By Betty Tran, MD, MSc, Editor

SYNOPSIS: In a prospective cohort study of adults hospitalized with community-acquired pneumonia, higher serum procalcitonin levels on admission were associated with an increased risk of invasive respiratory and/or vasopressor support within 72 hours and improved the performance of pneumonia severity scores in identifying high-risk patients.

SOURCE: Self WH, Grijalva CG, Williams DJ, et al. Procalcitonin as an early marker of the need for invasive respiratory or vasopressor support in adults with community-acquired pneumonia. Chest 2016 Apr 20 [Epub ahead of print].

There is significant recent interest in studying procalcitonin (PCT) as a biomarker for the management of critically ill patients with sepsis, as its synthesis and secretion are upregulated by bacterial-specific pro-inflammatory cytokines.1 Several studies have focused on the use of PCT in diagnosing sepsis, as a prognostic marker in sepsis, and as a guide to antibiotic decisions in sepsis. Research by Self et al adds to the growing literature on PCT by examining whether it is helpful in early severity assessment and risk stratification for patients admitted with community-acquired pneumonia (CAP), particularly with regard to ICU admission.

This was a prospective cohort study of 1,770 adults hospitalized with CAP at three centers in Chicago and two hospitals in Nashville, TN, between 2010 and 2012 who had serum PCT measurements. The primary study outcome was the need for invasive respiratory and/or vasopressor support (IRVS), defined as intubation for respiratory failure or vasopressor administration for septic shock within 72 hours of hospital presentation. Overall, 115 patients required IRVS, with 47 requiring both, 37 requiring respiratory support only, and 31 requiring vasopressor support only. The area under the receiver operator curve (ROC) for PCT to discriminate between patients with and without IRVS was 0.69 (95% confidence interval [CI], 0.67-0.71), which the authors noted to be higher than the area for WBC (0.54; 95% CI, 0.51-0.56).

Overall, there was a significant association between PCT level and risk of IRVS. For undetectable levels of PCT (< 0.05 ng/mL), the risk of IRVS was 4.0% (95% CI, 3.1-5.1%). For levels of PCT between 0.05 ng/mL and 10 ng/mL, there was a linear risk of IRVS, with each increase in PCT of 1 ng/mL corresponding to a 1-2% absolute increase in IRVS risk. For PCT levels of 5 ng/mL and 10 ng/mL, the risk of IRVS was 14.2% (95% CI, 11-18.1%) and 22.4% (95% CI, 16.3-30.1%), respectively. The risk of IRVS was observed to plateau when PCT levels reached > 10 ng/mL.

The addition of PCT levels to existing pneumonia severity scoring systems such as the ATS Minor Criteria, Pneumonia Severity Index (PSI), and SMART-COP scores increased the area under the ROC curves and improved the risk stratification ability in predicting IRVS for each severity score.

COMMENTARY

The ability to risk stratify patients with sepsis appropriately has important clinical repercussions. Theoretically, accurate prognostication can result in quicker triage for sicker patients to the ICU and expedite crucial interventions such as appropriate antibiotics, searches for occult infection, and methods of source control.

In the Self et al study, PCT levels on admission for patients hospitalized with CAP strongly correlated with the risk of invasive respiratory and/or vasopressor support, interventions that are performed in the ICU. Specifically, patients with PCT levels of 5 ng/mL and 10 ng/mL were three and five times more likely, respectively, to require IRVS than patients with levels < 0.05 ng/mL. When added to ATS minor criteria, PCT levels improved the ability to accurately identify patients at risk for IRVS who would benefit from admission to an ICU.

The authors appropriately acknowledged that the PCT level alone is insufficient in deciding whether to admit a patient with CAP to the ICU. This study suggested yet another unique potential use for PCT in the management of patients with sepsis beyond what has previously been reported in terms of sepsis diagnosis and antibiotic management. There are, however, several issues to consider. First, PCT is mainly upregulated in bacterial infections; its application to non-bacterial pneumonia patients is unclear. Second, its use as a factor in the appropriate triage of sick CAP patients to the ICU will depend on how quickly the value is made available to healthcare providers, especially in the ED. Third, only a single PCT level on admission was used in this study; it may be more helpful to examine changes in PCT over time, as prior studies have reported that changes in PCT rather than absolute values correlate with patient outcomes such as mortality.2-4 Finally, it is necessary to note that the decision to admit a patient to the ICU is likely to depend on other clinical and social factors besides the risk of IRVS, and PCT levels may not influence decision-making in these situations. Despite its known limitations, it will be interesting to see if PCT will gain more widespread use similar to how clinicians use BNP, lactate, or D-dimer as part of medical decision-making in specific clinical situations.

REFERENCES

  1. Nakamura M, Kono R, Nomura S, et al. Procalcitonin: Mysterious protein in sepsis. J Basic Clin Med 2013;2:7-11.
  2. Karlsson S, Heikkinen M, Pettila V, et al. Predictive value of procalcitonin decrease in patients with severe sepsis: A prospective observational study. Crit Care 2010;14:R205.
  3. Schuetz P, Maurer P, Punjabi V, et al. Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients. Crit Care 2013;17:R115.
  4. Jensen JU, Heslet L, Jensen TH, et al. Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 2006;34:2596-2602.