Sử dụng màng lọc Oxiris trong lọc máu liên tục điều trị bệnh nhân sốc nhiễm khuẩn và tổn thương thận cấp
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<b>Thomas RIMMELE – MD PhD</b>
<b>Anesthesiology and Intensive Care Medicine</b>
<b>Edouard Herriot Hospital</b>
<b>LYON, FRANCE</b>
<b></b>
Use of Oxiris during CVVH
in patients with septic shock and AKI
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Conflicts of Interest
Scientific partnership with the following companies:
- Baxter
- Fresenius Medical Care
- Bbraun
- Nikkiso
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OUTLINE
- Introduction
- Pathophysiology: how does blood purification work?
- Techniques for blood purification in 2018
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OUTLINE
<b>- Introduction</b>
- Pathophysiology: how does blood purification work?
- Techniques for blood purification in 2018
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<b>Hotchkiss et al. Nat Med 2009</b>
<b>TNF, IL-6, IL-8 (early deaths)</b>
<b>IL-4, IL-10, IL-1ra (late deaths) </b>
<b>- No clinical signs of this </b>
<b>immunosuppression</b>
<b>- Increased risk of HAI</b>
<b>- 70-80% of total mortality</b>
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<b>Singer et al. JAMA 2016 </b>
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<b>Singer et al. JAMA 2016 </b>
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<b>Immunology</b>
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<b>Initiation of a RRT session: 2 possible goals for the intensivist doctor </b>
AKI Sepsis-induced AKI Sepsis
RRT: Renal support Renal support Blood purification
+ Blood purification
1- Renal support for AKI
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+ + +
+ + +
<b> </b>
<b> </b>
<b>-Ionic (or electrostatic) interactions</b>
<b>Van der Waals </b>
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OUTLINE
- Introduction
<b>- Pathophysiology: how does blood purification work? </b>
- Techniques for blood purification in 2018
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<b>Endotoxin </b>
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- Interaction sorbent-leucocyte leading to a modification of expression
of leucocyte surface markers (ex: HLA-DR increase)
- Removal by adsorption of activated leucocytes
<b>Rimmelé et al. Crit Care 2013</b>
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<b>Electronic microscopy and immunofluorescence pictures showing leucocytes adsorption on adsorptive polymer </b>
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OUTLINE
- Introduction
- Pathophysiology: how does blood purification work?
<b>- Techniques for blood purification in 2018 </b>
</div>
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• High-volume hemofiltration
• Cascade hemofiltration
• Plasma exchanges
• Coupled Plasma Filtration Adsorption
• Hemoperfusion
• New membranes (high adsorptive hemofiltration and high cut-off membranes)
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• High-volume hemofiltration
• Cascade hemofiltration
• Plasma exchanges
• Coupled Plasma Filtration Adsorption
<b>• Hemoperfusion</b>
• New membranes (high adsorptive hemofiltration and high cut-off membranes)
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Hemoperfusion devices
<b>Device</b> <b>Company</b> <b>Composition</b> <b>Substance eliminated</b>
PMX Toray, Japan PMX covalently bound to
polypropylene-polystyrene fiber Endotoxin
HA330 Jafron, China Neutral resin <sub>Cytokines</sub>
MG350 Biosun, China Neutral resin <sub>Cytokines</sub>
Cytosorb Cytosorbents, USA Polystyrenedivinyl benzene copolymer
beads with biocompatible
polyvinylpyrrolidone coating
Cytokines
LPS adsorber Alteco, Sweden Synthetic polypeptide bound to porous
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<b>EUPHAS study </b>
<b>Cruz et al. JAMA 2009</b>
- Multicenter RCT performed in 10 Italian ICUs from 2004 to 2007
- 64 patients in septic shock, randomized in 2 groups:
- Conventional treatment
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<i><b>Effects of </b></i>
<i><b>Hemoperfusion with a </b></i>
<i><b>Polymyxin B Membrane </b></i>
<i><b>in Peritonitis with </b></i>
<i><b>Septic shock</b></i>
<b>Dieppe</b>
<b>La Roche </b>
<b>sur Yon</b>
<b>LensLille</b>
<b>Limoges</b> <b></b>
<b>Clemont-Ferrand</b>
<b>Roanne</b>
<b>Paris</b>
<b>Rennes</b>
<b>Saint-Malo</b> <b>Strasbourg</b>
<b>Tours</b>
<b>Orleans</b>
<b>Bordeau</b>
<b>Poitiers</b>
<b>Rouen</b>
<b>Saint-Louis</b>
<b>Perpignan</b>
<b>PMX Trial in France </b>
<b>ABDO-MIX Study</b>
<b>Dr.Shoji</b>
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Primary outcome: day 28 mortality
-PMX HP (n=119) = 27%
-Conventional treatment (n=113) = 19%
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• High-volume hemofiltration
• Cascade hemofiltration
• Plasma exchanges
• Coupled Plasma Filtration Adsorption
• Hemoperfusion
<b>• New membranes (high adsorptive hemofiltration and « high cut-off » </b>
membranes)
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<b>Oxiris®</b> <b>: pathophysiology</b>
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Oxiris®
<b>CH<sub>2</sub></b>
<b>CH</b> <b>C</b>
<b>-CH<sub>2</sub></b>
<b>CH<sub>2</sub></b>
<b>CH<sub>3</sub></b>
<b>CN</b>
<b>SO<sub>3 </sub>Na</b>
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- Oxiris®: Adsorption of negatively charged endotoxins on mb surface
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<b>Oxiris</b>
<b>®</b><b>: animal data</b>
<i>- P. Aeruginosa porcine model of septic shock</i>
- 2 × 10 pigs : 6 h of HF with oxiris versus 6 h of HF with a standard mb
- Arterial and Swan-Ganz catheters to assess hemodynamics
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N=10 rats per group
<b>Rimmelé, Peng, Kellum. unpublished data</b>
oxiris <b>®</b>
Hemoperfusion
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<b>Shum et al. Hong Kong Med J 2013</b>
- Prospective case series study with historical controls
- From October 2011 to June 2012, 6 patients with sepsis-induced AKI due
to gram negative bacteria
- CVVH with Oxiris
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The 3 main advantages of Oxiris
- <b>Hybrid therapy: RRT for AKI + blood purification for sepsis</b>
- <b>Targets endotoxins + cytokines </b>
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OUTLINE
- Introduction
- Pathophysiology: how does blood purification work?
- Techniques for blood purification in 2017
</div>
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How to answer this question?
Please, come on…There have been in the
past some promising experimental, animal
and clinical observational studies about
blood purification for sepsis. That’s right.
<b>BUT, all recent human RCTs are </b>
<b>negative !!!!</b>
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How to answer this question?
Big NO !!!...
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<b>EUPHAS study </b>
<b>Cruz et al. JAMA 2009</b>
- Multicenter RCT performed in 10 Italian ICUs from 2004 to 2007
- 64 patients in septic shock, randomized in 2 groups:
- Conventional treatment
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<b>Livigni et al. BMJ Open 2014</b>
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Any limits in these works?
IVOIRE
ABDOMIX
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• High-volume hemofiltration
• Cascade hemofiltration
• Plasma exchanges
• Coupled Plasma Filtration Adsorption
<i><b>• Hemoperfusion outside PMX</b></i>
• New membranes
- high adsorptive hemofilters
- High cut-off membranes
<b>HAVE YOU NOTICED IN THE LITERATURE LARGE RCTs </b>
<b>ASSESSING THESE TECHNIQUES? </b>
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Promotor: Hospices Civils de Lyon PI: Thomas Rimmelé
Multicenter (7 centers in France), interventional, Randomized Controlled Trial
Primary goal: to assess oXiris™ adsorption capacities (endotoxins, cytokines) in septic patients
Secondary goal: to assess oXiris™ effects on hemodynamics and survival in septic patients
Main criteria: Endotoxin and cytokine plasma levels
Secondary criteria: Cytokine levels in ultrafiltrate, Hemodynamic parameters, Patient survival
Patients: Septic shock patients with confirmed peritonitis
CVVH with citrate regional anticoagulation
Intervention group: oXiris™ filter
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Negative large RCTs: importance of the studied population
Tested intervention
(Too?) large population
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Past Future
<b>Technological progress</b>
<b>Medical knowledge</b>
<b>MANY UNANSWERED QUESTIONS : </b>
<b>Which patients exactly? </b>
<b>Which Timing? </b>
<b>How do these therapies exactly work? </b>
<b>What to ultimately remove?</b>
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Futuristic technology?
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<b>The Aethlon Hemopurifier®: Ongoing research from San Diego University, USA </b>
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<b>IN THE FUTURE, we should find out what is best to remove in </b>
order to modulate the host immuno-inflammatory response!
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<b>1)</b> <b>Sepsis = frequent, poor prognosis, expensive</b>
<b>2)</b> <b>2017: Immunology is now part of the sepsis definition!</b>
<b>3)</b> <b>Patients die of septic shock because of immununosuppression</b>
<b>4)</b> <b>Extracorporeal blood purification as an adjuvant treatment for sepsis? </b>
<b>several promising techniques such as OXIRIS under investigation</b>
<b>5)</b> <b>Multicenter RCTs = negative studies… but were they well-designed?</b>
<b>6)</b> <b>Many unanswered questions that should be addressed in the near future: </b>
<b>Which patients exactly? Which Timing? Which technique is best?</b>
<b>How do these therapies exactly work? Hybrid technique? Futuristic technique? </b>
<b>What to ultimately remove (cytokines, endotoxins, leukocytes, bacteria or viruses)?</b>
<b>7) Research in this field should definitely continue </b>
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