A Critical Update of the Assessment and Acute Management of Patients with Severe Burns

Abstract

Significance: Burns are debilitating, life threatening, and difficult to assess and manage. Recent advances in assessment and management have occurred since a comprehensive review of the care of patients with severe burns was last published, which may influence research and clinical practice. Recent Advances: Recent advances have occurred in the understanding of burn pathophysiology, which has led to the identification of potential biomarkers of burn severity, such as protein C. There is new evidence about the potential superiority of natural colloids over crystalloids during fluid resuscitation, and new evidence about components of initial and perioperative management, including an improved understanding of pain following burns. Critical Issues: The limitations of the clinical examination highlight the need for imaging and biomarkers to assist in estimations of burn severity. Fluid resuscitation reduces mortality, although there is conjecture over the ideal method. The subsequent perioperative period is associated with significant morbidity and the evidence for preventing and treating pain, infection, and fluid overload while maximizing wound healing potential is described. Future Directions: Promising developments are ongoing in imaging technology, histopathology, biomarkers, and wound healing adjuncts such as hyperbaric oxygen therapy, topical negative pressure therapy, stem cell treatments, and skin substitutes. The greatest benefit from further research on management of patients with burns would most likely be derived from the elucidation of optimal fluid resuscitation protocols, pain management protocols, and surgical techniques from randomized controlled trials.

Keywords: acute care; biomarker; burns; healing; inflammation; perioperative care.

Thomas Charles Lang, MBBS, BAppSc (Phty)

Figure 1.

Severe burns. The patient is a 52-year-old male with 33% TBSA flame burns to the back, chest, abdomen, lower limbs, and hands, which were predominantly partial thickness. These photos were taken on admission to hospital. He received a mean daily intravenous fluid volume of 3.3 L over the first 72 h, underwent three procedures for excision and grafting, and remained in hospital for 14 days with a length of stay in ICU of 6 days. ICU, intensive care unit; TBSA, total body surface area.

Figure 2.

Severe burns. The patient is a 61-year-old female with 12% TBSA flame burns to the back and upper arm, which were predominantly partial thickness. The upper two photos were taken on admission. The burns on the upper arm were excised and grafted the day after admission and again a week later. The lower two photos were taken 2 weeks after admission. She underwent three excision and grafting procedures, and remained in hospital for 21 days, two of which were spent in ICU.

Figure 3.

Severe burns. The patient is a 20-year-old male with 18% TBSA superficial partial-thickness burns, primarily to the lower limbs. The circumferential burns were initially managed with fasciotomies and this photograph was taken on day 3 of admission. He underwent three excision and grafting procedures and remained in hospital for 10 days.

Figure 4.

The immune response in severe burns. The immune response to a severe burn is widespread, poorly regulated, and prolonged. It is affected by massive fluid shifts due to increased vascular permeability as well as hemoconcentration and dysfunction of the coagulation system (not shown), which is closely linked to inflammatory dysfunction. Significant tissue injury causes the release of cytokines and chemokines from the endothelium, which activates proinflammatory effector cells to the site of injury. There is also upregulation and differentiation of T cells in the thymus, lymph nodes, and other locations, such as the skin. These T cells release a variety of chemokines and cytokines to draw effector cells to the site of injury, some of which are proinflammatory, and some of which are anti-inflammatory. All of the components in the diagram have been measured in animals or patients with severe burns or systemic inflammation, and excessive or suppressed activity levels of some of these components are associated with poor outcomes following a burn injury (please see Excessive inflammation for more details). γδ T cells, gamma delta T cells; B, B cell; CRP, C-reactive protein; GM-CSF, granulocyte–macrophage colony-stimulating factor; IFN-γ, interferon gamma; IL, interleukin; M, macrophage (M1 and M2 are subtypes of macrophage); MCP-1, monocyte chemoattractant protein-1; MIP-1β, macrophage inflammatory protein-1 beta (also known as chemokine [C-C motif] ligand 4); Mo, monocyte; N, neutrophil; NK cell, natural killer cell; TGFβ, transforming growth factor beta; Th, T-helper cell (Th0, Th1, Th2, and Th17 are T-helper cell subtypes); TNF-α, tumor necrosis factor alpha; Treg, regulatory T cell. Figure was produced using Servier Medical Art.

Figure 5.

Proposed functions of the PC system in severe burns. PC is attached to the endothelial surface by endothelial PC receptor (not shown) and is cleaved by thrombin in response to tissue injury to produce APC. APC acts at the site of injury to manage the consequences of tissue damage and also has systemic effects on anticoagulation. APC is proposed to influence certain T cell subtypes such as the gamma delta T cell to influence modulation of the inflammatory response. APC, activated protein C; PC, protein C. Figure was produced using Servier Medical Art.

Figure 6.

Fluid compartments and intravenous fluid resuscitation in severe burns. The human body is 60% water by weight and contains two virtual fluid compartments: the intracellular compartment and the extracellular compartment. The intracellular compartment holds 55% of body fluid and exists within all 10¹⁴ human cells, which make up tissues contained within muscle, skin, and solid organs. Fluid movement between the intracellular compartment and the extracellular compartment is tightly regulated by the semipermeable cell membrane and its ion channels and pumps. The extracellular compartment holds 45% of body fluid and is comprised of the interstitial compartment, and the intravascular compartment, as well as the water of dense connective tissue, bone, and transcellular fluid. Fluid resuscitation of a patient with burns directly affects the volume of the intravascuar, interstitial and the intracellular compartments. The interstitial compartment makes up 80% of the extracellular fluid and exists solely within the space between cells, while the intravascular compartment holds 7.5% of the extracellular fluid and exists solely within the vascular system. Fluid movement between the intravascular and interstitial space occurs through the capillary wall, which has increased permeability after a burn. The main goal of intravenous fluid resuscitation after a burn is to maintain tissue perfusion and this is thought to be achieved by maintaining a full intravascular compartment while avoiding overfilling of the interstitial compartment. Figure was produced using Servier Medical Art.

Figure 7.

Nociception in severe burns. Local and systemic inflammation characterized by vascular release of lipid agonists and release of cytokines by immune cells cells is associated with activation of TRPV1 and TRPA1 in peripheral nociceptive neurons. These first-order neurons synapse with second-order neurons in the dorsal horn of the spinal cord, which synapse with ascending neurons within the spinothalamic tract. These neurons are sensitized by astrocytes and microglia. The spinothalamic neurons terminate in the thalamus then synapse to neurons which travel to the somatosensory cortex. The transmission of nociceptive stimuli to the cortex is modulated by descending inhibitory neurons (not shown). TRPA1, transient receptor potential cation channel subfamily A member 1; TRPV1, transient receptor potential cation channel subfamily V member 1. Figure was produced using Servier Medical Art.

Figure 8.

Opioid analgesia, tolerance, and hyperalgesia. During early treatment, opioids such as fentanyl and morphine bind to their opioid receptors in the cell wall of peripheral and central neurons. The opioid receptor is coupled with G proteins, which are composed of Gαβγ subunits. These subunits inhibit calcium channels and activate potassium channels leading to hyperpolarization of the neuronal membrane. The subunits also inhibit downstream AC enzymes, which decreases cyclic adenosine monophosphate levels. In the short term, these events reduce excitability and nociception and result in analgesic effects through decreased activation of the higher pain centers. However, after repeated exposure, particularly to morphine, opioid receptors become a substrate for G-protein–coupled receptor kinase (GRK), which leads to recruitment and binding of β-arrestin protein to the receptor. The opioid receptors are then less responsive to opioids and are degraded, leading to lower numbers of less-responsive opioid receptors, therefore increased doses are required to achieve the same effect on pain. Important intracellular events associated with this phenomenon in patients with burns include increased activity of AC (which increases cyclic adenosine monophosphate levels), increased phosphorylation by protein kinases (PK) and upregulation of N-methyl-_D-aspartate (NMDA) receptors. AC, adenylate cyclase. Figure based on an illustration from Martyn et al. Figure produced using Servier Medical Art.

Figure 9.

NSAID analgesia. NSAIDs bind to, and inhibit intracellular COX-2 and COX-1 (not shown). Their analgesic effect comes primarily from inhibition of COX-2. Inhibited COX-2 cannot convert arachidonic acid, which is derived from the cell membrane phospholipids, to prostaglandins such as prostacyclin. This leads to reduced vasodilatation and edema and reduced inflammation and activation of nociceptors, which is excessive in patients with severe burns. This is the primary mechanism of analgesia in NSAIDs, however, animal models have also shown non-COX-mediated analgesic mechanisms from NSAIDs within microglia. These include activation of PPAR-γ-RXR complex and inhibition of NFκB, which together lead to reduced transcription of proinflammatory intermediates. COX, cyclo-oxygenase; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; NSAID, nonsteroidal anti-inflammatory drug; PPAR-γ, peroxisome proliferator-activated receptor-gamma; RXR, retinoid X receptor. Figure was produced using Servier Medical Art.