Pathophysiologic Response to Severe Burn Injury

Abstract

Objective To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial. Summary Background Data A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated. Methods Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course. Results Average age was 8 ± 0.2 years, and average burn size was 56 ± 1% TBSA with 43 ± 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (−0.05% ± 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (−4.1% ± 1.9%); P < 0.05. Patients lost 3% ± 1% of their bone mineral content (BMC) and 2 ± 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 ± 0.2 infections and 17% sepsis. Conclusions In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn response is profound, occurring in a timely manner, with derangements that are greater and more protracted than previously thought.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

“…Serum AST, ALT, and ALKP are elevated between 50% to 200% from baseline when compared with normal levels (Figure 2). Jeschke et al (16,26) observed that serum AST and ALT peaked during the first day postburn and ALKP during the second day postburn. During hepatic regeneration, all enzymes returned to baseline during acute hospitalization.…”

“…These responses are present in all trauma, surgical, or critically ill patients, but the severity, length, and magnitude is unique for burn patients (7). Marked and sustained increases in catecholamine, glucocorticoid, glucagon, and dopamine secretion are thought to initiate the cascade of events leading to the acute hypermetabolic response with its ensuing catabolic state (7,8,26,(61)(62)(63) (Figure 4). The cause of this complex response is not well understood.…”

“…Albumin is the most abundant serum protein, its synthesis accounting for 11% to 15% of total hepatic synthesis. Synthesis of albumin is influenced by nutrition, thyroxin, insulin, glucagons, cortisol, and cytokines produced during the systemic inflammatory response (16,26).…”

Toll-Like Receptor Signaling in Burn Wound Healing and Scarring

“…34 The inflammatory cascade is initiated in the wound as signals, including DAMPs, ignite local inflammation. The inflammation, as well as damaged and clogged blood vessels, cause local edema, increased hydrodynamic pressure, I/R injury, and redox imbalance, which contribute to local spreading of tissue damage (burn injury progression) and an immune response that can spillover into the circulation to result in systemwide capillary leak, edema, and the release of large amounts of oxygen and nitrogen radical species.…”

Morphological Changes in the Rats’ Myocardium under the Conditions of Infusion Correction of the Experimental Burning Disease

“…Велика опікова травма викликає суттєві гемодинамічні та кардіодинамічні порушення, які сприяють розвитку сепсису, поліорганної недостат-ності та смерті. Кардіогенний стрес є відмінною ознакою гострої фази відповіді, а гірші результати лікування опікового пошкодження пов'язані саме з важкою серцевою дисфункцією [2,3,6]. Скомпро-метована серцева функція призводить до гіпопер-фузії органів, порушення периферичної мікроцир-куляції, збільшення зони опіку та зниження резис-тентності до бактеріальної інфекції в ділянці опіко-вої поверхні [2].…”