Introduction
Sepsis is a systemic inflammatory response of the
body to an antigen (1) caused by
infection. Severe sepsis can lead to 27 organ dysfunction and/or
tissue perfusion, and even shock (2). It can become a life-threatening
condition by triggering a cascade of changes leading to multiple
organ failure. Sepsis has a relatively high incidence in intensive
care unit (ICU) in Poland (3). The
majority of deaths associated with sepsis are incurred by organ
failures, especially heart failures (4,5).
However, there is a lack of effective biomarkers that facilitate
prognosis. N-terminal of the prohormone brain natriuretic peptide
(NT-proBNP) and cardiac troponin T (cTnT) are myocardial injury
markers. These markers are used as a screening tool for the
diagnosis of cardiovascular complications (6). Different levels of NT-proBNP and cTnT
in the plasma of patients with sepsis may play different roles on
the prognosis of the disease (7–9).
In the present study, 38 cases of hospitalized
patients having sepsis were investigated to examine the plasma
levels of NT-proBNP and cTnT and to investigate their prognostic
significance. The results showed that the plasma levels of
NT-proBNP and cTnT may be used as routine clinical biomarkers to
assess the prognosis of patients with sepsis.
Materials and methods
Patients
A total of 38 cases were identified from the ICU of
the Xiangyang Hospital Affiliated to Hubei University of Medicine
(Hubei, China). Patient diagnosis was confirmed as per the criteria
issued in 2001, by the American College of Chest Physicians or
Society of Critical Care Medicine (10). Any patients with acute coronary
syndrome, congestive heart failure and increasing levels of
NT-proBNP and cTnT incurred by cardiopulmonary resuscitation,
cardiothoracic surgery, hepatic and renal dysfunction within one
month, were excluded. Of the 38 cases, 21 cases were male and 17
cases were female, with an age of 52–71 years. Following admission,
the patients were administered early fluid resuscitation and bundle
treatment in accordance with the guidelines (2). The levels of NT-proBNP and cTnT as well
as organ functions were monitored. Based on their prognosis, the
patients were divided into the survival and death groups. The
survival group comprised 22 cases, 13 cases were male and 9 cases
were female, with an average age of 57.96±13.66 years. The
infection sites identified were as follows: 13 cases, lung; 5
cases, abdomen; 1 case, urinary tract and 3 cases, other sites. The
death group included 16 cases with 8 cases being male and 8 cases
being female, with an average age of 60.94±10.03 years. The
infection sites for this group were: 11 cases, lung; 3 cases,
abdomen; 1 case, urinary tract and 1 case, other site. Differences
regarding age, gender, and infection site between the two groups
were not statistically significant (P>0.05).
Blood sampling
Venous blood (3 ml) was collected from patients
under quiescent condition every morning on the 1st, 3rd and 7th day
of admission. The blood samples were placed into test tubes with
EDTA to prevent anticoagulation and were immediately sent for
analysis to determine NT-proBNP and cTnT levels.
Analysis for NT-proBNP and cTnT
The NT-proBNP detector was provided by Roche
Diagnostics GmbH (Mannheim, Germany), combined with
electrochemiluminescence for detection of plasma levels. Detection
was carried out strictly by a specially-assigned pathologist. The
normal reference value was taken as <900 pg/ml.
Electrochemiluminescence was applied to measure the level of serum
cTnT. A detector was produced using the kit provided by Roche
Diagnostics GmbH. The normal reference value was considered as 0.1
ng/ml.
Statistical analysis
SPSS 20.0 statistical software (IBM SPSS, Armonk,
NY, USA) was used for statistical analysis. Measurement data were
presented by mean ± standard deviation, and the t-test was applied
to make comparisons between groups. The linear correlation analysis
was performed to determine any correlations between NT-proBNP and
cTnT. P<0.05 was considered to indicate a statistically
significant difference.
Results
As shown in Table I,
the level of NT-proBNP in the death group was significantly higher
than that in the survival group and the difference was
statistically significant (P<0.05). Similarly the levels of cTnT
were significantly higher than those in the survival group
(P<0.05) (Table II).
 | Table I.Comparison of the level of NT-proBNP
between the survival and death groups on the 1st, 3rd and 7th day
of admission. |
Table I.
Comparison of the level of NT-proBNP
between the survival and death groups on the 1st, 3rd and 7th day
of admission.
|
| NT-proBNP
(pg/ml) |
|---|
|
|
|
|---|
| Group | Day 1 | Day 3 | Day 7 |
|---|
| Survival group | 1839.14±1060.27 | 2786.21±1206.23 | 2074.08±970.43 |
| Death group | 3965.74±1462.65 | 6268.56±1825.49 | 5384.46±1049.62 |
| P-value | <0.05 | <0.05 | <0.05 |
| Table II.Comparison of the level of cTnT
between survival and death groups on the 1st, 3rd and 7th day of
admission. |
Table II.
Comparison of the level of cTnT
between survival and death groups on the 1st, 3rd and 7th day of
admission.
|
| cTnT (pg/ml) |
|---|
|
|
|
|---|
| Group | Day 1 | Day 3 | Day 7 |
|---|
| Survival group | 0.53±0.21 | 0.68±0.17 | 0.62±0.23 |
| Death group | 1.03±1.04 | 1.57±0.86 | 1.38±0.53 |
| P-value | <0.05 | <0.05 | <0.05 |
The correlation analysis between NT-proBNP and cTnT
showed that the blood levels of NT-proBNP and cTnT in patients with
sepsis showed a significantly positive correlation (r=0.756,
P<0.05). Thus, NT-proBNP and cTnT levels are increased in the
plasma collectively in a directly proportional manner.
Discussion
Sepsis is a type of systemic inflammatory response
syndrome resulting from infection. Myocardial damages incurred by
sepsis, also known as pyemic cardiomyopathy or pyemic myocardial
dysfunction, likely increases the mortality risk of sepsis
(7,8). At least one half of mortalities
associated with sepsis were caused by the impairment of the
cardiovascular system (10). During
sepsis, regional blood flows abnormally, leading to
microcirculation disturbance and resulting in the ischemia of
various organs, including the heart as well as mitochondrial
structural change on myocardial cells. This condition eventually
results in cell metabolic dysfunction and eventually death
(11,12). In clinic, NT-proBNP and cTnT are
usually used as markers to reflect myocardial injury.
Sepsis usually concurs with cardiac insufficiency
(13–15). Under sepsis condition, a large amount
of fluids or media produces a toxic effect on the heart. When the
entire body becomes affected by a strong inflammatory reaction, the
homeostasis of cardiovascular system changes, leading to cardiac
insufficiency. Early ventricular systolic dysfunction has been
proven in patients with sepsis (16). NT-proBNP mainly primarily stems from
ventricle. Patients with cardiac failures showed higher levels of
NT-proBNP in plasma, suggesting an important indication for heart
failure diagnosis, treatment and prognosis. Current investigations
have confirmed that the level of NT-proBNP on patients with sepsis
is likely to increase (17–19). However, myocardial function
impairment was not the only factor likely to result in the increase
of NT-proBNP. Charpentier and other authors (20–22,28) have
determined that the increase of certain NT-proBNP was associated
with the increased secretion or reduced inactivation of NT-proBNP
under an inflammatory response. Therefore, the basic
pathophysiological changes of sepsis may be a reason for the
increase of the NT-proBNP level (23–25). The
results of our study have shown that the plasma level of NT-proBNP
in patients with sepsis was significantly increased and that of the
death group was significantly higher in comparison to the survival
group. The result was consistent with the abovementioned study
results.
Cardiac troponin is an important protein that could
adjust the contraction of striated muscle (17,26,27).
When the myocardium cell membrane of heart is intact, cTnT is
unable to get into the blood circulation. Thus, the plasma in
healthy individuals usually has no or a low level of cTnT. The
mechanism for the increasing level of cTnT in patients with sepsis
remains to be determined. It was estimated that myocardial damage
in patients with plasma may be associated with the direct damage on
myocardial cells incurred by the release of a large amount of
cytokines and reactive oxygen species and the toxic effect of
bacterial endotoxin on myocardial cells subsequent to bacterial
infection (28). Sepsis is always
accompanied with microcirculation disturbance, which results in the
ischemia of myocardial cells and reperfusion damage. When
myocardial cells are impaired, the cytomembrane suffers damage and
therefore cTnT is released into the blood, and becomes evident as
higher levels in plasma. The increasing level of troponin may
reflect a worse myocardial function, and is potentially associated
with the patient prognosis (29).
The results of our study have shown that the change of level of
myocardial injury markers was significantly different between the
survival and death groups. The level of cTnT in the death group was
significantly higher than that in the survival group, indicating
that the myocardial troponin level in patients with sepsis was
positively associated with the severity of disease. There are
currently no reports confirming that the level of troponin may be
used as an independent predictor for prognosis of patients with
sepsis. Therefore, this aspect remains to be investigated.
The result of the correlation analysis showed that
the plasma levels of NT-proBNP and cTnT in the death group were
significantly higher than those in the survival group, and the
plasma levels of NT-proBNP and cTnT were positively correlated,
indicating that the increasing levels of NT-proBNP and cTnT exert a
predictive effect on the prognosis of patients with sepsis.
In conclusion, monitoring of the levels of NT-proBNP
and cTnT is crucial and can demonstrate the status of cardiac
health with a potential to circumvent the severity of disease.
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