|Year : 2021 | Volume
| Issue : 3 | Page : 144-149
Study of serum procalcitonin in patients with sepsis, septic shock and systemic inflammatory response syndrome (SIRS)
Swaroopa Deme1, Sravan K Appani2, Bhaskar Kakarla3, Goveen Manda1, Y S N. Raju1
1 Department of General Medicine, NIMS, Hyderabad, Telangana, India
2 Department of Rheumatology, Rishi Rheumatology Hospital, Karimnagar, Telangana, India
3 Department of Pulmonary Medicine, NIMS, Hyderabad, Telangana, India
|Date of Submission||24-Jan-2021|
|Date of Decision||28-Apr-2021|
|Date of Acceptance||30-Apr-2021|
|Date of Web Publication||17-Mar-2022|
Dr. Swaroopa Deme
Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
Background: Sepsis is a complex syndrome caused by an uncontrolled systemic inflammatory response of infectious origin characterized by dysfunction or failure of one or more organs and even death. Procalcitonin (PCT) has been one of the promising markers in bacterial sepsis.
Aim: This study was done to evaluate the diagnostic and prognostic value of PCT in systemic inflammatory response syndrome (SIRS), sepsis, and septic shock, and to assess its relation with sequential organ failure assessment (SOFA) Score and serum lactate.
Materials and Methods: This is a prospective observational study carried out in our institute between May 2012 and September 2013. Patients with suspicion of sepsis and SIRS were included. PCT, SOFA Score, and serum lactate were assessed at admission or within 12 hours and analyzed.
Results: A total of 114 patients with SIRS (n = 14), sepsis (n = 63), and septic shock (n = 29) were included. Urinary tract and respiratory tract infections were the common sources of sepsis in 28.1 and 26.3% of the patients, respectively. The PCT levels were elevated in 83 patients. The mean values of serum PCT in SIRS, sepsis, and septic shock were (in ng/mL) 0.36, 6.81, 26.7, respectively. The mean values of SOFA Score in SIRS, sepsis, and septic shock were 3.4, 6.1, and 12.2, respectively. The mean values of serum lactate of SIRS, sepsis, and severe sepsis were (in mmol/L) 1.6, 2.3, and 3.9, respectively.
Conclusion: Serum PCT was 82.6% sensitive, 71.4% specific, and had a positive predictive value of 95.0% in diagnosing sepsis and showed no association with SIRS. It was positively associated with high mortality and higher SOFA levels.
Keywords: Lactate, procalcitonin, sepsis, SIRS, SOFA
|How to cite this article:|
Deme S, Appani SK, Kakarla B, Manda G, Raju Y S. Study of serum procalcitonin in patients with sepsis, septic shock and systemic inflammatory response syndrome (SIRS). J NTR Univ Health Sci 2021;10:144-9
|How to cite this URL:|
Deme S, Appani SK, Kakarla B, Manda G, Raju Y S. Study of serum procalcitonin in patients with sepsis, septic shock and systemic inflammatory response syndrome (SIRS). J NTR Univ Health Sci [serial online] 2021 [cited 2022 Nov 30];10:144-9. Available from: https://www.jdrntruhs.org/text.asp?2021/10/3/144/339797
| Introduction|| |
Morbidity and mortality in intensive care units (ICU) are commonly related to severe infections and sepsis. Clinical data alone may be unreliable in distinguishing between patients with bacterial sepsis and non-bacterial systemic inflammatory response syndrome (SIRS). Sepsis is a heavy burden on health services all over the world, both from economic and social points of view. About 49 million sepsis cases have occurred all over the world in 2017 resulting in 11 million preventable deaths. This amounts to 20% of total deaths annually. An inverse relationship has been observed between incidence, mortality of sepsis, and income. Not only in-hospital and ICU mortality are affected by sepsis but long-term mortality is also observed—one in three persons dying within a year. In India, in 2017, there was 11 million sepsis with 3 million deaths. In a survey conducted in eastern India, severe sepsis (sepsis with organ dysfunction) constituted 17% of all admissions to the ICU. This cohort carried very high mortality of 45%. However, there are few Indian studies available on the diagnostic efficacy of PCT in sepsis and SIRS. There is a need for an effective and accurate biochemical marker to support or exclude the diagnosis of infection. Thus, there is a requirement for an ideal, sensitive, specific, and quick laboratory tool that can distinguish between sepsis and other inflammatory conditions.
The currently available markers for sepsis are white blood cell count (WBC), C-reactive protein (CRP), PCT, soluble triggering receptor expressed on myeloid cells (sTREM), interleukin 1 (IL-1), complement factors, endothelin-1, phospholipase A2, prostaglandins (PGE 2), lactoferrin, neopterin, and elastase. However, none of them are specific to sepsis and diagnosis must be evaluated in the context of the clinical evidence of sepsis. Microbiological cultures require time, do not reflect the host response of systemic inflammation nor the onset of organ dysfunction, and may not be positive in sepsis patients for a number of reasons. Consequently, there is a demand for better markers of sepsis for clinical applications. Various markers of sepsis including CRP, tumor necrosis factor (TNF) α, interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) have all been studied for their ability to differentiate SIRS from sepsis.,,
PCT has been one of the most promising markers, owing to its specificity to bacterial infections, especially for use in hospital emergency departments and ICU. After successful treatment, the PCT value decreases, indicating a prognostic value. Persistently high or even further increasing levels are indicators for poor prognosis. The PCT molecule is a very stable molecule both in vivo and in vitro. Therefore, it is an ideal laboratory test in the clinical scenario to adopt in the evaluation of fever in the emergency setup. The test does not need special requirements for pre-analytical sample handling and storage.
Studies have shown that PCT has been a more reliable marker in sepsis than either CRP or IL-6. Studies in adults have shown high accuracy in PCT levels. Literature is available highlighting the role of PCT in bacterial sepsis. However, paucity of South Indian studies made us evaluate the role of PCT as a diagnostic and prognostic marker in a wide spectrum of sepsis, SIRS, and septic shock.
| Materials and Methods|| |
All patients with suspected sepsis, septic shock, and SIRS criteria in Emergency Medical Department, Acute Medical Care, General Wards of Nizam's Institute of Medical Sciences during the study period were screened and a total of 114 patients fulfilling the inclusion criteria and willing to participate in the study were included after taking the informed consent. Patients with posttraumatic sepsis, postoperative sepsis, and malignancy were excluded from the study. On admission, detailed history was taken and clinical examination was done. Patients were assigned to the septic classification as SIRS, sepsis, and septic shock according to American College of Chest Physician/Society of Critical Care Medicine(ACCP/SCCM) international consensus conference 1992. Blood sample was drawn at the time of admission or within 12 hours. Investigations like complete blood counts, blood culture, serum lactate, and serum PCT were done for all patients. Other investigations like arterial blood gases, urine microscopy and culture, specimen culture, serum electrolytes, renal function test, liver function test, and, chest X-ray were done as per the requirement. Patients were treated as per instructions of the treating physician. Electrochemiluminescence immunoassay analyzer (ECLIA) for the determination of PCT in human serum or plasma on the automated Roche Cobas e411 immunoassay analyzer was used. Assay characteristics include ECLIA and the sandwich principle. The sample volume is 30 μL of serum. The test duration is 18 min and has a measuring range of 0.02–100 ng/mL. Ethical committe approval has been taken on 12-05-2012 with letter no .EC/NIMS/1319/2012.
Variables included were demographic data, SOFA Score, serum lactate, and PCT levels. Descriptive statistical analysis has been carried out on the continuous variables and frequency analysis carried out on categorical variables. Graphical representation has been shown with bar diagrams for categorical variables and distribution plots (Box-Whisker) for continuous variables. In our study, Statistical Analysis System (SAS) statistical software version 9.3 is used for analysis. Multivariate logistic regression analysis has been carried out to predict the probability of an event based on the different independent variable information. Odds ratio was also used for predicting a chance of dependent variable event occurrence based on each independent variable category of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were used to predict diagnostic accuracy of a marker. The sample size was calculated based on the prevalence of sepsis.
| Results|| |
Out of 114 patients, 4.4% were <20 years, 40.4% were between 20 and 39 years, 31.6% were between 40 and 59 years, and 23.7% were >60 years. The males were 55.3% and females were 44.7%. The male-to-female ratio was 1.2:1.
The commonest presenting symptom was fever in 109 (95.6%) patients followed by breathlessness in 62 (54%), cough in 48 (42.1%), and less frequent symptoms were altered sensorium, vomiting, dysuria, loose stools, pain in the abdomen, oliguria, myalgias, joint pains, pedal edema, jaundice, bleeding manifestations, rash, and headache.
As PCT is not a marker of viral infection. Patients with proven and suspected viral cases were separately categorized to improve diagnostic validity. Sepsis constituted a major part of diagnosis in our study constituting 63 (55.3%) of the patients followed by septic shock in 29 (25.4%), SIRS in 14 (12.3%), and viral etiology in 8 (7%) patients.
Out of the 114 patients enrolled, 83 (72.8%) patients had PCT value ≥0.5 and 31 (27.2%) patients had PCT value <0.5 ng/mL. We observed 4 (28.5%) out of 14; 49 (77.8%) out of 63, and 27 (93.2%) out of 29 patients in SIRS, sepsis, and septic shock were positive for serum PCT. Sepsis and septic shock were associated with elevated PCT (≥0.5 ng/mL) and statistically significant (P-value <0.0001). In our study, patients with sepsis and septic shock, serum PCT had a sensitivity of 82.6%, specificity of 71.4%, positive predictive value of 95.0%, and negative predictive value of 38.5% [Figure 1].
|Figure 1: Number of patients by diagnosis. Footnotes: Depicts higher levels of procalcitonin in sepsis patients|
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In our study, urinary tract infection (UTI) was identified as the primary focus in 28.1%, followed by respiratory system in 26.3%, gastrointestinal tract in 7.9%, cellulitis in 1.8%, and central nervous system in 0.9%.
Hemoglobin (Hb) levels were <8 g/dL in 25 (21.9%), 8–12 g/dL in 74 (64.9%), and >12 g/dL in 15 (13.2%). In the present study, 9 patients (7.9%) had leucopenia (<4000/dL), 41 (36%) had normal counts, and 64 (56.1%) had leukocytosis (>12000/dL). In the sepsis group, 6 patients had leucopenia and 22 patients had normal counts; 35 patients had leukocytosis. In the septic shock group, 2 patients had leucopenia, 8 patients had normal counts, 19 patients had leukocytosis. P value 0.7566, i.e., there is no significant association between sepsis diagnosis and leucocyte count among the study group; 4 (3.5%) of them had platelet count of 20,000; 8 (7%) had platelet count between 20,000 and 50,000; 12 (10.5%) had platelet count of 50,000–1,00,000; 37 (32.5%) had platelet count between 1.0 and 1.5,00,000; and 53 (46.5%) had platelet count of >1.5,00,000.
Blood culture was positive in 18 (19.6%) patients and in 74 (80.4%) patients no organism was isolated. This low yield could be due to prior antibiotic usage. The mean PCT value was 22.3 in blood culture-positive patients. Mean PCT of 5.64 was observed in 11 patients diagnosed to have scrub typhus. Urine culture was positive in 16 out of 78 (20.6%) patients, Escherichia More Details coli (E. coli) was isolated in 13 (16.7%), Enterococcus faecium 2.6%), and Klebsiella pneumonia in 1 (1.3%) patient [Table 1].
Patients with leukocytosis, tachycardia, and high-serum lactate are 2.7, 2.9, and 3.7 times more likely to have a positive PCT, respectively [Table 2].
The mean values of SOFA Score in SIRS, sepsis, and septic shock were 3.4, 6.1, and 12.2 respectively with significant P value between these three groups. SOFA Score was higher in septic shock compared to sepsis and SIRS [Figure 2]. In our study, we observed a linear trend between PCT and SOFA Score with a significant P value of 0.0002 [Table 3].
|Figure 2: SOFA score distribution by diagnosis. Footnotes: Mean SOFA Score was higher in septic shock compared to sepsis and SIRS. (P-value 0.0001)|
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Mean values of serum lactate of SIRS, sepsis, and septic shock were (in mol/L) 1.6, 2.3, 3.9, respectively. We observed that the mean lactate values were higher in septic shock compared to sepsis and SIRS.
In our study, patients enrolled with sepsis and septic shock. Serum lactate had a sensitivity of 90.1%, specificity of 50.0%, the positive predictive value of 92.4%, and negative predictive value of 42.9%. We observed high sensitivity and positive predictive value [Table 4].
In our study, we observed a linear trend between PCT- SOFA score (P-value of 0.0002) and PCT-lactate (P-value of 0.037).
Among 114 patients, 91 (79.8%) were discharged while 23 (20.2%) of them died.
| Discussion|| |
When managing patients with sepsis, early diagnosis of the infection is crucial since it has the greatest impact on clinical course and patient survival. Despite the use of new treatment modalities, improvements in technology, mortality of patients with sepsis, septic shock remain high. Such an unfavorable prognosis of patients with sepsis is partly due to delayed diagnosis.
Diagnosis of severe infections is hampered by non-specific clinical signs, low sensitivity, and specificity of the laboratory tests. In this context, interest in markers of severe infection has been growing. PCT has shown diagnostic accuracy in diseases like pneumonia, endocarditis, urinary tract infections, and other bacterial infections. PCT concentrations were detected at a significantly higher frequency among patients with severe sepsis.
Among 114 patients in our study, males were 63 (55.3%) and females constituted 51 (44.7%). The male-to-female ratio was 1.2:1. A study done by Martin G.S. et al. showed that sepsis was more common in males, accounting for 48.1% of the cases on an average per year with the mean annual relative risk of 1.28. Another Indian study done by Todi S, et al., a multicenter trial done at 12 centers, showed that sepsis was more common in males (67%) than in females (58%). [3, 4, 9]
The commonest presenting symptoms in our patients were fever in 109 (95.6%), breathlessness in 62 (54%), and cough in 48 (42.1%). In a study by Sreedharan et al., respiratory symptoms such as cough and breathlessness were present in 34% of the patients. However, in our study, the primary source of infection was the urinary tract (28.1%) followed by respiratory infections (26.3%).
Sepsis constituted a major part of diagnosis in our study constituting 63 (55.3%) of the patients followed by septic shock constituting 29 (26.4%), and SIRS constituting 14 (12.3%). Corinne Alberti, et al. in their international prospective cohort study showed sepsis and severe sepsis constituted 52% and septic shock constituted 30%.
Blood culture was positive in 18 (19.6%) patients, gram-negative organisms were seen in 78.3% and gram positive in 21.7%, Acinetobacter baumannii the commonest. This finding is similar to a study done by George K Varghese et al.; The commonest organism was E. coli followed by Klebsiella and Salmonella More Details.
Urine culture was sent in 78 patients and positive yield was seen in 79.5% of the patients—the most common isolated organism was E. coli, similar to a study by George K Varghese et al.
In the present study, 9 (7.9%) patients had leucopenia, 41 (36%) had normal counts, and 64 (56.6%) had leukocytosis. We also observed that patients who had leucopenia are 1.3 times more likely to have a positive PCT, and those who have leukocytosis are 2.7 times more likely to have positive PCT. Earlier studies done by Lee et al. have shown that the white blood cell count and absolute neutrophil counts are the most accurate predictors of occult bacteremia, and when available, should be used if presumptive antibiotic therapy is being considered.
In the present study, we observed patients with lactate >1 mmol/L are 3.7 times more likely to have positive PCT; positive is significantly correlated with lactate positive with P value = 0.037.
In the present study, a positive association was observed between PCT and SOFA scores (P-value = 0.0002). This was similar to the study conducted by Michael Meisner et al. which concluded that higher SOFA score levels were associated with significantly higher PCT.
In the present study with PCT, the cut-off value of 0.5 ng/mL offered diagnostic sensitivity of 82.6%, specificity of 71.4%, the positive predictive value of 95.0%, and negative predictive value of 38.5%. In the study by Sudhir et al., serum PCT has 94% sensitivity. Harbarth et al. reported a sensitivity of 97%. The results of the present study demonstrated that serum PCT is the most promising sepsis marker in critically ill patients. It is capable of complementing clinical signs and routine laboratory parameters in severe infection at the time of ICU admission.
Mean values of serum PCT in SIRS, sepsis, and septic shock were 0.36 ng/mL, 6.81 ng/mL, 26.7 ng/mL, respectively. We observed the mean PCT values were higher in septic shock. A study by Zeni et al. and Oberhoffer et al. showed increasing PCT concentrations during more severe stages of sepsis (severe sepsis and septic shock). In a study by Al-Nawas et al., very low PCT concentrations were measured during SIRS, but high concentrations when septic shock was diagnosed.
In our study, 23 (20.2%) patients have died. This is comparable to a study done by Sands KE et al. in eight academic medical centers with a mortality of 34%.
Out of 25 patients who had a PCT level of more than 10 ng/mL, 11 died (P = 0.0048) indicating a strong correlation between PCT levels and mortality. We also observed in our study that three patients who died had serum PCT levels <0.5 ng/mL. Luzzani et al. studied 70 adults by the means of daily PCT assays demonstrating that this mediator is correlated with progression to multiorgan system failure. However, in our study, we did not do daily PCT assays to assess the changes in the PCT values with the disease progression.
Serial serum PCT levels were not done. Viral sepsis cannot be ruled out in some of the cases because of the non-availability of diagnostic modality for confirmation of viral infections. The sample size is small.
| Conclusion|| |
There is a positive association between serum PCT levels and the severity of sepsis. In view of the high sensitivity and positive predictive value of PCT, it can be used as a diagnostic marker of sepsis whereas SIRS was negatively associated. PCT levels were higher in patients who died due to sepsis. High SOFA score and serum lactate levels were associated with significantly higher PCT.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]