Question: During evaluation of several patients during Trauma Rotation there were several patients that had negative blood cultures a persistent fever and received multiple days of antibiotics. In one specific case, the patient was post op day # 3 and spiked a fever. It was suspected that she had an infected pulmonary contusion. She never had + blood cultures and stayed past possible discharge to finish a course of IV antibiotics. Procalcitonin is utilized in medical ICUs to distinguish sepsis vs SIRS. It is also used to trailor and in certain instances can be used to deescalate antibiotics. Is there evidence to suggest that Procalcitonin could be utilized in trauma patients?
Procalcitonin is a polypeptide prohormone of calcitonin. In healthy individuals it is produced by C Cells in the thyroid and neuroendocrine cells in the lung. In the presence of bacterial infection, serum PCT levels become elevated. The septic release of procalcitonin ends up coming from several sources. Several medical studies have indicated that procalcitonin is useful in determining sepsis from non infectious SIRS in medical patients. Sepsis is listed as the most common cause of late death in polytrauma patients. So the ability to differentiate between sepsis and non infectious SIRS is of the utmost importance. 2 recent studies that I found, listed below, spoke specifically to polytrauma patients and procalcitonin. The first study was published in Injury Biomarkers predicting sepsis in polytrauma patients: current evidence. This study used a "best evidence synthesis" method to evaluate existing roles of biomarkers for the prediction of sepsis in polytrauma patients. They evaluated thirty studies and decided that there was "strong evidence" for the early use of procalcitonin as a early indicator of post traumatic sepsis as a grade B recommendation. They made several Grade B recommendations for clinical practice. These included that PCT can be used in the clinical setting as an early predictor of trauma patients prone to develop septic complications, it cannot be used as a single indicator because of its sensitivity and specificity, the trend of PCT appears to have the most clinical significance with further elevation of procalcitonin after the peak is reached in 24 - 48 hours can be considered as potential for septic complications, CRP is not effective in predicting sepsis after major trauma. The second paper I found was in the Journal of Trauma Acute Care Surgery Volume 73 number 2 as a plenary paper presented at EAST January 2012. This paper was a prospective observational cohort study conducted in a Level I trauma facility. The authors wanted to determine the natural course of PCT in trauma patients, the utility of PCT as a marker to differentiate SIRS and Sepsis, and the association of PCT with mortality. PCT assays were completed at 6, 12, 24 hours and daily thereafter up to 30 days. Patient s were considered SIRS Sepsis or neirther sepsis nor sirs (neither group) post hoc. 80 patients total were evaluated after exclusion criteria. They discovered that there was a transient increase in the PCT level in both groups in the first 24- 48 hours post trauma, a second peak was seen in septic patients at days 9 and 13. The most common infections found were VAP, Bacteremia, UTI, and other. There results concluded that PCT levels were significantly higher in the sepsis group vs the sirs and neither group. PCT above 5ng/dl had a significantly increased mortality rate, , a PCT level of .82 ng/dl produced sensitivity of 87% and specificity of 82% for sepsis with an area under the curve of 92%. It should be noted that this study was funded by a PCT analyzer company. Previous specificity and sensitivities for PCT was listed in the 70s.
In the end, I believe that it is too early to use PCT as a single indicator for sepsis in the trauma patient. However, in the patient I listed above that was greater than 3 days post operative and several days out from her initial trauma with SIRS but unkown source the edition of procalcitonin could have allowed us to deescalate antibiotics in the face of multiple negative cultures and no clear source.
Townsend Sabiston Textbook of Surgery 19th edition Chapter 23 Surgical Critical Care Sepsis
"Procalcitonin has been evaluated as a means to delineate sepsis from other noninfectious causes of SIRS; there have been some initially promising data from small, single-center studies showing a greater sensitivity compared with white blood cell (WBC) count and CRP in detecting infection when daily procalcitoninlevels were followed, even in situations in which the change in procalcitonin levels were subtle. There is also emerging support for using procalcitonin as a marker in long-term, critically ill patients because WBC and CRP tend to become even less accurate markers for these patients. All this enthusiasm is tempered by the cost and clinical impracticality of drawing and determining daily procalcitoninlevels, so further study will likely focus on the benefit of following them on less frequently."
Lancet Infect Dis. 2013 May;13(5):426-35. doi: 10.1016/S1473-3099(12)70323-7. Epub 2013 Feb 1.
Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis.
FINDINGS:
Our search returned 3487 reports, of which 30 fulfilled the inclusion criteria, accounting for 3244 patients. Bivariate analysis yielded a mean sensitivity of 0 · 77 (95% CI 0 · 72-0 · 81) and specificity of 0 · 79 (95% CI 0 · 74-0 · 84). The area under the receiver operating characteristic curve was 0 · 85 (95% CI 0 · 81-0 · 88). The studies had substantial heterogeneity (I(2)=96%, 95% CI 94-99). None of the subgroups investigated--population, admission category, assay used, severity of disease, and description and masking of the reference standard--could account for the heterogeneity.
INTERPRETATION:
Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment.
J Trauma Acute Care Surg. 2012 Aug;73(2):413-8; discussion 418. doi: 10.1097/TA.0b013e31825ff5b7.
The utility of procalcitonin in critically ill trauma patients.
Inova Regional Trauma Center, Falls Church, Virginia, USA. Joseph.Sakran@uphs.upenn.
BACKGROUND:
Procalcitonin (PCT), the prohormone of calcitonin, has an early and highly specific increase in response to systemic bacterial infection. The objectives of this study were to determine the natural history of PCT for patients with critical illness and trauma, the utility of PCT as a marker of sepsis versus systemic inflammatory response syndrome (SIRS), and the association of PCT level with mortality.
A total of 856 PCT levels from 102 patients were analyzed, with mean age of 49 years, 63% male, 89% blunt trauma, mean Injury Severity Score of 21, and hospital mortality of 13%. PCT concentration for patients with sepsis, SIRS, and neither were evaluated. Mean PCT levels were higher for patients with sepsis versus SIRS (p < 0.0001). Patients with a PCT concentration of 5 ng/mL or higher had an increased mortality when compared with those with a PCT of less than 5 ng/mL in a univariate analysis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9; p = 0.04). In a multivariate logistic analysis, PCT was found to be the only significant predictor for sepsis (odds ratio, 2.37; 95% confidence interval,1.23-4.61, p = 0.01).
CONCLUSION:
Conclusion: PCT levels are significantly higher in ICU patients with trauma and sepsis and may help differentiate sepsis from SIRS in critical illness. An elevated PCT level was associated with increased mortality.
Use of procalcitonin for the detection of sepsis in the critically ill burn patient: a systematic review of the literature.
Source
University of Texas Health Sciences Center, Houston, TX - School of Nursing, USA.Elizabeth.Mann@us.army.mil
Erratum in
Burns. 2011 Sep;37(6):1085Abstract
The purpose of this systematic review was to assess the evidence for use of routine procalcitonin testing to diagnose the presence of sepsis in the burn patient. The electronic databases MEDLINE, Cochrane, CINAHL, ProQuest, and SCOPUS were searched for relevant studies using the MeSH terms burn, infection,procalcitonin, and meta-analysis. The focus of the review was the adult burn population, but other relevant studies of critically ill patients were included as data specific to the patient with burns are limited. Studies were compiled in tabular form and critically appraised for quality and level of evidence. Four meta-analyses, one review of the literature, one randomized controlled trial, nine prospective observational, and three retrospective studies were retrieved. Six of these studies were specific to the burn population, with one specific to burned children. Only one meta-analysis, one adult burn and one pediatric burn study reported no benefit of procalcitonin testing to improve diagnosis of sepsis or differentiate sepsis from non-infectious systemic inflammatory response. The collective findings of the included studies demonstrated benefit of incorporating procalcitonin assay into clinical sepsis determination. Evaluation of the burn specific studies is limited by the use of guidelines to define sepsis and inconsistent results from the burnstudies. Utility of the procalcitonin assay is limited due to the lack of availability of rapid, inexpensive tests. However, it appears procalcitonin assay is a safe and beneficial addition to the clinical diagnosis of sepsis in the burn intensive care unit.
Ann Intensive Care. 2013 Jul 8;3(1):21. doi: 10.1186/2110-5820-3-21.
Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy.
"In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has been obtained.
For ICU patients who have nonbacteremic sepsis from a known site of infection, antibiotics can be stopped if the PCT level at day 3 is < 0.5 ng/mL or has decreased by >80% relative to the highest level recorded, irrespective of the severity of the infectious episode; in bacteremic patients, a minimal duration of therapy of 5 days is recommended." .
from Anthony Anibal Acosta, MD
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