Correlation of Quick SOFA Score and Procalcitonin with Mortality in the Emergency Department

Journal of Advances in Medicine and Medical Research

32(6): 64-69, 2020; Article no.JAMMR.56300 ISSN: 2456-8899 (Past name: British Journal of Medicine and Medical Research, Past ISSN: 2231-0614, NLM ID: 101570965)

Mandip Singh Bhatia1*, Ritu Attri2, Kumar Rajni Kant3 and Saurabh C. Sharda1

1Department of Internal Medicine, PGIMER, Chandigarh, India. 2Department of Internal Medicine, Government Medical College, Patiala, India. 3Anaesthesia and Critical Care, SGHS Hospital, Mohali, India.

Authors’ contributions

This work was carried out in collaboration among all authors. Authors MSB and RA designed the study, performed the statistical analysis, wrote the protocol and wrote the first draft of the manuscript. Authors KRK and SCS managed the analyses of the study. Author SCS managed the literature searches. All authors read and approved the final manuscript.

Article Information

DOI: 10.9734/JAMMR/2020/v32i630434 Editor(s): (1) Dr. Rameshwari Thakur, Muzaffarnagar Medical College, India. Reviewers: (1) Dinesh Yadav, Madhav Hospital, India. (2) Apeksha Niraula, Nepal. (3) Marcel Cerqueira Cesar Machado, University of São Paulo, Brazil. Complete Peer review History: http://www.sdiarticle4.com/review-history/56300

Received 25 February 2020 Accepted 01 May 2020 Original Research Article Published 08 May 2020

ABSTRACT

Introduction: Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection with high mortality. Early diagnosis and treatment can decrease mortality. Methods: We studied 2031 patients presenting to an emergency department with fever or suspected infection to find the correlation between q SOFA SCORE and procalcitonin levels with mortality. Results: It is seen that mortality is directly proportionate to qSofa score and we also found that the value of procalcitonin is directly proportionate to qSofa score. Conclusion: Combination of qSofa score with procalcitonin is a sensitive marker of death in sepsis. qSofa score of 2 or more is associated with increased mortality but its, not death sentence if all such patients treated aggressively & timely then the majority of them would survive.

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*Corresponding author: E-mail: [email protected];

Bhatia et al.; JAMMR, 32(6): 64-69, 2020; Article no.JAMMR.56300

Keywords: Procalcitonin; mortality; emergency department, sepsis; life-threatening organ dysfunction.

1. INTRODUCTION resuscitation. The reported incidence of sepsis is increasing [2,3] likely reflecting ageing Sepsis is defined as life-threatening organ populations. The mortality of septic shock is dysfunction caused by the dysregulated host 40%, four times more than sepsis. Therefore response to infection. Organ dysfunction can be early diagnosis and early aggressive treatment identified as an acute change in SOFA score >2 can decrease the mortality [4]. qSOFA criteria points consequent to infection [1]. SOFA score were devised along with new sepsis 3 definitions >2 reflects an overall mortality risk of to identify adult patients with suspected infection approximately 10% in a general hospital who are likely to have poor outcomes. qSOFA is population. The septic shock which is defined as calculated based on three parameters: Altered persisting hypotension requiring vasopressor to mentation, systolic blood pressure of 100 mmHg maintain MAP>65 mmHg and having serum or less and respiratory rate of 22 minutes. lactate level >2 mmol/l despite adequate fluid Various biomarkers are also available for early

Table 1. Effect of microbiologic and clinical factors on procalcitonin levels

Microbiologic & Rise more then 0.25 ng/ml Rise less then 0.25 ng/ml clinical factors Infections Bacterial Typical Most reported thus far respiratory Atypical . Chlamydia pneumoniae respiratory . Mycoplasma pneumoniae Mycobacteria Legionella spp May or may not rise Other bacteria May or may not rise European Borrelia spp (Lyme Orientia tsutsugamushi (scrub typhus) borreliosis) Fungal Candida spp . Aspergillosis . Coccidioidomycosis . Mucormycosis Parasitic Plasmodium spp (malaria) Toxin-mediated . Severe Clostridioides (formerly C. difficile colonization illnesses Clostridium) difficile-associated disease . Mushroom poisoning Severe . Burns physiologic stress . Trauma . Surgery . Bowel ischemia . Pancreatitis . Intracerebral hemorrhage . Ischemic stroke . Shock of any kind (septic, anaphylactic, hemorrhagic, or cardiogenic) Malignancies . Medullary thyroid cancer . Lymphoma . Lung cancers with neuroendocrine . Sarcoma components . Pancreatic cancer . Renal cell carcinoma Other . Renal insufficiency . comorbidities Drugs . Alemtuzumab (CD52 antibody) . Glucocorticoids . Granulocyte transfusions . Interleukin 2 . Rituximab (anti-CD20 antibody) . T-cell antibodies

Bhatia et al.; JAMMR, 32(6): 64-69, 2020; Article no.JAMMR.56300

diagnosis of sepsis. The most popular biomarker procalcitonin was 7.5 and in the subgroup, with among physicians is procalcitonin but in rare qSOFA score 3, the mean value of serum cases the value of procalcitonin can false procalcitonin value was 28. Thus it was found positive or negative some examples illustrated in that the value of procalcitonin is directly Table 1. Therefore this study was done to see proportionate to qSOFA score as shown in the correlation of qSOFA with procalcitonin levels Graph 2. The median value of procalcitonin in for early diagnosis of sepsis and their 1790 patients who survived their illness was relationship with mortality. 0.377 as compared to 212 patients who succumbed to their illness it was 6. Thus, it was 2. METHODS seen that when the procalcitonin value was below 0.5, risk of death was very less and as the This was a prospective study conducted for a value of procalcitonin increases so does the risk period of 2 years from January 2017 to February of death. 2019 in a tertiary care hospital. All-new adult patients who presented to the emergency 3.1 Statistical Analysis department with a history of fever or suspected infection were enrolled. At the time of admission, The statistical analysis of all the data was done qSOFA score was calculated. Basic workup for using the Kruskal-Wallis Test and Mann-Whitney sepsis and appropriate cultures i.e. blood Test and p-value of < 0.001 was found which is cultures and other secretions cultures were sent. statistically significant. Procalcitonin levels were also measured at the time of initial assessment. The samples 4. DISCUSSION were processed according to the standard procedures. VIDAS (ELFA) test was used for the Sepsis is a clinical syndrome that has estimation of procalcitonin. The patients were physiologic, biologic, and biochemical started on appropriate empirical antibiotics abnormalities caused by a dysregulated according to their clinical presentation which was inflammatory response to infection. Sepsis later modified according to culture sensitivity carries high mortality ranging from 10-40% which report. Patients were followed up till discharge is even more than acute ST-elevation myocardial from the hospital or death during the infarction which has a mortality of 8.1% [5]. Early admission. identification and aggressive treatment can decrease mortality. In 2016, SCCM/ESICM task 3. RESULTS force has described an assessment score for patients outside the intensive care unit as a way Total of 2031 patients was enrolled during the to facilitate the identification of patients study period. Out of these, 1812 (89.2%) patients potentially at risk of dying from sepsis [1,6]. This survived whereas 219 (10.8%) succumbed to score is a modified version of the Sequential their illness. The number of patients had qSOFA (Sepsis-related) Organ Failure Assessment score of 1 were 1362 i.e (67.1%). The number of score (SOFA) called the quick SOFA (qSOFA) patients had qSOFA score of 2 were 477 i.e score. A score ≥2 is associated with poor (23.5%). The number of patients who had outcomes due to sepsis. qSOFA score of 3 was 192 i.e (9.5%). In the subgroup of patients with qSOFA score 1, The qSOFA score is easy to calculate since it majority 1320 patients i.e (96.9%) survived their only has three components, each of which is illness and only 42 patients i.e (3.1%) readily identifiable at the bedside and are succumbed to their illness. In the subgroup of allocated one point: patients with qSOFA score 2, mortality occurred in 128 patients i.e (26%) and 349 patients i.e  Respiratory rate ≥22/minute (73%) survived. In the subgroup of patients with  Altered mentation qSOFA score 3, mortality occurred in 49 patients  Systolic blood pressure ≤100 mmHg i.e (25.5%) and 143 patients i.e (74%) survived their illness. Therefore, it is seen that mortality is Various biomarkers for early detection of sepsis directly proportionate to qSOFA score as shown are also available but most reliable of them is in Graph 1. In the subgroup of patients with procalcitonin. It is a 116 amino-acid protein with qSOFA score 1 the mean value of procalcitonin a molecular weight of 13kDa. It is a precursor of was 0.42. In the subgroup of patients with calcitonin produced by C-cells of the thyroid qSOFA score 2, the mean value of serum gland, which is intracellularly cleaved by

Bhatia et al.; JAMMR, 32(6): 64-69, 2020; Article no.JAMMR.56300

proteolytic enzymes into the active hormone [7]. strongly associated with all-cause mortality in Procalcitonin was first described for the sepsis patients [9]. In healthy individuals, serum diagnosis of sepsis in 1993 [8]. Since then, it has concentrations of procalcitonin are below 0.1 been widely investigated as a potential biomarker ng/mL. In response to a bacterial infection, for sepsis and has been used widely in Europe damage-associated molecular patterns (DAMPs) as a biomarker in the management of infection and pathogen-associated molecular patterns and sepsis. Several meta-analysis data suggest stimulate cells to produce procalcitonin, which of heterogeneity for the procalcitonin testing; results in a significant increase in serum however, elevated procalcitonin concentrations concentrations [10].

Mortality 30

15 Mortality 10

0 1 2 3

Graph 1. qSOFA score is on X-axis and mortality percentage is on Y-axis

Mean procalcitonin 30

15 Mean procalcitonin

0 1 2 3

Graph 2. qSOFA score is on X-axis & procalcitonin (ng/ml) is on Y-axis

Bhatia et al.; JAMMR, 32(6): 64-69, 2020; Article no.JAMMR.56300

2000 1800 1600 1400 1200 1000 deaths 800 600 400 200 0 0.377 6

Graph 3. Median value of procalcitonin in ng/ml on X-axis & survivors and deaths on Y-axis

15 procalcitonin mortality 10

0 1 2 3

Graph 4. qSOFA score represented on X-axis and procalcitonin levels in ng/mL & mortality in percentage in Y-axis

The findings of our study showed that qSOFA increases the majority of the patients with score combined with procalcitonin has fair qSOFA score of 2 or more will survive if treated accuracy in predicting mortality. As qSOFA score aggressively. In the Graph 3 it is demonstrated increases, levels of serum procalcitonin also that 73% patients survived in spite of qSOFA increases and as both increases, there is a score of 2 or more. Therefore, it can be definite increase in mortality rates as shown in concluded that increased qSOFA score of 2 or Graph 4. more, is associated with increased mortality but it is not a death sentence. If all such patients are Our study also showed an important paradox that treated aggressively & timely, then the majority of though the mortality increases as qSOFA score them would survive. Serum procalcitonin levels

Bhatia et al.; JAMMR, 32(6): 64-69, 2020; Article no.JAMMR.56300

are more sensitively associated with mortality in Americans. J Am Geriatr Soc. 2012;60(6): patients with sepsis and the majority of patients 1070-1077. with increased serum procalcitonin of 6 ng/ml will 3. Gaieski DF, Edwards JM, Kallan MJ, Carr succumb to their illness. Combination of qSOFA BG. Bench marking the incidence and score with procalcitonin serves as a sensitive mortality of severe sepsis in the United marker of death in sepsis. States. Crit Care Med. 2013;41(5):1167- 1174. 5. CONCLUSION 4. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign guidelines Combination of qSOFA score with procalcitonin committee including the pediatric can serve as a sensitive marker of death in subgroup. Surviving Sepsis Campaign: sepsis. qSOFA score of 2 or more is associated International Guidelines for Management with increased mortality but if all such patients of Severe Sepsis and Septic Shock: 2012. treated aggressively & timely then the majority of Crit Care Med. 2013;41(2):580-637. them would survive. 5. Shah RU, Henry TD, Rutten-Ramos S, Garberich RF, Tighiouart M, Bairey Merz CONSENT CN. Increasing percutaneous coronary interventions for ST-segment elevation As per international standard or university myocardial infarction in the United States: standard written patient consent has been Progress and opportunity. JACC collected and preserved by the author(s). Cardiovasc Interv. 2015;8(1ptB):139-146. 6. Assessment of Clinical Criteria for Sepsis: ETHICAL APPROVAL For the Third International Consensus Definitions for Sepsis and Septic Shock As per international standard or university (Sepsis-3). Seymour CW, Liu VX, standard written ethical approval has been Iwashyna TJ, Brunkhorst FM, Rea TD, collected and preserved by the author(s). Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman COMPETING INTERESTS CS, Escobar GJ, Angus DC. JAMA. 2016;315(8):762-74. Authors have declared that no competing 7. Moya F, Nieto A, Jose LR. Calcitonin interests exist. biosynthesis: Evidence for a precursor. Eur J Biochem. 1975;55:407–13. REFERENCES 8. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum 1. Singer M, Deutschman CS, Seymour CW, procalcitonin concentrations in patients Shankar-Hari M, Annane D, Bauer M, with sepsis and infection. Lancet. Bellomo R, Bernard GR, Chiche JD, 1993;341:515–8. Coopersmith CM, Hotchkiss RS, Levy MM, 9. Dan L, Longxiang S, Gencheng H, Peng Y, Marshall JC, Martin GS, Opal SM, Lixin X. Prognostic value of procalcitonin in Rubenfeld GD, van der Poll T, Vincent JL, adult patients with sepsis: A systematic Angus DC. The Third International review and meta-analysis. PLoS One. Consensus Definitions for Sepsis and 2015;10(6):e0129450. Septic Shock (Sepsis-3). JAMA. 10. Müller B, White JC, Nylén ES, Snider RH, 2016;315(8):801-10. Becker KL, Habener JF. Ubiquitous 2. Iwashyna TJ, Cooke CR, Wunsch H, Kahn expression of the calcitonin-1 gene in JM. Population burden of long-term multiple tissues in response to sepsis. J survivorship after severe sepsis in older Clin Endocrinol Metab. 2001;86:396–404. ______© 2020 Bhatia et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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