the role of miecc in modulating the systemic inflammatory ... · (neutrophils, endotelial cells,...

The role of MiECC in modulating the systemic

inflammatory response syndrome

FRANCESCO FORMICAAssistant Professor of Cardiac Surgery

University of Milano-BicoccaDepartment of Medicine and Surgery

Cardiac Surgery ClinicSan Gerardo Hospital

ITALY

Athens, 9-11 June 2016

UNIVERSITY OF MILANO-BICOCCADEPARTMENT OF MEDICINE AND SURGERY

Cardiac Surgery ClinicSan Gerardo Hospital

Director: Prof. Giovanni Paolini

Does extracorporeal circulation (ECC) activate

inflammation?


Definition from the American College of Physicians, Society of Critical Care Medicine, Consensus conference definition for SIRS. 1992


Ipoperfusion

EmbolizationInflammation

Organdysfunction


Cells activation(neutrophils, endotelial cells, platelets

CARDIOPULMONARY BYPASS

Interaction among air, blood and artificial sufacesSurgical trauma, ischemia-reperfusion

Retrasfusion of pericardial shed blood

• Increased emission of cytokines (IL-1, IL-6, IL-8, TNF-a), E-selectin, lactoferrin, myeloperoxidase, selectin, platelet b-thromboglobulin, polymorphonuclear elastase (PMNE).

• Increased emission of complement (C5a and C3a).• Increased producyion of Oxygen free radical, Nitric oxide (NO), arachidonic acid

Coagulation disorder, bleeding, arrhytmia, endotelial dysfunction with increased capillarypermeability, prolonged ventilation support, neurological complication.

MULTI-ORGAN DYSFUNCTION MULTI-ORGAN FAILURE

Inflammation after ECC

SIRS

SIRSTemp > 38°C or <36°C, HR>90,RR>20 or PaCO2<32 mmHg,WBC >12,000 or < 4,000

SEPSISSIRS + Infection

SEVERE SEPSISSepsis + End Organ Dysfunction

SEPTIC SHOCKSevere Sepsis + Hypotension

10%

20%

40%

80%

Clinical effects of SIRS


SIRS: therapeutic strategies


DRUGS ELIMINATION OR CHANGES IN THE

CPB

IMPROVED BIOCOMPATIBILITY

The MiECC should be

considered an innovative

perfusion management

approach rather than a

simple change of the

system itself.

Does MiECC reduce systemic inflammation?


Biocompatibility: ECC materials

Air-bloodcontact

Platelet adhesion, neutrophils activation

Complement activation:-Blood/surface

alternative pathway-Ab/Ag classic pathway

MonocytesCytokines

ComplementEndothelialadhesion molecules

Leukocytes sequestration

Haemolisis,Embolisation

Heparin, Protamine Heparin-protamine complex

MiECC: inflammation reduction

MiECC

MiECC

MiECC


Pericardialshed blood

Patient

Venous line

Oxygenator

Arterial line

Centrifugal pump

Patient

Venous line

Cardiotomy

Oxygenator

Arterial line

Roller pump

MiECC: the circuit

MiECCStandard ECC


MiECC: the circuit


Does literature support this evidence?


Study Primary end-point Design and pats Cytokines/inflammatory biomarkers Outcome Device manufacturer

Fromes (EJCTS 2002) SIRS MiECC (30) vs CECC (30)

IL-1b, IL-6, TNF-α, neutrophil elastase, b-thromboglobulin, S100 protein.

Reduced SIRS in MIECC; no difference of early clinical results.

Jostra MECC (Maquet, Germany)

Wipperman (EJCTS 2005) SIRS, coagulation MiECC (10) vs CECC (10) vs OPCABG (10)

IL6, free hemoglobin (fHb), von Willebrandfactor activity (vWf), thrombin–antithrombin-III-complex(TATc), prothrombin fragment 1.2 (F 1C2) and plasmin–antiplasmin complex (PAPc)

Reduced SIRS in MiECC compared to CECC. No difference between MiECC and OPCABG

CORx-system(CardioVention, USA)

Abdel-Rahman (ATS 2005) SIRS MiECC (101) vs CECC (103)

Plymorphonuclear elastase (PMNE); terminal complementcomplex (TCC)

Reduced SIRS in MIECC; no difference of early clinical results

CorX (Jostra, Germany)

Nollert (ATS 2005) SIRS MiECC (15) vs CECC (15)

IL-2 receptor, IL-6, IL-10, TNF-α receptor 55 and 75, C reactiveprotein.

Marginal SIRS reduction in MiECC; no early clinical benefit.

Carmeda-Affinity (Medtronic, USA)

Farneti (Perfusion 2008) SIRS MiECC (10) vs CECC (10)

IL-6, TNF-α; thrombin-antithrombin III complexes (TAT), prothrombin fragments (F1+2), beta-thromboglobulin (beta-TG) and sP-selectin (sCD62P)

Reduced activation of blood coagulationin MIECC; no difference in SIRS; no difference of early clinical results.

Sinergy (Sorin group, Italy)

Huybregts (ATS 2007) SIRS, renal and intestinalinjury

MiECC (25) vs CECC (20)

C-reactive protein, urine IL-6, urine N-acetyl-glucosaminidase(NGAL), intestinal fatty acid binding protein (IFABP).

Reduced SIRS in MiECC; no difference of early clinical results.

Sinergy (Sorin group, Italy)

Mazzei (Circulation 2007) SIRS, organ damage, 1 year follow-up

MiECC (150) vs OPCABG (150)

IL-6, S-100 protein No difference in SIRS. No difference of early clinical results.


Immer (ATS 2007) SIRS MiECC (30) vs CECC (30)

SC5b-9, IL-6, human lactoferrin (HL). Reduced SIRS in MiECC Jostra MECC (Maquet, Germany)

Kofidis (Perfusion 2008) SIRS and organ damage MiECC (50) vs CECC (30)

IL-6, IL-8 Reduced IL-8 liberation in MiECC Jostra MECC (Maquet, Germany)

Ohata (ASAIO 2008) SIRS, hemodilution MiECC (34) vs CECC (64)

IL-8, neutrophil elastase Reduced SIRS and hemodilution in MiECC

Capiox (Terumo, USA)

Formica (JCVTS 2009) SIRS and mycardialinflammatory response

MiECC (30) vs OPCABG (30)

IL-6, TNF-α (from systemic blood and coronary sinus) No difference in SIRS and myocardialinflammatory response


Svitek (Perfusion 2009) SIRS IL-6, PMN elastase and MCP-1 No difference

Stassano (ATS 2009) SIRS MiECC (35) vs short LVAD on beating heart (38)

IL-1B, IL-6, TNF-α, Plymorphonuclear elastase (PMNE) Reduced SIRS in patients with LVAD compared to MiECC patients


Gunaydin (Perfusion 2009) SIRS, hemodilution, myocardial damage

MiECC (20) vs CECC (20); high-risk pats

IL-6, C3a Attenuated SIRS in MiECC. ROCsafe (Terumo, USA)

Kiaii (Innovations 2012) SIRS MiECC (30) vsCECC (30)

TNF-α, IL-6, IL-10, IL-8, chemotactic protein-1 (MCP-1), interferon-inducible protein-10, C-reactive protein and complement protein 3

Reduced SIRS in MiECCC; no clinicalbenefit

Resting Heart System (Medtronic, USA)

Kolaklova (Mediators of Inflammations 2012)

SIRS MiECC (22) vs CECC (22)

IL-10, IL-10 receptor (IL-10R) Attenuated SIRS in MiECC; no clinicaldifference between groups

Minisystem Sinergy (Sorin, Italy)

Formica (Perfusion 2013) SIRS and mycardialinflammatory response

MiECC (19) vs CECC (20) vs OPCABG (22)

TNF-α, IL-6, monocytechemotactic protein-1 (MCP-1), and E-selectin.

No difference in SIRS and myocardialinflammatory response between MiECCand OPCABG;Increased SIRS in CECC


Nguyen (ATS 2016) SIRS MiECC (15) vs CECC (15)

Reactive oxygen species (ROS), nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), and leukocyte accumulation

Both p38-MAPK activation and ROS attenuated in MiECC (potentialreduced SIRS)

ECC.O System (Dideco, Italy)

N = 30 N = 30


MiECC vs CECC

SC5b-9 interleukin 6

lactoferrinMiECC = 30CECC = 30


MiECC

CECC



Evidence-based medicine (MiECC vs CECC)


MiECC vs OPCABG


MiECC vs OPCAB


Coronary sinus blood

Systemic blood

Systemic blood

Systemic blood

T0: before anesthesia

T1:

T2: intraoperatively

T3:

T4: end of operation

T5: 24 hours

T6: 48 hours


Evidence-based medicine (MiECC vs OPCABG)

In conclusion


• Strong evidences confirmed better clinical outcomes in MiECC patients compared to CECC

• Data on SIRS modulation with MiECC showed a trend towards a reduced nflammatory response compared to CECC

Class IIA , Level of evidence BBUT

Need for further trials Difficult to assess with specificmarkers in very large populations

THANKS


the role of miecc in modulating the systemic inflammatory ... · (neutrophils, endotelial cells,...

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