Skip Navigation LinksHome > January 2002 - Volume 96 - Issue 1 > Alveolar and Serum Procalcitonin: Diagnostic and Prognostic...
Anesthesiology:
Clinical Investigations

Alveolar and Serum Procalcitonin: Diagnostic and Prognostic Value in Ventilator-associated Pneumonia

Duflo, Frédéric M.D.*; Debon, Richard M.D.*; Monneret, Guillaume Ph.D.†; Bienvenu, Jacques Ph.D.‡; Chassard, Dominique M.D., Ph.D.§; Allaouchiche, Bernard M.D., Ph.D.∥

Free Access
Article Outline
Collapse Box

Author Information

Collapse Box

Abstract

Background: The potential role of serum and alveolar procalcitonin as early markers of ventilator-associated pneumonia (VAP) and its prognostic value were investigated.
Methods: Ninety-six patients with a strong suspicion of VAP were prospectively enrolled. VAP diagnosis was based on a positive quantitative culture obtained via a mini–bronchoalveolar lavage of 103 colony-forming units/ml or more. Blood and alveolar samples were collected for procalcitonin measurement and analyzed for diagnostic and prognostic evaluation on days 0, 3, and 6. Sensitivity, specificity, positive likelihood ratio, and receiver-operating characteristic curves were analyzed to define ideal cutoff values and approach the decision analysis.
Results: Serum procalcitonin was significantly increased in the VAP group (n = 44) compared with the non-VAP group (n = 52): 11.5 ng/ml (95% confidence interval, 5.9–17.0) versus 1.5 ng/ml (1.1–1.9). A serum procalcitonin concentration greater than 3.9 ng/ml (best cutoff value) was considered positive for the VAP diagnosis (sensitivity, 41%; specificity, 100%). Serum procalcitonin was significantly increased in the non-survivors compared with the survivors for the VAP group: 16.5 ng/ml (95% confidence interval, 8.1–24.9) versus 2.9 ng/ml (1.2–4.7). The best cutoff value for serum procalcitonin of the nonsurvivors in the VAP group was 2.6 ng/ml (sensitivity, 74%; specificity, 75%; positive likelihood ratio, 2.96). Regarding VAP diagnosis and prognosis, no significant differences were found for alveolar procalcitonin in all groups.
Conclusions: Serum but not alveolar procalcitonin seems to be a helpful parameter in the early VAP diagnosis and an appropriate marker for predicting mortality.
VENTILATOR-ASSOCIATED pneumonia (VAP) remains the second leading type of nosocomial infection according to the National Nosocomial Infection Survey of the Centers for Disease Control and Prevention (Atlanta, GA). 1 VAP seems to be associated with high mortality. 2,3 Delays in the administration of adequate antimicrobial treatment increase the risk of hospital mortality. 2,4 The optimal technique for the diagnosis of VAP has not been determined, but there are some acceptable methods. 5 However, results of quantitative cultures are not available until 24–72 h after the procedure. Rapid identification of VAP in critically ill patients is required to improve survival and to reduce toxicity of expensive treatment.
Better markers of sepsis should ease the diagnosis, help to control therapy, and assess prognosis. Although cytokines, such as interleukin (IL)-6 and IL-8, correlate to some degree with the severity of sepsis and patient outcome, they are not established for the diagnosis and clinical decision making at the bedside. 6 Numerous clinical studies have proposed procalcitonin as a specific marker of bacterial infection or general inflammation status. 7–10 Procalcitonin has also been described as a good predictor of disease severity and antibiotherapy efficiency. 11 Procalcitonin also is released rapidly and has a long half-life, and the assay is highly reproducible. Thus, procalcitonin could be a useful tool in the early diagnosis of VAP. Therefore, the aim of our study was to assess the usefulness and reliability of serum and bronchoalveolar lavage (BAL) procalcitonin in the early diagnosis and prognosis of VAP.
Back to Top | Article Outline

Material and Methods

After local ethics committee approval (Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale Lyon A, Lyon, France), 106 consecutive patients undergoing mechanical ventilation were included over a 2-yr period at the intensive care unit, Hotel-Dieu Hospital-Lyon (Lyon, France). Blood and BAL samples were collected from 10 routine postoperative patients and constituted the control group: all had elective gynecologic or intestinal surgical procedures and were not suspected to have VAP. Ninety-six patients were highly suspected to have VAP: all had a fever (≤ 38.5°C), purulent tracheal aspirates, leukocytosis (≥ 12 × 109/l), and new or persistent radiographic lung infiltrates unrelated to cardiogenic causes. Clinical and laboratory data were collected, including temperature, hemodynamics, respiratory rate, arterial blood gas data, white blood count, and serum and alveolar procalcitonin concentrations. BAL, blood culture, and urine tractus samples were screened for infectious specimen. Samples were only taken from patients who had not received systemic or topical antimicrobial therapy during the 3 days before the study.
Back to Top | Article Outline
Sampling Technique
We obtained 106 mini-BAL samples using the blinded PBAL catheter technique (Combicath; Plastimed, St. Leu La Foret, France). During the procedure, 100% oxygen was administered, and patients were sedated with intravenous narcotics and paralyzed with curare. Topical anesthesia was not used. Cardiovascular and oxygen saturation monitoring was performed during the entire procedure. Tracheal sputum was aspirated and collected before introducing the protected catheter. The PBAL catheter was inserted using the previously described technique. 12 After the blinded introduction in the bronchial system, the inner catheter was advanced until resistance was encountered, and 20 ml sterile saline was administered. The fluid was then withdrawn by hand suction into the infusion syringe. When at least 5 ml fluid had been sterilely retrieved, the entire catheter was removed. The entire sampling procedure lasted less than 2 min and was performed by the same physician. The PBAL was repeated on days 3 and 6 for procalcitonin measurements, except in the control group. Meanwhile, blood samples were collected. Some of the alveolar samples were sent to the laboratory for bacteriologic analysis (Gram staining and quantitative culture). Other alveolar samples were centrifuged (1,500 rpm, 10 min) and supernatants were immediately stored at −80°C until procalcitonin measurements.
Back to Top | Article Outline
Bacteriologic Analysis
The same technologist processed all bacterial analysis.
Back to Top | Article Outline
Microscopic Examination.
Aliquots of 0.2 ml from the original suspension were centrifuged at 300 g for 10 min. Slides were Gram stained and examined at high magnification (×100). The possible presence of microorganisms was assessed on 10–50 fields and classified according to Gram stain morphology.
Back to Top | Article Outline
Quantitative Cultures.
The fluid was diluted to obtain concentrations of 10−1, 10−3, and 10−5. Samples were then plated onto Petri dishes: Colombia agar, chocolate agar, trypticase soy, McConkey agar, and Sabouraud agar. Bacterial colonies were counted and identified using conventional techniques.
Back to Top | Article Outline
Immunologic Analysis
The same technologist performed all measurements. Procalcitonin was determined using an immunoluminometric assay (Lumitest; Brahms Diagnostica, Berlin, Germany). The procalcitonin assay had a lower limit of 0.10 ng/ml.
Back to Top | Article Outline
Diagnostic Categories
The final diagnosis of pneumonia (VAP group) was based on positive results of PBAL quantitative culture (≥ 103 colony-forming units/ml on any media). VAP was excluded if the one of the following criteria was fulfilled: negative or nonsignificant growth in culture of BAL and full recovery without antimicrobial therapy, or diagnosis of another disease of the chest accounting for the chest radiograph abnormality (non-VAP group).
Definition of the bacterial infection was based on the American College of Chest Physicians and the Society of Critical Care Medicine Consensus Conference Criteria to categorize patients into systemic inflammation response syndrome, sepsis, severe sepsis, and septic shock. 13 Antibiotherapy was started based on Gram staining results and adjusted based on quantitative culture and antibiogram results.
Back to Top | Article Outline
Statistical Analysis
Patients were divided into three groups. The VAP group contained patients suspected to have VAP with positive PBAL quantitative culture (VAP group); the non-VAP group contained patients suspected to have VAP with negative PBAL quantitative culture; the control group consisted of patients not suspected to have VAP.
Demographic and procalcitonin data are expressed as mean with 95% confidence interval. Sensitivity and specificity are expressed in percentage.
Statview 5.0 (SAS Institute Inc., Cary, NC) was used to analyze the experimental data. After confirming normally distributed data, demographic and clinical data were compared using the chi-square test or the Student t test when appropriate. The one-way analysis of variance with repeated measures was used to evaluate differences between the samples collected at different times (D0, D3, D6; significance, P < 0.05). The Bonferroni post hoc test was used to locate the significance. Sensitivity, specificity, and positive likelihood ratio were estimated using a standard formula. 14 Receiver-operating characteristic (ROC) curves were analyzed to define the optimal cutoff value using MEDCALC (Medcalc Software, Mariakerke, Belgium) as the biostatistics software.
Back to Top | Article Outline

Results

Table 1
Table 1
Image Tools
Table 1 shows demographic and clinical data of all patients divided into subgroups and shows the primary indications for ventilator support.
The diagnosis of VAP was established in 44 cases (VAP group): 17 patients had gram-negative bacilli, 13 patients had gram-positive cocci, and polymicrobial growth was seen in 14 patients. PBAL quantitative culture was negative in 52 patients (non-VAP group). During or after the sampling procedure, no major hemodynamic changes, pneumothorax, or hemorrhage were observed. The mini-BAL effluent had 1% squamous epithelial cells or less in all patients.
Fig. 1
Fig. 1
Image Tools
Fig. 2
Fig. 2
Image Tools
Fig. 3
Fig. 3
Image Tools
Serum procalcitonin was significantly increased in the VAP group compared with the non-VAP group until day 3: 11.5 ng/ml (95% confidence interval, 5.9–17.0) versus 1.5 ng/ml (1.1–1.9) on day 0 and 7.5 ng/ml (6.3–8.7) versus 1.25 ng/ml (1.03–1.47) on day 3 (fig. 1A). Regarding VAP diagnosis, no significant differences occurred in the VAP group compared with the non-VAP group for the alveolar procalcitonin (fig. 1B). The cutoff value of serum procalcitonin for the VAP diagnosis (from the ROC curve; area under the curve [AUC] = 0.787) was 3.9 ng/ml (sensitivity, 41%; specificity, 100%;fig. 2). Serum procalcitonin was significantly increased in the nonsurvivors compared with the survivors for the VAP group: 16.5 ng/ml (95% confidence interval, 8.1–24.9) versus 2.9 ng/ml (1.2–4.7) (fig. 3A). The cutoff value for serum procalcitonin of the nonsurvivors in the VAP group (from the ROC curve; AUC = 0.607) was 2.6 ng/ml (sensitivity, 74%; specificity, 75%; positive likelihood ratio, 2.96). Regarding VAP prognosis, no significant differences were found for the alveolar procalcitonin in all groups (fig. 3B).
When comparing the evolution of the serum procalcitonin values of the nonsurvivors and the survivors in the VAP group, significant differences were seen on days 3 and 6 (fig. 3A). When comparing the evolution of the alveolar procalcitonin values of the nonsurvivors and the survivors in the VAP group, significant differences were seen on days 0 and 3 (fig. 3B).
Back to Top | Article Outline

Discussion

Our study shows that patients with confirmed VAP have significantly increased concentrations of procalcitonin in serum. Our data suggest that procalcitonin measurements in serum may be useful for the early diagnosis of VAP. We also demonstrated that the presence of an increased concentration of procalcitonin in serum could be an original approach to the prognostic of VAP. Last, our results support the idea that the concentrations of procalcitonin in bronchoalveolar fluid are not helpful regarding the diagnosis and the prognosis of VAP.
Back to Top | Article Outline
Limitations of the Study
First, PBAL was considered the reference method to diagnose VAP. This technique has been advocated as a potentially better alternative compared with bronchoscopic procedures because of its minimal invasiveness, wide availability, and relative cost, 12,15 although the open lung biopsy represents the ideal criterion. However, this gold standard technique for evaluating the diagnosis of VAP remains problematic, and the appropriateness of studying a diagnostic test only among dead patients is debated. 16 Second, the lower threshold value (0.1 ng/ml) of the Lumitest kit assay may be inappropriate for detecting low significant alveolar concentrations. Third, because we used a blinded BAL fluid sampling method, noninvolved lung fluids could have been analyzed and could have underestimated alveolar procalcitonin concentrations. Nevertheless, Monton et al.17 did not confirm that cytokines production is compartmentalized; therefore, one would not expect to find increased alveolar concentration of procalcitonin. Last, antimicrobial therapy was started after the Gram staining results and thus before measurement of procalcitonin concentrations on days 3 and 6. Thus, procalcitonin concentrations could have been underestimated and therefore could not exhibit significant differences in the serial concentrations.
Limitations and inaccuracies in clinical decision making have motivated the development of techniques to establish the diagnosis of VAP. 18 Direct examination and cultures of tracheal aspirates have been commonly used to diagnose VAP but are nonspecific for establishing the presence of VAP partly because of tracheobronchial bacterial colonization. 18 Several methods have been developed in an attempt to improve their diagnostic specificity, including elastin fibers examination, 19 and identification of antibody-coated bacteria. 20 However, the sensitivity of these techniques varies from 55 to 75%, and they lack specificity in the presence of previous antibiotics administration or certain disease processes. 21,22 Bronchoscopic and nonbronchoscopic sampling of the lower airways seems to be accepted as the most accurate method of diagnosis of VAP, but bacterial results can be delayed. 19 Intracellular organisms examination, 23 endotoxin measurement, 24 and nuclear probes 25 have been applied to such samples to aid the VAP diagnosis. However, their cost or their unavailability did not lead to routine use.
According to our findings, the measurement of procalcitonin in serum represents a potential adjunct to the early diagnosis of VAP and possesses significant interest for the VAP prognosis. However, bronchoalveolar fluid procalcitonin concentrations remained at a low level, limiting their clinical utility.
Recently, Nijsten et al.26 showed that both in vivo and in vitro IL-6 and tumor necrosis factor α (TNF-α) release procalcitonin. Various studies have shown an increased inflammatory lung response in pneumonia, and TNF-α seems to be the key mediator of the inflammatory response to miscellaneous pathogens. 27 Monton et al.17 assessed the cytokine expression of 12 severe nosocomial pneumonia in the serum and in bronchoalveolar lavage and found that TNF-α and IL-6 concentrations were significantly higher systemically than in the lung. In alveolar fluid, IL-6 was the only cytokine to be significantly increased. Moreover, the intratracheal instillation of lipopolysaccharide in rats increased the concentration of alveolar TNF-α without increasing serum concentrations, 28 supporting the hypothesis that the alveolar membrane could be a strong filter to circulating cytokines. Dehoux et al.29 explored patients with unilateral pneumonia and found higher concentrations of cytokines in the involved lungs compared with the noninvolved lungs and blood. Therefore, because of the blinded alveolar sampling method, noninvolved lung fluids could have been analyzed and could have underestimated alveolar cytokines concentrations. Therefore, in our study, systemic cytokine production can explain increased serum procalcitonin concentrations, whereas the low alveolar procalcitonin release could be explained by the absence of the local mediators.
When comparing the evolution of the serum procalcitonin values between the VAP group and the non-VAP group, serum procalcitonin was significantly higher in the VAP group until day 3. Antibiotics were started according to the bacterial examination 24 h after the first mini-BAL procedure. Thus, serum procalcitonin did not have much time to decrease in case of effective treatment.
The cutoff ROC curve value of serum procalcitonin to diagnose VAP (3.9 ng/ml) exhibits a low sensitivity (41%) and an excellent specificity (100%). This fulfills physicians needs: highly specific tests to diagnose VAP, to avoid expensive and ineffective antibiotics and to decrease potential emergence of multiresistant microorganisms.
We found a significant relation between serum procalcitonin values and mortality. In our study, area under the ROC curve (AUC) was 0.787. Bossink et al.30 have demonstrated in 300 hospitalized medical patients with fever that AUC for mortality was 0.79 for respiratory rate, 0.69 for elastase-α1-antitrypsin concentration, 0.65 for heart rate, 0.61 for procalcitonin concentration, and 0.60 for leukocyte count. Thus, serum procalcitonin and elastase-α1-antitrypsin concentrations may predict microbial infection, bacteremia, and mortality more effectively than do clinical symptoms. The strong relation between serum procalcitonin and survival has been shown by Ugarte et al.31 in a large cohort of critically ill patients. In this latter work, infected nonsurvivors have higher concentrations of serum procalcitonin compared with infected survivors. Interestingly, Shröder et al.32 have recently studied 24 patients with septic shock and have shown that in nonsurvivors, serum procalcitonin remained increased, whereas the course of survivors was characterized by decreased values, which were significantly lower at every time point compared with those patients who died. In our study, the serum procalcitonin concentrations were more increased in nonsurvivors with VAP. This agrees in part with the significant correlation found by Monton et al.17 between serum concentrations of cytokines and scores designed to assess severity of illness. Recently, Bonten et al.33 investigated the correlation between the circulating IL-6 and IL-8 concentrations and the prognosis in patients with VAP. They found that high serum concentrations of cytokines were associated with higher mortality rates.
In summary, the current study supports new findings regarding procalcitonin. The bronchoalveolar concentrations of procalcitonin are not increased during VAP, whereas the values of circulating procalcitonin are associated with confirmed VAP. It is clear that high procalcitonin concentrations are found only in blood. 34 Serum concentrations of procalcitonin are also correlated with higher mortality rates in nonsurvivors with VAP. We found a positive likelihood ratio of 2.96. This means that a serum procalcitonin concentration greater than 2.6 ng/ml is almost three times more likely to occur in a nonsurvivor than in a survivor of VAP. Therefore, serum procalcitonin could be an interesting tool in the early diagnosis of VAP and a helpful marker of prognosis. These findings warrant further studies that will take into consideration the limitations of our work.
Back to Top | Article Outline

References

1. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM: CDC definitions for nosocomial infections. Am J Infect Control 1988; 16: 128–40

2. Kollef MH, Sherman G, Ward S, Fraser VJ: Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients. Chest 1999; 115: 462–74

3. Fagon JY, Chastre J, Vuagnat A, Trouillet JL, Novara A, Gibert C: Nosocomial pneumonia and mortality among patients in intensive care units. JAMA 1996; 275: 866–9

4. Dupont H, Mentec H, Sollet JP, Bleichner G: Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia. Intensive Care Med 2001; 27: 355–62

5. Chastre J, Fagon JY, Bornet-Lecso M, Calvat S, Dombret MC, al Khani R, Basset F, Gibert C: Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med 1995; 152: 231–40

6. Wakefield CH, Barclay GR, Fearon KC, Goldie AS, Ross JA, Grant IS, Ramsay G, Howie JC: Proinflammatory mediator activity, endogenous antagonists and the systemic inflammatory response in intra-abdominal sepsis. Scottish Sepsis Intervention Group. Br J Surg 1998; 85: 818–25

7. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C: High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341: 515–8

8. Gendrel D, Raymond J, Coste J, Moulin F, Lorrot M, Guerin S, Ravilly S, Lefevre H, Royer C, Lacombe C, Palmer P, Bohuon C: Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs viral infections. Pediatr Infect Dis J 1999; 18: 875–81

9. von Heimburg D, Stieghorst W, Khorram-Sefat R, Pallua N: Procalcitonin: A sepsis parameter in severe burn injuries. Burns 1998; 24: 745–50

10. Gendrel D, Raymond J, Assicot M, Moulin F, Iniguez JL, Lebon P, Bohuon C: Measurement of procalcitonin levels in children with bacterial or viral meningitis. Clin Infect Dis 1997; 24: 1240–2

11. Wanner GA, Keel M, Steckholzer U, Beier W, Stocker R, Ertel W: Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients. Crit Care Med 2000; 28: 950–7

12. Rouby JJ, Rossignon MD, Nicolas MH, Martin de Lassale E, Cristin S, Grosset J, Viars P: A prospective study of protected bronchoalveolar lavage in the diagnosis of nosocomial pneumonia. A nesthesiology 1989; 71: 679–85

13. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101: 1644–55

14. Dujardin B, Van den Ende J, Van Gompel A, Unger JP, Van der Stuyft P: Likelihood ratios: A real improvement for clinical decision making? Eur J Epidemiol 1994; 10: 29–36

15. Kollef MH, Bock KR, Richards RD, Hearns ML: The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with suspected ventilator-associated pneumonia. Ann Intern Med 1995; 122: 743–8

16. Cook DJ, Fitzgerald JM, Guyatt GH, Walter S: Evaluation of the protected brush catheter and bronchoalveolar lavage in the diagnosis of nosocomial pneumonia. J Intensive Care Med 1991; 6: 196–205

17. Monton C, Torres A, El-Ebiary M, Filella X, Xaubet A, de la Bellacasa JP: Cytokines expression in severe pneumonia: A bronchoalveolar lavage study. Crit Care Med 1999; 27: 1745–53

18. Kollef MH, Silver P: Ventilator-associated pneumonia: An update for clinicians. Respir Care 1995; 40: 1130–40

19. Salata RA, Lederman MM, Shlaes DM, Jacobs MR, Eckstein E, Tweardy D, Toossi Z, Chmielewski R, Marino J, King CH, Graham RC, Ellner JJ: Diagnosis of nosocomial pneumonia in intubated intensive care unit patients. Am Rev Respir Dis 1987; 135: 426–32

20. Wunderink RG, Russell GB, Mezger E, Adams D, Popovich J Jr: The diagnostic utility of the antibody-coated bacteria test in intubated patients. Chest 1991; 99: 84–8

21. Marquette CH, Copin MC, Wallet F, Neviere R, Saulnier F, Mathieu D, Durocher A, Ramon P, Tonnel AB: Diagnostic tests for pneumonia in ventilated patients: Prospective evaluation of diagnostic accuracy using histology as a diagnostic gold standard. Am J Respir Crit Care Med 1995; 151: 1878–88

22. Shepherd KE, Lynch KE, Wain JC, Brown EN, Wilson RS: Elastin fibers and the diagnosis of bacterial pneumonia in the adult respiratory distress syndrome. Crit Care Med 1995; 23: 1829–34

23. Papazian L, Autillo-Touati A, Thomas P, Bregeon F, Garbe L, Saux P, Seite R, Gouin F: Diagnosis of ventilator-associated pneumonia: An evaluation of direct examination and presence of intracellular organisms. A nesthesiology 1997; 87: 268–76

24. Kollef MH, Eisenberg PR, Ohlendorf MF, Wick MR: The accuracy of elevated concentrations of endotoxin in bronchoalveolar lavage fluid for the rapid diagnosis of gram-negative pneumonia. Am J Respir Crit Care Med 1996; 154: 1020–8

25. Allaouchiche B, Meugnier H, Freney J, Fleurette J, Motin J: Rapid identification of Staphylococcus aureus in bronchoalveolar lavage fluid using a DNA probe (Accuprobe). Intensive Care Med 1996; 22: 683–7

26. Nijsten MW, Olinga P, The TH, de Vries EG, Koops HS, Groothuis GM, Limburg PC, ten Duis HJ, Moshage H, Hoekstra HJ, Bijzet J, Zwaveling JH: Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med 2000; 28: 458–61

27. Nelson S, Mason CM, Kolls J, Summer WR: Pathophysiology of pneumonia. Clin Chest Med 1995; 16: 1–12

28. Nelson S, Bagby GJ, Bainton BG, Wilson LA, Thompson JJ, Summer WR: Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. J Infect Dis 1989; 159: 189–94

29. Dehoux MS, Boutten A, Ostinelli J, Seta N, Dombret MC, Crestani B, Deschenes M, Trouillet JL, Aubier M: Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 1994; 150: 710–6

30. Bossink AW, Groeneveld AB, Thijs LG: Prediction of microbial infection and mortality in medical patients with fever: plasma procalcitonin, neutrophilic elastase-alpha1-antitrypsin, and lactoferrin compared with clinical variables. Clin Infect Dis 1999; 29: 398–407

31. Ugarte H, Silva E, Mercan D, De Mendonca A, Vincent JL: Procalcitonin used as a marker of infection in the intensive care unit. Crit Care Med 1999; 27: 452–3

32. Schröder J, Staubach KH, Zabel P, Stuber F, Kremer B: Procalcitonin as a marker of severity in septic shock. Langenbecks Arch Surg 1999; 384: 33–8

33. Bonten MJ, Froon AH, Gaillard CA, Greve JW, de Leeuw PW, Drent M, Stobberingh EE, Buurman WA: The systemic inflammatory response in the development of ventilator-associated pneumonia. Am J Respir Crit Care Med 1997; 156: 1105–13

34. Gendrel D, Bohuon C: Procalcitonin as a marker of bacterial infection. Pediatr Infect Dis J 2000; 19: 679–87

Cited By:

This article has been cited 37 time(s).

Clinical Chemistry and Laboratory Medicine
The role of procalcitonin and IL-6 in discriminating between septic and non-septic causes of ALI/ARDS: a prospective observational study
Tsantes, A; Tsangaris, I; Kopterides, P; Kapsimali, V; Antonakos, G; Zerva, A; Kalamara, E; Bonovas, S; Tsaknis, G; Vrigou, E; Maniatis, N; Dima, K; Armaganidis, A
Clinical Chemistry and Laboratory Medicine, 51(7): 1535-1542.
10.1515/cclm-2012-0562
CrossRef
Plos One
Diagnostic Value of sTREM-1 in Bronchoalveolar Lavage Fluid in ICU Patients With Bacterial Lung Infections: A Bivariate Meta-Analysis
Shi, JX; Li, JS; Hu, R; Li, CH; Wen, Y; Zheng, H; Zhang, F; Li, Q
Plos One, 8(5): -.
ARTN e65436
CrossRef
Scandinavian Journal of Infectious Diseases
Combined measurement of procalcitonin and soluble TREM-1 in the diagnosis of nosocomial sepsis
Gibot, S; Cravoisy, A; Dupays, R; Barraud, D; Nace, L; Levy, B; Bollaert, PE
Scandinavian Journal of Infectious Diseases, 39(): 604-608.
10.1080/00365540701199832
CrossRef
European Respiratory Journal
Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators
Christ-Crain, M; Muller, B
European Respiratory Journal, 30(3): 556-573.
10.1183/09031936.00166106
CrossRef
Current Microbiology
Legionella pneumonia and serum procalcitonin
Franzin, L; Cabodi, D
Current Microbiology, 50(1): 43-46.
10.1007/s00284-004-4360-1
CrossRef
Intensive Care Medicine
Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia
Luyt, CE; Combes, A; Reynaud, C; Hekimian, G; Nieszkowska, A; Tonnellier, M; Aubry, A; Trouillet, JL; Bernard, M; Chastre, J
Intensive Care Medicine, 34(8): 1434-1440.
10.1007/s00134-008-1112-x
CrossRef
Revue Des Maladies Respiratoires
Nosocomial pneumopathy
Girault, C
Revue Des Maladies Respiratoires, 22(5): S59-S61.
10.1019/200530133
CrossRef
Burns
Evaluation of serum procalcitonin concentration in the ICU following severe burn
Barques, L; Chancerelle, Y; Catineau, J; Jault, P; Carsin, H
Burns, 33(7): 860-864.
10.1016/j.burns.2006.10.401
CrossRef
Annals of Clinical Biochemistry
C-reactive protein and procalcitonin concentrations in bronchoalveolar lavage fluid as a predictor of ventilator-associated pneumonia
Linssen, CFM; Bekers, O; Drent, M; Jacobs, JA
Annals of Clinical Biochemistry, 45(): 293-298.
10.1258/acb.2007.007133
CrossRef
Thorax
Diagnostic importance of pulmonary interleukin-1 beta and interleukin-8 in ventilator-associated pneumonia
Morris, AC; Kefala, K; Wilkinson, TS; Moncayo-Nieto, OL; Dhaliwal, K; Farrell, L; Walsh, TS; Mackenzie, SJ; Swann, DG; Andrews, PJD; Anderson, N; Govan, JRW; Laurenson, IF; Reid, H; Davidson, DJ; Haslett, C; Sallenave, JM; Simpson, AJ
Thorax, 65(3): 201-207.
10.1136/thx.2009.122291
CrossRef
American Journal of Respiratory and Critical Care Medicine
Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia
Luyt, CE; Guerin, V; Combes, A; Trouillet, JL; Ben Ayed, S; Bernard, M; Gibert, C; Chastre, J
American Journal of Respiratory and Critical Care Medicine, 171(1): 48-53.
10.1164/rccm.200406-746Oc
CrossRef
Mediators of Inflammation
Biomarkers: A Definite Plus in Pneumonia
Summah, H; Qu, JM
Mediators of Inflammation, (): -.
ARTN 675753
CrossRef
Critical Care
Diagnosis of ventilator-associated pneumonia: a systematic review of the literature
Rea-Neto, A; Youssef, NCM; Tuche, F; Brunkhorst, F; Ranieri, VM; Reinhart, K; Sakr, Y
Critical Care, 12(2): -.
ARTN R56
CrossRef
Pediatrics
Does interleukin-6 genotype influence cerebral injury or developmental progress after preterm birth?
Harding, DR; Dhamrait, S; Whitelaw, A; Humphries, SE; Marlow, N; Montgomery, HE
Pediatrics, 114(4): 941-947.
10.1542/peds.2003-0494-F
CrossRef
Intensive Care Medicine
Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia
Determann, RM; Millo, JL; Gibot, S; Korevaar, JC; Vroom, MB; van der Poll, T; Garrard, CS; Schultz, MJ
Intensive Care Medicine, 31(): 1495-1500.
10.1007/s00134-005-2818-7
CrossRef
European Respiratory Journal
C-reactive protein and procalcitonin as predictors of survival and septic shock in ventilator-associated pneumonia
Hillas, G; Vassilakopoulos, T; Plantza, P; Rasidakis, A; Bakakos, P
European Respiratory Journal, 35(4): 805-811.
10.1183/09031936.00051309
CrossRef
Surgical Infections
Changes in Pulmonary Cytokines during Antibiotic Therapy for Ventilator-Associated Pneumonia
Swanson, JM; Mueller, EW; Croce, MA; Wood, GC; Boucher, BA; Magnotti, LJ; Fabian, TC
Surgical Infections, 11(2): 161-167.
10.1089/sur.2008.067
CrossRef
New England Journal of Medicine
Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia
Gibot, S; Cravoisy, A; Levy, B; Bene, MC; Faure, G; Bollaert, PE
New England Journal of Medicine, 350(5): 451-458.

Seminars in Respiratory and Critical Care Medicine
Novel and innovative strategies to treat ventilator-associated pneumonia: Optimizing the duration of therapy and nebulizing antimicrobial agents
Goldstein, I; Chastre, J; Rouby, JJ
Seminars in Respiratory and Critical Care Medicine, 27(1): 82-91.

European Respiratory Journal
Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia
Ramirez, P; Garcia, MA; Ferrer, M; Aznar, J; Valencia, M; Sahuquillo, JM; Menendez, R; Asenjo, MA; Torres, A
European Respiratory Journal, 31(2): 356-362.
10.1183/09031936.00086707
CrossRef
Clinica Chimica Acta
Procalcitonin levels in plasma in oncohaematologic patients with and without bacterial infections
Ciaccio, M; Fugardi, G; Titone, L; Romano, A; Giordano, S; Bivona, G; Scarlata, F; Vocca, L; Di Gangi, M
Clinica Chimica Acta, 340(): 149-152.
10.1016/j.cccn.2003.10.014
CrossRef
Journal of Critical Care
The value of pretest probability and modified clinical pulmonary infection score to diagnose ventilator-associated pneumonia
Lauzier, F; Ruest, A; Cook, D; Dodek, P; Albert, M; Shorr, AF; Day, A; Jiang, X; Heyland, D
Journal of Critical Care, 23(1): 50-57.
10.1016/j.jcrc.2008.01.006
CrossRef
Journal of Leukocyte Biology
CCL2 as a trigger of manifestations of compensatory anti-inflammatory response syndrome in mice with severe systemic inflammatory response syndrome
Takahashi, H; Tsuda, Y; Kobayashi, M; Herndon, DN; Suzuki, F
Journal of Leukocyte Biology, 79(4): 789-796.
10.1189/jlb.0705372
CrossRef
Critical Care
Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia
Seligman, R; Meisner, M; Lisboa, TC; Hertz, FT; Filippin, TB; Fachel, JMG; Teixeira, PJZ
Critical Care, 10(5): -.
ARTN R125
CrossRef
Intensive Care Medicine
Microbiogical data, but not procalcitonin improve the accuracy of the clinical pulmonary infection score
Jung, B; Embriaco, N; Roux, F; Forel, JM; Demory, D; Allardet-Servent, J; Jaber, S; La Scola, B; Papazian, L
Intensive Care Medicine, 36(5): 790-798.
10.1007/s00134-010-1833-5
CrossRef
Chest
Prognostic role of clinical and laboratory criteria to identify early ventilator-associated pneumonia in brain injury
Pelosi, P; Barassi, A; Severgnini, P; Gomiero, B; Finazzi, S; Merlini, G; d'Eril, GM; Chiaranda, M; Niederman, MS
Chest, 134(1): 101-108.
10.1378/chest.07-2546
CrossRef
Chest
Diagnostic and Prognostic Values of Pleural Fluid Procalcitonin in Parapneumonic Pleural Effusions
Lin, MC; Chen, YC; Wu, JT; Ko, YC; Wang, CC
Chest, 136(1): 205-211.
10.1378/chest.08-1134
CrossRef
Chest
Soluble triggering receptor expressed on myeloid cell-1 is increased in patients with ventilator-associated pneumonia - A preliminary report
Horonenko, G; Hoyt, JC; Robbins, RA; Singarajah, CU; Umar, A; Pattengill, J; Hayden, JM
Chest, 132(1): 58-63.
10.1378/chest.06-2731
CrossRef
Journal of Parenteral and Enteral Nutrition
Procalcitonin and enteral nutrition tolerance in critically ill patients
Brown, RO; Alexander, E; Hanes, SD; Wood, GC; Kudsk, KA; Dickerson, RN
Journal of Parenteral and Enteral Nutrition, 27(1): 84-88.

New England Journal of Medicine
CURRENT CONCEPTS Hospital-Acquired Infections Due to Gram-Negative Bacteria
Peleg, AY; Hooper, DC
New England Journal of Medicine, 362(): 1804-1813.

Bmc Infectious Diseases
A composite score combining procalcitonin, C-reactive protein and temperature has a high positive predictive value for the diagnosis of intensive care-acquired infections
Robriquet, L; Sejourne, C; Kipnis, E; D'herbomez, M; Fourrier, F
Bmc Infectious Diseases, 13(): -.
ARTN 159
CrossRef
Psychophysiology
The effect of academic exam stress on mucosal and cellular airway immune markers among healthy and allergic individuals
Trueba, AF; Rosenfield, D; Oberdorster, E; Vogel, PD; Ritz, T
Psychophysiology, 50(1): 5-14.
10.1111/j.1469-8986.2012.01487.x
CrossRef
Journal of Burn Care & Research
American Burn Association Practice Guidelines for Prevention, Diagnosis, and Treatment of Ventilator-Associated Pneumonia (VAP) in Burn Patients
Mosier, MJ; Pham, TN
Journal of Burn Care & Research, 30(6): 910-928.
10.1097/BCR.0b013e3181bfb68f
PDF (342) | CrossRef
Critical Care Medicine
2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference
Levy, MM; Fink, MP; Marshall, JC; Abraham, E; Angus, D; Cook, D; Cohen, J; Opal, SM; Vincent, J; Ramsay, G; For the International Sepsis Definitions Conference,
Critical Care Medicine, 31(4): 1250-1256.
10.1097/01.CCM.0000050454.01978.3B
PDF (279) | CrossRef
Current Opinion in Critical Care
New diagnostic and prognostic markers of ventilator-associated pneumonia
Chastre, J; Luyt, C; Trouillet, J; Combes, A
Current Opinion in Critical Care, 12(5): 446-451.
10.1097/01.ccx.0000244125.46871.44
PDF (106) | CrossRef
Current Opinion in Critical Care
Biomarkers to improve diagnostic and prognostic accuracy in systemic infections
Schuetz, P; Christ-Crain, M; Müller, B
Current Opinion in Critical Care, 13(5): 578-585.
10.1097/MCC.0b013e3282c9ac2a
PDF (242) | CrossRef
Current Opinion in Pulmonary Medicine
Diagnostic strategies for nosocomial pneumonia
Soto, GJ
Current Opinion in Pulmonary Medicine, 13(3): 186-191.
10.1097/MCP.0b013e3280ef6941
PDF (116) | CrossRef
Back to Top | Article Outline

© 2002 American Society of Anesthesiologists, Inc.

Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.
Login

Article Tools

Images

Share