Critical care of thermally injured patient

Introduction

Only a minority of burn injured patients will require intensive care unit (ICU) admission and treatment. A burn is considered “major” when involving more than 20% BSA, with further severity steps at 40% and 60% TBSA, the later being called massive burn injury. The presence of inhalation injury will have further additive affects increasing the mortality. Major burns impact the function of all organs: the massive release of pro-inflammatory mediators and lipid peroxides by the thermally injured skin will induce oxidative stress and inflammatory responses, which in turn cause cardiovascular, respiratory, digestive, renal, endocrine, and metabolic alterations. All these responses are proportional to the severity of the injury. Age and presence of co-morbidities are important prognostic factors, even more than in any other critical care condition. The massively burned patient poses one of the greatest challenges in critical care. While patients with severe thermal injury share several characteristics with other critically ill patients, there are significant differences:

a.The patients suffer significant cutaneous exudative losses (proportional to the TBSA) of fluids containing large quantities of proteins, minerals and micronutrients. The electrolyte derangements will require close monitoring, and the loss of micronutrients will be large enough to cause acute deficiency syndromes.

Marc G. Jeschke et al. (eds.), Handbook of Burns

b.The body surface area injured and requiring repair is extensive. It frequently exceeds 1 m2, which poses an enormous anabolic challenge.

c.There is an increased infectious risk due to the loss of the skin barrier, but also to the rapid depression of humoral and cellular immune defences [94].

d.The duration of inflammatory and hyper-metab- olic response is immediate and long lasting and has no comparison with other conditions.

e.Venous access is more difficult due to the destruction of the skin at the puncture sites causing higher catheter related infection rates.

f.The thermally injured patient requires longer length of stay in the ICU compared with other trauma patients, and require more prolonged nutritional support.

Oxidative stress and Inflammation

The inflammatory response constitutes an organized defense mechanism aimed at protecting the body from further damage, restoring homeostasis and promoting wound repair. This includes a local reaction to injury, a systemic response (=SIRS: tachycardia, tachypnea, fever, leucocytosis), massive cytokine production, immense immune and endocrine changes, increased protein catabolism, and a reprioritization of hepatic synthesis. This response to in-

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jury includes a redistribution of the micronutrients (trace elements and vitamins) from the vascular compartment to organs with high rates of cell replication and metabolic activity. Cytokine production is strongly enhanced after major burns, the balance between pro-inflammatory and anti-inflammatory mediators in acute injury is lost [24]: the phenomenon further increases infectious complications. The intensity of this reaction is correlated with mortality [66]. Although inflammation is perceived as beneficial, its persistence for prolonged periods of time causes progressive loss of lean body cell mass, particularly of skeletal muscle, and an increased susceptibility to infection. It will favor development of organ dysfunction and failure.

Major thermal injury and the subsequent inflammatory response cause a massive production of free radicals (molecules containing one or more unpaired electrons with high oxidant reactivity). These can be divided into two major groups: the reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS are produced primarily by the mitochondrial respiratory chain, and by the activated leukocytes. It is a normal phenomenon in bacterial destruction, and cell signaling. In the case of burns an intense lipid peroxidation results partially from the direct effect of the burn injury on the lipids contained in skin, but mainly from the increased ROS production. Nitric oxide (NO) derived from the endothelium, has emerged as a fundamental regulatory signal, as well as a potent mediator of cellular damage. Most of the cytotoxicity attributed to NO is due to peroxynitrite, a RNS, produced from the reaction between NO and the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. The initial intense oxidative stress will persist for several days, and is reactivated by each septic episode.

The intensity and the duration of the inflammatory response in major burns are immense [89], and will result in the continued production of pro-in- flammatory cytokines for several weeks. The associated free radical production and oxidative stress will persist accordingly.

In healthy subjects, the endogenous antioxidant defense mechanisms are sufficient to cope with moderate free radical overproduction. In major

burns, these defenses are overwhelmed, leaving space for the deleterious effects of ROS, with proximity oxidation of nucleotides, proteins and lipids. The endogenous antioxidant defenses become acutely depleted by the massive production of free radical species derived from both oxygen and nitric oxide, associated with enormous losses of antioxidant micronutrients through their wounds [16], and acute unavailability of the same antioxidant micronutrients in the circulating compartment.

The pro-inflammatory cytokines (particularly IL-6) are responsible for the redistribution of micronutrients (including those with antioxidant properties) from the circulating compartment to tissues and organs with high synthetic and cell replication activity. In an animal burn model, Ding et al. showed that the serum concentrations of zinc decreases while at the same time liver content increases in association with increased expression of metallothionein [32]. When this phenomenon is added to the large exudative trace element losses it is easily understandable that the circulating compartments antioxidant capacity becomes acutely reduced, while simultaneously facing a massive oxidative stress.

Oxidative stress control strategies

Several strategies have been proposed to control oxidative stress:

a.Mechanical removal of the source of oxidants with early wound scar excision to reduce the release of lipid peroxide: this strategy has been shown to reduce mortality.

b.Topical application of anti-inflammatory agents.

c.Systemic administration of antioxidants (initiated as early as possible after injury).

In animal studies of thermal injury, the supplementation of antioxidant vitamins reduce cardiac NF-kB release [48], while continuous high dose vitamin C infusion can increase plasma antioxidant potential, and limit the endothelial injury and capillary leak [34]. In patients large supra-physiological doses of Vitamin C administered over the first 24 hours reduce post-burn fluid requirement by about 30% [99]. In animals, selenium supplements limit the peroxidative damage caused by burns [1]. In adult patients, supplementation with trace elements, particularly with selenium, reduces the lipid peroxidation pro-