| Background:Post-stroke infection is common in clinic, with an incidence of15～65%and associated with poor prognosis significantly. Early identification and treatment of post-stroke infection will help to improve the prognosis. But after stroke, there may have some interferential factors like central fever, which will affect the judgment of infection. So, we urgently need a relatively specific indicator to help distinguishing infection after stroke. The uses of traditional indicators of infection such as white blood cell (WBC), neutrophil count, are restricted, because their specificities are not high. Some even pointed out that, patients with infection or non-infection after stroke had no significant difference in WBC and neutrophil count at the time of admission. C-reactive protein (CRP), an acute reaction phase products of inflammation, is often used to help diagnosing bacterial infection. But it can also be elevated in other non-infectious inflammatory response, lacking of specificity.In recent years, procalcitonin (PCT) is considered to be a relatively specific indicator of bacterial infections. In a systematic review and meta-analysis, PCT was superior to WBC or CRP as a diagnostic indicator of pneumonia or other bacterial infections. However, some studies have found that PCT might also be elevated in the cases of non-infectious, such as severe trauma, heat stroke, post-surgery, cirrhosis, pancreatitis, mesenteric infarction, cardiogenic shock. So, before PCT is used as an indicator of infection in the early stage of acute stroke, we should make it clear that whether PCT could be elevated after acute stroke. Otherwise it might be misleading in judgment of infection. So far, there is little reported research about that.Objection:To explore the value of PCT in judgment of bacterial infection in the early stage of acute stroke, we investigated the dynamic changes of PCT through continuous detections of its concentrations within72hours of acute stroke without infection, with comparison of C-reactive protein (CRP).Methods:Patients from the department of Neurology of Nanfang Hospital, from July2012to January2013,with acute stroke were enrolled in this observational study. All patients or their family members signed an informed consent.1. Inclusion criteria were as follows:1) stroke onset within24hours;2) stroke diagnostic standards revised in line with the4th National Cerebrovascular Disease Conference (including cerebral hemorrhage and cerebral infarction);3) age≥18years old.2. Exclusion criteria were as follows:1) transient ischemic attack patients;2) co-infection within5days after stroke onset (including pneumonia, urinary tract infection, bloodstream infection, catheter-related infection, infectious diarrhea, sinusitis etc.), the diagnosis of infection missed hospital acquired infection diagnostic criteria (for trial implementation) issued by the Ministry of Health of the People’s Republic of China in2001;3) combining one of the following conditions:cardiopulmonary resuscitation, trauma, major surger, burns, acute respiratory distress syndrome, shock, heatstroke, neuroendocrine tumors, cardiopulmonary bypass, cirrhosis, pancreatitis, mesenteric infarction, useing proinflammatory cytokine release drugs, renal insufficiency;4) discharged or transferred within5days after stroke onset for any reasons.3. Collection of general data of all the patientsGender, age, type of stroke (cerebral hemorrhage, cerebral infarction), combining diseases, ICH score for cerebral hemorrhage patients and amount of bleeding were collected. Complete blood count, urinalysis, routine stool test, liver and kidney function, and chest X-ray were checked at admission. America’s National Institutes of Health Stroke Scale (NIHSS) was carried by specially trained neurologists at admission by the degree of neural function defect. Then the NIHSS scores were further divided into three groups:gentle group (NIHSS score≤6scores), moderate group (NIHSS score=7to14scores), serious group (NIHSS score≥15scores).4. Collection of infection indicatorsBody temperature was taken every4hours after admission. When body temperature was more than37.0℃or less than35.0℃, Complete blood count, urinalysis, erythrocyte sedimentation rate, chest X-ray/chest CT and abdominal B ultrasound were checked. When stool frequency increased and trait changed, stool culture was taken. When temperature more than38.5℃or less than35.0℃, took each blood sample from upper limb and lower limb for blood culture. When urine leukocyte urine was positive, mid-stream urine sample for bacterial and fungal culture was taken. When patients were with cough and expectoration, sputum sample for bacterial and fungal culture was taken. When no conventional site of infection was found, paranasal sinus CT was played. 5. PCT and CRP measureingThe concentrations of PCT and CRP in the serum were measured respectively at24hours,48hours and72hours after symptom onset. PCT was measured by double-antibody sandwich assay (cobas e601electrochemical luminescence automatic immunoassay system, Roche Diagnostics Ltd.). The serum sensitivity was less than0.02ng/ml, and the upper value of normal range was0.05ng/ml. CRP was measured by turbidimetric immunoassay (cobas c501analyzer, Roche/Hitachi), with an upper value of normal range of5.0mg/1.6. Statistical analysisNormal distribution measurement data was expressed as mean±standard deviation (x±s). Count data was expressed by frequency and percentage. PCT and CRP values at each time point were respectively compared with the upper value of normal range of each other by one-sample t-test. Dynamic changes of PCT and CRP within72hours of acute stroke were expressed by Error Bar. The relationships between PCT values at24hours after stroke and NIHSS score at admission were analyzed by Pearson correlation analysis, so as the age. PCT values within72hours of acute stroke in different gender groups were compared by two independent samples t-test. PCT values at24hours after acute stroke in different NIHSS groups were compared by the Kruskal-Wallis H test. All recorded data were statistically analyzed by SPSS13.0statistical software. All statistical analyzes were performed using two-sided test. P<0.05was considered to be statistically significant.Results:1. Baseline characteristics:63patients with an initial diagnosis of acute stroke within24hours missed the inclusion criteria during the study, of which22patients were excluded due to the following resones:(1) co-infection (n=19), including respiratory tract infection (n= 17), sinusitis (n=2);(2) cardiopulmonary resuscitation (n=1);(3) non-infectious arthritis (n=1);(4) transferred for surgery (n=1). Finally,41patients were included in the study.They were29males(70.73%) and12females (29.27%).23patients (56.10%) were with cerebral infarction,while the other patients (43.90%) were with cerebral hemorrhage. The patients had an mean age of56.46±13.84years.The youngest was30-year-old, while the oldest was91-year-old. The mean NIHSS score was7.26±5.72scores.The minimum NIHSS score was1score, while the maximum was28scores. The mean ICH score was1.28±0.83scores.The minimum ICH score was0score, while the maximum was3scores. Patients with cerebral hemorrhage had an mean bleeding amount of20.17±13.62ml. The minimum bleeding amount was5ml, while the maximum was45ml.2. Results of PCTThe maximum PCT concentration (0.34ng/ml) appeared at24hours after stroke onset. Most of the patients (22cases,53.67%) had a peak level of PCT at24hours.The number of patients having an absolute PCT value higher than the upper value of normal range (0.05ng/ml) at24hours,48hours,72hours after stroke onset,were respectively19cases(46.34%),21cases(51.22%),21cases(51.22%). But only2patients (4.88%) had a PCT concentration more than0.25ng/ml, and no patient had a PCT concentration more than0.50ng/ml.The mean PCT concentration at24hours,48hours and72hours after stroke onset, was respectively0.075±0.069(ng/ml),0.071±0.051(ng/ml) and0.064±0.040(ng/ml). All of them were significantly higher than the upper value of normal range (0.05ng/ml)(P<0.05). The concentration of PCT increased within24hours after symptom onset, but declined in the following72hours.3. Results of CRPThe maximum CRP concentration (205.2mg/1) appeared at72hours after stroke onset. Most of the patients (26cases,63.41%) had a peak level of CRP at72hours.The number of patients having an absolute CRP value higher than the upper value of normal range (5.0mg/l) at24hours,48hours,72hours after stroke onset,were respectively9cases(21.95%),19cases(46.34%),21cases(51.22%). The mean CRP concentration at24hours and48hours after stroke onset, was respectively5.342±9.675(mg/l) and11.098±21.646(mg/l). None of them had significant difference with the upper value of normal range (5.0mg/l)(P>0.05). However, the mean CRP concentration at72hours after stroke onset was18.449±40.354(mg/l), which had significant difference with the upper value of normal range (P<0.05). The concentration of CRP continuously increased in the first72hours after symptom onset.4. Results of correlation analysis between PCT values at24hours and NIHSS score at admissionNo correlation was found between PCT values at24hours after acute stroke onset and NIHSS scores at admission (P=0.33).5. Results of comparing PCT values at24hours in different NIHSS score groupsGentle group (NIHSS score≤6scores), moderate group (NIHSS score=7to14scores) and serious group (NIHSS score≥15scores) respectively contained17patients,19patients and5patients. The mean PCT concentration at24hours after stroke onset, was respectively0.092±0.098(ng/ml),0.062±0.026(ng/ml),and0.063±0.025(ng/ml) in gentle, moderate and serious group. PCT values at24hours after acute stroke onset had no significant difference in different NIHSS score groups (χ2=0.510, P=0.775).6. Results of correlation analysis between PCT values within72hours of acute stroke and ageNo correlation was found between PCT values respectively at24hours,48 hours,72hours after acute stroke onset and age (respectively P=0.904,0.675,0.752).7. Results of comparing PCT values within72hours of acute stroke in different gender groupsPCT values at24hours,48hours,72hours after acute stroke onset all had no significant statistical difference in different gender groups (all P>0.05).Conclusions:1. PCT values would be elevated at24hours,48hours,72hours after acute stroke onset. Compared with the upper value of normal range of PCT, they all had a significant statistically difference. Using PCT in judgment of bacterial infection in the early stage of acute stroke, the influence of elevating PCT concentrations by stroke itself should be considered. Otherwise, it might be misleading to the use of antibiotics.2. Although the proportions of patients with elevated PCT concentrations at24hours,48hours,72hours after acute stroke onset were all about50%. But only2patients with a PCT concentration^0.25ng/ml, and none of patients with a PCT concentration^0.5ng/ml. It suggested that the influence of elevating PCT concentrations by stroke itself was gentle, and it had little interference to the judgment of bacterial infection after acute stroke. PCT might have a helpful role in the judgment of bacterial infection in the early stage of acute strok.3. PCT concentrations were elevated the most highly at24hours after acute stroke onset, but no correlation weas found between them and NIHSS scores at admission. The NIHSS scores were further divided into three groups:gentle group (NIHSS score≤6scores), moderate group (NIHSS score=7to14scores), serious group (NIHSS score≥15scores). When comparing the PCT values at24hours after acute stroke onset in different NIHSS score groups, it also had no significant difference. It suggested that PCT values had no significant correlation with the degree of neurological deficit. Using PCT for judgment of bacterial infection in the early stage of acute stroke, it might have no need to consider the influence of degree of neurological deficit to PCT. But as the sample size was small in this study, it was necessary to take a further large sample study to confirm the results.4. There was no correlation found between PCT values and age,respectively at24hours,48hours,72hours after acute stroke onset (P=0.904,0.675,0.752). Also PCT values at24hours,48hours, and72hours after acute stroke onset all had no significant statistical difference in different gender groups (P>0.05).It suggested that PCT values in the early stage of acute stroke had nothing to do with age or gender. Using PCT for jugement of bacterial infection in the early stage of acute stroke, it might have no need to consider the influence of age or gender to PCT. But this conclusion also could not exclude the impact of the small sample size of this study.5. The concentration of CRP continuously increased in the first72hours after symptom onset, while the concentration of PCT increased within24hours after symptom onset, but declined in the following72hours. PCT usually reached its peak level earlier than CRP and returned into normal range faster than CRP, which might be more valuable than CRP in diagnosis of bacterial infection in the early stage of acute stroke. It is worthy of playing a further prospective study.6. The ideal cut-off of PCT for judgment of bacterial infection in the early stage of acute stroke was not clear. It needed further large sample size studies to make sure, with disease stratification and comparing with co-infected patients. |
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