Procalcitonin: Early Detection of Infection as Cause for ARDS
Procalcitonin: Early Detection of Infection as Cause for ARDS
Abstract & Commentary
Synopsis: Procalcitonin determination in early ARDS could help to discriminate between septic and nonseptic underlying disease.
Source: Brunkhorst FM, et al. Crit Care Med 1999; 27:2172-2176.
Brunkhorst and colleagues carried out a prospective study to assess whether the sepsis marker procalcitonin (PCT) is useful to discriminate between septic and nonseptic causes of acute respiratory distress syndrome (ARDS). They studied 27 patients with ARDS of known cause, enrolled between May 1994 and May 1995. Patients were surveyed for 72 hours after the onset of ARDS. During this period, serum samples were drawn every 4-6 hours for measurement of PCT, neopterin, interleukin-6, and C-reactive protein.
Seventeen of 27 patients who fulfilled all criteria of sepsis and had positive microbiological results from at least one blood culture or from bronchoscopic material, with detection of bacteria not likely to be contaminants, were diagnosed as having septic ARDS (most of them with bacterial pneumonia). Ten of 27 patients with negative microbiological results, in whom a nonseptic disease known to be associated with ARDS could be ascertained in the clinical course, were diagnosed as having nonseptic ARDS. The severity of lung damage was similar in both groups but the nonseptic patients had significantly lower Acute Physiology and Chronic Health Evaluation II scores. Determination of PCT, neopterin, interleukin-6, and C-reactive protein serum values was performed from stored samples only, when all samples had been collected and the patients had already been allocated to the infectious or noninfectious groups.
Brunkhorst et al found that PCT serum levels were significantly higher (P < 0.0005) in the patients with septic ARDS than in the patients with nonseptic ARDS. Moreover, there was no overlap between the two groups, although the critically ill patients with nonseptic ARDS displayed serum PCT levels up to 2.9 ng/mL, substantially higher than the level described for healthy controls. The difference was already present in the early phase of evolving ARDS before the results of microbiological testing are generally available. In addition, neopterin allowed a differentiation (P < 0.005), but a substantial overlap between serum levels of septic and nonseptic patients was observed. No discrimination could be achieved by determination of C-reactive protein and interleukin-6 levels.
COMMENT BY FRANCISCO BAIGORRI, MD, PhD
The term sepsis is used when an acute activation of the inflammatory network is induced by infection. Numerous interconnecting inflammatory pathways are activated immediately after the initial insult. The numerous products that have been shown to be elevated during sepsis include acute-phase protein components, such as C-reactive protein and heat-shock proteins, that are induced along with products more difficult to classify, such as procalcitonin.
Mechanisms that activate the inflammatory system are probably nonspecific and similar, whatever the initial trigger. This could explain why high levels of cytokines, adhesion molecules, PCT, and C-reactive protein have been found in both sepsis and other kinds of noninfectious insults such as severe trauma, pancreatitis, burns, hemorrhagic and cardiogenic shock, and heat stroke. However, in most studies, the levels of mediators produced are far higher when the initial trigger is infectious.
PCT could represent a good diagnostic marker candidate to differentiate infectious from noninfectious activators of inflammation. PCT is a peptide that is virtually undetectable in the circulation of healthy human individuals (< 0.5 ng/mL). The exact source and function of PCT in septic patients remain uncertain, but the amount of PCT produced and the degree of increase in plasma levels may be correlated with the extent of the inflammatory reaction to infection (Assicot M, et al. Lancet 1993;341:515-518; de Werra I, et al. Crit Care Med 1997;25:607-613). In fact, it has been shown that a cut-off level of 1.8 ng/mL predicts infectious complications during pancreatitis with 87% accuracy (Rau B, et al. Gut 1997;41:832-840). The study of Brunkhorst et al supports the usefulness of PCT to differentiate infectious from noninfectious causes of inflammation in critically ill patients.
Thus, PCT monitoring may be useful in patients likely to develop a systemic inflammatory response of infectious origin, such as ICU patients after major surgery or trauma and immunocompromised patients. Abrupt increases in or high PCT levels in these patients justify a search for a source of infections. PCT could also represent a useful adjunctive to discriminate between infectious and noninfectious causes in patients presenting with systemic inflammatory response syndrome, when clinical and bacteriologic findings are equivocal. Perhaps the combination with other biological markers, such as C-reactive protein, could result in higher specificity as suggested by Ugarte and colleagues (Ugarte H, et al. Crit Care Med 1999;27:498-504).
Plasma procalcitonin concentration in patients with inflammatory reaction to infection:
a. has been found consistently decreased.
b. is not higher than 0.5 ng/mL.
c. has been found consistently increased.
d. is always normal unless ARDS is present.
e. is negligible contrary to what was expected.
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