Clinical study on local application of low-dose insulin for promoting wound healing after operation for deep burns

Abstract

Transplanted free skin flaps are often needed to treat deep burns; their survival, however, is less than optimal. This study examined whether local low-dose insulin injections can promote flap survival and wound healing after surgery. A total of 165 patients who underwent free skin flap transplantation for simple deep burns were enrolled in the study and divided into 5 groups of 33 patients each: Blank control group (no local subcutaneous drug injections), saline control group (saline injections), low-dose insulin group (0.5 units regular insulin injections), medium-dose group (1.0 units regular insulin injections) and high-dose group (2.0 units regular insulin injections). Wound healing and flap survival conditions were assessed and compared among groups. The best wound healing rate found was that of the low-dose insulin injection group where all the parameters measured improved significantly: The healing time was shorter; the blood flow volume, the flap survival, the number of fibroblasts and new vessels increased; the re-epithelialization occurred faster; the infiltration of inflammatory cells was reduced; the expression levels of heat shock protein-90, vascular endothelial growth factor, transforming growth factor-β and interleukin-1 were higher; and the plasma glucose levels only fluctuated slightly. The results clearly demonstrate that a local low-dose insulin regime after flap transplantation can accelerate the healing time and improve the surgical outcome without exerting detrimental secondary effects on the glucose plasma level of deep burn patients.

Localised insulin administration for wound healing in non‐diabetic adults: A systematic review and meta‐analysis of randomised controlled trials

“…20,21,23,25 This was due to the fifth study using a different parameter to explore the rate of healing-percentage at Days 7 and 14 instead of mm 2 /day. 26 Despite omission, the study showed a statistically significant difference favouring the insulin groups, where p < 0.001 at both Days 7 and 14. Table 3 displays the mean rate of healing for each study with the standard deviation and p-value.…”

“…The seven RCTs included in this review were published between August 2009 and November 2021. [20][21][22][23][24][25][26] These were undertaken in either of the following countries: China, Egypt, India or Iran. Four of the seven studies had a two-armed RCT design, where the therapeutic group explored insulin as a treatment for wound healing and the control group had a standard saline placebo.…”

“…Five studies assessed the primary outcome of exploring the rate of healing in wounds due to insulin intervention. 20,21,23,25,26 However, only four were included in the quantitative analysis as shown in Table 3. 20,21,23,25 This was due to the fifth study using a different parameter to explore the rate of healing-percentage at Days 7 and 14 instead of mm 2 /day.…”

“…As shown, 70% of studies had an unclear risk of bias arising from the randomisation process. 20,21,[24][25][26] This was primarily due to no information given in the studies regarding the randomisation of allocation sequence and/or the concealment of allocation sequence until participants were enrolled and assigned to interventions. For the other domains in the RoB 2 tool, the studies were judged as having a low risk of bias.…”

Anabolic and anticatabolic agents used in burn care: What is known and what is yet to be learned

“…(124)(125)(126)(127) In the context of hypermetabolism secondary to severe burns, insulin seems to be an effective and safe anabolic agent for burn patients for several reasons: (1) it is less expensive than rhGH or IGF-1, (2) its side effect profile is well established and is limited primarily to hypoglycemia, (3) it seems to improve outcome by decreasing serum glucose levels and (4) it apparently enhances wound healing, both systemically and locally administered. (128)(129)(130)(131)(132) It is widely used in critically ill adult and pediatric patients that require glycemic control. From an anabolic perspective, the risk of causing hypoglycemia in a normoglycemic patient must be taken into consideration.…”