Burn injury

Abstract

Burn injuries are under-appreciated injuries that are associated with substantial morbidity and mortality. Burn injuries, particularly severe burns, are accompanied by an immune and inflammatory response, metabolic changes and distributive shock that can be challenging to manage and can lead to multiple organ failure. Of great importance is that the injury affects not only the physical health, but also the mental health and quality of life of the patient. Accordingly, patients with burn injury cannot be considered recovered when the wounds have healed; instead, burn injury leads to long-term profound alterations that must be addressed to optimize quality of life. Burn care providers are, therefore, faced with a plethora of challenges including acute and critical care management, long-term care and rehabilitation. The aim of this Primer is not only to give an overview and update about burn care, but also to raise awareness of the ongoing challenges and stigmata associated with burn injuries.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Burn depth.

Burn depth is an important factor in assessing patient care needs and, in particular, surgical needs; in general, the deeper the burn the more challenges there are to achieve good scar outcomes. First-degree (superficial thickness, affecting the epidermis only) burns are typically benign, very painful, heal without scarring and do not require surgery. Burns extending into the underlying skin layer (dermis) are classed as partial thickness or second-degree; these burns frequently form painful blisters. These burns range from superficial partial thickness, which are homogeneous, moist, hyperaemic and blanch, to deep partial thickness, which are less sensate, drier, may have a reticular pattern to the erythema and do not blanch. Third-degree (full thickness) and fourth-degree burns require surgery and, paradoxically, usually present with almost no pain.

Fig. 2. Four phases of natural wound healing.

Haemostasis occurs immediately after the injury and involves vasoconstriction, platelet activation and aggregation, and release of clotting and growth factors (such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and transforming growth factor-β (TGFβ)) by platelets, keratinocytes, macrophages and fibroblasts, resulting in fibrin clot deposition at the injury site, which serves as a provisional matrix for subsequent stages of healing. Monocytes (and macrophages) and neutrophils are recruited to the injury site owing to localized vasodilation and initiate the inflammation phase. Inflammation begins within 24 hours of the injury and lasts for weeks to months depending on the severity of injury. Neutrophils and macrophages release cytokines and chemokines (including IL-1, IL-8 and tumour necrosis factor (TNF)) and growth factors (including TGFβ, insulin-like growth factor (IGF) and vascular endothelial growth factor (VEGF)), and remove debris and pathogens from the injury site. The next phase, proliferation, involves the recruitment and activation of fibroblasts and keratinocytes to the wound site. Proliferation is characterized by replacement of the provisional matrix with a connective tissue matrix, granulation (new connective tissue and microscopic blood vessels), angiogenesis and epithelialization. Keratinocytes assist in both epithelialization (wound surface closure) and angiogenesis (restoration of blood flow), which are vital to wound healing. Endothelial cells are activated by growth factors (VEGF, hepatocyte growth factor (HGF) and fibroblast growth factors (FGFs)) to initiate angiogenesis. Resident fibroblasts are transformed to myofibroblasts, which are involved in extracellular matrix (ECM) deposition. In the final phase, remodelling, granulation tissue matures and the ECM is remodelled under the influence of growth factors, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), which leads to increased tensile strength. The length of healing depends on multiple factors including the injury severity, inflammatory cascade activation and nutrition. IFN, interferon.

Fig. 3. Hypermetabolic state in burn injury.

Severe burn injury induces a unique and remarkably complex response that involves the release of stress hormones and pro-inflammatory mediators. The immediate response leads to a hypometabolic response that lasts for ~72–96 hours (ebb phase), but then rapidly turns into the flow phase that can persist for years after the initial injury. Stress mediators, such as catecholamines, glucocorticoids and cytokines, are released into the system and cause a plethora of systemic responses. The heart goes into a hyperdynamic overdrive, increasing circulation and blood flow to increase oxygen and nutrient delivery. However, increased stress signalling causes changes in organ function and metabolic demand. Protein is degraded to deliver energy for hepatic function, the gut develops mucosal atrophy to absorb more nutrients but also enabling bacterial translocation. The kidneys are hyperperfused but oxygen delivery is decreased, leading to acute kidney injury and stress signals from the kidney. The interplay between these organs accumulates, leading to metabolic and inflammatory overdrive that subsequently causes white adipose tissue to change to brown adipose tissue. Brown adipose tissue releases energy and induces substantial lipolysis with the accompanying expression of lipotoxic intermediates, such as triglycerides, free fatty acids and diacylglycerols (DAG), all of which are transferred to the liver. The liver is unable to metabolize all of the accumulating substances and develops hepatomegaly. In turn, hyperlipidaemia and hyperglycaemia with insulin resistance is present, which worsens the hypermetabolic and inflammatory state. If hypermetabolism cannot be diminished or decreased, holistic catabolism ensues and, subsequently, multiple organ failure and death. CNS, central nervous system.

Fig. 4. Events leading to sepsis and multiple organ failure following burn injury.

Tissue injury following severe burns results in release of endogenous damage-associated molecular patterns (DAMPs) such as mitochondrial DNA and double-stranded RNA (dsRNA), which along with exogenous pathogen-associated molecular pattern molecules (PAMPs) such as lipopolysaccharides (LPS) and peptidoglycans, can induce vascular leak, an inflammatory response and metabolic changes. Vascular leak and transfer of intravascular fluid to third spaces leads to tissue oedema and further injury. The inflammatory response can result in immunosuppression and ineffective response to bacterial invasion. Metabolic changes include increased muscle protein degradation, insulin resistance and increased cardiac load. The culmination of these events is often systemic inflammatory response syndrome (SIRS), an inflammatory state affecting the whole body, which can lead to multiple organ failure, and ultimately, death. MHC, major histocompatibility complex; PGE2, prostaglandin E2; TNF, tumour necrosis factor. Adapted from ref., Springer Nature Limited.

Fig. 5. The Haddon Matrix for burn prevention.

The Haddon Matrix is a means of understanding traumatic injury that examines aetiological relationships instead of using descriptive terms. This approach is essential to transition from the concept of burn injury as an ‘accident’ that is unpreventable, to the concept of injury being related to factors that can be modified. For example, we shift the concept from a child ‘accidentally’ turning on the hot water in a bathtub, to an unsupervised (change supervision) child turning on the hot water (control the water temperature at the boiler, or with a mixing valve). In using this approach, it is important not to assign blame, but to recognize the resources needed or factors that influence the cause of the traumatic event. For example, by examining the reasons why the child was unsupervised (parental mental health, other young siblings in the family, overstretched parents) and how to control the hot water (turn down the water heater, child-proof lockable tap, preset water temperature at the tap), programmes can be established to address them.

Fig. 6. Lund and Browder diagrams for estimating burn size in terms of TBSA.

In adults, the ‘Rule of Nines’ (that is, using multiples of 9) is used to assess the proportion of the total body surface area (TBSA) affected and to help guide immediate treatment decisions, such as amount of fluid resuscitation, that are based on the size of the burn injury. However, owing to different head to body size ratios, the proportion of the TBSA affected in children is estimated differently; the Rule of Nines is inaccurate. Another challenge is the body habitus. For example, the Rule of Nines and the estimate that each hand comprises 1% of the TBSA are inaccurate in patients who have obesity or cachexia. The body areas are separated by colour and the numbers are percentages of the TBSA and include front and back coverage; for example, ‘32’ in the diagram of the trunk relates to the chest, abdomen and back that make up 32% of the TBSA. The hand, including the palm, fingers and back of the hand, represents 2% of the TBSA and can be a useful tool for quick calculation of the size of a burn — especially irregularly shaped scald burns.

Fig. 7. The phases of burn care.

Acute care for severe burns can be compartmentalized into five distinct phases that overlap during the first days to weeks after burn injury. Phase I is the initial assessment and triage, in which the injurious cause is removed and the primary and secondary surveys are conducted. Phase II is focused on fluid resuscitation to address hypovolaemia. In phase III, the wound is covered to promote healing and reduce infection risk. Phase IV focuses on supportive or critical care. If the patient survives, phase V of care focuses on rehabilitation, which includes physical and mental health support to enable the patient in returning to regular life. IV, intravenous; TBSA, total body surface area.

Fig. 8. Autologous split-thickness skin grafts.

For a patient with a severe burn injury to survive, the burn wounds need to be excised and covered. Temporary measures using allograft or various biological substitutes are available but, at this time only the patient’s skin (autologous) can permanently accomplish coverage. Several graft methods are available to cover burn wounds using autologous skin. a | Sheet grafts are the most aesthetically pleasing but require a lot of skin to cover wounds and, therefore, are usually reserved for small burns or for skin grafts to complex and important areas such as the face, hands and breasts. Full-thickness sheet grafts are reserved for smaller defects (usually lower eyelids and re-occurring upper eyelids) and play a more important part during the reconstructive phase. These are harvested using a dermatome. A split-thickness graft can be placed as a sheet graft or used for meshing. b | Use of meshed split thickness skin grafts is usually the method of choice to cover larger areas. The goal of meshing skin is to expand the donor skin to obtain greater coverage; skin can be meshed in ratios of 1:1.5, 1:2, 1:3, 1:4 or 1:6. Although increased meshing increases the coverage size, meshed skin becomes increasingly fragile. c | An alternative technique is the Meek technique, in which skin squares can be spread out to a large extent and added to the wound bed, covering large areas (up to a ratio of 1:9). This technology is reserved for extensive burns for which donor sites are sparse. d | A freshly meshed split-thickness skin graft (left) and its healing over time (right). Images in part c courtesy of R. Nijlant, Humeca B.V., Netherlands.

Fig. 9. Skin substitutes.

Skin substitutes have undergone development over the past decade from temporary materials used to induce wound healing towards permanent tissue-engineered materials that offer definitive healing. This figures reflects a summary of some promising skin substitutes or treatments to induce wound regeneration. a | The common principle of skin substitutes is to the deliver proteins, growth factors and/or cells via a delivery vehicle or matrix that will then be integrated into the wound and form new autologous skin. b | ReCell is not a composite skin substitute, but a device that sprays a cell suspension of skin cells including epithelial cells, fibroblasts melanocytes and other resident cells onto the wound or grafted area to improve healing and scarring. c | The skin gun (RenovaCare) delivers autologous cells and/or stem cells to wounds to improve wound healing. Although this is a promising approach, no clinical trials or substantial evidence have been reported that indicate that the skin gun will enter the clinical arena. d | Recently, a hand-held device has been designed that can print 3D autologous skin. This device is based on microfluidic technology and can deliver cells specifically and accurately in an ‘ink’, which serves as a matrix. e | A skin substitute using autologous cells from a healthy donor and a matrix shows self-assembly of dermal and epidermal structures. Although the ideal tissue-engineered skin derivative has not been described, this technology will change the way burn care is delivered and will improve acute and long-term outcomes. Image in part b courtesy of Avita Medical. Image in part c courtesy of RenovaCare Inc. Part d provided by A. Guenther (University of Toronto, Canada), and adapted with permission from ref., Royal Society of Chemistry. Panel e is reprinted from ref., CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).