L utilizzo della Procalcitonina in Medicina d Urgenza Stefania Battista Dirigente Medico S.C. Medicina d Urgenza Azienda Ospedaliero-Universitaria San Giovanni Battista di Torino Savona, 15 ottobre 2009
PCT cellular sources Bacterial infections PCT produced in many sites PCT not transformed into Calcitonin Under normal conditions PCT is the pro-hormone of Calcitonin in the thyroid tissue
PCT mrna in sepsis
PROCALCITONIN SITES OF PRODUCTION (extrathyroideal) Leukocytes (monocytes) Liver cells Neuroendocrine cells (lung, intestine) PHYSIOLOGICAL ROLES Cytokine regulation Leukocyte chemoattractant Modulation of nitric oxide synthesis Non-steroideal analgesic effects
Nu1 PROCALCITONIN Pathophysiological aspects Acute phase protein Multifactorial induction (infection related and/or organ-dysfunction related) SIRS/SEPSIS and SEPTIC SHOCK Diagnostic biomarker Prognostic factor Guide for empiric antibiotic therapy
Diapositiva 5 Nu1 Nome utente; 19/05/2009
The induction phase PCT Increases after 3 hours Normalizes after 2-3 days Half-life 22,5 hours PCR Increases after 24 hours Has a prolonged response with delayed concentration peaks Normalizes after 3-7 days
No induction of PCT synthesis Autoimmune disorders (lupus e. 0,5 ng/ml) Cancer Graft rejection Allergic reactions Localized infections (with the exception of lung) Infections of viral origin In HIV infections PCT is increased only when sepsis develops
PCT as a prognostic marker In ICU patients with infections, those with worse outcome have higher PCT concentrations than subjects who survive Ugarte,, H et al.(1999) Crit Care Med 27: 498-504 PCT levels are significantly correlated to the outcome of sepsis Oberhoffer,, M et al.(1999) Clin Chem Lab Med 37:363-8
PCT in the Emergency Room (ER) Decision making concerning treatment alternatives and the admission to the ICU/ITU Relation between critical illness (death or ICU transfer) and PCT value range
Am J Respir Crit Care Med 2001; 164:396-402 Good diagnostic accuracy of PCT in newly admitted patients with suspected sepsis Additive effect of PCT to improve the predictive power of routinely available sepsis parameters Good concordance of PCT plasma levels with the clinical evolution of septic patients
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Study objectives Decisional threshold(s) Clinical application EMERGENCY DEPARTMENT
Study design Method (PCT assay) Automated immunofluorescent (BRAHMS Kryptor) Patients 207 newly admitted (93 females and 114 males, mean age 58.3 years) Suspected infection or signs of SIRS or Septic shock Classification according to diagnosis at discharge
Results PATIENT CLASSIFICATION 1. Sepsis and/or septic shock with documented microbial pathogens (n= 49) 2. Localized or viral infection with negative coltural specimens (n= 66) 3. Non infectious disorders (n= 60) 4. SIRS (n= 32)
PCT (ng/ml) 350 300 250 200 150 100 50 0-50 p < 0.0001-100 Sepsis Localized or viral Non-infectious SIRS Diagnosis n Mean SD 95% CI of Mean Median IQR 95% CI of Median Sepsis 49 42,5 68,7 22,7 62,2 15,6 34,6 11,0 26,5 Localized or viral 66 3,1 3,7 2,1 4,0 1,6 3,2 0,8 2,5 Non-infectious 60 0,9 1,3 0,6 1,3 0,4 0,9 0,3 0,6 SIRS 32 25,2 47,8 7,9 42,4 8,6 24,5 2,6 19,7
100 90 80 70 60 % 50 40 30 20 10 0 patients with sepsis % patients without sepsis % PCT (ng/ml) < 0.5 3 6,1 58 36,7 PCT (ng/ml) 0.5-1.9 3 6,1 40 25,3 PCT (ng/ml) 1.9-10.8 11 22,5 40 25,3 PCT (ng/ml) > 10.8 32 65,3 20 12,7
Area 95% CI of Area 0,84 0,78-0.91 Sensitivity (true positives) 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 No discrimination PCT 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 1 - Specificity (false positives)
Decisional limit Sensitivity Specificity PPV NPV (ng/ml) % % % % 16.0 50 93 69 85 5.0 80 82 58 93 2.5 88 67 45 95 0.5 94 37 32 95
False positive results at high PCT concentrations (>16.0 ng/ml) 4 patients with cardiogenic shock 3 patients with acute pancreatitis 1 patient with massive pulmonary embolism 1 with hemorrhagic shock 2 patients with exacerbation of chronic obstructive lung disease
Unspecific PCT-increases Surgical Trauma up to 7 ng/ml Polytrauma around 5 ng/ml Cardiogenic Shock up to 10 ng/ml Neonates up to 20 ng/ml day 2 Medications (OKT3) up to 50 ng/ml Burns around 2 ng/ml Extracorporeal Circulation 2 100 ng/ml Tumors up to 50 ng/ml Liver cirrhosis up to 4 ng/ml Haemodialysis around 1 ng/ml Goodpasture Syndrome av. 34 ng/ml Alzheimer, Dementia up to 0,6 ng/ml
Conclusions Clinical efficacy of a single-point PCT assessment at admission (high-suspicious cases) One per day control is almost always enough to monitor and assess therapy Patient stratification according to documented infection with systemic involvement Occurrence of false positive results To rule out sepsis in a low prevalence clinical setting (not as a screening tool in the whole population)