Emergency Treatment of Severely Burned Pediatric Patients: Current Therapeutic Strategies

Gerd G. Gauglitz; David N. Herndon; Marc G. Jeschke


Pediatr Health. 2008;2(6):761-775. 

In This Article

Glucose Control

One prominent component of the hypermetabolic response postburn is insulin resistance.[111] Stress-induced insulin resistance and its associated hyperglycemia results from both, an increase in hepatic gluconeogenesis and an impaired insulin-mediated glucose transport into skeletal muscle cardiac muscle, and adipose tissue,[112,113] leading to elevated blood glucose levels in association with normal or elevated serum insulin concentrations.[114,115] Both are of serious clinical concern, since hyperglycemia is frequently linked to impaired wound healing, increased number of infectious complications and increased incidence of mortality in those patients.[116,117,118] Thus, recent studies have focused on elucidating potential treatment options in order to overcome insulin resistance- induced hyperglycemia in the acute period following surgery or medical illness. A recent milestone single-center, randomized study including 1548 patients found that intensive insulin therapy decreased mortality in critically ill patients.[119] Insulin given at doses to maintain blood glucose below 110 mg/dl prevented the incidence of multiorgan failure and, thus, improved clinical outcome and rehabilitation.[119] It is worth noting that the impact of intervention increased with the duration of its application and that a substantial benefit was present with at least 3 days of intensive insulin therapy.[119] Besides saving lives, intensive insulin therapy has shown to prevent several critical illness-associated complications, including the development of critical illness polyneuropathy, blood stream infections, anemia, acute renal failure and hyperbilirubinemia.[119,120] A smaller prospective, randomized, controlled study performed in a predominantly general surgical patient population demonstrated decreased incidence of total nosocomial infections with intensive insulin therapy.[121] However, a recent multicenter, randomized, two-by-two factorial trial including 537 patients with severe sepsis found an increased risk for the development of hypoglycemic events and its associated consequences by a factor of 5-6 in this patient population.[122] Thus, clinical research is currently investigating alternative strategies in order to attenuate trauma-related hyperglycemia utilizing other glucose-lowering drugs that do not cause hypoglycemia as frequently as insulin. Metformin (glucophage), a biguanide, has recently been suggested as an alternative means to correct hyperglycemia in severely injured patients.[123] By inhibiting gluconeogenesis and augmenting peripheral insulin sensitivity, metformin directly counters the two main metabolic processes that underlie injury-induced hyperglycemia.[124,125,126] In addition, metformin has been rarely associated with hypoglycemic events, thus possibly eliminating this concern associated with the use of exogenous insulin.[127] Experience with metformin in burn patients is limited. In a small, randomized study reported by Gore and colleagues, metformin reduced plasma glucose concentration, decreased endogenous glucose production and accelerated glucose clearance in severely burned patients.[123] A follow-up study investigating the effects of metformin on muscle protein synthesis confirmed these observations, and demonstrated an increased fractional synthetic rate of muscle protein and improvement in net muscle protein balance in metformin-treated patients.[126] Therefore, metformin may - analogous to insulin - have efficacy in critically injured patients as both, an antihyperglycemic and muscle protein anabolic agent. Despite the advantages and potential therapeutic uses, treatment with metformin, or other biguanides, has been associated with lactic acidosis.[127,128] To avoid metformin-associated lactic acidosis, the use of this medication is contraindicated in certain diseases or illnesses in which there is a potential for impaired lactate elimination (hepatic or renal failure) or tissue hypoxia. However, several reports have questioned the causal relationship between metformin and lactic acidosis.[129,130,131] Several other trials investigating the decrease in postburn hyperglycemia include the use of glucagon-like-peptide-1 and PPAR-γ agonists (e.g., pioglitazone and thioglitazone) or the combination of various antidiabetic drugs.[132]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: