Adsorbtion of Cytokines Early in Septic Shock: the ACESS trial
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1 Adsorbtion of Cytokines Early in Septic Shock: the ACESS trial Prof. Zsolt Molnár Department of Anaesthesia and Intensive Care University of Szeged Hungary
2 Pathophysiology
3 Local insult goes systemic I n s u l t Endotoxin, Trauma, Sterile inflammation, Operation, etc. Sepsis M a c r o and p h a g e s TNF; IL-1,6,10; PAF Humoral activity Interferon, Complement Fisiol. reactions Fever, Metabolic changes E n d o t h e l P M N FR, PAF, Chemotaxis It isn t the insult, but host response what determines NO, severity E-selectin, NFkB and outcome Sepsis, SIRS MSOF Molnár and Shearer Br J Int Care Med 1998; 8: 12
4 DAMP = Damage Associated Molecular Pattern PAMP = Pathogen Associated Molecular Pattern DAMP PAMP
5 Health=balance between the antagonistic forces Acid Base Oxidants Anti-oxidants Procoagulation Anticoagulation Proinflammation Antiinflammation
6 Nature Reviews Immunology Volume 13 December Proinflammation Antiinflammation
7 Nature Reviews Immunology Volume 13 December Overwhelming inflammation vs. prolonged immunosupression: Both can be deadly! Proinflammation Antiinflammation Attenuating the cytokine storm: may enhance recovery and improve outcome
8 Sepsis 3 From: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA. 2016;315(8): doi: /jama Good! J Life-threatening organ dysfunction Hmm? caused by L dysregulated host response to a non-infectious insults is: DIRS? Sepsis is not a definitive disease but a consensus
9 Journal of Immunology Research, 2015; Volume 2015, ID , 13 pages
10 Rationale Kellum JA et al., (GenIMS Study); Arch Intern Med 2007; 167:
11 At the moment: experimental data Attenuates inflammatory response of leukocytes Eliminates pro-inflammatory cytokines Keeps infection localised Improves hemodynamics
12 At the moment: case reports Proved to be safe Atenuated inflammatory response (PCT, IL-6) Improved organ function Survival
13 Attenuating the cytokine storm early? The ACESS trial Adsorbtion of Cytokines Early in Septic Shock
14 ACESS - Inclusion criteria Suspected sepsis of medical etiology IPPV PCT >3 ng/ml Norepinephrine 10 µg/min PiCCO confirmed normovolemia and CO Signs of hypoperfusion: ScvO 2, lactate, dco 2, oligo-anuria metabolic acidosis
15 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 PAMP Surgical patients: SIRS: PCT = 5.7 ( ) ng/ml Septic shock: PCT = 34 (7-76) ng/ml DAMP+PAMP 1 ng/ml, sens: 80% - spec: 94% 9.7 ng/ml, sens: 91% - spec: 74%
16 Interpreting PCT at the bedside Fazakas J, Trásy D, Molnar Z. Annual Update in Intensive and Emergency Medicine
17 Interpreting PCT at the bedside 2016 Fazakas J, Trásy D, Molnar Z. Annual Update in Intensive and Emergency Medicine 2016
18 ACESS - Inclusion criteria Suspected sepsis of medical etiology IPPV PCT >3 ng/ml Norepinephrine 10 µg/min PiCCO confirmed normovolemia and CO Signs of hypoperfusion: ScvO 2, lactate, dco 2, oligo-anuria metabolic acidosis 8 patients over 6 months!
19 ACESS preliminary results *
20 ACESS preliminary results *
21 How to put that into clinical practice?
22 Case history year old woman Admitted with acute respiratory complaints Looks poorly on assessment Low SpO 2 despite on O 2 Laboured breathing Transfer to the ICU at 02:00
23 After routine care on ICU at 03:00 Circulation Heart rate (min -1 ) 105 MAP (mmhg) 62 ScvO 2 (%) 63 Noradrenaline (µg/min) 25 Renal function Urine output (ml/h) 20 Creatinine (µmol/l) 110 Respiratory FiO PEEP (cmh 2 O) 10 PaO 2 (mmhg) 73 Inflammatory markers Temp (C) 38.6 PCT (ng/ml) 8.5
24 At 4:00 am Circulation Renal function Respiratory 02:00 04:00 02:00 04:00 Heart rate (min -1 ) FiO MAP (mmhg) PEEP (cmh 2 O) ScvO 2 (%) PaO 2 (mmhg) Noradrenaline (µg/min) YES, for CytoSorb! Urine output (ml/h) Inflammatory markers Temp (C) Creatinine (µmol/l) PCT (ng/ml)
25 Case history 46 year old woman Admitted with cholangitis to medical ward via A&E OE: Looks poorly, hypotensive, clammy Transfer to the ICU at 9:30
26 After routine care on ICU at 10:00 Circulation Renal function A&E ICU A&E ICU Heart rate (min -1 ) UO (ml/h) 50 MAP (mmhg) BUN (mmol/l) ScvO 2 (%) Creat (umol/l) Noradrenaline (µg/min) Arterial BG Inflammation ph pco 2 (mmhg) HCO 3 (mmol/l) Lactate (mmol/l) PCT (nmol/l) CRP (mmol/l) Temp (C)
27 PiCCO and 1 hour later CI (L/m 2 ) 3.07 HR (min -1 ) 112 SVI (ml/m 2 ) 26 N: dpmax (mmhg -s ) 1970 N: > 1200 GEDVI (ml/m 2 ) 379 N: EVLWI (ml/kg) 7 N: 3-10 Consider Fluid resuscitation CytoSorb!
28 After routine care on ICU at 17:00 Circulation Renal function 10:00 17:00 10:00 17:00 Heart rate (min -1 ) UO (ml/h) MAP (mmhg) BUN (mmol/l) ScvO 2 (%) Creat (umol/l) Noradrenaline (µg/min) Arterial BG Inflammation ph pco 2 (mmhg) HCO 3 (mmol/l) Lactate (mmol/l) PCT (nmol/l) CRP (mmol/l) Temp (C) CytoSorb: Sit tight!
29 After routine care on ICU at 09:00 Circulation Renal function 17:00 09:00 17:00 09:00 Heart rate (min -1 ) UO (ml/h) MAP (mmhg) BUN (mmol/l) ScvO 2 (%) Creat (umol/l) Noradrenaline (µg/min) Arterial BG Inflammation ph pco 2 (mmhg) HCO 3 (mmol/l) Lactate (mmol/l) PCT (nmol/l) CRP (mmol/l) Temp (C) CytoSorb: No!
30 Final thoughts on sepsis
31 Thinking has no alternative! Auguste Rodin: The Thinker (1880)
32 Motto It doesn t matter whether you ve done the right thing, but whether you ve done everything to do the right thing (Rephrased by ZM from Bhagavad Gita)
33 Deadline for manuscripts: Publication date: 22 April September 2016 For further information:
34 Free for junior doctors (<29)! November 2016, Budapest
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