Use of procalcitonin for the detection of sepsis in the critically ill burn patient: A systematic review of the literature

Abstract

The purpose of this systematic review was to assess the evidence for use of routine procalcitonin testing to diagnose the presence of sepsis in the burn patient. The electronic databases MEDLINE, Cochrane, CINAHL, ProQuest, and SCOPUS were searched for relevant studies using the MeSH terms burn, infection, procalcitonin, and meta-analysis. The focus of the review was the adult burn population, but other relevant studies of critically ill patients were included as data specific to the patient with burns are limited. Studies were compiled in tabular form and critically appraised for quality and level of evidence. Four meta-analyses, one review of the literature, one randomized controlled trial, nine prospective observational, and three retrospective studies were retrieved. Six of these studies were specific to the burn population, with one specific to burned children. Only one meta-analysis, one adult burn and one pediatric burn study reported no benefit of procalcitonin testing to improve diagnosis of sepsis or differentiate sepsis from non-infectious systemic inflammatory response. The collective findings of the included studies demonstrated benefit of incorporating procalcitonin assay into clinical sepsis determination. Evaluation of the burn specific studies is limited by the use of guidelines to define sepsis and inconsistent results from the burn studies. Utility of the procalcitonin assay is limited due to the lack of availability of rapid, inexpensive tests. However, it appears procalcitonin assay is a safe and beneficial addition to the clinical diagnosis of sepsis in the burn intensive care unit.

Introduction

Severe burn frequently results in multiple organ dysfunction and sepsis [1]. The cause of death in 28–65% of fatal burn cases has been attributed to sepsis [2], [3]. Yet due to chronic baseline inflammatory response [4] and immune dysregulation [5] the traditional markers of acute infection are difficult to identify in the burn patient. Consensus definitions for sepsis in the critically ill population couple criteria for systemic inflammatory response syndrome (SIRS) with the documented presence of infection [6]. However, the SIRS criteria of more than one of the following clinical findings of temperature >38 °C or <36 °C; heart rate (HR) >90 beats/min; respiratory rate (RR) > 20/min or PaCO₂ <32 mmHg; or white blood cell count (WBC) >12,000 or <4,000 cells/μl are the norm for the hypermetabolic burn patient [7]. A consensus panel for the American Burn Association has developed specific guidelines for the diagnosis of sepsis in the burn patient that include higher thresholds for temperature (>39 °C or <36.5 °C), HR (>110 beats/min) and RR (>25/min) in addition to presence of thrombocytopenia (platelet count < 100,000/mcl), and indications of insulin resistance or feeding intolerance [7]. In addition to these clinical indicators, documented presence of infection or clinical response to antimicrobials is required. Because these guidelines are based on consensus and not founded in prospective clinical studies, more precise methods of detecting sepsis in this vulnerable population are necessary. Evidence of an increased risk of mortality in the burn patient infected with the ubiquitous pathogen Pseudomonas aeruginosa is suggested if appropriate antibiotic therapy is delayed for only 2 days [8].

Detection of sepsis would be expedited if a simple, inexpensive test could be performed routinely, with a high degree of accuracy in correctly differentiating sepsis from SIRS. Such an assay should improve the ability to identify severe infection, guide treatment and reduce the duration of antibiotic exposure. Emergence of a test that meets these criteria is the assay of the procalcitonin (PCT) molecule, a precursor of calcitonin, produced in both thyroidal and extra-thyroidal tissues, including adipose tissue [9]. Release of PCT occurs to varying degrees in response to bacterial infection, fungal infection, trauma, surgery and other types of conditions. The greatest elevations of serum PCT occur in the presence of bacterial infection and multi-organ failure resulting from trauma [10], and no change is found due to viral infection [9]. Compared to other sepsis markers used clinically such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) or C-reactive protein (CRP) the reactive pattern of PCT has an onset within 4 h of response to infection or injury, peaks at 6 h with a plateau of 8–24 h, then returns to baseline in 2–3 days. This is compared to a 90 min onset for TNF-α with return to baseline in 6 h; a 3-h onset for CRP with return to baseline in 8 h; and a 12–24 h onset for CRP with a 20–72-h plateau and 3–7-day return to baseline [11]. The relatively early rise of PCT with a long plateau of up to 24 h after response to sepsis makes this marker ideal for routine daily measurement; a sudden rise in PCT level is an indicator of sepsis onset [9]. The normal serum value of PCT in a healthy individual without inflammation is less than 0.05 ng/mL [9]. PCT levels associated with local infection, possible systemic infection, sepsis, or severe sepsis are: <0.5 ng/mL, 0.5–2 ng/mL, 2–10 ng/mL, and >10 ng/mL respectively [12].

Numerous clinical trials and meta-analyses of ability to detect sepsis in acutely and critically ill populations using PCT assay have produced promising results [13], [14], [15]. Multiple studies specifically in the burn population have been performed [16], [17], [18], [19]. While European and Asian countries have been the leaders in this new technology; widespread availability or use of the PCT assay in the United States is lacking. A systematic review of the literature was conducted to identify evidence supporting use of the procalcitonin diagnostic test to detect sepsis in the critically ill burn patient.