Safety and Efficacy of Intensive Insulin Therapy in Critical Neurosurgical Patients

Bilotta, Federico; Caramia, Remo; Paoloni, Francesca; Delfini, Roberto; Rosa, Giovanni

doi:10.1097/aln.0b013e318198004b

Cited by 142 publications

(92 citation statements)

References 46 publications

(31 reference statements)

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“…The general consensus among caretakers is that blood glucose should be maintained below 180 mg/dL (Oddo et al, 2008). However, recent studies have provided evidence that although blood glucose above a certain level may be harmful, strict management of serum glucose levels through use of intensive insulin therapy is also not ideal for TBI patients (Bilotta et al, 2008(Bilotta et al, , 2009Vespa et al, 2006). TBI increases the cellular demand for glucose, and Vespa and colleagues (2006) associated this metabolic shift with a decrease in extracellular glucose and an increase in glutamate concentrations within the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the apparent relationship between high blood glucose and poor outcome, several studies have demonstrated that tight management of blood glucose in headinjured patients by intensive insulin therapy leads to an increased incidence of hypoglycemia (Bilotta et al, 2008(Bilotta et al, , 2009Vespa et al, 2006). Further, a microdialysis study conducted with patients 1-5 days post-injury found that low levels of extracellular glucose were correlated with decreased neurological outcome at 6 months post-injury .…”

Section: Introductionmentioning

confidence: 99%

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High Blood Glucose Does Not Adversely Affect Outcome in Moderately Brain-Injured Rodents

Hill

Zhao

Dash

2010

Journal of Neurotrauma

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In a number of clinical studies researchers have reported that acute hyperglycemia is associated with increased mortality and worsened neurological outcome in patients with traumatic brain injury (TBI). In contrast, it has been demonstrated that intensive insulin therapy to lower blood glucose can lead to an increased frequency of hypoglycemic episodes and poor outcome. Consistent with this, experimental and clinical studies have shown that TBI causes a ''metabolic crisis'' in the injured brain, suggesting that a reduction in glucose availability may exacerbate brain damage. We therefore examined the consequences of hyperglycemia on cognitive and pathological measures. Using a rodent model of TBI, we find that when acute hyperglycemia is induced in animals prior to injury, there is little to no change in motor and cognitive performance, contusion volume, or cerebral edema. To examine the consequences of persistent hyperglycemia (as seen in diabetic patients), animals were treated with streptozotocin (STZ) to induce type 1 diabetes. We find that the presence of persistent STZ-induced hyperglycemia results in a reduction of brain edema. Insulin therapy to reduce blood glucose reverses this beneficial effect of hyperglycemia. Taken together, our results indicate that an acute increase in blood glucose levels may not be harmful, and that intervention with insulin therapy to lower blood glucose levels in TBI patients may increase secondary brain damage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High Blood Glucose Does Not Adversely Affect Outcome in Moderately Brain-Injured Rodents

Hill

Zhao

Dash

2010

Journal of Neurotrauma

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“…No differences in neurological outcome or mortality rates were found in patients after severe traumatic brain injury (Bilotta et al, 2008;Coester et al, 2010). A trial in 483 patients undergoing elective or emergency brain surgery revealed that intensive insulin therapy significantly reduced the length of stay in the ICU (6 vs. 8 days), and the infection rate (25.7% vs. 39.3%) without a significant effect on neurological outcome or survival at 6 months (Bilotta et al, 2009). In the UK Glucose Insulin in Stroke Trial (GIST-UK) patients p r e s e n t i n g w i t h i n 2 4 h o u r s o f stroke onset were randomly assigned to receive glucosepotassium-insulin infusion aiming at a capillary glucose between 72-126 mg/dL or no glucose intervention (Gray et al, 2007).…”

Section: Intensive Insulin Therapy In Brain Injurymentioning

confidence: 99%

Hypoglycemia in Critically Ill Patients

Hoedemaekers¹,

Hoeven²

2011

Diabetes - Damages and Treatments

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“…The primary genesis of this approach stems from a 2001 randomized, controlled study that reported significant decreases in ICU and hospital mortality when blood glucose levels (BGLs) were maintained between 80 -100 mg/dL compared to a less aggressive level of 180 -200 mg/dL [19]. Subsequent enthusiasm for aggressive glucose management, however, has tempered as multiple groups attempting to replicate those results were unable to show comparable reductions in morbidity and mortality and have consistently observed high rates of hypoglycemia [20], [21], [22], [23], [24], [25]. Whether the lack of mortality benefit in these studies can be directly attributed to the high rates of hypoglycemia is uncertain.…”

Section: Introductionmentioning

confidence: 99%

Evaluation and Enhancement of an Intraoperative Insulin Infusion Protocol via In-Silico Simulation

Kohl

Chen

Mullen-Fortino

et al. 2013

2013 IEEE International Conference on Healthcare Informatics

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Intraoperative glycemic control, particularly in cardiac surgical patients, remains challenging. Patients with impaired insulin sensitivity and/or secretion (i.e., type 1 diabetes mellitus) often manifest extremely labile blood glucose measurements during periods of stress and inflammation. Most current insulin infusion protocols are developed based on clinical experiences and consensus among a local group of physicians. Recent advances in human glucose metabolism modeling have established a computer model that invokes algorithms representing many of the pathways involved in glucose dysregulation for patients with diabetes. In this study, we used an FDA approved glucose metabolism model to evaluate an existing institutional intraoperative insulin infusion protocol via closedloop simulation on the virtual diabetic population that comes with the computer model. A comparison of simulated responses to actual retrospective clinical data from 57 type 1 diabetic patients undergoing cardiac surgery managed by the institutional protocol was performed. We then designed a proportional-derivative controller that overcomes the weaknesses exhibited by our old protocol while preserving its strengths. In-silico evaluation results show that our proportionalderivative controller more effectively manages intraoperative hyperglycemia while simultaneously reducing hypoglycemia and glycemic variability. By performing insilico simulation on intraoperative glucose and insulin responses, robust and seemingly efficacious algorithms can be generated that warrant prospective evaluation in human subjects. KeywordsIntraoperative glycemic control, in-silico evaluation, proportional-derivative controller, insulin infusion protocol, computer model Abstract-Intraoperative glycemic control, particularly in cardiac surgical patients, remains challenging. Patients with impaired insulin sensitivity and/or secretion (i.e., type 1 diabetes mellitus) often manifest extremely labile blood glucose measurements during periods of stress and inflammation. Most current insulin infusion protocols are developed based on clinical experiences and consensus among a local group of physicians. Recent advances in human glucose metabolism modeling have established a computer model that invokes algorithms representing many of the pathways involved in glucose dysregulation for patients with diabetes. In this study, we used an FDA approved glucose metabolism model to evaluate an existing institutional intraoperative insulin infusion protocol via closedloop simulation on the virtual diabetic population that comes with the computer model. A comparison of simulated responses to actual retrospective clinical data from 57 type 1 diabetic patients undergoing cardiac surgery managed by the institutional protocol was performed. We then designed a proportional-derivative controller that overcomes the weaknesses exhibited by our old protocol while preserving its strengths. In-silico evaluation results show that our proportional-derivative controller more effectively manag...

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Safety and Efficacy of Intensive Insulin Therapy in Critical Neurosurgical Patients

Abstract: 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.

Cited by 142 publications

References 46 publications

High Blood Glucose Does Not Adversely Affect Outcome in Moderately Brain-Injured Rodents

High Blood Glucose Does Not Adversely Affect Outcome in Moderately Brain-Injured Rodents

Hypoglycemia in Critically Ill Patients

Evaluation and Enhancement of an Intraoperative Insulin Infusion Protocol via In-Silico Simulation

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