Importance of kinetics of procalcitonin in septic patients. János Fazakas MD, PhD Semmelweis University, Department of Transplantation and Surgery

Transcription

1 Importance of kinetics of procalcitonin in septic patients János Fazakas MD, PhD Semmelweis University, Department of Transplantation and Surgery

2 Host pathogen interactions the innate and the adaptive Lancet Infect Dis 2008; 8: Early virulome genes anticomplement antiphagocytic adhesins replication activation Late virulome genes exotoxins endotoxins superantigens antibiotic resistance

3 Plasma and peritoneal fluid cytokines at Day 1 Local Innate local + adaptive infection local peaceful response 66 secondary peritonitis: 35% septic shock and 35% mortality Systemic Riche et al. Critical Care 2013, 17:R201 doi: /cc12895

4 local infection local response systemic response Sepsis as a cytokine storm The plasma TNFα, IL-6, IFNγ and IL-10 with septic shock and no septic shock The plasma TNFα, IL-6, IFNγ and IL-10 in nonsurvivors and survivors Riche et al. Critical Care 2013, 17:R201 doi: /cc12895

5 More organs involved, more critical illness, What we know actually about PCT? more PCT Immuncell based synthesis Organ - tissue based synthesis CRP PCT Procalcitonin in sepsis and systemic inflammation: a biomarker and a therapeutic target. Br J Pharm 2010, 159:

6 The monocytes and the PCT production Prof. M. Meissner: PCT monograph PCT storm

7 Prosp, obs. study, n=23 MIB1 dg accuracy for SBP But they measured local and systemic PCT Lesisnska et al. Advances in Medical Sciences 59 (2014) 52 56

8 LOCAL SYSTEMIC Prosp, obs. study, n=66 PCT local and systemic levels in PPPE and PE setting Higher local PCT compared to the systemic pleural fluid procalcitonin (PF-PCT) serum PCT (S-PCT) levels in the parapneumonic pleural effusion (PPPE) or PE

9 Procalcitonin increase in early identification of critically ill patients at high risk of mortality Jensen JU et al. Crit Care Med 2006; 34: ng/ml Am J Physiol Lung Cell Mol Physiol 303: L355 L363, 2012

10 Differential diagnostic value of procalcitonin in surgical and medical patients with septic shock Clec h et al. Crit Care Med 2006; 34: Medical patients: SIRS: PCT = 0.3 ( ) ng/ml Septic shock: PCT = 8.4 ( ) ng/ml Surgical patients: SIRS: PCT = 5.7 ( ) ng/ml Septic shock: PCT = 34 (7-76) ng/ml 1 ng/ml, sens: 80% - spec: 94% 9.7 ng/ml, sens: 91% - spec: 74%

11 The innate immune response DAMP and / or PAMP Innate immune response = DAMP SIRS versus PAMP SIRS Surgery, Trauma, Pancreatitis

12 Trauma DAMP SIRS Immunosuppression PAMP SEPSIS 4 days after admission

13 MHC-II expression on blood monocytes is is decreased in surgical septic patients

14 Differential diagnostic value of procalcitonin in surgical and medical patients with septic shock Clec h et al. Crit Care Med 2006; 34: Medical patients: SIRS: PCT = 0.3 ( ) ng/ml Septic shock: PCT = 8.4 ( ) ng/ml Surgical patients: SIRS: PCT = 5.7 ( ) ng/ml Septic shock: PCT = 34 (7-76) ng/ml 1 ng/ml, sens: 80% - spec: 94% 9.7 ng/ml, sens: 91% - spec: 74%

15 Different magnitude of innate immune response INNATE

16 Monocyte HLA-DR expression/ first 24 h site of infection Monocyte HLA DR expression/ first 24 h implicated pathogens Gogos et al. Critical Care 2010, 14:R96

17 Different immune response: site of infection Altered site of infection Changing PCT values Lung > abdomen > urinary system INNATE PCT Immune-tolerance zone

18 in relation to etiology of sepsis HLA-DR expressions in gram-positive and gram-negative sepsis

19 Different type of bacteria Changing PCT values Gram-negative > Gram positive n=166 Reliability of PCT in G- bacteremia The ROC curves of PCT (AUC 0.871) and CRP (AUC 0.705) for the diagnosis of G- bacteremia.

20 in relation to severity of sepsis HLA-DR expressions and genetic expression: mrna - HLA DR

21 Charles at al.: BMC Infectious Disease 2009;9:49-58 INFECTION PAMP SEPSIS IMMUNOSUPPRESSION PAMP SEPSIS lower PCT maximum value on secondary infection onset López-Collazo et al. Critical Care 2010, 14:435 Am J Resp CCM 2012, 186: % 55 ng/ml monocyte 6.4 ng/ml HLA DR I II

22 Otto et al. Critical Care 2011, 15:R183

23 much lower PCT maximum value on fever onset 2 fold increase PCT of previous day Tsangaris at al.: BMC Infectious Disease 2009;9: PCT AUC: 0,85 n=50/27 The PCT value on the day of fever onset must be compared with previous day PCT values (chronic critically ill patient)

24 Deaths: cardiovascular collapse, metabolic derangements, MOF Sepsis Survival guideline Pro- and Anti- Inflammation in Sepsis Hotchkiss RS et al. Lancet Infect Dis 2013; 13: cycling between hyper- and hypoinflammatory states PCT - guided Goal - directed AB - therapy Sepsis Survival guideline

25 Eighty-two patients with intraoperative proven secondary peritonitis

26 Elderly pts., anergic pts., prolonged ICU stay: multi-trauma, several surgical re-intervention? Much Lower PCT maximum value PCT value changes PCT ng/ml Appropriate treatment Inappropriate treatment?

27 Immunotherapy of sepsis Nature Reviews Immunology Volume 13 December

28 We are Several types of immune responses! Infection onset = day 0 Admission day =? Day 1....Day 6 Transplant No source controll Waterhouse-Friedrichsen syndr

29 The concept PCT - guided Goal - directed AB therapy 1. Increasing PCT/24 h: May be a good indicator of infection 2. Early Kinetics of PCT / T 0 -T 12 -T 24 : May indicate effective AB treatment 3. Surgical patients Medical patients: PCT mono-induction by tissue injury ( DAMP) 4. Medical patients are different patients: Site of infection affect PCT values 5. Regarding the pathogens: Gram neg. vs Gram poz. PCT values 6. Late Kinetics of PCT: may help to identify immunoparalysis patients