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Eur J Cardiothorac Surg 2005;27:1074-1078
© 2005 Elsevier Science NL
a Department of Thoracic and Cardiovascular Surgery, Jean-Minjoz Hospital, Boulevard Fleming, 25000, Besançon, France
b Department of Medical Biochemistry, Saint-Jacques Hospital, Besançon, France
c Department of Biostatistics and Epidemiology, Medical School, Besançon, France
Received 21 November 2004; received in revised form 20 February 2005; accepted 21 February 2005.
* Corresponding author. Tel.: +33 3 81668664; fax: +33 3 81668661. (E-mail: pierre-emmanuel.falcoz{at}wanadoo.fr).
| Abstract |
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Key Words: Biochemistry Complications of surgery General thoracic surgery Lung infection Morbidity Procalcitonin
| 1. Introduction |
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The aim of this prospective clinical study was twofold: to assess the accuracy of PCT as a marker of postoperative infection after thoracic surgery and to compare it with C-reactive protein (CRP).
| 2. Materials and methods |
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2.2. Procedure
The following data were registered preoperatively (shortly before induction of anesthesia), at hours 8 and 12 following surgery, and daily until postoperative day 5: body temperature, cardiac rhythm, clinical signs of infection or inflammation, white blood cell counts, serum levels of CRP and PCT. Chest radiography was performed preoperatively and daily until postoperative day 5. In addition, based on the registered data, the American College of Chest Physicians definition criteria for systemic inflammatory response syndrome (SIRS) and sepsis were evaluated in all patients [8]. A 24-h perioperative antibiotic prophylaxis was administered to all patients using cefuroxime (Zinnat®, GlaxoSmithKline, Marly-le-Roy, France): 1.5g at the induction of anesthesia, 750mg every 2h during surgery, and 750mg every 8h for 24h following surgery. Chest physiotherapy was started immediately on arrival in the intensive care unit, and early mobilization, usually on postoperative day 1, was implemented.
Diagnosis of postoperative infection was done by bedside clinical examination, systematic screening included chest radiography, leukocyte counts, blood cultures (BACTECPLUS, Becton Dickinson Diagnostic Instrument Systems, Sparks, MD) and, if pneumonia or atelectasis was suspected, bronchial secretion cultures obtained by endotracheal suction. Bacteriological samples were drawn in patients before any antibiotic treatment, other than the systematic perioperative antibiotic prophylaxis. Data collected regarding postoperative infections were blinded to PCT level results. Assessment of infection was defined as the postoperative occurrence of either: pneumonia, empyema, bronchopleural fistula, or wound infection. Postoperative pneumonia was suspected if purulent sputum (yellow or green) was collected or bronchial secretion showed more than 25 leukocytes and yielded growth of relevant pathogens on culture and if at least two of the following criteria were met: (1) white blood cell count greater than 12,000/mm3, (2) body temperature above 38°C, and (3) new or increasing lung infiltrate or atelectasis on conventional chest radiograph. Definitive diagnosis of pneumonia was established in accordance with the definitions of the Centers for Disease Control and Prevention [9]. Each patient presenting the aforementioned criteria of postoperative infection received systematic antibiotic treatment with amoxicillin and clavulanate (Augmentin®, GlaxoSmithKline, Marly-le-Roy, France): 3x1g per day until antibiogram results were received, at which point the treatment was adapted to pathogen(s) involved. Patients were then classified according to their postoperative infectious status into two groups: non-infected patients and infected patients. Mortality was defined as in-hospital death at any time during the postoperative hospitalization period or death within 30 days of surgery.
2.3. Blood sampling and laboratory method
All members of our interdisciplinary team were blinded to the PCT values. All PCT assays were processed at our central laboratory. PCT samples were centrifuged and immediately frozen and stored at 70°C. Assays were performed in batches at the end of the study period. Each of the assays lasted 1
h. The circulating PCT level was measured by LUMItest PCT (BRAHMS Diagnostica GmbH, Berlin, Germany). This immunolumimetric assay is based on the reaction of two antigen-specific monoclonal antibodies that bind procalcitonin (as an antigen) to calcitonin and katacalcin segments. The inter-assay precision of the kit is 610%, the lower limit of detection was 0.08ng/mL, and the normal range for hospital inpatients was found to be <0.5ng/mL. A particle-enhanced turbidimetric immunoassay technique was used to determine the CRP level (IMMAGE, Beckman Coulter Inc., Fullerton, CA). A normal CRP value is less than 5mg/L. The white blood cell count was performed using the ADVIA 60 counter (Bayer Vital GmbH, Leverkusen, Germany). A normal white blood cell count is less than 12,000/mm3.
2.4. Statistical analysis
We analyzed the comparability of the infected and the non-infected group by the
2 test (or Fisher's exact test), the two-group t-test, or the MannWhitney-U test, as appropriate. Analysis of variance/covariance, adjusted on pack-year history in smokers and duration of the operation, was used to compare PCT and CRP concentrations in the two groups.
Sensitivity, specificity, and predictive values of PCT and CRP for discrimination between infected and non-infected patients were calculated. The best cutoff value for both serum PCT and CRP was chosen as the value that optimized sensitivity, specificity, and predictive values. Receiver operating characteristic (ROC) curves were plotted, and the respective areas under them were calculated. The areas under the ROC curves were compared using the Z statistic (two-tailed test).
Data analysis was anonymous and data collection and processing were approved by the institutional review board of our hospital. All statistical analyses were performed with SAS software, version 8.02 (SAS Institute Inc., Cary, NC). Discrete variables are expressed as counts (%) and continuous variables as mean±standard deviation, unless otherwise stated. A P-value
0.05 was considered statistically significant.
| 3. Results |
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3.2. Markers in non-infected patients (n=132)
Fig. 1 shows the PCT and CRP kinetics during the perioperative period for the 132 patients with no postoperative infection. Baseline PCT concentration was 0.23±0.17ng/mL. PCT concentration increased significantly compared to the baseline concentration, with a peak on day 1: 0.37±0.58ng/mL (P=0.02). PCT levels then decreased rapidly and values returned to preoperative levels by day 3. Baseline CRP concentration was 9.15±18.66mg/L. CRP concentration increased significantly versus baseline with a peak on day 2: 69.68±47.13mg/L (P=0.0001). The PCT value was significantly higher in patients having undergone a pneumonectomy (0.73±0.78ng/mL versus 0.54±0.25ng/mL for lobectomy and 0.50±0.35ng/mL for video-surgery; P=0.04). The median CRP value was high in all patients irrespective of the group. PCT concentrations rose moderately above the normal range (
0.5ng/mL) in 35% of patients and exceeded 1ng/mL in 3.8%, whereas CRP increased in all patients.
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| 4. Discussion |
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In the present study, a PCT value of 1ng/mL was found to be the best cutoff value for diagnosis of infection. Thus, in patients with no postoperative infection, a PCT level which is <1ng/mL or steadily decreases is reassuring and may be helpful in deciding on a safe early discharge. Effectively, the negative predictive value of a PCT level below 1ng/mL in the diagnosis of postoperative infection was 97.5%. However, using the threshold of 1ng/mL for diagnosis of infection, five patients were falsely positive in our study (PCT was >1ng/mL in the absence of infection). For these five patients, the increase in PCT concentration in the absence of infection was the result of a persistent postoperative SIRS. Increase in PCT values has been reported previously in patients with SIRS and lung injury. Both Meisner [6] and Molter [7] reported a postoperative increase in PCT values in patients suffering from SIRS in the absence of infection. It is especially noteworthy that the median PCT value we obtained with these five patients was much closer to the median PCT value in Meisner's study [6]: 1.32 and 1.61ng/mL, respectively. Hensel [10] also showed high PCT values in patients with acute lung injury after cardiac surgery in the absence of infection. On the other hand, with the 1ng/mL cutoff, one of our patients with criteria for pneumonia was falsely negative (PCT was <1ng/mL in the presence of proven infection). Apart from the fact that this patient had had preoperative chemotherapy, no satisfactory explanation was found for this discordance in findings.
A result that might be somewhat disturbing to readers is that the 63% positive predictive value we calculated with a PCT cutoff of 1ng/mL is relatively low. However, the positive predictive value depends on the prevalence of the disease in a given population [11]. In the present study, the prevalence of infection was 16%. If we had performed a post hoc analysis by restricting the scope of this work to the 40 patients with SIRS criteria (body temperature >38°C and a ventricular rate >90 beat per minute), the prevalence would have been 62.5% and the positive predictive value, therefore, 90%. Comparing the patients presenting with or without postoperative SIRS, a significant difference in PCT concentration between groups was observed (1.89±4.65ng/mL in patients with SIRS versus 0.82±0.83ng/mL in patients without SIRS; P=0.01). Accordingly, combining SIRS criteria with PCT levels allows to detect patients at risk for infection and help to select those in whom antibiotic prophylaxis should be transformed into early curative treatment.
Interestingly, another study on the diagnostic role of PCT in early detection of infection after cardiac surgery [12] used the same cutoff value as ours1ng/mL. PCT has also been found useful in differentiating bacterial infection from acute rejection after heart and lung transplantation [13]. In this circumstance, a PCT value >1ng/mL was considered suggested of infection. Similar results have been reported in liver [14] and renal transplanted patients [15].
One limitation does need to be mentioned. Although this study was built to take into account all types of postoperative infection, the population of patients studied only developed pneumonia. Obviously, our observations need to be confirmed in further studies before definite recommendations can be made regarding the use of PCT during the postoperative course of thoracic surgery in general and the optimal cutoff value of PCT in particular.
In conclusion, PCT can be used as a reliable diagnostic marker to detect and to monitor infectious complications in the postoperative period after thoracic surgery, especially in patients felt to be at higher risk (SIRS). It provides more information about the course of the disease than CRP does, and can be detected before the occurrence of clinical infection.
| Acknowledgments |
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| Footnotes |
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Presented at the joint 18th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 12th Annual Meeting of the European Society of Thoracic Surgeons, Leipzig, Germany, September 1215, 2004. | References |
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