ABSTRACTS from 16th International COnference on ... - CRRT Online

D20
Extracorporeal Techniques for Sepsis 1: Pathophysiology and Targets
Educational Objectives:
1. Describe the model characteristics, the advantages and limitations of
the model and how the models can be best optimized.
2. Describe the end-points for defining success of these methods.
Martin Matejovic MD
10:00-11:30
Wednesday, February 15
Content Description:
The uncontrolled and deregulated systemic inflammatory response to infection plays a central role in the pathophysiology
of sepsis. This response is mediated by a broad spectrum of endogenous mediators leading to dysfunction
in multiple organs remote <strong>from</strong> the primary infectious site. The failure of numerous clinical trials aimed
at eliminating a single mediator stimulated the research to focus on non-selective removal of excessively produced
mediators of sepsis. This „detoxification“ forms the theoretical basis and biological rationale for the use of
hemopurification therapies as an adjunctive treatment of sepsis. While high-quality human data are lacking,
much of the evidence originates <strong>from</strong> experimental studies. However, a multitude of emerging strategies that
have been found effective in experimental models, failed to show any benefit in clinical studies. One of the reasons
for the failure to translate the results <strong>from</strong> animals to humans could be attributed to animals models and
experimental setting that do not fully mimic clinical scenario. Majority of experimental studies investigating the
effectiveness of blood purification methods in the treatment of sepsis utilized hypodynamic, unresuscitated models
of endotoxicosis and the treatment was started before or very early after the insult. By contrast, only a few
studies were performed in hyperdynamic septic shock models aimed at replicating typical features of adequately
resuscitated human septic shock. In addition, many unanswered questions remain, including the best surrogate
markers to assess the efficacy of hemopurification methods and relevant biological targets.
Suggested Reading:
Rimmelé T, Kellum JA. Clinical review: blood purification for sepsis. Crit Care. 2011;15(1):205.
Ronco C, Piccinni P, Kellum J.Rationale of extracorporeal removal of endotoxin in sepsis: theory, timing and
technique.Contrib Nephrol. 2010;167:25-34
Cruz D, Bellomo R, Kellum JA et al. The future of extracorporeal support. Crit Care Med. 2008;36:S243-S252.
Zanotti-Cavazzoni SL, Goldfarb RD. Animal models of sepsis. Crit Care Clin 2009;25:703-19
Sykora R, Chvojka J, Krouzecky A, Radej J, Karvunidis T, Varnerova V, Novak I, Matejovic M. High versus
standard-volume haemofiltration in hyperdynamic porcine peritonitis: effects beyond haemodynamics? Intensive
Care Med. 2009; 35:371-80
Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J
Clin Invest 2009;119:2868-78
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