit (ICU) after severe traumatic brain injury (TBI)., Methods and Results: Ninety-seven patients admitted after severe TBI, were enrolled and randomly assigned to two groups of target glycemia. Insulin was infused at conventional rates when blood glucose levels exceeded 220 mg/dl (12.22 mmol/l) or at intensive rates, to maintain glycemia at 80-120 mg/dl (4.44-6.66 mmol/l). The following primary and outcome variables were measured during follow-up: hypoglycemic episodes, duration of ICU stay, infection rate, and 6-month mortality and neurologic outcome measured using the Glasgow Outcome Scale (GOS). Episodes of hypoglycemia (defined as blood glucose <80 mg/dl or 4.44 mmol/l) were significantly higher in patients receiving intensive insulin therapy: median (min-max) conventional insulin therapy 7 (range 0-11) vs. intensive insulin therapy 15 (range 6-33); P<0.0001. Duration of ICU stay was shorter in patients receiving intensive insulin therapy (7.3 vs. 10.0 days; P < 0.05); while infection rates during ICU stay (25.0% vs. 38.8%, P = 0.15), and GOS scores and mortality at 6 months were similar in the two groups., Conclusions: Intensive insulin therapy significantly increases the risk of hypoglycemic episodes. Even though patients receiving intensive insulin therapy have shorter ICU stays and infection rates similar to those receiving conventional insulin therapy, both groups have similar follow-up mortality and neurologic outcome. Hence if intensive insulin therapy is to be used, great effort must be taken to avoid hypoglycemia.

It is unclear if avoiding hyperglycemia during intensive care after acute brain injury improves morbidity, mortality, and neurologic outcome. This prospective randomized trial tested whether intensive insulin therapy affected infection rates, vasospasm, mortality, or long-term neurologic outcome in subarachnoid hemorrhage patients during their intensive care unit (ICU) stay. Comparison was made against conventional insulin therapy using a randomized trial design. The primary outcome measure was infection rate until the fourteenth postoperative day in the ICU or until patient discharge. Secondary end points were the incidence of vasospasm until the fourteenth postoperative day in the ICU or until patient discharge, and neurologic outcome and mortality at 6 months follow-up. A total of 78 patients were prospectively enrolled and randomly assigned either to conventional insulin therapy or to intensive insulin therapy (38 and 40 patients, respectively). The infection rate during the study was significantly higher in patients who received conventional insulin therapy than in patients who received intensive insulin therapy (42% vs. 27%; P<0.001). The incidence of vasospasm during the study was also similar in conventional and intensive therapy groups (31.5% vs. 27.6% in the conventional and intensive insulin therapy groups; P=0.9). Overall mortality rates at 6 months were similar in the 2 groups (18% vs.15%; P=0.9), as was the neurologic outcome at 6 months [modified Rankin score >3 in 22/38 patients (57.8%) in the conventional therapy group vs. 21/40 patients (52.5%) in the intensive insulin therapy group; P=0.7]. Intensive insulin therapy in patients with acute subarachnoid hemorrhage admitted to a postoperative neurosurgical ICU after surgical clipping of intracranial aneurysms decreases infection rates. The benefit of strict glycemic control on postoperative vasospasm, neurologic outcome, and mortality rates does not seem to be affected by intensive insulin therapy.

A letter to the editor is presented in response to the article "Safety and Efficacy of Intensive Insulin Therapy in Critical Neurosurgical Patients," by F. Bilotta and colleagues in the 2009 issue.