DIAGNOSIS AND INVESTIGATIONS FOR SEPSIS. B. Mrara

Transcription

1 DIAGNOSIS AND INVESTIGATIONS FOR SEPSIS B. Mrara CH C.H. Baragwanath ICU

2 OUTLINE Introduction Diagnostic issues in sepsis Diagnosis and investigations for sepsis: clinical and laboratory lb investigations i i Sepsis biomarkers

3 Introduction

4 Definition of sepsis: consensus definition SIRS criteria plus infective cause. Severe sepsis, septic shock Scale of problem: PISA STUDY, SOAP STUDY

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6 Diagnostic Issues Overlapping pathologies in the ICU, which also predispose to sepsis Localising Site of Infection Interpreting microbiological findings: e.g. infection or colonisation Need dfor early initiation iti of treatment t t (antibiotics and antifungals) Need for antibiotic stewardship

7 Non infective causes of SIRS Tissue Injury: trauma, MI, Metabolic :Thyroid storm Therapy related: blood products Malignancy Neurologic: SAH

8 KUMAR CCM (6)

9 Antibiotic Stewardship

10 CCM 2004 vol 34

11 Diagnosis of Sepsis Clinical: Temp, sepsis focus Nonspecific markers: WCC and neutrophilia, neutropenia nonspecific Blood cultures: problems Cohen et al CCM 2004 vol 32

12 Blood Cultures Required din severe sepsis diagnosis: i Problems: only % positivity in severe sepsis or shock Better yield with organ failure and chills Depends on site of infection: pneumonia and soft tissue infection: BC neither sensitive nor specific Technique influences sens and specificity: amount of blood, site, cleaning: alcohol based solutions, +swabbing the bottle stopper, +needle change Chlorhexidine Alcohol superior to Povidone Iodine for antisepsis Darouiche, Rabih NEJM 2010

13 Blood Cultures Obtaining i blood for culture through ha central catheter or arterial line, not recommended unless new line No of blood cultures: 2 max 3 should ldbe obtained. No specified time between cultures. As soon as possible following onset of fever. Fever follows bacteraemia by 30 to 90 min. Repeat blood cultures recommended if special culture media necessary or non response to therapy within hrs. Single positive culture: clinically valuable if pathogenic organism

14 Diagnosis of Central Venous Culture Infection Only 10 72% of infected dcvc s cause bacteraemia Infection can be proven definitively in only 9 26% of removed catheters. t Definite CRBI: pos cath culture + pos periph culture before cath removal + same micro organism. Probable: bacteraemia plus any of 1. pus at cath insertion site 2. catheter hub culture positive ii 3. pos CVC blood culture growing 5 X > org than periph blood Cr ill pt: cath removal and culture of cath tip recommended for definitive diagnosis.

15 Modern Blood Culture Techniques PCR, Hybridisation techniques

16 Klouche et al Clin Chem Lab Klouche et al Clin Chem Lab Med 2008;46(7) 888

17 Diagnosis of fungal infections Diagnosis i significant ifi tif: candidaemia, i candida from CVC tip, isolated from sterile site except urine. Problem: distinguishing ginfection from colonisation Clinical: non specific, chorioretinitis < 15 % Micro: no. of colonised sites> 2, high sensitivity low specificity i 22% Candida colonisation index and SCORE improves sens and spec Blood cultures, now improved, but poor yield(< 50 %) and negative predictive value. Gold standard is histopathologic diagnosis of tissue samples limited value

18 TPN, Sepsis, multifocal colonisation,surgery CCM 2009;

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20 Diagnosis of fungal infection: newer methods Detection of components of fungal cell wall invasive i aspergillosis(ia) and invasive candidiasis(ic) Gl Galactomannan: IA antigen detection, dt ti 2 methods: ELISA(low sens, high spec) and latex agglutination (good spec and sens). Draw back is need for series of samples due to rapid elimination of antigen. Significant if ng/ml Mannan: IC, albicans, glabrata, tropicalis sens spec %. Lower with krusei and parapsilosis. Need for frequent blood sampling to improve diagnostic yield

21 Diagnosis of fungal infection: newer methods (1 3) B D glucan: part of outer cell wall of saprophytic hti and pathogenic fungi except mucor, rhizopus and cryptococcus. Not found in humans or viruses. Shed into systemic circulation in infected patients on or not on antifungals Dx of fungaemia, asperg, candidiasis, PCP Commercially available: Fungitec G and Fungitell. Fungitell cut off of pg/ml sens 70 % spec 87%. Goodfor IC, except parapsilosis Kinetics rises within 5 days. Precedes clinical infection by 9 days. For IA and PCP monitoring response to treatment(small studies)

22 Kedzierska Eur J Kedzierska Eur J Microbiol Infect Dis 2007;26 755

23 Retrospective study, N==50 PCT > 5.5 NPV 100% for Candida and PPV 65%

24 Need for biomarker use Is there an infection? What organism? Systemic sepsis or local infection? Responseto therapy? Duration of treatment? Ideal biomarker: cost, sensitivity, specificity, positive and negative predictive values, short time lag with onset of infection. CCM 2009, vol 37

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26 Biomarkers of Sepsis Ideal Biomarker What is being used What is available to us

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28 Sepsis biomarkers More useful to rule out sepsis than rule in PCT : 99% NPV at 0.2 ng/ml Others: aptt waveform (96%), FDPs (100% NPV for gram negative sepsis) i) Pierrakos and Vincent Cr Care 2010, 14, R15

29 Procalcitonin Biology: prohormone of calcitonin. lit i Synth by all cells after stimulation by pro inflammatory cytokines following bacterial invasion. Viral infections induce alpha interferon which inhibits TNF therefore no PCT induction Pharmacokinetics: detectable by 4 hrs, peaks at hrs Measurement: LUMI(1 st gen) 0.5ng/ml, TRACE 0.05 ng/ml (highly sensitive)

30 PCT uses Diagnosis i of sepsis, severe sepsis, septic shock better than CRP at differentiating from SIRS Castelli et al Crit Care 2004;8 Diagnosis of severe bacterial infection Uzzan CCM 2006 (34) Marker for effectiveness of source control and prognosis Chastre Curr opin cr care 2006;124 PCT guided antibiotic stewardship: % decrease in antibiotic exposure without adverse effect Christ Crain et al Lancet 2004; 363

31 PCT uses PCT in specific indications i 1. Pancreatitis: low PCT in sterile less severe pancreatitis compared to SAP or infected pancreatic necrosis 2. Fungal infection: elevated in some, non specific 3. Bacteramia 4. Transplantation: better at distingushing infection from rejection

32 Non infectious causes of PCT induction Major surgery and trauma Severe burns Cardiogenic shock Heat shock Immune therapy e.g. Granulocyte transfusions Autoimmune disease: Kawasaki, vasculitis paraneoplastic syndromes

33 7 RCTs 1131 ICU patients Decreased duration of AB by 2 days, No adverse outcomes in 28 day mortality, LOS ICU, infection relapse Kopterides CCM 2010 p 38(11

34 C reactive protein 1 st acute phase reactant to be described d1930 C = fraction C of polysaccharide of Strep Pneumoniae, Biochem: Ca dependant ligand binding plasma protein. Synthesized by hepatocytes in response to cytokines esp IL 6. (might not increase with sepsis in patients with liver failure) Plasma half life 19 hrs N < 8 mg/dl

35 CRP Biomarker of disease: chronic inflammatory states RA, crohns; acute inflammation: pancreatitis,?asthma, COPD, cardiovascular disease Diagnosis of infection: sens and spec of 93% and 86% and for cut off of mg/dl, Plus temp > 38.2 up to 100 % specificity Infection Probability score: SIRS criteria, CRP, SOFA score PPV 80%, NPV 86 % Peres Bota CCM 2003; CRP variation more helpful than absolute number: variation of > mg/dl sens of 92 % spec 71% Povoa Crit Care 2006;10 R63

36 CRP Infective organism: general overlap. virus< fungus< gram positive < gram negative. Cut off value of 10.0 between fungal and bacterial Prognostication: high CRP at ICU discharge is predictor of ICU readmission and mortality Ho et al ICM 2008; Therapeutic guidance: resolution of sepsis 25% decrease per day, sens 97% spec 95%. PPV 97% Difficult to define nadir plasma concentration to discontinue antibiotics in adults due to baseline variability in CRP level.

37 CRP vs. PCT 2 meta analysis concluded dthat PCT > CRP for diagnosis of sepsis But for CAP, CRP> PCT for diagnosis and PCT good as severity marker. Review of 18 studies in critically ill patients PCT can t reliably distinguish inflammation from sepsis Tang et al Lancet Infect Dis 2007;7 210, overall sens and spec of 71% Cost of assays PCT = 5 X CRP,?cost offset by savings on hosp admission. PCT POC also expensive

38 33 studies, 4000 patients, medical/surgical ICUs 33 studies, 4000 patients, medical/surgical ICUs PCT> CRP CCM 2006;

39 Conclusion Diagnosis i of sepsis is difficult, requires high h index of suspicion Clinical presentation is important, presence of organ failure. Blood cultures poor, Molecular techniques emerging Biomarkers have good NPV but poor PPV. no biomarker convincingly shown to be useful Combinationsof of clinicalparameters and biomarkers perform better.