|Year : 2019 | Volume
| Issue : 7 | Page : 881-884
Value of procalcitonin levels as a predictive biomarker for sepsis in pediatric patients with burn injuries
MF Kundes1, M Kement2
1 Department of General Surgery, University of Health Sciences, Kartal Training and Research Hospital, Istanbul, Turkey
2 Department of General Surgery, Medical School of Bahcesehir University, Istanbul, Turkey
|Date of Acceptance||14-Mar-2019|
|Date of Web Publication||11-Jul-2019|
Dr. M F Kundes
Department of General Surgery, University of Health Sciences, Kartal Training and Research Hospital, Istanbul
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: The aim of the present study was to investigate the value of serum procalcitonin (PCT) measurements for the prediction of sepsis in pediatric patients with burn injuries. Method: All pediatric patients with burn aged between 1 and 15 years who were treated at Burn Centre of Kartal Training and Research Hospital, Istanbul, Turkey between January 2014 and January 2015 were included in this study. The patients were classified into three groups according to levels of serum PCT. Groups one, two, and three consisted of patients with PCT levels lower than 0.5 ng/dl, patients with PCT levels 0.5--2.0 ng/dl, and patients with PCT levels greater than 2.0 ng/dl, respectively. Demographic data (age, gender), burn etiology, body region of burns, percentage of affected total body surface area (TBSA), antibiotic requirement, intensive care unit (ICU) requirement, hospitalization time, blood culture results, and mortality were evaluated in relation to PCT levels. Results: The mean PCT level at admittance was 2.2 ± 5.8 ng/dl. There were 52, 7, and 11 patients in group one, two, and three, respectively. Higher PCT levels were significantly associated with higher percentage TBSA (P < 0.001), positive blood cultures (P < 0.001), higher requirement of antibiotics and intensive care (P = 0.004 and P < 0.001, respectively), and longer hospitalization time (P < 0,001). Conclusion: High PCT levels may be a predictive biomarker for the development of sepsis in pediatric patients with burn injury. However, more comprehensive prospective studies may be required to validate this finding.
Keywords: Burn, pediatric burns, procalcitonin, septicemia
|How to cite this article:|
Kundes M F, Kement M. Value of procalcitonin levels as a predictive biomarker for sepsis in pediatric patients with burn injuries. Niger J Clin Pract 2019;22:881-4
|How to cite this URL:|
Kundes M F, Kement M. Value of procalcitonin levels as a predictive biomarker for sepsis in pediatric patients with burn injuries. Niger J Clin Pract [serial online] 2019 [cited 2019 Jul 22];22:881-4. Available from: http://www.njcponline.com/text.asp?2019/22/7/881/262518
| Introduction|| |
Burn injury can cause not only local but also systemic response through inflammatory mediators. Increase in vascular permeability is a major consequence of burn injuries with accompanying loss of water, proteins, and electrolytes; as a result of these, hypovolemic shock may occur. Any delay in the appropriate treatment of burn injuries can be fatal. In the past, hypovolemia was one of the most common causes of mortality in burned patients, current therapeutic approaches usually overcome hypovolemia. Nowadays, sepsis remains the major cause of mortality., In burn patients, early diagnosis and treatment of sepsis play a major role in preventing mortality. Thus, reliable biomarkers which can help to recognize sepsis early, even in the absence of clinical symptoms, are required.
Procalcitonin (PCT), a protein that consists of 116 amino acids, is a precursor of calcitonin which participates in thecalcium metabolism. PCT is mainly produced by C-cells of the thyroid gland and it is also synthesized in the liver, kidneys, lungs, and adipose tissues in response to endotoxins, cytokines, and other mediators.,,, Under normal circumstances, healthy individuals carry very low levels of PCT. However, in the presence of bacterial and fungal infections, dramatically increased levels of PCT may be seen.,,,,,,,
Several previous studies have shown the importance of PCT in the diagnosis and prognosis of sepsis in burned patients.,,,, However, there are still some controversies in the application of PCT levels.,, In the present study, we aimed to investigate the value of PCT levels as a predictive biomarker for sepsis in pediatric patients with burn injuries.
| Materials and Methods|| |
All pediatric patients with burns aged between 1 and 15 years who were treated at the Burn Centre of Kartal Training and Research Hospital, Istanbul, Turkey between January 2014 and January 2015 were included in this study. All data were obtained retrospectively from patients' charts. Patients who did not present in the first 24 hours after sustaining burn injury, as well as patients who had more than 70% total body surface area (TBSA), and those who were treated as outpatients were excluded.
The patients were classified into three groups according to levels of serum PCT. Groups one, two, and three consisted of patients with PCT levels lower than 0.5 ng/dl, patients with PCT levels 0.5--2.0 ng/dl, and patients with PCT levels greater than 2.0 ng/dl, respectively. Demographic data (age, gender), burn etiology, body region of burns, percentage of affected TBSA, antibiotic requirement, ICU requirement, hospitalization time, blood culture results, and mortality were evaluated in relation to PCT levels. PCT levels were measured using an automated immunoanalyzer (Roche Hitachi Modular E 170, USA).
All statistical analysis was done through IBM SPSS Statistics for Windows, version 20 (IBM Corp, Armonk, NY, USA). Continuous variables were expressed in means, standard deviations, and ranges. Normally distributed continuous variables were compared by Student's t-test, whereas Mann--Whitney U test was used to compare means of variables that were not normally distributed. The frequencies of categorical variables were compared using Pearson Chi-square (χ2) or Fisher's exact test, when appropriate. A value of P < 0.05 was considered statistically significant. Sensitivity was calculated by true positives/(true positive + false negative), whereas specificity was calculated by true negatives/(true negative + false positives).
| Results|| |
During the study period, a total of 76 pediatric patients were treated in our burn center. Six of them (7.9%) were excluded from the study according to the exclusion criteria (three patients who did not present in the first 24 hours, one patient who had more than 70% TBSA and two patients who were treated as outpatients). A total of 70 cases were included.
The mean age of the patients was 4.5 ± 4.2 years with a range of 1--15 years. Forty-six of them (65.7%) were males. Average TBSA was 16.1% (ranged 1--49%). Forty-three patients (61.4%) had third degree burns, whereas 27 (38.6%) had second-degree burns. Intensive care was required in 11 (15.7%) patients. The mean stay time in intensive care unit (ICU) was 16,3 ± 10,2 days. A total of 48 cases (68.5%) received antibiotics. Dual antibiotic therapy was used in 11 (15.7%) cases, whereas three different antibiotics were required in 11 (15.7%) cases. There was no mortality in our study.
The mean PCT level at admittance was 2.2 + 5.8 ng/dl. There were 52, 7, and 11 patients in group one, two and three, respectively. [Table 1] shows the relationships between PCT levels and the clinical characteristics of the patients. Higher PCT levels were significantly associated with higher percentage TBSA (P < 0.001), positive blood cultures (P < 0.001), higher requirement of antibiotics and intensive care (P = 0.004 and 0,001, respectively), and longer hospitalization time (P < 0.001).
|Table 1: Relationships between PCT levels and the clinical characteristics of the patients|
Click here to view
PCT levels greater than 0.5 ng/dl were found to be 100% sensitive and 83% specific for predicting septicemia (positive blood cultures) in the patients studied. The positive predictive value (PPV) was 44.4% and the negative predictive value (NPV) was 100% [Table 2].
|Table 2: Predictive value of PCT levels for septicaemia (positive blood culture)|
Click here to view
| Discussion|| |
We evaluated the association between serum PCT assay and septicemia in pediatric burns in this study. Complications of severe burns remain one of the major causes of multiorgan failure and sepsis. Sepsis is responsible for 28--65% of mortality in burn cases.,, Excessive inflammatory response and attenuation of immune system in burned patients may have a negative impact on the reliability of traditional biomarkers, which are used in the diagnosis of sepsis.,,,
There are strong clinical evidences that PCT allows differentiation between noninfectious systemic inflammatory response and microbiological infections by bacteria or fungi. PCT also plays a major role in the diagnosis and predictivity of antibiotic need in septic patients in ICU.,,,,,,,
Cies et al. reported that a PCT value greater than or equal to 1 ng/mL predicted having a serious bacterial infection and exhibited a sensitivity of 70%, a specificity of 68%, a PPV of 28%, and a NPV of 93% in children. In a prospective study, Rey et al. demonstrated that a PCT level greater than 1.63 ng/mL had 85% sensitivity and 83% specificity for determining septicemia in pediatric ICU patients. It should be noted that there are modest changes in the reported diagnostic accuracy of PCT. These variations can be contributed to a variety of factors including laboratory cutoffs, designated end points, patient population, and when PCT levels are drawn relative to the patient's clinical course.
Burns, regardless of TBSA, cause significant increases in conventional inflammatory biomarkers, including CRP, TNF-α, IL-6, and PCT even in the absence of infection. Because of underlying inflammation, the ability of PCT assay to distinguish septicemia from noninfectious SIRS is not very clear. The utility of PCT as an adjunct tool for the diagnosis of sepsis during hospitalization is difficult to assess because of the significant individual variations in PCT levels secondary to the underlying inflammation associated with thermal injury. In a comprehensive systematic review of adult burn patients, Mann et al. concluded that PCT assay had moderate ability to differentiate septicemia from noninfectious SIRS.
To our knowledge, there are few studies investigating value of PCT in pediatric burns. In a study including 42 children (age range, 2 months to 7 years) with burns, Abdel-Hafez et al. reported significantly higher values of WBC, CRP, TNFa, IL-6, leptin, bFGF, TGFa, and PCT than controls. In their study, pediatric patients with sepsis had significantly higher values of WBC, CRP, PCT, TNFa, and IL-6 than cases without sepsis. Also, pediatric patients with larger TBSA (>30%) and nonsurvivors showed significantly higher levels of PCT, WBC, CRP, TNFa, IL-6, and leptin than cases with smaller TBSA. They recommended monitoring immunological parameters such as PCT and/or IL-6 for early detection of infectious complications following thermal injury. Similar to Abdel-Hafez et al.'s study, we showed that higher PCT levels were related to higher TBSA, more positive blood cultures, higher requirement of antibiotics and intensive care unit, and also longer hospitalization time.
Neely et al. presented a study at ABA meeting in 2004. In their study, they found that sensitivity of PCT was 42% and specificity was 67% in predicting sepsis in 20 pediatric patients with mean age 6.1 years and mean TBSA 40.4%. However, they demonstrated that consequent CRP measurements were more reliable than PCT in the diagnosis of septic conditions. Contrary to Neely et al.'s study, our study demonstrated effectiveness of PCT measurement in the early diagnosis of sepsis in the pediatric patients with burn. In our study, PCT levels greater than 0.5 ng/dl were calculated as 100% sensitive and 83% specific for predicting septicemia.
Because of the retrospective nature of the study, PCT levels could not be monitored in the patients during follow-up. This is a limitation of the study.
| Conclusion|| |
High PCT levels may be a predictive biomarker for the development of sepsis in pediatric patients with burn injury. However, more comprehensive prospective studies may be required to validate this finding.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Pereira CT, Barrow RE, Stems AM, Hawkins HK, Kimbrough CW, Jeschke MG, et al
. Age-dependent differences in survival after severe burns: A unicentric review of 1674 patients and 179 autopsies over 15 years. J Am Coll Surg 2016;202:536-48.
Krishnan P, Frew Q, Green A, Martin R, Dziewulski P. Cause of death and correlation with autopsy findings in burns patients. Burns 2013;39:583-8.
Riedel S, Melendez JH, An AT, Rosenbaum JE, Zenilman JM. Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am J Clin Pathol 2011;135:182-9.
Schuetz P, Raad I, Amin DN. Using procalcitonin-guided algorithms to improve antimicrobial therapy in ICU patients with respiratory infections and sepsis. Cur Opin Crit Care 2013;19:453-60.
Quenot JP, Luyt CE, Roche N, Chalumeau M, Charles PE, Claessens YE, et al
. Role of biomarkers in the managment of antibiotic therapy: An expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy. Ann Intensive Care 2013;3:21.
Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: A systematic review and meta-analysis of randomized controlled trials. Crit Care Med 2010;38:2229-41.
Bouadma L, Luyt CE, Tubach F, Cracco C, Alveraz A, Schwebel C, et al.
Use of procalcitonin to reduce patients' exposure to antibiotic in intemsive care units (PRORATA trial): A multicentre randomised controlled trial. Lancet 2010;375:463-74.
Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algoritms for antibiotic therapy decision. Arch Intern Med 2011;171:1322-31.
Matthaiou DK, Ntani G, Kontogiorgi M, Poulakou G, Armaganidis A, Dimopoulos G. An ESICM systematic review and meta-analiysis of procalcitonin guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care Med 2012;38:940-9.
Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, et al
. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Evidence-Based Child Heal 2013;8:1297-371.
Von Heimburg D, Stieghorst W, Khorram-Sefat R, Pallua N. Procalcitonin-asepsis parameter in severe burn injuries. Burns 1998;24:745-50.
Sachse C, Machens HG, Felmerer G, Berger A, Henkel E. Procalcitonin as a marker fort he early diagnosis of severe infection after thermal injury. J Burn Care Rehabil 1999;20:354-60.
Lavrentieva A, Kontakiotis T, Lazaridis L, Tsotsolis N, Koumis J, Kyriazis G, et al
. Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis? Burns 2007;33:189-94.
Avrentieva A, Papadopoulou S, Kioumis J, Kaimakamis E, Bitzani M. PCT as a diagnostic and prognostic tool in burn patients. Whether time course has a role in monitoring sepsis treatment. Burns 2012;38:356-63.
Mann EA, Wood GL, Wade CE. Use of procalcitonin fort he detection of sepsis in the critically ill burn patient: A systematic review of the literature. Burns 2011;37:549-58.
Bargues L, Chanceralle Y, Catineau J, Jault P, Carsin H. Evaluation of serum procalcitoin concentration in the ICU following severe burn. Burns 2007;33:860-4.
Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersan MH, et al
. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: A randomized trial. Crit Care Med 2011;39:2048-58.
Carsin H, Assicot M, Feger F, Roy O, Pennacino I, Le Bevert H, et al
. Evolution of circulating procalcitonin levels compared with IL-6, TNF? and endotoxin levels early after thermal injury. Burns 1997;23:218-24.
Fitzwater J, Purdue GF, Hunt JL, O'Keefe GE. The risk factors and time course of sepsis and organ dysfunction after burn trauma. J Trauma 2003;54:959-66.
D'Avignon L, Hogan B, Murray C, Loo F, Hospenthal D, Cancio L, et al
. Contribution of bacterial and viral infections attributable to mortality in patients with severe burns: an autopsy series. Burns 2010;36:773-9.
Sharma BR, Harish D, Singh VP, Bangar S. Septicemia as acause of death in burns: an autopsy study. Burns 2006;32:545-9.
Finnerty CC, Herndon DN, Przkora R, Pereira CT, Oliveira HM, Queiroz DM, et al
. Cytokine expression profile over time in severely pediatric patients with burn injury. Shock 2006;26:13-9.
Murray CK, Hoffmaster RM, Schmit DR, Hospenthal DR, Ward JA, Cancio LC, et al
. Evaluation of white blood cell count, neutrophil percentage, and elevated temperatures as predictors of bloodstream infection in burn patients. Arch Surg 2007;142:639-42.
Greenhalgh DG, Saffle JR, Holmes JH, Gamelli RL, Palmieri TL, Horton JW, et al
. American Burn Association consensus conference to define sepsis and infection in burns. J Burn Care Res 2007;28:776-90.
Lodise TP Jr, Patel N, Kwa A, Graves J, Furuno JP, Graffunder E, et al
. Predictors of 30-day mortality among patients with pseudomonas aeruginosa bloodstream infections: İmpact of delayed appropriate antibiotic selection. Antimicrob Agents Chemother 2007;51:3510-5.
Cies JJ, Chopra A. Procalcitonin use in a pediatric intensive care unit. Pediatr Infect Dis J 2014;33:984-6.
Rey C, Los Arcos M, Concha A, Medina A, Prieto S, Martinez P, Prieto B. Procalcitonin and creactive protein as markers of systemic inflammatory response syndrome severity in critically ill children. Intensive Care Med 2007;33:1108-9.
Abdel-Hafez NM, Saleh Hassan Y, El-Metwally TH. A study on biomarkers, cytokines, and growth factors in children with burn injuries. Ann Burns Fire Disasters 2007;20:89-100.
Neely AN, Fowler LA, Kagan RJ, Warden GD. Procalcitonin in pediatric burn Patients: An early indicator of sepsis? J Burn Care Rehabil 2004;25:76-80.
[Table 1], [Table 2]