Refining perioperative glucose management in patients experiencing, or at risk for, ischemic brain injury.

ISCHEMIC brain injury is the third leading cause of death in the United States, and survivors of ischemic brain injury represent the leading cause of major disability. Most of these ischemic events begin outside the hospital. However, patients who enter the hospital neurologically intact may experience new-onset cerebral ischemia, e.g., in association with cardiac or cerebrovascular surgery. Those who have experienced a single ischemic event (whether beginning outside or inside the hospital) are at risk for exacerbation of their injury during hospitalization due to secondary insults resulting from cardiac arrhythmias, systemic hypotension, surgical interventions, cerebral vasospasm, and other causes. During hospitalization, clinicians have many opportunities to lessen the risk of both primary and secondary ischemic injury. One such possibility is the disciplined monitoring and management of blood glucose concentrations. Although the issue of intensive insulin therapy and glycemic control is pertinent to critically ill patients in general, as addressed by Blasi-Ibanez et al., and reviewed by Lipshutz and Gropper in last month’s issue of ANESTHESIOLOGY, patients who have experienced or are at risk for ischemic brain injury represent a special population (for reasons we will later review). There is considerable, consistent evidence from animal models and human studies that outcome after a cerebral ischemic insult is partially modulated by blood and brain glucose concentrations. However, the current literature offers little guidance for the clinician on how to apply the existing data such that outcome can be optimized during the care of neurologically at-risk patients, particularly with respect to how rigidly glucose should be controlled and the magnitude of risk in executing such control. Two human studies reported in this issue of ANESTHESIOLOGY focused on this issue. Bilotta et al. report on the challenges and pitfalls of glucose management in patients requiring intracranial surgical procedures. Likewise, Thiele et al. report on the effect of institution of a strict blood glucose management protocol on outcome in critically ill patients with subarachnoid hemorrhage. Glucose management in patients with cerebral insultsin-evolution may be problematic. Specifically, physiologic stress, use of corticosteroids or other drugs (e.g., sympathomimetics), neuroendocrine disorders, nutritional support, and other factors may all combine to make the fine tuning of blood glucose concentrations difficult. Data from experiments in animal models inform us that modest changes in blood glucose concentrations, on the order of 40 mg/dl, are sufficient to modulate outcome after an ischemic insult. Further, optimum neurologic outcome, based on animal and human research, will likely occur at blood glucose concentrations of 130 mg/dl or less. However, it is unclear whether more rigorous glucose reduction is beneficial. Specifically, there is concern that hypoglycemia can cause irreversible brain injury and cardiovascular compromise independent of the presence of cerebral ischemia. To address these challenges, Bilotta et al. prospectively studied 483 patients presenting for elective or emergent intracranial procedures. Patients were randomized to either intensive (target blood glucose concentration 80–110 mg/dl) or conventional (target blood glucose concentration 215 mg/dl) glycemic management. The primary goal of this investigation was to compare the rates of hypoglycemic episodes (blood glucose 50 mg/dl) between groups. Other outcome metrics evaluated were length of intensive care unit stay, infection rate, 6-month Glasgow Outcome Score, and mortality. A greater fraction of patients in the intensive glucose treatment group had hypoglycemic episodes (94% vs. 63% for conventional treatment; P 0.0001), but they also had a lesser incidence of infections (26% vs. 39% for conventional therapy; P 0.002) and a shorter median duration of intensive care unit stay (6 days vs. 8 days; P 0.0001). Despite these differences, there was no difference in 6-month Glasgow Outcome Scores (P 0.984) or mortality (P 0.689) between groups. A related study in this issue of ANESTHESIOLOGY retrospectively reported on an intensive glucose control protocol introduced at the University of Virginia Health System on January 1, 2002. Target blood glucose concentration was 90–120 mg/dl. Thiele et al. compared clinical outcome in patients with subarachnoid hemorrhage managed before (1995–2001, n 343) or after (2002–2007, n 491) institution of the glucose-management protocol. Despite statistically positive results regarding glucose endpoints, the difference between preprotocol and postprotocol median blood glucose concentration was exThis Editorial View accompanies the following two articles: Thiele RH, Pouratian N, Zuo Z, Scalzo DC, Dobbs HA, Dumont AS, Kassell NF, Nemergut EC: Strict glucose control does not affect mortality after subarachnoid hemorrhage. Anesthesiology 2009; 110:603–10; and Bilotta F, Caramia R, Paoloni FP, Delfini R, Rosa G: Safety and efficacy of intensive insulin therapy in critical neurosurgical patients. ANESTHESIOLOGY 2009; 110:611–9.