Diagnostic Value of Procalcitonin on Early
Postoperative Infection After Pediatric Cardiac
Surgery
Xia Li, MD1; Xu Wang, MD1; Shoujun Li, MD2; Jun Yan, MD2; Dan Li, PhD1
Objectives: Assess the diagnostic value of serial monitoring of
procalcitonin levels on early postoperative infection after pediatric
cardiac surgery with cardiopulmonary bypass.
Design: Prospective, observational study.
Setting: A pediatric cardiac surgical ICU (PICU) and pediatric
cardiac surgery department at Fuwai Hospital, Chinese Academy
of Medical Sciences, Peking Union Medical College.
Patients: Patients were 3 years old and below, underwent cardiac
surgery involving cardiopulmonary bypass, the Aristotle Compre-
hensive Complexity score was 8 or higher and free from active
preoperative infection or inflammatory disease.
Interventions: Blood samples for measurement of procalcitonin,
C-reactive protein, and WBC were taken before surgery and daily
for 7 days in postoperative period. Clinical, laboratory, and imag-
ing data were collected on enrollment. Procalcitonin, C-reactive
protein, WBC levels, and procalcitonin variation were calculated
and compared between those with and without infection.
Measurements and Main Results: Two hundred and thirty-eight chil-
dren were enrolled. Presence of infection within 7 days of surgery,
length of intubation, and ICU stay were documented. Two indepen-
dent experts in regard to the complete medical chart determined the
final diagnosis of postoperative infection. Infection was diagnosed in
45 patients. Procalcitonin peaked on the first postoperative day. No
differences were found on procalcitonin within 3 days after operation
between the infected and the noninfected patients, and significant
correlation was found between procalcitonin on postoperative days
1–3 and cardiopulmonary bypass duration. Serum procalcitonin
1
Department of Pediatric Intensive Care Unit, National Center for
Cardiovascular Disease and Fuwai Hospital, Chinese Academy of
­ infection (1), has emerged as an early, sensitive, and
Medical Sciences, Peking Union Medical College, Beijing, The People’s
Republic of China.
2
Department of Surgery, Pediatric Cardiac Center,National Center for
Cardiovascular Disease and Fuwai Hospital, Chinese Academy of
Medical Sciences, Peking Union Medical College, Beijing, The People’s
Republic of China.
The authors have disclosed that they do not have any potential conflicts
of interest.
Address correspondence and requests for reprints to: Xu Wang, MD,
E-mail: fwpicu@163.com
Copyright © 2017 by the Society of Critical Care Medicine and the World
Federation of Pediatric Intensive and Critical Care Societies
DOI: 10.1097/PCC.0000000000001118
Pediatric Critical Care Medicine www.pccmjournal.org 1
Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
concentration was always higher than 1.0 ng/mL within 7 days after
surgery and/or procalcitonin variation between postoperative days 4
and 7 was positive in the infected patients. Best receiver operating
characteristics curves area under the curve were obtained for pro-
calcitonin and procalcitonin variation from postoperative days 5 to 7.
WBC- and C-reactive protein–related receiver operating character-
istics curves area under the curve revealed a very poor ability to pre-
dict infection. Logistic regression found that only procalcitonin on
postoperative day 7 and PICU stay was independently correlated
to the infection status. There was no significant correlation between
the absolute value of procalcitonin and timing of infection.
Conclusions: Procalcitonin was more accurate than C-reactive
protein and WBC to predict early postoperative infection, but the
diagnostic properties of procalcitonin could not be observed dur-
ing the first 3 postoperative days due to the inflammatory process
related to cardiopulmonary bypass. The dynamic change of pro-
calcitonin is more important than the absolute value to predict
postoperative infection. The maintenance of a high level (procal-
citonin > 1.0 ng/mL) within 7 days after surgery and/or a second
increase in procalcitonin between the fourth and the seventh
postoperative day could be used as an indicator of postoperative
infection. Continuous procalcitonin monitoring might help to dis-
cover infection earlier. (Pediatr Crit Care Med 2017; XX:00–00)
Key Words: cardiac surgery; cardiopulmonary bypass; congenital
heart disease; postoperative infection; procalcitonin
P
rocalcitonin (PCT), initially described as a marker for
specific indicator of bacterial infection during the last
decade (2, 3). However, recent studies showed that PCT levels
also increased in clinical situations without infections such as
cardiopulmonary bypass (CPB), massive blood transfusion,
trauma, burns, shock, or major surgery (4–7).
Pediatric cardiac surgery with CPB is a major surgery, which
can induce an acute inflammatory response (8). This inflam-
matory response is a result of several stimuli, such as exposure
of blood to nonphysiologic surfaces, surgical trauma, myo-
cardial ischemia-reperfusion, and endotoxin release (9, 10).
Because of this response, conventional clinical and biologic
 Li et al
signs may be misleading in the diagnosis of early postoperative
infection, and the value of PCT remains a matter of debate in
the setting of pediatric cardiac surgery with CPB.
Therefore, the primary aim of our study was to assess the
diagnostic value of serial monitoring of PCT levels on early
postoperative infection in children undergoing pediatric cardiac
surgery with CPB, and to compare it with those of C-reactive
protein (CRP) and WBC count. The secondary objective
included observing the normal profile of PCT, CRP, and WBC.
METHODS
This was a prospective and observational study. The study was
approved by Institutional Review Board of Fuwai Hospital.
Written informed consents for research were obtained from
caretakers of all enrolled patients.
Study Setting and Patient Characteristics
The study setting is a pediatric cardiac surgical ICU (PICU; 22
beds) and pediatric cardiac surgery department (120 beds) at
Fuwai Hospital (1,500 beds), Chinese Academy of Medical Sci-
ences, Peking Union Medical College, Beijing, China.
All children admitted to our PICU after pediatric cardiac
surgery involving CPB from March 2015 to June 2015 were
screened for study eligibility, and finally 238 patients met
the inclusion criteria: 1) Patients were 3 years old and below;
2) Patients underwent cardiac surgery involving CPB; 3) The
Aristotle Comprehensive Complexity (ACC) score (11) was 8
or higher; and 4) Patients were free from active preoperative
infection or inflammatory disease (all of the following criteria
were achieved at study entry: WBC count < 12 × 109/L, PCT <
0.5 ng/mL, body temperature < 37.5°C).
Anesthesia, CPB, and Perioperative Management
Anesthesia was induced with midazolam (0.05 mg/kg) and
fentanyl (5–10 µg/kg), maintained with continuous infusion
of fentanyl (0.05–0.1 µg/kg/min). Trachea intubation was per-
formed after adequate muscular relaxation had been obtained
with pancuronium (0.1 mg/kg). Monitoring included electro-
cardiography, pulse oximetry, end-tidal carbon dioxide, and
invasive arterial blood pressure using a radial artery cath-
eter. Prophylactic antibiotics consisted of cefuroxime-sodium
15–20 mg/kg after induction and maintained q8h within 2 days
after operation.
Heparin (300 UI/kg) was administrated before CPB for
anticoagulant in every patient. Myocardial protection during
CPB was performed with intermittent infusion of cold crystal-
loid cardioplegia and moderate hypothermia (32°C).
After surgery, body temperature, microbiological and radio-
logic examinations, were performed daily, and a blood gas analy-
sis was performed every 4 hours when the patients were in the
PICU. After transferring to general ward, blood gas analysis,
microbiological, and radiologic examinations were performed
when deemed necessary by the physicians. Blood culture was
performed when body temperature was above 38.5°C, and a
secretion sample for microbiological examination was per-
formed when the wound was swelling.
2 www.pccmjournal.org XXX 2017 • Volume XX • Number XXX
Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
Tracheal extubation was performed when patients met all
the following criteria: no severe arrhythmias, no bleeding,
hemodynamic stability, adequate muscle strength, full con-
sciousness, and adequate ventilation.
Biologic Measurement
Blood samples for measurement of serum concentrations of
PCT, CRP, and WBC were obtained separately after induction
of anesthesia (baseline) and daily until the seventh postopera-
tive day (POD).
PCT was measured by an immunoluminometric assay
whose detection limit ranging from 0.05 to 25 ng/mL and nor-
mal value was less than 0.5 ng/mL. CRP was measured by auto-
matic lasernephelometry with normal value less than 8 mg/L.
WBC was determined by using an automatic counter with a
normal value between 4,000 and 10,000 cells/mm3. The coef-
ficient of variation of the measurements was less than 5%.
Diagnosis of Postoperative Infection and Grouping
Postoperative infections were defined as: 1) pneumonia (12):
a) One of the following symptoms occurs: purulent sputum,
auscultation findings suspicious of pneumonia or hypoxemia,
body temperature higher than 38°C; b) Infiltrate on chest radio-
graph; c) Leukocytosis (> 12,000 cells/mm3); and d) Microor-
ganism isolated in bronchial secretions. 2) Deep sternal wound
infection and mediastinitis (13): a) Body temperature greater
than 38°C; b) Leukocytosis (> 12,000 cells/mm3); and c) Pres-
ence of pus, bacterial growth, or both, identified in mediastinal
tissue samples obtained during surgical reexploration. 3) Sep-
sis (14) (according to American College of Chest Physicians/
Society of Critical Care Medicine Consensus Conference).
The final diagnosis of postoperative infection was determined
by two independent experts in regard to the complete medical
chart. In cases of disagreement between the two experts, a third
expert reached a consensus. Each final diagnosis was classified as
certain (high probability), possible, low probability (unlikely),
or absent. The final diagnosis was reached when it was classi-
fied as certain or possible by the experts and ruled out when the
experts classified it as absent or unlikely. Experts were blinded
for PCT but not for WBC and CRP, which are routinely used.
Patients were divided into two groups: the noninfection
group, who did not develop any postoperative infection within
7 days after surgery, and the infection group, who developed
postoperative infection within 7 days after surgery.
Diagnosis of Noninfectious Complications
Because postoperative infection could also be combined with
other noninfectious complications, which interfered with PCT
level, we also assessed postoperative noninfectious complica-
tions. In this study, postoperative noninfectious complications
were defined as: 1) low cardiac output syndrome (LCOS) char-
acterized by clinical signs and symptoms of low cardiac output
(oliguria, tachycardia, poor perfusion, and cardiac arrest) that
required inotropic support greater than or equal to 100% above
baseline, administration of a new inotropic agent, or malignant
ventricular arrhythmia, high output failure necessitating use of
delayed sternal closure/extracorporeal membrane oxygenation
 Cardiac Intensive Care

support or other maneuvers used to improve cardiac output
(i.e., cardiac pacing); 2) renal insufficiency needs peritoneal
dialysis or continuous venovenous hemofiltration treatment;
3) neurologic complication (stroke, ischemic injury); and 4)
gastrointestinal complication (ischemia, bleeding).
Data Collection
At study entry, data regarding patient demographics, anatomic
diagnosis, and ACC score were collected. The CPB time, aor-
tic cross clamp time, vasoactive-inotropic scores (VIS) at 24
hours, the levels of serum aspartate aminotransferase (AST),
alanine aminotransferase (ALT), creatinine and blood urea
nitrogen (BUN) on POD1, the duration of mechanical ventila-
tion, the length of PICU stay, mortality, presence of infection
within 7 days of surgery, and noninfectious complications were
recorded. Serum PCT, CRP, and WBC concentrations were also
recorded daily until POD7. PCT variation was defined by the
equation ([PCTdelayed – PCTinitial]/PCTinitial) × 100%. PCTinitial is
PCT concentration on POD1; PCTdelayed is blood PCT concen-
tration measured at POD2 to POD7. A negative value indicates
a decrease in PCT concentration. VIS is calculated as dopa-
mine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100
× epinephrine dose (μg/kg/min) + 100 × norepinephrine dose
(μg/kg/min) + 15 × milrinone dose (μg/kg/min) + 10,000 ×
vasopressin dose (U/kg/min) (15).
Statistical Analysis
Quantitative variables are presented as mean ± sd or median
(95% CI) in nonnormally distributed variables (Kolmogorov-
Smirnov test), and qualitative data are given as number and
percentage. The values results were not normally distributed
and thus were analyzed nonparametrically. Noninfection and

Table 1. Clinic Characteristics of Patients in the Noninfection and Infection Groups

Infection Group Noninfection Group
Variable (n = 45) (n = 193) p

Age (mo) 8 (0.6–32) 9 (0.7–34) 0.608

Body weight (kg) 7.58 ± 3.01 8.21 ± 2.93 0.149
Male sex (n, %) 29 (64.4) 120 (62.2) 0.417
Aristotle Comprehensive Complexity score 9.47 ± 1.47 9.51 ± 1.53 0.783
Cardiac diagnose 0.586
  Tetralogy of Fallot 12 52
  Total anomalous pulmonary venous connection 5 20
  Double-outlet of right ventricular 6 31
  Total endocardial cushion defect 7 33
  Pulmonary arterial atresia 5 19
  Coarctation of the aorta + ventricular septal defect 4 16
  Transposition of great arteries 6 22
Cardiopulmonary bypass duration (min) 126.3 ± 49.9 121.6 ± 42.5 0.665
Aortic cross clamp (min) 85.7 ± 34.1 81.6 ± 38.7 0.639
Vasoactive-inotropic scores at 24 hr 14.2 ± 6.5 13.9 ± 5.9 0.488
Aspartate aminotransferase (U/L) 152.9 ± 63.1 151.4 ± 59.2 0.606
Alanine aminotransferase (U/L) 28.8 ± 10.5 25.8 ± 8.8 0.281
Creatinine (µmol/L) 44.6 ± 13.2 43.1 ± 12.1 0.329
Blood urea nitrogen (mmol/L) 8.2 ± 2.5 8.1 ± 2.6 0.815
Mechanical ventilation duration (hr) 22 (6–126) 18 (5–54) 0.136
PICU stay (d) 5 (3–15) 3 (1–5) 0.013
Death (n, %) 1 (2.22) 0 0.050
Noninfectious complications (n, %) 5 (11.1) 18 (9.3) 0.554
  Low cardiac output syndrome 3 11
  Renal insufficiency (peritoneal dialysis/continuous 2 7
venovenous hemofiltration)
Data are expressed as mean ± sd, median (95% CI), or number (%).

Pediatric Critical Care Medicine www.pccmjournal.org 3

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
 Li et al

infection were compared by the Mann-Whitney U test or t
test for continuous variables and by chi-square test, and when
appropriate, Fisher exact test for categorical variables. Linear
regression analysis was performed to describe the relationship
between serum PCT concentration and CPB duration. Correla-
tion and scatterplots were calculated and constructed between
the infected patient’s timing of infection and the absolute value
of PCT on the day of infection.
Because WBC, CRP, PCT, and PCT variation are numerical
data, receiver operating characteristics (ROC) curves and area
under the curve (AUC) were computed. For infection predic-
tion, cutoff values for WBC, CRP, and PCT were chosen to cor-
respond to the best respective Youden’s index calculated as follows:
Youden’s index = sensitivity + specificity − 1. Results are expressed
for area under the ROC curves (AUC) as mean (95% CI).
Logistic regression was performed to discriminate if PICU
stay, PCT on POD4 to POD7, PCT variation of POD4 to
POD7–POD1, and WBC on POD2 were independently cor-
related to the infection status.
A p value of less than or equal to 0.05 was considered signif-
icant. All analyses were conducted using SPSS version 20 (IBM
Corporation, New York, NY).
RESULTS
Patient Characteristics
Nine hundred and seventy-six patients were admitted to the
PICU after pediatric cardiac surgery during the study period.
Of these, 238 patients (24.4%) were included in this study,
149 (62.6%) male and 89 (37.4%) female, with a mean age of
9 months (0.6–34 mo) and weight of 8.08 ± 2.96 kg. Cardiac
diagnoses were all complex malformation with an average
ACC score of 9.50 ± 1.51.
Forty-five patients were categorized into the infection
group, 37 patients (82.2%) had pneumonia, one (2.2%) had
mediastinitis, and seven (15.6%) had sepsis, and there was an
excellent agreement between experts for the diagnosis of infec-
tion (98%).
Characteristics of the patients in the two groups are pre-
sented in Table 1. No significant differences were found
regarding age, body weight, sex, ACC score, cardiac diagnose,
duration of CPB and aortic cross clamp, VIS at 24 hours, the
levels of AST, ALT, creatinine and BUN on POD1, the duration
of mechanical ventilation, and noninfectious complications.
The length of PICU stay was longer in the infection group (5 vs
3 d; p = 0.013). One patient (2.22%) in infection group devel-
oped LCOS necessitating use of extracorporeal membrane
oxygenation support and died (1/45 vs 0/173; p = 0.05).
WBC, CRP, PCT, and the Value of PCT Variation in the
Infected and Noninfected Patients
Baseline WBC (8.32 ± 1.71 vs 8.66 ± 2.16 mm–6; p = 0.546),
CRP (7.9 ± 2.1 vs 8.1 ± 2.4 mg/L; p = 0.449), and PCT (0.34
[0.16–0.48] vs 0.26 [0.12–0.38] ng/mL; p = 0.328) were not
significantly different between the infection and noninfection
groups. All preoperative WBCs were less than 12 × 109/L, and
serum PCT concentration was less than 0.5 ng/mL.
After CPB, serum PCT concentration increased signifi-
cantly, peaked on the first POD, and began to decrease from
POD2. In the noninfection group, serum PCT concentration

Table 2. Serum Procalcitonin Concentrations and Procalcitonin Variation of Patients in

the Noninfection and Infection Groups
Infection Group Noninfection Group
Variable (n = 45) (n = 193) p

Baseline PCT (ng/mL) 0.34 (0.16–0.48) 0.26 (0.12–0.38) 0.328

POD1 PCT (ng/mL) 12.69 (1.3–25) 12.09 (1.3–25) 0.928
POD2 PCT (ng/mL) 8.80 (0.5–25) 7.92 (0.9–25) 0.859
POD3 PCT (ng/mL) 4.45 (0.3–25) 3.83 (0.23–25) 0.534
POD4 PCT (ng/mL) 3.35 (0.44–16.3) 1.23 (0.31–8.7) 0.015
POD5 PCT (ng/mL) 2.59 (0.37–6.5) 0.44 (0.1–3.8) < 0.001
POD6 PCT (ng/mL) 2.15 (0.25–4.7) 0.35 (0.05–2.2) < 0.001
POD7 PCT (ng/mL) 1.35 (0.28–3.7) 0.22 (0.05–1.2) < 0.001
Variation PCT POD2 to POD1 (%) –0.28 (–0.89 to 1.58) –0.40 (–0.77 to 1.19) 0.729
Variation PCT POD3 to POD1 (%) –0.51 (–0.98 to 1.47) –0.74 (–0.98 to 0.02) 0.194
Variation PCT POD4 to POD1 (%) –0.66 (–0.98 to 2.36) –0.88 (–0.98 to –0.07) 0.006
Variation PCT POD5 to POD1 (%) –0.75 (–0.96 to 1.52) –0.93 (–0.99 to –0.56) 0.002
Variation PCT POD6 to POD1 (%) –0.81 (–0.97 to 0.04) –0.96 (–0.99 to –0.74) < 0.001
Variation PCT POD7 to POD1 (%) –0.87 (–0.98 to 0.10) –0.97 (–1.0 to –0.84) < 0.001
PCT = procalcitonin, POD = postoperative day.
Data are expressed as median (95% CI).

4 www.pccmjournal.org XXX 2017 • Volume XX • Number XXX

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
 Cardiac Intensive Care

decreased progressively and returned to baseline values on The value of PCT variation was significantly higher in the
POD5, whereas in the infection group, PCT remained elevated noninfected patients than in the infected ones between POD4
thereafter. No differences were found on PCT value within and POD7; from the 95% CI, we can see there were some
3 days after operation between the infected and noninfected positive values in the infection group that indicates a second
patients (p > 0.05), but there were significant differences increase in PCT, whereas in the noninfection group, all values
on PCT level from POD4 to POD7 between the two groups of PCT variation were negative (Table 2).
(p < 0.05) (Table 2 and Fig. 1). Significant correlation Of the 45 infected patients, 19 patients maintain a high level
was found between PCT on POD1 to 3 and CPB duration of PCT (> 1 ng/mL) during the first 7 PODs, whereas in other
(r2 = 0.76, 0.68, and 0.59, respectively). 26 infected patients, the PCT levels showed a different trend,
descended to normal range
within 3 days after surgery, but
appeared a secondary increase
on the fourth and seventh PODs.
WBC and CRP peaked on
POD2 and remained elevated
after the seventh POD in the
two groups (Fig. 1). There
were significant differences of
WBC on POD2 (12.98  ± 
2.28
vs 15.79 ± 4.72 mm–6; p = 0.019)
while the CRP level was not sig-
nificantly different between the
two groups on each POD (Fig. 1).

Diagnostic Value of
WBC, CRP, PCT, and PCT
Variation
ROC curves, AUC for WBC
on POD2, CRP on POD2 (the
maximum value), PCT and PCT
variation from POD4 to 7 were
calculated, and the most accu-
rate cutoff values to distinguish
infection and noninfection were
evaluated. Best ROC curves
AUC were obtained for PCT
and PCT variation from POD5
to POD7 (Table 3). WBC- and
CRP-related ROC curves AUC
revealed a very poor ability to
predict infection (Table 3 and
Fig. 2). When comparing the
ROC curves, PCT and PCT
variation were more accurate
than CRP and WBC for the
diagnosis of postoperative infec-
tion (Fig. 2). The diagnostic vari-
ables of each biologic marker are
depicted in Table 3: PCT was
better than CRP and WBC.

Multivariate Analysis
Between the Infection and
Figure 1. Comparison of (A) WBC count, (B) C-reactive protein (CRP), and (C) procalcitonin (PCT) in the Noninfection Patients
noninfection (circles and dotted line; n = 193) and infection (square and unbroken line; n = 45) groups.
Data are expressed as mean or median. * p < 0.05 (between-group comparisons, Mann-Whitney U test with Logistic regression found that
Bonferroni correction). only PCT on POD7 and PICU

Pediatric Critical Care Medicine www.pccmjournal.org 5

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
 Li et al

Table 3. Comparison of Area Under the Receiver Operating Characteristic Curve and
Efficiency of WBC, C-Reactive Protein, Procalcitonin and Procalcitonin Variation in the
Diagnosis of Postoperative Infection
Area Under
the Receiver
Operating Positive Positive Negative Negative
Characteristic Predictive Likelihood Predictive Likelihood
Variable Threshold Curve Sensitivity Specificity Value Ratio Value Ratio

POD2 WBC 14.1 × 109/L 0.64 0.68 0.67 0.68 2.05 0.67 0.48
(0.48–0.77) (0.45–0.86) (0.43–0.85) (0.45–0.86) (1.3–3.1) (0.43–0.85) (0.2–1.1)
POD2 C-reactive 73.5 mg/L 0.49 0.67 0.47 0.27 1.29 0.84 0.68
protein (0.41–0.58) (0.50–0.83) (0.38–0.57) (0.18–0.37) (1.0–1.7) (0.73–0.92) (0.4–1.1)
POD4 PCT 1.9 ng/mL 0.69 0.63 0.71 0.76 2.11 0.56 0.53
(0.56–0.79) (0.46–0.77) (0.50–0.86) (0.58–0.89) (1.5–3.0) (0.38–0.73) (0.3–1.1)
POD5 PCT 0.97 ng/mL 0.81 0.89 0.71 0.85 3.13 0.79 0.15
(0.68–0.90) (0.75–0.97) (0.48–0.89) (0.70–0.94) (2.3–4.2) (0.54–0.94) (0.05–0.5)
POD6 PCT 0.86 ng/mL 0.85 0.81 0.79 0.85 2.91 0.81 0.12
(0.73–0.93) (0.65–0.92) (0.54–0.94) (0.70–0.94) (2.1–4.0) (0.54–0.96) (0.03–0.4)
POD7 PCT 0.80 ng/mL 0.86 0.70 0.89 0.93 6.68 0.61 0.33
(0.74–0.94) (0.53–0.84) (0.67–0.98) (0.77–0.99) (5.1–8.7) (0.41–0.79) (0.08–1.3)
Variation PCT
POD4 to POD1 –0.77 0.73 0.64 0.71 0.80 2.16 0.58 0.51
(0.61–0.83) (0.45–0.77) (0.50–0.86) (0.61–0.92) (1.5–3.0) (0.41–0.75) (0.2–1.0)
POD5 to POD1 –0.92 0.77 0.84 0.67 0.82 2.51 0.70 0.24
(0.64–0.87) (0.68–0.94) (0.43–0.85) (0.66–0.92) (1.8–3.5) (0.46–0.88) (0.09–0.6)
POD6 to POD1 –0.91 0.82 0.89 0.79 0.89 4.24 0.79 0.14
(0.69–0.91) (0.75–0.97) (0.54–0.94) (0.75–0.97) (3.3–5.5) (0.54–0.94) (0.04–0.5)
POD7 to POD1 –0.95 0.80 0.89 0.63 0.83 2.42 0.75 0.17
(0.67–0.89) (0.75–0.97) (0.38–0.84) (0.67–0.93) (1.7–3.5) (0.48–0.93) (0.06–0.5)
PCT = procalcitonin, POD = postoperative day.
Data are expressed as value
(95% CI).

stay were independently correlated to the infection status with
a p value equals to 0.013 (odds ratio [OR] =3.23 [95% CI,
1.28–8.14]) and p value equals to 0.046 (OR = 1.52 [95% CI,
1.01–2.29]), respectively (Table 4).
The Absolute Value of PCT and the Timing of
Infection
The average time of infection in the 45 infected patients was
5.6 ± 0.9 days after operation, and the average absolute value
of PCT on the day of infection was 3.7 ± 1.8 ng/mL. Figure 3
shows the scatterplot of infected patient’s timing of infection
and the absolute value of PCT on the day of infection, and no
significant correlation was found between them (r2 = 0.147).
DISCUSSION
Very few pediatric studies have analyzed the serial PCT measure-
ments and the value of PCT variation as indicators for postopera-
tive infection after cardiac surgery. To our knowledge, this was the
first study about correlating PCT variation with infection in pedi-
atric patients with complex congenital heart disease. In contrast to
adults, children with complex congenital heart disease are easier to
be affected by longer duration of CPB time, and the inflammatory
response induced by CPB is stronger. All congenital heart disease
(CHD) patients enrolled in this study were complicating complex
malformation (ACC score ≥ 8), which was also a common pre-
disposing factor for pneumonia in children with CHD. Although
patients might be free from active preoperative infection or inflam-
matory disease, they were still a high-risk population of postop-
erative infection. For them, it is difficult to distinguish the higher
level of PCT arises mainly from inflammatory response induced
by CPB or/and infection. We believe that the study about dynam-
ics of PCT levels of this special population will help us discover
and diagnose infection earlier, so as to promote the recovery and
improve prognosis. In our study, we observed that the absolute
value of PCT was higher and the value of PCT variation was lower
in patients with postoperative infection after pediatric cardiac sur-
gery and that PCT was more accurate than WBC and CRP to pre-
dict postoperative infection. Furthermore, the dynamic change of
PCT permitted an early diagnosis. The persistent high level of PCT
(> 1.0 ng/mL) within 7 days after surgery and/or a second increase
in PCT between the fourth and the seventh PODs could be used as
an indicator of postoperative infection.

6 www.pccmjournal.org XXX 2017 • Volume XX • Number XXX

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
 Cardiac Intensive Care

reported to rise earlier than

WBC and CRP after the
onset of bacterial infection
and to decrease earlier dur-
ing the course of controlled
infection (7, 19).
In our study, the diagnostic
value of PCT was higher than
WBC and CRP to predict post-
operative infection (Table 3).
PCT has already been postu-
lated to be superior to CRP
or WBC, and to even correlate
with the severity of bacterial
infection (20−21). The superi-
ority of PCT may be explained
by its more specific increase
in case of bacterial infection
but also by its perioperative
kinetics after CPB. Indeed,
PCT was only transiently
increased after CPB, whereas
the increase in WBC and CRP
was more prolonged and CRP
occurs similarly in infected
Figure 2. Comparison of the receiver operating characteristic curves showing the relation between sensitivity and noninfected patients
(true positive) and 1-specificity (true negative) in determining the predictive value of procalcitonin (PCT) (value (Fig. 1). Therefore, PCT might
on postoperative day [POD] 7), PCT variation (values of POD6 to POD1), C-reactive protein (CRP) (maximum be useful in the early recogni-
value on POD2), and WBC (value on POD2) for the diagnosis of postoperative infection.
tion of an infection after CPB.
Nevertheless, it should be
After CPB, activation of inflammatory cascades may occur, pointed out that the diagnostic properties of PCT could not be
and this reaction shows strong similarity to those observed in observed during the first 3 PODs (Fig. 1 and Table 2).
sepsis (16). In our study, we described the postoperative PCT, After CPB, the cutoff value of PCT as a marker of infection
CRP, and WBC kinetics after cardiac surgery with CPB (Fig. 1) remains a matter of debate. Aouifi et al (22) showed that, in the
and observed that they were all significantly increased after CPB. presence of fever, PCT was reliable for diagnosis of infection
The postoperative rise observed in the noninfected patients after cardiac surgery, with sensitivity and specificity, respec-
is in agreement with previous studies (8, 11, 17). Indeed, an tively, at 0.85 and 0.95, and with a cutoff value of 1 ng/mL.
increase in PCT after CPB in the absence of postoperative Using a cutoff value of 0.5 ng/mL, Al Nawas et al (23) found
infection has already been noted by Minami et al (18). Our sensitivity and specificity of 60% and 79%, respectively. In
study observed an elevated PCT greater than 3 ng/mL within our study, for prediction of infection by PCT, the sensitiv-
3 days after CPB, and no differences between the infected and ity and specificity were 89% and 71%, and with a cutoff value
noninfected patients. This increase interferes with the diag- of 0.97 ng/mL on the POD5, whereas sensitivity and specific-
nosis of infection during the immediate postoperative period. ity on POD6 were 81% and 79% with a threshold of 0.86 ng/
However, in contrast to WBC and CRP that remain elevated mL, and a threshold of 0.80 ng/mL on POD7 had a sensitivity
for up to 1 week after surgery even in the absence of infection, of 70% and a specificity of 89%. However, it should be pointed
PCT has a transient rise and decreased progressively to nor- out that this threshold could be modified by the clinical condi-
mal value by POD5 in the absence of infection. PCT has been tions of the patient. Indeed, we observed high PCT values (>

Table 4. Multivariate Analysis Between the Infection and the Noninfection Groups
95% CI

Variable p OR Inferior Superior

Postoperative day 7 procalcitonin 0.013 3.23 1.28 8.14

PICU stay 0.046 1.52 1.01 2.29
OR = odds ratio.

Pediatric Critical Care Medicine www.pccmjournal.org 7

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
 Li et al

infections (24). Conversely,

we noted that the diagnosis of
infected patients could occur
earlier with continuous PCT
monitoring, allowing an ear-
lier administration of antibi-
otics in infected patients, and
it should be emphasized that
an earlier therapeutic inter-
vention may improve the
prognosis in sepsis and severe
sepsis (3).
Several limitations should
be considered to interpret this
study. First, it was an observa-
tional analysis whose results
support an association and not
necessarily causation. Second,
data come from a single cen-
ter and institution-specific
variables may have influenced
the present results. Therefore,
our results must be further
validated by other multicenter
studies. Third, there were many
Figure 3. Correlation between the infected patient’s timing of infection and the absolute value of procalcitonin manipulations of the PCT data
(PCT) on the day of infection. POD = postoperative day.
and its clinical utility is thus
decreased. A more straightfor-
1 ng/mL) during the first 7 PODs in 19 infected patients, and a
ward data analysis without manipulation could improve the
second increase of PCT between the fourth and seventh PODs
generalizability and utility of the findings. And how to improve
in the other 26 infected patients, and at this time, no clinical
the generalizability and utility of the findings will be the direc-
sign of an infection was evident. There was no significant cor-
tion of our research work in the future.
relation between timing of infection and the absolute value of
PCT (Fig. 3). In summary, the dynamic change of PCT is more
important than the absolute value to predict postoperative CONCLUSIONS
infection, and the maintenance of a high level and/or a delayed PCT was more accurate than CRP and WBC to predict early
increase in PCT beyond the first 3 PODs could be used as an postoperative infection, but the diagnostic properties of PCT
indicator of postoperative infection. could not be observed during the first 3 PODs due to the
Our study provides some interesting information regard- inflammatory process related to CPB. The dynamic change of
ing the kinetics of PCT that is important for conducting future PCT is more important than the absolute value to predict post-
research. First, it is obvious that, because of the inflammatory operative infection. The maintenance of a high level (PCT >
process related to CPB, all biomarkers increased during the first 1.0 ng/mL) within 7 days after surgery and/or a second increase
3 PODs, thus precluding any diagnostic usefulness (Fig. 1). At in PCT between the fourth and the seventh PODs could be
least in pediatric cardiac surgery, only the maintenance of a high used as an indicator of postoperative infection. Continuous
level and/or a delayed increase in PCT beyond the early period PCT monitoring might help to discover infection earlier and
could be used as an indicator of postoperative infection. This to know in whom there is a need for intensified monitoring.
has several important consequences: 1) timing of the dosage is
an important issues; 2) the early postoperative period, during ACKNOWLEDGMENTS
which the diagnostic value of the biomarker is expected to be We would like to thank the nurses and staff of the PICU and
null because of the inflammatory process, should be precisely pediatric cardiac surgery department at Fuwai Hospital for
defined; and 3) beyond that early period, any maintenance of a their valuable contributions to our project.
high level or further increase in the biomarker should be con-
sidered for the diagnosis of postoperative infection.
From our study, we thought the diagnostic value of PCT REFERENCES
1. Laffey JG, Boylan JF, Cheng DC: The systemic inflammatory
would help to decide which patients should be treated with anti- response to cardiac surgery: Implications for the anesthesiologist.
biotics, as already shown in patients with lower respiratory tract Anesthesiology 2002; 97:215–252

8 www.pccmjournal.org XXX 2017 • Volume XX • Number XXX

Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited

2. Abraham E, Matthay MA, Dinarello CA, et al: Consensus confer-
ence definitions for sepsis, septic shock, acute lung injury, and acute
respiratory distress syndrome: Time for a reevaluation. Crit Care Med
2000; 28:232–235
3. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy
Collaborative Group: Early goal-directed therapy in the treatment of
severe sepsis and septic shock. N Engl J Med 2001; 345:1368–1377
4. Assicot M, Gendrel D, Carsin H, et al: High serum procalcitonin
concentrations in patients with sepsis and infection. Lancet 1993;
341:515–518
5. Gendrel D, Assicot M, Raymond J, et al: Procalcitonin as a marker
for the early diagnosis of neonatal infection. J Pediatr 1996;
128:570–573
6. Harbarth S, Holeckova K, Froidevaux C, et al; Geneva Sepsis
Network: Diagnostic value of procalcitonin, interleukin-6, and inter-
leukin-8 in critically ill patients admitted with suspected sepsis. Am J
Respir Crit Care Med 2001; 164:396–402
7. Claeys R, Vinken S, Spapen H, et al: Plasma procalcitonin and
C-reactive protein in acute septic shock: Clinical and biological cor-
relates. Crit Care Med 2002; 30:757–762
8. Lecharny JB, Khater D, Bronchard R, et al: Hyperprocalcitonemia in
patients with perioperative myocardial infarction after cardiac surgery.
Crit Care Med 2001; 29:323–325
9. Dörge H, Schöndube FA, Dörge P, et al: Procalcitonin is a valuable
prognostic marker in cardiac surgery but not specific for infection.
Thorac Cardiovasc Surg 2003; 51:322–326
10. Prat C, Ricart P, Ruyra X, et al: Serum concentrations of procalcitonin
after cardiac surgery. J Card Surg 2008; 23:627–632
11. Kallel S, Abid M, Jarraya A, et al: [Kinetics, diagnostic and prognostic
value of procalcitonin after cardiac surgery]. Ann Biol Clin (Paris)
2012; 70:567–580
12. Society of Critical Care Medicine Consensus Conference Committee,
American College of Chest Physicians/Society of Critical Care
Medicine Consensus Conference: Definitions for sepsis and organ
failure and guidelines for the use of innovative therapies in sepsis. Crit
Care Med 1992; 20:864–874
Pediatric Critical Care Medicine www.pccmjournal.org 9
Copyright © 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
Cardiac Intensive Care
13. El Oakley RM, Wright JE: Postoperative mediastinitis: Classification
and management. Ann Thorac Surg 1996; 61:1030–1036
14. Hanley JA, McNeil BJ: A method of comparing the areas under
receiver operating characteristic curves derived from the same cases.
Radiology 1983; 148:839–843
15. Lacour-Gayet F, Clarke D, Jacobs J, et al; Aristotle Committee: The
Aristotle score for congenital heart surgery. Semin Thorac Cardiovasc
Surg Pediatr Card Surg Annu 2004; 7:185–191
16. Aouifi A, Piriou V, Blanc P, et al: Effect of cardiopulmonary bypass
on serum procalcitonin and C-reactive protein concentrations. Br J
Anaesth 1999; 83:602–607
17. Prat C, Ricart P, Ruyra X, et al: Serum concentrations of procalcitonin
after cardiac surgery. J Card Surg 2008; 23:627–632
18. Minami E, Ito S, Sugiura T, et al: Markedly elevated procalcitonin in
early postoperative period in pediatric open-heart surgery: A prospec-
tive cohort study. J Intensive Care 2014; 2:38–42
19. Oberhoffer M, Karzai W, Meier-Hellmann A, et al: Sensitivity and
specificity of various markers of inflammation for the prediction of
tumor necrosis factor-alpha and interleukin-6 in patients with sepsis.
Crit Care Med 1999; 27:1814–1818
20. Gendrel D, Raymond J, Assicot M, et al: Measurement of procalcito-
nin levels in children with bacterial or viral meningitis. Clin Infect Dis
1997; 24:1240–1242
21. BalcI C, Sungurtekin H, Gürses E, et al: Usefulness of procalcitonin
for diagnosis of sepsis in the intensive care unit. Crit Care 2003;
7:85–90
22. Aouifi A, Piriou V, Blanc P, et al: Effect of cardiopulmonary bypass
on serum procalcitonin and C-reactive protein concentrations. Br J
Anaesth 1999; 83:602–607
23. Al Nawas B, Krammer I, Shah PM: Procalciltorin in diagnosis of
severe infections. Eur J Med Res 1996; 1:331–333
24. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al: Effect of pro-
calcitonin-guided treatment on antibiotic use and outcome in lower
respiratory tract infections: Cluster-randomised, single-blinded inter-
vention trial. Lancet 2004; 363:600–607