Biomarkers in Burn Patient Care

Introduction

Each year, more than 8 million people are burned. Approximately 1 million sustain severe burn injuries covering more than 30% of the total body surface area (TBSA). Burns cause considerable morbidity and mortality; burn injuries are often complicated by inhalation injury, infections, and sepsis, all of which can lead to systemic inflammation, acute respiratory distress syndrome (ARDS), multiple organ dysfunction (MODS), and death. Despite advances in critical care and resuscitation, infections develop and lead to sepsis in 40–60% of burn patients. The ability to prospectively identify or monitor organ function, infections, clinical trajectory, or patient outcome in severely burned patients would enable early intervention, reduce morbidity and mortality, and significantly lower the cost of clinical care. In recent years, biomarkers ranging from single proteins (e.g., procalcitonin, interleukin-8 [IL-8]) to the combination of variables (e.g., proteins, urinary markers, clinical parameters) have been used to predict or identify the risk of infection, sepsis, organ failure, or likelihood of survival, in patients with severe burns. The first 72 hours postinjury are critical for the prevention of complications, so the ability to use biomarkers to guide care during this period enhances our ability to improve patient care. We and others have identified candidate biomarkers that can be used to identify infection or sepsis, predict patient survival, reveal injury severity, or monitor organ function or wound healing. Biomarkers can take the form of single molecules, gene or protein families, injury characteristics, or clinical parameters. A good biomarker can be used for either diagnostic or prognostic purposes, be sensitive, specific, easy to measure, and reproducible. When applicable, the expression of the biomarker of interest can be modified by pharmacologic interventions, and this altered expression then monitored to determine impact on patient outcome.

Burn injury also affects long-term health and quality of life. With the many body systems that are impacted and negative sequelae that can result, the ability to predict patient outcomes or to determine whether therapy is efficacious would enable targeted therapies to improve patient outcomes. Here we review candidate biomarkers in burn patients for infections and sepsis, survival, inhalation injury, organ function, and wound healing.

Prediction of Sepsis and Infection

The expression of pro- and antiinflammatory cytokines is significantly altered following burn injury, and the concentration of these cytokines alone or with respect to each other (the expression profile) can be used to predict patient outcome. Characterization of the post-burn cytokine response shows an immediate spike in the expression of mediators such as IL-6 and IL-8, among others, that then slowly returns to levels detected in nonburned patients over the next several weeks to months. The cytokine expression profile at the time of admission and during the course of the hospital stay can predict which patients may develop sepsis or multiple organ failure (MOF). The expression of the following pro- and antiinflammatory cytokines has been linked to patient outcome: tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1β, IL-I7, IL-4, IL-6, and IL-8. Increased expression of inflammatory cytokines contributes significantly to the burn-induced hypermetabolic response and to the increased incidence of infection and sepsis. While initial studies focused on the correlation of single cytokines with patient outcomes, technologies allowing detection of multiple proteins at a single time enable the correlation of analyte expression profiles back to clinical trajectory or other outcome. The standard criteria for diagnosing sepsis in the critically ill are not used in the burn population due to overlap with the pathophysiological response to burn injury. Because the clinical presentation of sepsis in the burn patient is sufficiently unique, a burn-specific definition of sepsis was developed. Given the massive inflammatory, acute-phase, and coagulopathic responses induced by burn injury and the perturbations of these responses that occur with infection, there are many candidate biomarkers for the identification and/or prediction of sepsis and infection.