Optimal blood glucose control in severely burned patients: a long way to go, but one step closer

Over the past years there has been a significant decrease in mortality and morbidity in patients suffering from severe burns due to improved burn wound management and approaches in critical care. Survival is no longer the exception, but unfortunately death still occurs. One of the key elements concerning state-of-the-art burn care is blood glucose control and insulin therapy; it is well known that burn-induced hyperglycaemia is associated with adverse clinical outcomes. However, controversy for insulin therapy and tight glycaemic control in critically ill and burn patients exists. The increased incidence of hypoglycaemia is the dominant argument against this treatment, because hypoglycaemia is also associated with an increased risk for death in critically ill patients. Taking all current data together, insulin therapy appears both a friend and a foe in the treatment of ICU patients. In order to overcome the limits of tight glycaemic control resulting from hypoglycaemic episodes, current efforts have been directed towards the development of protocols allowing for implementation of clinically feasible and safe guidelines. Among the strategies addressing this problem are closed loop techniques, which are supported by studies demonstrating their capability of exerting tight glycaemic control without the risk of developing hypoglycaemic episodes. Although closed loop techniques have become readily available, we require further evidence to ensure their safety in various ICU environments, notably in ICUs dealing with burn patients. Nonetheless, it is important to emphasise that glycaemic control and adequate insulin therapy are crucial factors for the final outcome (survival) and require our attention.


Introduction
With great interest we have read the paper by Jeschke, providing a very helpful, current best-practice overview on blood glucose control in burned patients [1]. Blood glucose control is one of the key elements in critical burn care and treatment. Over the past years there has been a signifi cant decrease in mortality and morbidity in patients suff ering from severe burns due to improved burn wound management and approaches in critical care [2,3]. Survival is no longer the exception, but unfortunately death still occurs [2]. Hyperglycaemia is associated with adverse clinical outcomes; in particular, burned patients with poor glucose control had a signifi cantly higher incidence of bacteraemia/fungaemia, exhibited enhanced catabolism, and demonstrated increased mortality rates [4].
Insulin is not just a molecule mediating glucose control, but can act as a therapeutic agent per se. Recent studies showed that insulin improved muscle protein synthesis and therefore post-burn lean body mass [5]. Furthermore, insulin increased protein synthesis in the skin, accelerated wound healing [6,7], and had a massive impact on infl ammatory and acute phase responses [8]. Some of these metabolic infl uences were linked to cellular changes, improving intracellular hepatic ATP, glucose, and lactate levels post burn -all indicators for a positively balanced energy effi ciency. In addition, a burnsepsis two-hit model demonstrated improved survival resulting from insulin's tweaking not just of the metabolic system but also the immune system. In sum, insulin's benefi cial eff ects are procured on multiple levels, making it a fascinating agent in the treatment of burn patients.
However, controversy exists for insulin therapy and tight glycaemic control in critically ill and burn patients. Th e increased incidence of hypoglycaemia is the dominant argument against it, which is supported by a majority of related studies in the fi eld. A recent retrospective study reported the relationship between mild (<81 mg/dl) to severe (<40 mg/dl) hypoglycaemic episodes and death, and found in patients with hypoglycaemic episodes that mortality was 36.6% compared with 19.7% in those who did not experience

Abstract
Over the past years there has been a signifi cant decrease in mortality and morbidity in patients suff ering from severe burns due to improved burn wound management and approaches in critical care. Survival is no longer the exception, but unfortunately death still occurs. One of the key elements concerning state-of-the-art burn care is blood glucose control and insulin therapy; it is well known that burninduced hyperglycaemia is associated with adverse clinical outcomes. However, controversy for insulin therapy and tight glycaemic control in critically ill and burn patients exists. The increased incidence of hypoglycaemia is the dominant argument against this treatment, because hypoglycaemia is also associated with an increased risk for death in critically ill patients. Taking all current data together, insulin therapy appears both a friend and a foe in the treatment of ICU patients. In order to overcome the limits of tight glycaemic control resulting from hypoglycaemic episodes, current eff orts have been directed towards the development of protocols allowing for implementation of clinically feasible and safe guidelines. Among the strategies addressing this problem are closed loop techniques, which are supported by studies demonstrating their capability of exerting tight glycaemic control without the risk of developing hypoglycaemic episodes. Although closed loop techniques have become readily available, we require further evidence to ensure their safety in various ICU environments, notably in ICUs dealing with burn patients. Nonetheless, it is important to emphasise that glycaemic control and adequate insulin therapy are crucial factors for the fi nal outcome (survival) and require our attention.
hypogly caemia [9]. Despite the lack of evidence for a causal relationship, the NICE SUGAR trial group also proved hypoglycaemia to be associated with an increased risk for death in critically ill patients [10]. Taking all current data together, insulin therapy appears both a friend and a foe in the treatment of ICU patients [11].
To overcome the limits of tight glycaemic control resulting from hypoglycaemic episodes, current eff orts have been directed towards the development of protocols allowing for implementation of clinically feasible and safe guidelines [11]. Among the strategies addressing this problem are closed loop techniques [12][13][14], which are supported by studies demonstrating their capability of exerting tight glycaemic control without the risk of develop ing hypoglycaemic episodes. Although closed loop techniques have become readily available, we require further evidence to ensure their safety in various ICU environments, notably in ICUs dealing with burn patients.
With regard to optimal blood glucose levels, Jeschke evoked blood glucose levels of 130 mg/dl to be an ideal target [1]. Th is target reduces the risk for developing hypo glycaemic states as well as avoiding protein glycolysation at levels ≥150 mg/dl, which is in agreement with current sepsis guidelines and is supported by various meta-analyses.
Because of the raised awareness of hypoglycaemia being an unwanted side eff ect of tight glycaemic control, current guidelines for the treatment of either critically ill, septic, trauma, or burn patients have been calling for less strict glucose control regimes supporting blood levels of 130 to 150 mg/dl [15]. Interestingly, burn patients have a higher incidence of hypoglycaemic events as compared with other patient populations, which is predominantly related to the special nature of the injury triggering a cascade of catabolic events. In addition, burn patients pose many diffi culties in maintaining adequate tight glycaemic ranges resulting from feeding interruptions and variability in gastrointestinal tolerance. Owing to the require ment for almost weekly operations and daily dressing changes, enteral nutrition needs to be stopped occasionally -further disrupting the gastrointestinal motility, and complicating adjustments [15]. Furthermore, hyperbaric oxygen, which has been advocated as an adjuvant treatment option in burn care, has also been shown to increase peripheral sensitivity to insulin [16].
In conclusion, it is important to emphasise that glycaemic control and adequate insulin therapy are crucial factors that require our attention for improving the outcome of severely burned patients in the future. At the same time, we must consider the use of management strategies minimising the risk of triggering iatrogenic hypo gly caemic events. A glucose range of 90 to 140 mg/ dl there fore seems ideal for treating burn patients.