B·R·A·H·M·S PCT™ LIA is an immunoluminometric assay (ILMA) and B·R·A·H·M·S PCT™ sensitive KRYPTOR™ is an immunofluorescent assay. Both used to determine the concentration of PCT (procalcitonin) in human serum and plasma. They are intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock.
What is sepsis?
Sepsis is a common and frequently fatal medical condition that is the result of the body’s inflammatory response to an infection. Angus, D. et al., reported in Critical Care Medicine that 751,000 severe sepsis cases occurred in the US in 1995 and mortality was 28.6%, or 215,000 deaths nationally.1
Hall, M.J. et al., reported in a Centers for Disease Control and Prevention (CDC) NCHS Data Brief that US hospitalizations for septicemia or sepsis as the principal or a secondary diagnosis increased from 621,000 in 2000 to 1,141,000 in 2008 (ICD-9-CM diagnosis codes of 038.xx, 995.91 and 995.92).2
In 2009, septicemia or sepsis was the single most expensive condition treated in U.S. hospitals. Costs for stays with a principal diagnosis of septicemia totaled nearly $15.4 billion.3
PCT is the prohormone of calcitonin. Calcitonin is produced exclusively in the thyroid gland. In 2001, Muller, B. et al., found that PCT is ubiquitously and uniformly expressed in multiple tissues throughout the body in response to sepsis. Elevated circulating levels of PCT are important markers in response to microbial infections and a powerful tool in the early detection of sepsis.4
PCT concentrations and sepsis risk 5-7
- Less than 0.5 ng/mL — Low risk for progression to
severe sepsis and/or septic shock.
- Between 0.5 and 2 ng/mL — Sepsis should be
- Greater than 2 ng/mL — High risk for progression to
severe sepsis and/or septic shock.
PCT levels must always be interpreted in the clinical context.
Early identification and intervention is crucial to improving sepsis outcomes. A retrospective study by Kumar, A. et al., (1989 – 2004) showed that administration of an effective antimicrobial therapy within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hours was associated with an average decrease in survival of 7.6%.9 However, early identification of sepsis can be challenging due to its non-specific symptoms.
Following stimulus by a bacterial endotoxin or trauma, PCT plasma concentrations:13,14
- Rise 3 – 6 hours after bacterial invasion
- Are significant after 6 hours
- Exhibit peak values between 12 – 48 hours
- Have an observed half-life of 24 hours
This rapid and sustained response to bacterially induced systemic inflammation is an important hallmark of PCT as a marker of sepsis risk.
PCT vs. lactate and other markers
Lactate can be elevated in many disease states or in cases of poor tissue perfusion. Müller, B. et al. reported in Critical Care Medicine that serum PCT concentrations are more sensitive and are specific markers of sepsis as compared with serum lactate, CRP, and IL-6 levels.6
Important considerations when interpreting PCT results
Increased PCT levels may not always be related to systemic infection. These conditions include, but are not limited to:
- The first days after a major trauma, major surgical intervention, burns, treatment with OKT3 antibodies and other drugs stimulating the release of pro-inflammatory cytokines, small cell lung cancer, medullary C-cell carcinoma of the thyroid, neonates (first 2 days of life).7,10-12
- Patients with prolonged or severe cardiogenic shock or prolonged severe organ perfusion anomalies. Low PCT levels may also be observed during the early course of infection, in localized infections, and in subacute endocarditis.
Mike Broyles PharmD, BSPharm - Director of Pharmacy and Laboratory Services at Five Rivers Medical Center
Improving outcomes with diagnostic tools: using Procalcitonin in the ICU
The Global Sepsis Alliance has declared September to be World Sepsis Month—and September 13 World Sepsis Day. The effort seeks to draw attention to the common, deadly and often preventable condition worldwide. Every year, severe sepsis affects more than three quarters of a million patients—and as many as 40 percent of these patients die.
Early identification of septic patients is crucial for physicians such as Dr. Eric Gluck at Chicago's Swedish Covenant Hospital; because studies show that patient outcomes significantly improve the earlier treatment can begin.
Sepsis presents few specific clinical symptoms or signs in its early phases, however, physicians can deploy Procalcitonin biomarker testing as one of several evaluation tools to improve risk assessment for sepsis. Dr. Gluck and his team administer the test when a patient enters the ICU, "With this test, you don’t have to give up sensitivity and specificity to get speed – you get it all. We have results in 45 minutes to one hour – in medicine that’s fast."
Dr. Eric Gluck, Chicago's Swedish Convenant Hospital
Every year, severe sepsis affects more than three quarters of a million patients - and as many as 40 percent of these patients die. Dr. Gluck explains how early identification of septic patients is crucial.
Stephen Barnes BSN, RN, Alumnus CCRN, Clinical Consultant, Thermo Fisher Scientific
Mr. Barnes provides an overview of sepsis, incidence of sepsis in the U.S., importance of early detection, treatments for sepsis and survival rates.
1. Angus DC, et al., Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care, Crit Care Med 2001;29(7):1303-1310. 2. Hall MJ, et al., Inpatient Care for Septicemia or Sepsis: A Challenge for Patients and Hospital, CDC NCHS Data Brief 2011 June;62. 3. Elixhauser A, et al., Septicemia in U.S. Hospitals, 2009. HCUP Statistical Brief #122; October, 2011. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb122.pdf 4. Müller B, et al., Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 2001 Jan;86(1):396-404. 5. Harbarth S, et al., Diagnostic value of procalcitonin,interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001;164:396-402. 6. Müller B, et al., Procalcitonin for Diagnosis and Monitoring of Therapy of Bacterial Infections Crit Care Med 2000; 28(4):977-983. 7. Meisner M, Procalcitonin – Biochemistry and Clinical Diagnosis – 1st edition – Bremen: UNI-MED, 2010 ISBN 978-3-8374-1241-3. 8. Morgenthaler N, et al., Detection of Procalcitonin (PCT) in Healthy Controls and Patients with Local Infection by a Sensitive ILMA, Clin Lab 2002;48:263-270. 9. Kumar A, et al., Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock, Crit Care Med 2006,34:1589-1596. 10. Meisner M, et al., Postoperative plasma concentrations of procalcitonin after different types of surgery, Intensive Care Med 1998;24:680-684. 11. Chiesa C, et al., Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates, Clinical Infectious Diseases 1998;26:664-72. 12. Reith HB, Procalcitonin in early detection of postoperative complications, Dig Surg 1998;15:260-265. 13. Brunkhorst FM, et al., Kinetics of procalcitonin in iatrogenic sepsis. Intens Care Med. 1998;24:888-892. 14. Meisner M, Procalcitonin: Experience with a new diagnostic tool for bacterial infection and systemic inflammation. J Lab Med 1999;23(5):263-272. 15. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis, Crit Care Med 1992 Jun;20 (6):864-74. 16. Levy M, et al., 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference, Crit Care Med 2003;31(4).