Hindawi

Disease Markers
Volume 2018, Article ID 5607932, 6 pages
https://doi.org/10.1155/2018/5607932

Research Article
Roles of Procalcitonin and N-Terminal Pro-B-Type Natriuretic
Peptide in Predicting Catheter-Related Bloodstream Infection in
Severe Burn Injury Patients

Baochun Zhou , Jianjun Zhu, Ziruo Mao, and Lijun Liu

Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

Correspondence should be addressed to Lijun Liu; [email protected]

Received 5 July 2018; Revised 8 October 2018; Accepted 31 October 2018; Published 22 November 2018

Academic Editor: Michael Hawkes

Copyright © 2018 Baochun Zhou et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. To investigate the characteristics of early catheter-related bloodstream infection (CRBSI) in severe burn injury patients
induced by a massive aluminum dust explosion. Methods. Sixty-eight severe burn injury patients experienced a massive dust
explosion in Kunshan were included in this study. Patients received central venous catheter placement, arterial catheterization
to monitor blood pressure and PiCCO cardiac monitoring, tracheostomy, mechanical ventilation, analgesics and sedation
treatment, and fluid resuscitation. Clinical data including age, gender, burn surface area, fluid intake and output, urine
temperature, and APACHE II score information were collected from each patient. Ultrasound screening was performed to
exclude heart failure, which may lead to the change of NT-proBNP. When CRBSI was suspected, 10 ml central venous blood
and peripheral arterial blood were sent for testing. For patients with suspected CRBSI, the level of PCT and NT-proBNP were
monitored every day until the infection was controlled. Results. Among the 68 patients, 29 showed CRBSI. The most common
pathogenic bacteria of CRBSI were A. baumannii (39.8%), P. aeruginosa (26.4%), and K. pneumoniae (13.7%). Procalcitonin
(PCT) (2.98 ng/ml) and NT-proBNP (355 pg/ml) were significantly associated with CRBSI results. The sensitivity of PCT, NT-
proBNP, WBC, and CRP was 94.2%, 89.7%, 88.3%, and 90.5%, respectively (P < 0 05). The area under curve (AUC) of PCT
combined with NT-proBNP for prediction of CRBSI was 0.981, and the sensitivity and specificity was 0.812 and 0.857,
respectively. Conclusion. PCT and NT-proBNP combination improves the diagnosis of CRBSI. PCT and NT-proBNP may be
alternative candidates for potential prediction of CRBSI in patients with severe injury.

1. Backgrounds Procalcitonin (PCT) has been considered as a serum

marker for assessing infection and systemic inflammatory
Catheter-related blood stream infection (CRBSI), one of response syndrome (SIRS) [5]. Recently, it has been used
the most frequent and lethal nosocomial infections, is an to evaluate infection in patients with burn injury [6, 7].
important cause for hospital-acquired infection with a However, in patients with severe blast injury, little is known
high morbidity and mortality. Individuals with extensive about the accuracy of PCT in CRBSI diagnosis [8–10]. Brain
skin injury and rupture of anatomic barrier are reported natriuretic peptide (BNP) and N-terminal pro-B-type natri-
to show high risks of CRBSI. Generally, the symptoms of uretic peptide (NT-proBNP), two important markers of
CRBSI are usually vague as they are covered by systemic heart failure recently reported to be associated with infec-
signs and sustained inflammatory reaction resulting from tion, are also important predictors of infection-related mor-
severe thermal injury. In clinical setting, delayed diagnosis tality in nonburn sepsis patients [11]. However, rare studies
is still the major challenge due to the lack of diagnostic have been carried out to investigate the roles of these
markers with high sensitivity and specificity [1–4]. There- markers in predicting CRBSI [12].
fore, it is necessary to identify potential biomarkers of In this study, serum PCT and NT-proBNP in patients
CRBSI in a population with severe burn injury. with severe burn were detected in a dynamical manner.
2 Disease Markers

We aim to evaluate the potential roles of serum PCT and Table 1: General information of the patients.
NT-proBNP in predicting CRBSI in patients with severe
explosion injury. General information Value
Gender (male/female) 47/21
2. Material and Methods Age 38.3 ± 7.3
Total burn surface area (%) 91.5 ± 7.1
2.1. Patients. This is an observational study of a cohort of
Burn surface area of stage II partial thickness (%) 23.6 ± 4.5
patients with burn injury in August 2014 in Kunshan.
Patients admitted to the ICUs in the Second Affiliated Hos- Burn surface area of stage II full thickness (%) 50.1 ± 5.7
pital of Soochow University, the First Affiliated Hospital of Burn surface area of stage III (%) 21.7 ± 8.3
Soochow University, Suzhou Municipal Hospital, and the ICU length of stay (days) 71.2 ± 17.8
First People’s Hospital of Kunshan were included in this Initial time of CRBSI (ICU day) 10.6 ± 3.4
study. The end point of this study was mortality or transfer Admission APACHE II score 22.3 ± 7.6
of patients on day 90 after ICU hospitalization. Severe burn Outcome (90 days)
was formulated in accordance with the Chinese consensus of
Death 21
severe burns in 1970 in which total burn is categorized as a
surface area with more than 50% burn [13]. Patients with a Continuous ICU management 25
total burn area of less than 50% were not included in this Transferred to regular wards 22
study. Written informed consent was obtained from the
relatives of the patients. The study protocols were approved
by the local ethics committee.
2.2. Clinical Treatment. Upon ICU admission, all patients
received general management including central venous cath-
eter placement (two-lumen central venous catheterization, 10.9%
Arrow), Foley catheter placement, fentanyl and midazolam
for analgesia and sedation, tracheal cannula or tracheos- 9.20%
tomy, mechanical ventilation, invasive arterial catheter
39.80%
placement to monitor blood pressure, continuous cardiac
output monitoring, fluid resuscitation, and target tempera-
13.70%
ture management (target temperature: 36-37°C). Besides,
wound care including partially exposed or exposed care
was given to these patients. For circumferential burns
(degree three) or tension scar, escharotomy was performed
to prevent ischemia and necrosis of the distal or deep tissue 26.40%
or to correct restrictive respiratory or circulatory function.
Broad-spectrum antibiotics (Carbapenems) were used to
prevent infection. After the acute phase, all patients contin-
uously received mechanical ventilation, analgesics and seda-
tion, nutritional support, debridement, and skin grafting.
A.baumannii MRSA
2.3. Diagnosis of CRBSI. The diagnostic criteria of CRBSI P.aeruginosa Others
were in accordance with the guidelines of the Infectious K.pneumoniae
Disease Society of America [14]. Upon suspicious symptoms
of CRBSI including fever, chills, hypotension, and SIRS, Figure 1: Bacterial spectrum of CRBSI-positive catheters.
10 ml central venous blood and peripheral arterial blood
were sent for aerobic or anaerobic culture using BACTEC-
9120, VITEK-32 automatic microbial analysis system and catheters were recorded including fluid infusion quantity,
supporting culture bottles, bacterial identification card, and antibiotic utilization, indwelling days, maintenance fre-
anaerobic culture kits and medium (bioMérieux, France). quency and material, fever, and blood culture. Sampling
The culture temperature was set at 35.5°C. Negative report of each removed catheter was conducted to monitor
timeline was usually set as 5 days after incubation. When catheter-related infections. Strict aseptic procedures were
positive results were reported, the cultures were implanted carried out to avoid contaminating the wound near the
to the corresponding medium and the pathogenic strains insertion site. Ultrasound screening was performed, and
were isolated by aerobic and/or anaerobic culture at 36°C. the cardiac parameter (LA diameter, LA diameter, LV sys-
All the isolated strains obtained from the anaerobic culture tolic dimension, ventricular septal thickness, and ventricu-
were subject to oxygen tolerance test. lar septal thickness) were recorded every 3 days. For
patients with suspected infection, the level of PCT and
2.4. Data Measurement. For each patient, the circumstances NT-proBNP (Roche Diagnostics) were monitored every
of insertion and the parameters related to indwelling day until infection was controlled.
Disease Markers 3

Table 2: Body temperature, white blood cell, CRP, PCT, and fluid balance during the first week in the ICU.

Data D1 D2 D3 D4 D5 D6 D7
Temperature (°C) 35.19 ± 1.02 36.22 ± 1.55 36.44 ± 0.92 36.52 ± 0.90 36.74 ± 1.40 36.96 ± 0.94 37.39 ± 1.04
WBC (109/l) 36.29 ± 13.91 20.16 ± 5.20 10.80 ± 3.52 8.03 ± 2.41 7.49 ± 3.17 8.93 ± 4.27 8.41 ± 2.77
CRP (mg/l) 37.26 ± 24.29 72.77 ± 34.97 70.53 ± 38.85 67.42 ± 44.82 62.79 ± 31.35 90.01 ± 40.63 96.53 ± 49.91
PCT (ng/ml) 11.83 ± 8.11 7.78 ± 5.20 4.89 ± 3.92 2.72 ± 1.88 1.62 ± 1.22 1.57 ± 0.94 1.34 ± 0.90
NT-proBNP (pg/ml) 100 ± 22 160 ± 30 200 ± 11 250 ± 41 180 ± 33 120 ± 29 310 ± 51
Fluid balance (ml) 4791 ± 324 1782 ± 418 2928 ± 2356 2297 ± 504 4289 ± 482 3290 ± 120 3324 ± 107
D1–D7: day 1 to day 7.

Table 3: Cardiac parameter followed by echocardiogram.

Cardiac parameter Minimum Maximum Mean ± SD

LA diameter (mm) 30.7 46.6 37.9 ± 4.4
LV diastolic dimension (mm) 41.0 54.2 49.6 ± 3.4
LV systolic dimension (mm) 26.5 39.8 31.7 ± 3.9
Ventricular septal thickness (mm) 8.1 12.0 9.4 ± 3.1
LV ejection fraction (%) 58.0 74.0 66.1 ± 5.2

Table 4: ROC curve analysis of PCT, NT-proBNP, WBC, and CRP during the first week.

Parameter Area under the curve Best cutoff value Sensitivity Specificity Youden index 95% CI P value
PCT (ng/ml) 0.856 2.98 0.909 0.583 0.492 0.743~0.970 0.000
NT-proBNP (pg/ml) 0.963 355 1.000 0.625 0.625 0.918~1.00 0.000
WBC 0.514 12 0.682 0.583 0.265 0.342~0.687 0.088
CRP (mg/ml) 0.190 55 0.545 0.833 0.378 0.062~0.319 0.065

Table 5: ROC curve analysis of PCT, NT-proBNP, WBC, and CRP during the second week.

Parameter Area under the curve Best cutoff value Sensitivity Specificity Youden index 95% CI P value
PCT 0.793 3.67 0.942 0.523 0.502 0.861~0.967 0.000
NT-proBNP 0.849 285 0.897 0.661 0.629 0.907~0.994 0.003
WBC 0.722 19 0.883 0.514 0.556 0.782~0.938 0.014
CRP 0.698 72 0.905 0.679 0.611 0.707~0.929 0.009
PCT + NT-proBNP 0.981 0.812 0.857 0.753 0.853~0.908 0.000

2.5. Statistical Analysis. Data with normal distribution were unhealed large wound or respiratory support, and 22
expressed as mean ± standard deviation (SD). These data patients were transferred to the regular wards.
were analyzed with SPSS 19 software. The specificity and
sensitivity of PCT, NT-proBNP, WBC, and CRP for 3.2. Bacterial Spectrum of CRBSI Catheters. Bacterial
CRBSI were evaluated, and ROC (receiver operating char- spectrum of CRBSI-positive catheters is shown in Figure 1.
acteristic) curves were plotted. P < 0 05 was considered to The most common pathogenic bacteria were Acinetobacter
be statistically significant. baumannii (39.8%), followed by Pseudomonas aeruginosa
(26.4%), Klebsiella pneumoniae (13.7%), and Methicillin-
resistant Staphylococcus aureus (MRSA, 9.2%).
3. Results
3.3. Body Temperature, WBC Count, CRP, PCT, NT-proBNP,
3.1. Patients’ Characteristics. A total of 68 patients (male: and Fluid Balance during the First Week in the ICU. On the
41; female: 27; mean age: 38.3 ± 7.3 years) were finally first day after burn, the average body temperature decreased.
included in this study (Table 1). The burn area ranged Thereafter, the average temperature increased steadily from
from 75% to 99%. The mean duration of ICU stay was day 2 to day 7 (Table 2). The average WBC count was signif-
71.2 ± 17.8 days. APACHE II score at admission was icantly elevated on day 1 after burn and then declined back
22.3 ± 7.6. About 90 days after admission, 21 patients died, to normal by day 4. CRP had a slight increase but no obvious
25 patients received further treatment in the ICU for trend in changing. PCT was significantly elevated on day 1
4 Disease Markers

after burn and then decreased each subsequent day. On PCT, a precursor of calcitonin, is produced by the liver,
day 7, PCT was still higher than normal. No significant fat cells, lung, and muscle cells [22]. Lipopolysaccharide
correlation was noticed between NT-proBNP and fluid (LPS) and sepsis-related inflammatory factors such as
balance (P > 0 05). TNF-α and IL-6 can regulate the secretion of PCT [23].
Severe inflammatory factors, including IL-6 and TNF-α that
3.4. Echocardiogram of Patients Every 3 Days during exist in severe burn patients, contribute to the secretion of
Hospitalization. Table 3 shows the echocardiogram of the PCT [22]. Indeed, it may be a mechanism in which PCT
patients performed every 3 days during hospital stay. Our showed initial increase. PCT has been considered as a
data showed that there were no obvious abnormalities in marker of infection [5], but there are substantial disputes
cardiac function among these patients (Table 3). on its ability in predicting infection in patients with burn
injury [1, 6, 7, 24, 25]. Partly, such uncertainty may result
3.5. ROC Curve Analysis. ROC curves were depicted to from a wide range of infection including wound, pulmonary,
evaluate the specificity, sensitivity, and accuracy of PCT, urinary tract, and blood, which may elicit differing PCT
NT-proBNP, WBC, and CRP in CRBSI within 2 weeks. responses. We are aware that there is no specific study on
The sensitivity of PCT and NT-proBNP were 90.9% and PCT for the prediction of CRBSI in burn patients [8–10].
100% during the first week, respectively (Table 4). This Our study indicated that PCT might serve as a candidate
indicated that PCT and NT-proBNP were statistically biomarker for predicting CRBSI in burn patients.
significant to predict CRBSI during the first week. BNP and NT-proBNP are neurohormones secreted from
However, CRP and WBC were not found to be sensitive cardiac ventricles in response to left ventricular strain or
during this period (P > 0 05). Additionally, during the fluid overload [26]. At present, BNP is mainly used as a
second week, the sensitivity of PCT, NT-proBNP, WBC, biomarker for heart failure [27]. Among these young and
and CRP was 94.2%, 89.7%, 88.3%, and 90.5%, respectively adult cases, cardiomyopathy indicated no obvious changes
(P < 0 05, Table 5). This implied that PCT, NT-proBNP, in the cardiac function. Therefore, no correlation was
WBC, and CRP were markedly sensitive for predicting noticed between NT-proBNP elevation and cardiac
CRBSI (P < 0 05). The area under curve (AUC) of PCT function. Recently, several studies have reported that BNP
combined with NT-proBNP for prediction of CRBSI was and NT-proBNP are also elevated in the setting of
0.981, and the sensitivity and specificity were 0.812 and infection [28–31]. In a previous study, the severity of the
0.857, respectively. infection was positively associated with the elevation of
BNP [32]. Our data indicated that NT-proBNP was highly
4. Discussion sensitive and reasonably specific for predicting CRBSI in
burn patients, which was superior to PCT. Under normal
Indwelling central venous catheterization is necessary for the conditions, NT-proBNP is a nonactive precursor of BNP
management of critically ill patients. This increases the risk of cleared primarily by the kidney [33]. In case of infection,
CRBSI. Infection is the main cause of death in well-managed the clearance of BNP is impaired [34], which may trigger an
patients with severe burn injury [15]. Therefore, prediction of elevation of NT-proBNP in CRBSI. Besides, further studies
CRBSI is more important in clinical implications. In the are required to investigate the potential mechanisms. The
present study, patients with severe burn injury in Kunshan combination of PCT and NT-proBNP contributed to the
were almost at a young age with a healthy condition before diagnosis accuracy of CRBSI, which was in line with the
injury. We found that the leading three bacterial species previous study [35].
were A. baumannii, P. aeruginosa, and K. pneumonia. Our Indeed, there are some limitations in this study. The
data showed that PCT and NT-proBNP combination patients included in this study were those who suffered from
improves the diagnosis of CRBSI. PCT and NT-proBNP burn injury due to sudden onset of explosion that was
could serve as candidates for predicting CRBSI. uncontrolled. Besides, this study was not a randomized
In a previous study, gram-negative bacteria are the major control study.
pathogenic bacteria in burn patients [15], which differ from In summary, PCT and NT-proBNP combination
the pathogenic bacteria of CRBSI in nonburn ICU patients improves the diagnosis of CRBSI. PCT and NT-proBNP
[16]. The elevation of WBC, NT-proBNP, and CRP caused may be alternative candidates for the potential prediction
by excessive inflammatory reactions in burn patients may of CRBSI in patients with severe injury.
affect their efficiency for prediction of infection [17–19].
WBC and N-proBNP could be easily influenced by many
factors, such as severe stress, trauma, bleeding, and certain Data Availability
medications (e.g., steroids). CRP is an acute phase reaction
protein synthesized by the liver and mediated by All the data were available upon appropriate request.
interleukin-6 (IL-6) and tumor necrosis factor (TNF) [20].
Prior studies indicated that CRP could not be used as a
marker of infection in burn patients [4, 21]. In this study, Conflicts of Interest
WBC and CRP could not be utilized to predict CRBSI in
the first week, but they were markedly associated with The authors declare that there is no conflict of interest
CRBSI during the second week. regarding the publication of this paper.
Disease Markers 5

Authors’ Contributions [12] N. Li, Y. Zhang, S. Fan, J. Xing, and H. Liu, “BNP and NT-
proBNP levels in patients with sepsis,” Frontiers in Bioscience,
Baochun Zhou and Jianjun Zhu contributed equally to vol. 18, no. 4, pp. 1237–1243, 2013.
this work. [13] Third Military Medical University burn prevention research
collaboration group, Burn Therapy Beijing: People's Medical
Publishing House, pp. 164-165, Burn Prevention and Cure
Acknowledgments Research Collaboration Group of Third Military Medical
University, 1977.
The study was supported by a project of Health Department [14] L. A. Mermel, M. Allon, E. Bouza et al., “Clinical practice
of Government of Jiangsu Province (H201466), a project of guidelines for the diagnosis and management of intravascular
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