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Sharing breakthrough technologies and solutions in laboratory science

Issue 02 / June 2013

www.siemens.com/healthcare

Lab-trendz Newzflash

1 •Introduction

•Needforearlydiagnosisofsepsis

•Clinicaldefinitionofsepsis

2 •Sepsis-Whoisatriskanddiagnosis methods

•WhatisProcalcitonin(PCT)?

•PCTlevelsanddiseaseseverity

3 •ADVIACentaur®PCTassayanditsperformance

•CustomerStudy:UtilityofProcalcitoninincriticalcaresetting

4 •ADVIACentaur®broadtestmenu

•Quiz#2

•ReferencesandResources

Dear Reader,

We have received great appreciation for our first issue of Lab-trendz Newzflash and we promise to keep you updated and excited with every issue. Thank you all for the encouragement and support.

We, at Siemens, are proponents of prevention and early diagnosis. This issue is dedicated to this facet of ours as we cover Sepsis – a potentially fatal inflammatory response to an infection and how early diagnosis aided by ADVIA Centaur® PCT (Procalcitonin) assay can significantly help decrease fatality. I thank Mission Hospital, Durgapur (W.B.) for sharing their clinical experiences in this issue.

Lastly, I would appreciate your feedback by writing to us at labtrendz.in@siemens.com. It keeps us motivated and strengthens our focus of increasing clinical awareness among the healthcare industry.

Sushant KinraVice President – South Asia Diagnostics Division Healthcare Sector, Siemens Ltd.

Introduction to sepsis and the need for early diagnosis

Sepsis is a syndrome that is defined as a systemic inflammatory response to an infection. It challenges every clinician caring for his/her patients in a hospital or emergency department setting. Sepsis can result in significant morbidity and could be fatal. Early diagnosis of sepsis and of the underlying cause is still a significant clinical challenge. The onset of sepsis can

be so rapid, the pathology so severe, that it is often recognized late, eliminating the critical window for early intervention when treatment is most likely to be successful. Delay in diagnosis by as little as one hour, decreases patient survival, thus generating a critical need for faster tools that can aid clinicians in early diagnosis of this potentially fatal condition.

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SIRS Sepsis Severesepsis

Septicshock

Clinical definition of sepsis

The broad term sepsis encompasses several degrees of disease severity that include SIRS, and are defined as sepsis, severe sepsis and septic shock (Table 1).1,2 These classifications also denote mortality risk. The mortality risk for sepsis increases with disease severity: (Figure 1) SIRS<sepsis<severe sepsis<septic shock.

Table1:ConsensusdefinitionforSIRS,sepsis,severesepsisandsepticshock1,2

Condition Definition

Systemic Inflammatoryresponse syndrome (SIRS)

Manifested by two or more of the following conditions:1. temperature >38°C or

<36°C2. heart rate >90 beats per

minute3. respiratory rate >20

breaths per minute or PaC02, <32 mm Hg

4. white blood cell count >12,0001/µl, <4,000/ µl or >10% immature (band) forms

Sepsis Systemic inflammatory response (SIRS) in the presence of a confirmed or suspected infection

Severesepsis Sepsis associated with organ dysfunction, hypoperfusion or hypotension

Septic shock Sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalitiesFigure1:MortalityratesofICUpatientswith

SIRS,sepsis,severesepsisandsepticshock3

2 Lab-trendz Newzflash Issue 2 / 2013

Who is at risk for sepsis?Everyone has some level of risk for developing sepsis: patients with acute and chronic diseases, the very young and the very old, those with indwelling prostheses or medical devices and the previously healthy. Individuals with underlying health conditions are at higher risk for developing and dying from sepsis. Without timely and appropriate treatment even the previously healthy can die from sepsis.

Sepsis diagnosis methods4,5

An ideal marker for diagnosing sepsis would be specific for systemic inflammation resulting from infection. As most cases of sepsis are associated with bacterial or fungal infection, culture often is considered the gold standard for diagnosis of infection. However, culture lacks sensitivity and specificity. Nevertheless, current guidelines recommend culture for all patients suspected of having sepsis, with the caveat that >50% of cultures may be negative in patients who have severe sepsis or septic shock. In addition, there is a substantial time delay of at least 24 hours for a positive culture report to 5 days for a negative culture report. This delay hinders clinicians’ ability to make informed treatment decisions in situations that require immediate action.

Traditional markers of systemic inflammation, such as C-reactive protein (CRP) and white blood cell count (WBC), also have proven to be of limited utility in identifying ill patients who require antimicrobial therapy. The sensitivity and specificity of these measurements for bacterial infection are low.

These shortcomings in both culture and available blood tests have driven researchers to find other more sensitive and specific markers. In recent years, Procalcitonin (PCT) has been the focus of much attention as a candidate marker for systemic inflammation, infection and sepsis, both in children and adults.

What is PCT6,7,8,9,10? PCT is a 116-amino-acid prohormone of the hormone calcitonin. PCT can be produced by several cell types in response to inflammation or infection. The exact biological role of PCT remains unknown; however, recent experimental studies suggest that PCT may play a pathologic role in sepsis. 3 Bacterial endotoxins and proinflammatory cytokines (IL-1, IL-2, IL-6, TNFα) are powerful stimuli for PCT production.

PCT [ng/ml] 0.05 0.5 2 10

Clinicalcondition

Healthy Local

infections

Systemic

infections

(sepsis)

Severe

sepsis

Septic shock

How do PCT levels relate to disease severity?

In a healthy population, PCT concentrations are negligible11. It is an early biomarker specifically increased during bacterial infection and sepsis; and aids in both diagnosis and prognosis. Concentrations remain fairly low in infections of viral or non-specific cause12. In septic conditions, it is detected in 3-6 hours of infectious challenge and peaks in 6-12 hours. Increasing values indicate severity of infection and organ failure (Figure 2).

Increased PCT levels is an indicator of mortality risk for patients in ICU and emergency departments13 (Figure 3). As the septic infection resolves, PCT returns below 0.5 ng/mL. Consequently, PCT assay is useful to monitor course and prognosis of life-threatening systemic bacterial infection and to tailor therapeutic interventions more efficiently. It is useful in monitoring patients with ventilator associated pneumonia.

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Patients with increasing PCT levels

Patients with decreasing PCT levels

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Increasing levels of PCT are associated with lower survival rates

Figure3:ProcalcitoninLevelsandSurvivalintheICU

Systematic use of PCT for sepsis diagnosis and monitoring could have a positive impact on reduction of antibiotic treatment, allowing shorter stay in ICU and lower costs per case14.

• In normal subjects, PCT concentrations are below 0.1 ng/ mL.

Adapted from S.Harbarth et al. Am J Respir Crit Care Med 2001;164:396

Figure2:ClinicalUtility–Interpretationofresults

3 Lab-trendz Newzflash Issue 2 / 2013

ADVIA Centaur® and ADVIA Centaur® XP Immunoassay Systems’ BRAHMS PCT (Procalcitonin assay)*

The Siemens Healthcare Diagnostics PCT assay is a one-step homogenous sandwich chemiluminescent immunoassay used for the determination of PCT in human serum and plasma on the ADVIA Centaur® and ADVIA Centaur® XP Immunoassay Systems.

PerformPCTtestinganytime,dayornight

• The ADVIA Centaur® and ADVIA Centaur® XP Immunoassay Systems enable PCT testing to become part of your routine workflow

• “Always Ready” instrument operation

• Dedicated “STAT” port

• Integrated onto a random access analyzer with 65+ assays available*

* Not all assays available in all countries or on all systems. Check with your local Siemens Healthcare Diagnostics representative for assay availability.

OutstandingPCTAssayPerformance

• Broad dynamic assay range (0.02 – 75 ng/mL)

• Concentration range 0.2 to 1000 ng/mL

• High analytical sensitivity at 0.02 ng/mL

• Excellent functional sensitivity at < 0.05 ng/mL

• Stable in-vitro and in-vivo

• Time to first result: 29 minutes

Customer Study: Utility of Procalcitonin in critical care setting

Dr.MoushumiLodhM.B.B.S, MD Biochemistry, Senior Consultant, Institute of Laboratory Medicine and Research, The Mission Hospital, Durgapur, West Bengal drmoushumilodh@gmail.com

Author of the book ‘Assessing plaque vulnerability in acute coronary syndrome, novel biochemical markers’

We conducted a retrospective analysis of data of patients of systemic inflammatory response syndrome in critically ill adult patients admitted to the Medical ICU department of The Mission Hospital between January 01 and March 15 2013. 337 patients, clinically diagnosed on the basis of features like temperature >38 °C, heart rate >90 beats/min, respiratory rate >20 breaths/minute or paCO2 <32 mm Hg, leucocytosis or leucopenia or >10 % immature form of cells were tested for Procalcitonin, C-reactive protein, lactate, etc at admission.

Outofthe337patientsadmittedtotheICU…

120 patients showed local infection

121 patients showed sepsis (systemic infection)

61 patients showed severe sepsis

35 patients showed septic shock

The PCT values ranged from 0.06 ng/mL to 165.9 ng/mL for the above 337 patients. Out of these, 217 patients had a positive blood culture. Based on the PCT values, these patients were immediately started on appropriate antimicrobial treatment.

Follow up PCT tests were done after 48 hours and also around the fifth day. In cases where PCT values were decreasing, patient discharge was planned accordingly from the ICU.

Findings:

• PCT test results are available within 30 minutes thus enabling better patient management.

• In critically ill patients, PCT levels correlate with the severity of bacterial infection.

Conclusion:

• Integrating PCT in sepsis management can lead to improved patient outcomes in terms of effective patient treatment and patient prognosis.

• PCT is therefore a better marker for sepsis than blood cultures or other available sepsis markers in the laboratory. More patient lives can thus be saved!

• Procalcitonin guided treatment of infections is able to significantly reduce antibiotic use in this type of disease without any compromise in outcome. Low serum procalcitonin concentrations identified patients without clinically relevant bacterial infections, in whom antimicrobial therapy can be safely withheld. Thus, in view of the current overuse of antibiotics, especially in acute respiratory tract infections, treatment based on procalcitonin measurement may have important financial and clinical implications. In addition to lower costs, a reduction of antibiotic use also results in fewer side effects and, in the long-term, leads to diminishing drug resistance.

4 Lab-trendz Newzflash Issue 2 / 2013

Compiled by Clinical Marketing Team, Healthcare Sector, Siemens Ltd., Plot No. 78, JIL Building, Sector 18, Gurgaon -122 015. Customer Care No.: 1-800-419-7478. Tel: 91-124-3870149. Fax: 91-124-3870162. www.siemens.com/healthcare.

Consulting Editor: Dr. Rani R, Hitech Diagnostic Centre, Chennai

Technological innovations spur new clinical applications. This

gives the medical community an edge in diagnosis and helps

detect / treat diseases at an early stage. This in turn will help

the society at large. These are the primary objectives with

which we developed Lab-trendz. We would like to know how

we can make this initiative more valuable for your practice

and the wellbeing of patients.

© 2013 by Siemens Ltd., India

All trademarks are properties of Siemens AG or associate companies. Third-party trademarks are properties of their respective companies. The content of this publication does not necessarily reflect the opinion of the publisher. Reproduction of articles in whole or in part requires the permission of the editorial office. This also applies to storage in electronic databases and on the internet.

Intended for use by Registered Medical Practitioners or Pathologists or Laboratory or Hospital Staff only. The medical information in this newsletter is for individuals of the healthcare community and not for general public. The information and reference materials contained here are intended solely for the general information of the reader and is neither intended to dictate what constitutes reasonable, appropriate or best care for any given health issue, nor is it intended to be used as a substitute for the independent judgment of a pathologist or physician for any given health issue.

Quiz #2

1. Which of the following is false?

PCT helps in -a. Diagnosis of bacterial infectionb. Assessment of severity of infectionc. Identification of pathogend. Antibiotic guidance (when to safely stop antibiotic

treatment)

2. Where is PCT of interest in a hospital setting?a. Intensive care unitb. Neonatal/ Paediatric departmentc. Surgery departmentd. All of the above

3. Which of the following is a characteristic of PCT?a. Takes time to rise after infectionb. Difficult to measurec. Correlates with severity of infectiond. Raised in viral infection

Please send your answers along with your contact details and the lucky five will receive a special prize.

E-mail to labtrendz.in@siemens.com

Ifyouhaveinterestingcasestobeshared,pleasee-mailusatlabtrendz.in@siemens.com

Our next edition will be equally exciting with the latest innovations and solutions in laboratory science.

References:1. 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 June;101(6):1644-55.

2. Linde-Zwirble WT, Angus DC. Severe sepsis epidemiology: sampling, selection, and society. Crit Care 2004 August;8(4):222-6.

3. Salvo I, de CW, Musicco M et al. The Italian SEPSIS study: preliminary results on the incidence and evolution of SIRS, sepsis, severe sepsis and septic shock. Intensive Care Med 1995 November;21 Suppl 2:S244-S249.

4. Kristopher A. McGee, MD and Nikola A. Baumann, PhD. ‘Procalcitonin’ Clinical Utility in Diagnosing Sepsis, AACC: July 2009: Volume 35, Number 7.

5. UK Standards for Microbiology Investigations, Bacteriology, B 37, Issue no: 7, Issue date: 27.03.13, Page: 9.

6. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 2008 March;36(3):941-52.

7. Christ-Crain M, Muller B. Procalcitonin in bacterial infections--hype, hope, more or less? Swiss Med Wkly 2005 August 6;135 (31-32):451-60.

8. Maruna P, Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin. Physiol Res 2000;49 Suppl 1:S57-S61.

9. Schneider HG, Lam QT. Procalcitonin for the clinical laboratory: a review. Pathology 2007 August;39(4):383-90.

10. Steinbach G, Bolke E, Grunert A, Storck M, Orth K. Procalcitonin in patients with acute and chronic renal insufficiency. Wien Klin Wochenschr 2004 December 30;116(24):849-53.

11. Barassi A, Pallotti F, Melzi d’Eril GV. Biological variation of procalcitonin in healthy individuals. Clin Chem 2004;50:1878.

12. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515-518.

13. Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M. Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 2006 October;34(10):2596-602.

14. MH Wilke,1 RF Grube,1 and KF Bodmann The use of a standardized PCT-algorithm reduces costs in intensive care in septic patients - a DRG-based simulation model .. Eur J Med Res. 2011; 16(12): 543–548.

Additionalresources:1. Siemens sepsis website: http://healthcare.siemens.com/laboratory-

diagnostics/

2. Procalcitonin testing: http://www.procalcitonin.com/

3. Sepsis alliance: www.sepsisalliance.org/

4. International Sepsis forum website: www.sepsisforum.org/

5. Surviving sepsis campaign: www.survivingsepsis.org/

Allergy

Anemia/Iron Metabolism

Bone Metabolism

Cardiac

Diabetes

Hepatitis and HIV

Immunosuppressants

Liver Fibrosis

Metabolic

Oncology

Reproductive Endocrinology

Sepsis

Special ID

Therapeutic Drug Monitoring

Thyroid

TestsavailableonADVIACentaur®Immunoassayplatform

SiemensDiagnosticsportfoliocateringtoSepsis

Siemens Healthcare Diagnostics offers an extensive portfolio of tools, including IL-6 and LBP immunoassays that can aid in sepsis diagnosis and care in the contexts of inflammation/anti-inflammation and immuno-competence, hemostasis, blood gas, hematology, microbiology and clinical chemistry. An early and accurate diagnosis can save precious time, expense and most importantly, lives.