Articles
Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis

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Summary

Background

Procalcitonin is a promising marker for identification of bacterial infections. We assessed the accuracy and clinical value of procalcitonin for diagnosis of sepsis in critically ill patients.

Methods

We searched Medline, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, and Science Direct, from inception to Feb 21, 2012, and reference lists of identified primary studies. We included articles written in English, German, or French that investigated procalcitonin for differentiation of septic patients—those with sepsis, severe sepsis, or septic shock—from those with a systemic inflammatory response syndrome of non-infectious origin. Studies of healthy people, patients without probable infection, and children younger than 28 days were excluded. Two independent investigators extracted patient and study characteristics; discrepancies were resolved by consensus. We calculated individual and pooled sensitivities and specificities. We used I2 to test heterogeneity and investigated the source of heterogeneity by metaregression.

Findings

Our search returned 3487 reports, of which 30 fulfilled the inclusion criteria, accounting for 3244 patients. Bivariate analysis yielded a mean sensitivity of 0·77 (95% CI 0·72–0·81) and specificity of 0·79 (95% CI 0·74–0·84). The area under the receiver operating characteristic curve was 0·85 (95% CI 0·81–0·88). The studies had substantial heterogeneity (I2=96%, 95% CI 94–99). None of the subgroups investigated—population, admission category, assay used, severity of disease, and description and masking of the reference standard—could account for the heterogeneity.

Interpretation

Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment.

Funding

Ministry of Education and Research, the Deutsche Forschungsgemeinschaft, Thuringian Ministry for Education, Science and Culture, the Thuringian Foundation for Technology, Innovation and Research, and the German Sepsis Society.

Introduction

Worldwide, sepsis and its sequelae are still a common cause of acute illness and death in patients with community-acquired and nosocomial infections.1, 2 The American College of Chest Physicians and the Society of Critical Care Medicine Consensus Conference (Northbrook, IL, USA; August, 1991) defined sepsis as systemic inflammatory response caused by infection.3 However, no gold standard exists for proof of infection. Bacteraemia is identified in only about 30% of patients with sepsis, depending on previous antibiotic treatment.4, 5 Furthermore, early clinical signs of sepsis, such as fever, tachycardia, and leucocytosis, are non-specific and overlap with signs of systemic inflammatory response syndromes of non-infectious origin, especially in patients who have undergone surgery. Other signs, such as arterial hypotension, thrombocytopenia, or increased lactate concentrations suggest, too late for life-saving treatment, progression to organ dysfunction. Thus, delay in diagnosis and treatment of sepsis increases mortality, prolongs length of hospital stay, and increases costs,6, 7 highlighting the need for early and reliable diagnostic biomarkers for sepsis.

Several humoral and cellular systems are activated during sepsis, with a subsequent release of various molecules that mediate the host response to infection. Several potential bloodstream biomarkers have been investigated for their ability to diagnose sepsis, estimate its severity, and provide a prognosis. The 116-aminoacid polypeptide procalcitonin had been termed the “the champion so far” for identification of bacterial infections8 because it has several advantages over other potential biomarkers—ie, wide biological range, short time of induction after bacterial stimulus, and long half-life.9

However, only two meta-analyses have investigated the accuracy of procalcitonin for the diagnosis of sepsis, with conflicting results.10, 11 Both were limited by selected populations, did not include a heterogeneous patient population, and, most importantly, were biased by the choice of a gold standard for the definition of sepsis. Additionally, new studies of procalcitonin have been done since the publication of the meta-analyses and our understanding of procalcitonin is still developing.

We did a meta-analysis to investigate the ability of procalcitonin to differentiate between sepsis and systemic inflammatory response syndromes of non-infectious origin in critically ill patients and address the heterogeneity of patients and the affect of individual covariates.

Section snippets

Search strategy and selection criteria

We systematically searched Medline (via PubMed), Embase (via OvidSP), ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, and Science Direct for studies that assessed the accuracy of procalcitonin for the diagnosis of sepsis.

Our medical subject heading terms (for Medline), EMTREE terms (for Embase), and text (for others) were “(procalcitonin OR PCT) AND (sepsis OR “bacterial infection” OR “systemic inflammatory response syndrome” OR SIRS)”. To reduce the number of results, for

Results

Our database search retrieved 3487 articles. After reviewing the titles and abstracts, we excluded 3321. After a full text review we excluded a further 136, leaving 30 studies for inclusion (figure 1). Because in one study investigators reported diagnostic accuracy separately for medical and surgical patients, the study was divided into two parts, thus we analysed 31 datasets. Search of the reference lists of the identified articles and previous systematic reviews10, 11, 23 did not identify any

Discussion

Procalcitonin can differentiate effectively between sepsis and systemic inflammatory response syndrome of non-infectious origin. Previously, two meta-analyses have investigated the diagnostic accuracy of procalcitonin in critically ill patients, with conflicting results.10, 11

In a meta-analysis from 2006, including studies published between April, 1996, and October, 2004, Uzzan and colleagues11 reported that the summary receiver operating characteristics curve for procalcitonin was better than

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