ORIGINAL ARTICLE |
https://doi.org/10.5005/jp-journals-10057-0216 |
Correlation of C-reactive Protein, Procalcitonin, and Lactate Levels with Mortality in Sepsis
1–8Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
Corresponding Author: Pallaavi Goel, Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India, Phone: +91 9689848155, e-mail: drpallaavigoel@gmail.com
Received on: 11 January 2023; Accepted on: 21 March 2023; Published on: 16 September 2023
ABSTRACT
Background: There is no gold standard tool to definitively diagnose sepsis and no consistent system to predict outcomes. In any clinical setup, laboratory biomarkers are very important and can serve in determining the suitable treatment course. Serum lactate is one of these biomarkers that is known to be linked with mortality in patients with sepsis. Even procalcitonin (PCT) has been said to be a biomarker very useful in diagnosing sepsis. C-reactive protein (CRP) is an acute phase reactant and another sensitive marker of sepsis.
Materials and methods: A prospective observational study was conducted in a tertiary care center in Jaipur, Rajasthan, India, including 160 study participants who were admitted to the intensive care unit (ICU) and diagnosed with sepsis. Detailed history and examination were made, followed by blood investigations. Written informed consent was obtained from all participants, and Institutional Ethics Committee approval was taken at the beginning of the study. Statistical analysis was done after adequate data collection.
Results: Mean CRP (mg/L) was 9 ± 1.41, mean PCT (ng/mL) was 1.6 ± 0.56, and mean lactate (mmol/L) was 2.1 ± 1.97 among the study subjects. Mean CRP was found to be significantly higher in expired subjects (77 ± 31.1) as compared to survivors (9 ± 1.41). This difference was statistically significant as p < 0.05. Mean PCT (ng/mL) was found to be significantly higher in expired subjects (11.1 ± 0.14) as compared to survivors (1.6 ± 0.56). This difference was statistically significant as p < 0.05. Mean serum lactate was found to be higher in expired (3.4 ± 0.77) subjects as compared to survivors (2.1 ± 1.97), but this difference was not statistically significant as p > 0.05.
Conclusion: The combined biomarker approach using CRP, PCT, and lactate depicted a better performance in predicting 28-day mortality.
How to cite this article: Goel P, Rijhwani P, Garg S, et al. Correlation of C-reactive Protein, Procalcitonin, and Lactate Levels with Mortality in Sepsis. J Mahatma Gandhi Univ Med Sci Tech 2022;7(3):75–77.
Source of support: Nil
Conflict of interest: None
Keywords: C-reactive protein, Lactate, Procalcitonin, Sepsis
INTRODUCTION
Fatal organ dysfunction due to any disorganized response of the host to infection is called sepsis.1,2 It is one of the major reasons for bereavement among serious patients, with a total mortality of 30%.3,4 Sepsis limits the skill of the host to bring down any infection leading to variable grades of organ malfunction; this is every so often labeled as multi-organ dysfunction syndrome and can lead to death. In any clinical setup, the laboratory biomarkers are of diagnostic and prognostic importance and can serve in determining the suitable protocol for management. So, >100 such laboratory biomarkers have been anticipated to be beneficial for the diagnosis and prognosis of sepsis.5 CRP is a precise indicator for sepsis, being an acute phase reactant.6 Even PCT has been used as a very suitable marker in the diagnosis of sepsis.7,8 Serum lactate is one of these biomarkers that is identified to be linked with 28-day mortality in cases of sepsis and septic shock.9,10
MATERIALS AND METHODS
A prospective hospital-based observational study directed in the Department of General Medicine at a tertiary care hospital in Jaipur over a period of 15 months. Patients who happened to be admitted to the ICU and were diagnosed with sepsis underwent a thorough medical history and physical examination followed by laboratory tests. Institutional Ethics Committee approval was taken beforehand. Written and informed consent was acquired from all participants before acceptance into the study. A total of 160 patients were included in the study; all of those diagnosed with sepsis were above 18 years of age. The data was obtained and entered into a Microsoft Excel worksheet. Suitable statistical tests were used to find significant correlations and predict mortality.
RESULTS
Mean CRP (mg/L) was 9 ± 1.41, mean PCT (ng/mL) was 1.6 ± 0.56, mean lactate (mmol/L) was 2.1 ± 1.97, mean alanine transaminase (ALT) (U/L) was 66.5 ± 4.94, mean aspartate aminotransferase (AST) (U/L) was 61 ± 8.48, mean bilirubin, (umol/L) was 1.4 ± 0.35, and mean creatinine (mg/dL) was 2.1 ± 0.07 among the study subjects (Table 1). In our study, out of 160 subjects, 96 (60%) survived, and 64 (40%) expired (Table 2 and Fig. 1). Mean CRP was found to be significantly higher in expired subjects (77 ± 31.1) as compared to survivors (9 ± 1.41). This difference in mean CRP was statistically significant as p < 0.05 (Table 3 and Fig. 2). Mean PCT (ng/mL) was found to be significantly higher in expired subjects (11.1 ± 0.14) as compared to survivors (1.6 ± 0.56). The difference in mean PCT was statistically significant as p < 0.05 (Table 4 and Fig. 3). Mean serum lactate was found to be higher in expired (3.4 ± 0.77) subjects as compared to survivors (2.1 ± 1.97), but this difference in mean lactate was not statistically significant as p > 0.05 (Table 5 and Fig. 4).
| Parameters | Mean | Standard deviation (SD) |
|---|---|---|
| CRP (mg/L) | 9.0 | 1.41 |
| PCT (ng/mL) | 1.6 | 0.56 |
| Lactate (mmol/L) | 2.1 | 1.97 |
| ALT (U/L) | 66.5 | 4.94 |
| AST (U/L) | 61 | 8.48 |
| Bilirubin (umol/L) | 1.4 | 0.35 |
| Creatinine (mg/dL) | 2.1 | 0.07 |
| Outcome | N | % |
|---|---|---|
| Survived | 96 | 60% |
| Died | 64 | 40% |
| Total | 160 | 100 |
Fig. 1: Outcome among the study subjects
| Parameters | Survived | Expired | t-test |
|---|---|---|---|
| CRP (Mean ± SD) | 9 ± 1.41 | 77 ± 31.1 | 3.53 |
| CRP (Maximum) | 67 | 287 |
Fig. 2: Comparison of CRP with respect to the outcome
| Parameters | Survived | Expired | t-test | p-value |
|---|---|---|---|---|
| PCT (mean ± SD) | 1.6 ± 0.56 | 11.1 ± 0.14 | 2.35 | 0.02 |
| PCT (maximum) | 3.2 | 22 |
Fig. 3: Comparison of PCT with respect to the outcome
| Parameters | Survived | Expired | t-test | p-value |
|---|---|---|---|---|
| Serum lactate (mean ± SD) | 2.1 ± 1.97 | 3.4 ± 0.77 | 1.654 | 0.1 |
| Serum lactate (maximum) | 4.2 | 9.5 |
Fig. 4: Comparison of serum lactate with respect to the outcome
DISCUSSION
Sepsis is a serious and intricate condition. Its pathophysiology involves factors associated with both the host and the microorganism causing infection. For a long time, the description of sepsis has aimed at inflammatory excess and termed as an infection with at least two out of four of the systemic inflammatory response syndrome criteria, which includes tachycardia or bradycardia, elevated or reduced total leucocyte count, and fever or hypothermia.11 Out of 160 subjects, 98 (61.25%) were males, and 62 (38.75%) were females. Song et al., in their study, found that males were more commonly affected compared to females; the same was the case in our study.12 In our study, the mean age of the study subjects was 55 ± 25.5 years. Garbero et al., in their study, revealed that the mean patient age was 58 years, with the male sex being the majority (58%), which is approximately similar to our study.13 Gaini et al., in their study, revealed that patients diagnosed with sepsis were significantly older, with equal distribution of males and females.14
Mean CRP (mg/L) was 9 ± 1.41, mean PCT (ng/mL) was 1.6 ± 0.56, mean lactate (mmol/L) was 2.1 ± 1.97, mean ALT (U/L) was 66.5 ± 4.94, mean AST (U/L) was 61 ± 8.48, mean bilirubin, [umol/L] was 1.4 ± 0.35, and mean creatinine (mg/dL) was 2.1 ± 0.07 among the study subjects. Gaini et al., in their study, revealed approximately similar biochemical profiles among the study subjects.14 In our study, out of 160 subjects, 96 (60%) survived, and 64 (40%) expired. Garbero et al. in their study found that overall sample mortality was 51.63%, which is approximately similar to our study.13 In our study, mean serum lactate, CRP, and PCT were found to be significantly higher in expired subjects as compared to survivors. Mean CRP was found to be significantly higher in expired subjects (77 ± 31.1) as compared to survivors (9 ± 1.41). This difference in mean CRP in survived and expired groups was statistically significant as p < 0.05. Mean PCT (ng/mL) was found to be significantly higher in expired subjects (11.1 ± 0.14) as compared to survivors (1.6 ± 0.56). This difference in mean PCT in survived and expired groups was also statistically significant as p < 0.05. Mean serum lactate was found to be higher in expired (3.4 ± 0.77) subjects as compared to survivors (2.1 ± 1.97), but this difference of mean lactate in survived and expired groups was not statistically significant as p > 0.05. Similarly, Song et al., in their study, reported that the observed values of these biomarkers were higher in the perished group.12 Lactate is the single most frequently utilized and indispensable biomarker for the prediction of mortality in sepsis patients. Conferring to a published review article, in sepsis, the single marker for the severity of the disease and for the prediction of death is serum lactate. Although, two other articles specified that the use of lactate alone as a biomarker for sepsis exhibited only a mediocre prognostic value of 28-day mortality.15,16 Likewise, PCT had a modest predictive value in sepsis, but the worth of every single marker was inadequate. Due to this constraint of the solitary biomarker approach, quite a few researchers have explored the predictive value of biomarker combinations in foreseeing mortality. In agreement with this study, these researchers also revealed that the collective biomarker approach with more than one biomarker had a better prognostication than the solitary biomarker method.17,18
CONCLUSION
This collective biomarker approach uses CRP, PCT, and lactate. This study depicted a better implementation in predicting 28-day mortality among the patients identified with sepsis. Further, more multicentric studies are required to further investigate the predictive value of these biomarkers and scores in sepsis.
ORCID
Pallaavi Goel https://orcid.org/0000-0001-6861-6731
Puneet Rijhwani https://orcid.org/0000-0002-9454-736X
REFERENCES
1. Lever A, Mackenzie I. Sepsis: definition, epidemiology, and diagnosis. BMJ 2007;335(7625):879–883. DOI: 10.1136/bmj.39346.495880.AE
2. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315(8):801–810. DOI: 10.1001/jama.2016.0287
3. Strehlow MC, Emond SD, Shapiro NI, et al. National study of emergency department visits for sepsis, 1992 to 2001. Ann Emerg Med 2006;48(3):326–331. DOI: 10.1016/j.annemergmed.2006.05.003
4. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43(3):304–377. DOI: 10.1007/s00134-017-4683-6
5. Marshall JC. Sepsis: rethinking the approach to clinical research. J Leukoc Biol 2008;83(3):471–482. DOI: 10.1189/jlb.0607380
6. Anush MM, Ashok VK, Sarma RI, et al. Role of C-reactive Protein as an Indicator for Determining the Outcome of Sepsis. Indian J Crit Care Med 2019;23(1):11–14. DOI: 10.5005/jp-journals-10071-23105
7. Arora S, Singh P, Singh PM, et al. Procalcitonin Levels in Survivors and Nonsurvivors of Sepsis: Systematic Review and Meta-Analysis. Shock 2015;43(3):212–221. DOI: 10.1097/SHK.0000000000000305
8. Liu D, Su L, Han G, et al. Prognostic Value of Procalcitonin in Adult Patients with Sepsis: A Systematic Review and Meta-Analysis. PLoS One 2015;10(6):e0129450. DOI: 10.1371/journal.pone.0129450
9. Mikkelsen ME, Miltiades AN, Gaieski DF, et al. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009;37(5):1670–1677. DOI: 10.1097/CCM.0b013e31819fcf68
10. Filho RR, Rocha LL, Corrêa TD, et al. Blood lactate levels cutoff and mortality prediction in sepsis-time for a reappraisal? A retrospective cohort study. Shock 2016;46(5):480–485. DOI: 10.1097/SHK.0000000000000667
11. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101(6):1644–1655. DOI: 10.1378/chest.101.6.1644
12. Song J, Moon S, Park DW, et al. Biomarker combination and SOFA score for the prediction of mortality in sepsis and septic shock: A prospective observational study according to the Sepsis-3 definitions. Medicine (Baltimore) 2020;99(22):e20495. DOI: 10.1097/MD.0000000000020495
13. Garbero RF, Simões AA, Martins GA, et al. SOFA and qSOFA at admission to the emergency department: Diagnostic sensitivity and relation with prognosis in patients with suspected infection. Turk J Emerg Med 2019;19(3):106–110. DOI: 10.1016/j.tjem.2019.05.002
14. Gaini S, Relster MM, Pedersen C, et al. Prediction of 28-days mortality with sequential organ failure assessment (SOFA), quick SOFA (qSOFA) and systemic inflammatory response syndrome (SIRS) - A retrospective study of medical patients with acute infectious disease. Int J Infect Dis 2019;78:1–7. DOI: 10.1016/j.ijid.2018.09.020
15. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care 2014;18(5):503. DOI: 10.1186/s13054-014-0503-3
16. Hu C, Zhou Y, Liu C, et al. Pentraxin-3, procalcitonin and lactate as prognostic markers in patients with sepsis and septic shock. Oncotarget 2018;9(4):5125–5136. DOI: 10.18632/oncotarget.23701
17. Pallás Beneyto LA, Rodríguez Luis O, Saiz Sánchez C, et al. [Prognostic value of interleukin 6 for death of patients with sepsis]. Med Clin (Barc) 2016;147(7):281–286. DOI: 10.1016/j.medcli.2016.06.001
18. Shukeri WFWM, Ralib AM, Abdulah NZ, et al. Sepsis mortality score for the prediction of mortality in septic patients. J Crit Care 2018;43:163–168. DOI: 10.1016/j.jcrc.2017.09.009
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