Intensive Insulin Therapy in Severely Burned Pediatric Patients

Abstract

Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. Objectives: To determine whether intensive insulin therapy is associated with improved post-burn morbidity. Methods: A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n 5 60) or control (n 5 179). Measurements and Main Results: Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acutephase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P , 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P , 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P , 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P , 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P 5 0.14). Conclusions: In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

“…An RCT of strict glycemic control compared to moderate control using insulin in a pediatric ICU population found a reduction in mortality with an increase in hypoglycemia. Insulin therapy should only be conducted with frequent glucose monitoring in view of the risks for hypoglycemia which can be greater in newborns and children due to a) relative lack of glycogen stores and muscle mass for gluconeogenesis, and b) the heterogeneity of the population with some excreting no endogenous insulin and others demonstrating high insulin levels and insulin resistance [622][623][624][625][626][627][628].…”

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

“…Although not limited to sepsis cases, several successively announced large‐scale RCTs484, 485, 486, 487 have assessed the significance of implementing strict glycemic management in critically‐ill children. Thus, investigating the importance of this type of intervention in patients with severe sepsis is considered to be an important task.…”

“…While four RCTs484, 485, 486, 487 targeting critically‐ill pediatric patients were adopted for a meta‐analysis of strict glycemic management (Srinivasan and Agus488), all four studies involved intensive care unit (ICU) patients other than sepsis patients, and no subgroup analysis limited to sepsis patients was reported.…”

Physiologic considerations of Enhanced Recovery After Surgery (ERAS) programs: implications of the stress response

“…The administration of high doses of insulin has been successful in attempting to normalize this catabolic state. 16 Several methods to measure insulin resistance have been proposed; however, the hyperinsulinemic-normoglycemic clamp (HNC) technique represents the gold standard procedure 17 whereby insulin is infused at a constant rate to obtain a steady-state insulin concentration above the fasting level. Based on frequent measurements of plasma glucose levels, glucose is intravenously infused at variable rates to maintain normoglycemia (4-6 mmolÁL -1 ).…”