CytoSorbents Corporation (CTSO)

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Does the use of a cytokine 'filter' during cardiopulmonary bypass make sense?

G Clermont1, J Kellum1, J Bartels2, S Chang2, C Chow1 and Y Vodovotz1

1 University of Pittsburgh, Pennsylvania, USA
2 Immunetrics, Inc., Pittsburgh, Pennsylvania, USA

From 24th International Symposium on Intensive Care and Emergency Medicine
Brussels, Belgium. 30 March – 2 April 2004

Critical Care 2004, 8(Suppl 1):P149doi:10.1186/cc2616

Published: 15 March 2004

Objective
Very high or sustained high levels of the inflammatory cytokines tissue necrosis factor (TNF) and interleukin (IL)-6 are believed to be responsible for adverse clinical effects in patients undergoing cardiopulmonary bypass (CPB). We explored, using a mathematical model, whether modulation of this response might be beneficial.

Methods
We developed a mathematical model of the acute inflammatory response that was calibrated from rat endotoxemia and hemorrhagic shock data. The model accommodates a variety of initiators of acute inflammation, provides a dynamic profile of serum markers of inflammation over time, and expresses outcome in as global tissue dysfunction. Irreversible dysfunction is interpreted as death. We constructed a population of 100,000 cases that differed by level of initial stress and propensity to mount an inflammatory response. Initial stress was chosen to result in 4% cohort mortality and to last less than 6 hours, such as CPB. The intervention consisted of the removal of circulating TNF, IL-6 and IL-10 over a period of 6 hours, during which stress was inflicted and acute inflammation triggered. We equated the degree of removal of cytokines to that observed with the application of a biocompatible adsorbent polymer hemoperfusion column in endotoxemic rats.

Results
Death correlated to serum IL-6 and to a lesser degree TNF cumulative levels. Patients with the highest levels of IL-6 6–24 hours after the insult are those that will go on to die (Fig. 1). Examination of the results show that, if the IL-6 levels were decreased by > 60% and TNF levels by > 50% in the period at or shortly after the CPB, over 99% of all patients would survive, compared with 96% in the control arm.

Conclusions
Global, nonspecific, reduction of inflammation improves outcome in simulations of an acute inflammatory challenge such as CPB.

http://ccforum.com/content/8/s1/p149