The Prognostic Value of Serum Procalcitonin Measurements in Critically Injured Patients

A Systematic Review

Aziza N. AlRawahi; Fatma A. AlHinai; Christopher J. Doig; Chad G. Ball; Elijah Dixon; Zhengwen Xiao; Andrew W. Kirkpatrick

Disclosures

Crit Care. 2019;23(390) 

In This Article

Abstract and Introduction

Abstract

Background: Major trauma is associated with high incidence of septic complications and multiple organ dysfunction (MOD), which markedly influence the outcome of injured patients. Early identification of patients at risk of developing posttraumatic complications is crucial to provide early treatment and improve outcomes. We sought to evaluate the prognostic value of serum procalcitonin (PCT) levels after trauma as related to severity of injury, sepsis, organ dysfunction, and mortality.

Methods: We searched PubMed, MEDLINE, EMBASE, the Cochrane Database, and references of included articles. Two investigators independently identified eligible studies and extracted data. We included original studies that assessed the prognostic value of serum PCT levels in predicting severity of injury, sepsis, organ dysfunction, and mortality among critically injured adult patients.

Results: Among 2015 citations, 19 studies (17 prospective; 2 retrospective) met inclusion criteria. Methodological quality of included studies was moderate. All studies showed a strong correlation between initial PCT levels and Injury Severity Score (ISS). Twelve out of 16 studies demonstrated significant elevation of initial PCT levels in patients who later developed sepsis after trauma. PCT level appeared a strong predictor of MOD in seven out of nine studies. While two studies did not show association between PCT levels and mortality, four studies demonstrated significant elevation of PCT levels in non-survivors versus survivors. One study reported that the PCT level of ≥ 5 ng/mL was associated with significantly increased mortality (OR 3.65; 95% CI 1.03–12.9; p = 0.04).

Conclusion: PCT appears promising as a surrogate biomarker for trauma. Initial peak PCT level may be used as an early predictor of sepsis, MOD, and mortality in trauma population.

Introduction

Trauma is the leading cause of death during the first four decades of life and the third leading cause of death overall, across all age groups.[1,2] Each year, trauma accounts for 41 million emergency department visits and 2.3 million hospital admissions in the USA. Of these, 192,000 die as a result of their injuries.[2] The triphasic peaks of death after injury have long been described epidemiologically. Essentially, catastrophic non-survivable injuries occur at the time of injury, with subsequent airway obstruction, respiratory failure, and especially hemorrhage predominating as the second peak. The recognition of non-recoverable head injury and especially sepsis/systemic inflammatory response syndrome-related deaths constitute the third.[3,4] Although the global burden of traumatic death is ominous in its predicted future increase as the developing world mechanizes, great strides have recently been made in addressing both the primary peak with injury prevention and safety conscious designs, and in the second peak related to dramatic advances in resuscitation for hemorrhage, among other interventions.[5,6] Progress in improving the outcomes of posttraumatic sepsis/SIRS is urgently required. Sepsis remains a major challenge in critically injured patients with an incidence range between 2 and 17% during the posttraumatic period, with associated mortality rates reaching as high as 23%.[7]

Major trauma provokes a strong systemic inflammatory response syndrome (SIRS) early after traumatic injury as a result of tissue damage, hypotension, hypoxia, cytokine release, and inflammation.[8] The prognosis is strongly related to the posttraumatic balance between pro- and anti-inflammatory responses.[9–12] Following this induction of the inflammatory cascade is an increase in counter regulatory anti-inflammatory cytokines, which subsequently results in immunosuppression and increased susceptibility to infection and complications such as sepsis. Together, the consequence of initial injury and inflammation, subsequent immune suppression and infection, results in multiple organ dysfunction (MOD) or multiple organ failure (MOF).[9,12] MOD/MOF unfortunately remains the leading cause of late death following trauma.[13]

Early identification of patients at risk of developing posttraumatic complications is crucial to allow the provision of early and appropriate therapy for sepsis. It has been demonstrated that prompt and appropriate management of sepsis prevents MOD, reduces mortality, and improves clinical outcomes.[14,15] Thus, any test or clinical information that facilitates an earlier diagnosis or safely triggers the earlier appropriate treatment of sepsis may save lives. Past research has explored a number of some inflammatory markers for their prognostic value, but no clear message regarding what, if any, marker to rely on has emerged, despite promise.[16–18]

This is especially true with regard to measurement of serum procalcitonin (PCT) levels, which has been of recent interest as a potential and more accurate marker of sepsis in critically ill patients. PCT is a 116-amino acid polypeptide precursor of calcitonin produced by the C cells of the thyroid gland. Healthy individuals typically have serum PCT levels less than 0.05 ng/ml. In response to bacterial endotoxins or pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), various cell types outside the thyroid gland produce PCT, resulting in up to a 1000-fold increase in levels.[19,20] These PCT increases occur with severe inflammation, including systemic infection and especially severe sepsis.[21–23] PCT levels are thus closely related to the severity of systemic inflammation, with higher levels associated with severe sepsis, and potentially most importantly, declining levels are associated with the resolution of infection.[24] Given these unique characteristics and reliable kinetics, PCT level has emerged as a promising biomarker. Therefore, it has been suggested that serum PCT level determination may be superior to previously studied biomarkers for use in the diagnosis of sepsis, monitoring sepsis course and severity, and guiding antimicrobial therapy.[16,18,25–27]

However, in heterogeneous populations of critically ill patients, the results concerning PCT performance remain conflicting. Therefore, in this review, we attempt to extend the scope of previous reviews by evaluating the prognostic value of serum PCT levels, in a more homogenous group of critically injured adult patients, as related to severity of injury, sepsis, organ dysfunction, and mortality.

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