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Coupled plasma filtration adsorption in experimental septic shock


Authors: Sýkora Roman 1,2;  Chvojka Jiří 1,2;  Kroužecký Aleš 1,2;  Raděj Jaroslav 1,2;  Kuncová Jitka 3;  Varnerová Veronika 2;  Karvunidis Thomas 1,2;  Novák Ivan 1,2;  Matějovič Martin 1,2
Authors‘ workplace: Jednotka intenzivní péče, I. interní klinka, Fakultní nemocnice Plzeň 1;  Lékařská fakulta v Plzni, Univerzita Karlova v Praze 2;  Ústav fyziologie, Lékařská fakulta v Plzni, Univerzita Karlova v Praze 3
Published in: Anest. intenziv. Med., 21, 2010, č. 2, s. 95-103
Category: Intensive Care Medicine - Original Paper

Overview

Objective:
Coupled plasma filtration adsorption (CPFA) was developed as an adsorptive hemopurification method aimed at nonselective removal of circulating soluble mediators potentially involved in the pathogenesis of sepsis. We hypothesized that this nonselective hemopurification could protect from detrimental consequences of long- -term, volume-resuscitated porcine septic shock.

Design and setting:
Randomized, controlled experimental study.

Materials and methods:
In sixteen anesthetized and mechanically ventilated piglets hyperdynamic septic shock secondary to peritonitis was induced by intraperitoneal inoculation with faeces. The piglets were treated with fluid resuscitation and norepinephrine infusion as needed to maintain mean arterial pressure above 65 mm Hg for 22 hours. After 12 hours of peritonitis the animals were randomized to receive either supportive treatment (Control, n = 8) or CPFA treatment (CPFA, n = 8).

Results:
Systemic, hepatosplanchnic and renal hemodynamics, oxygen exchange, energy metabolism (lactate/pyruvate and ketone body ratios), ileal mucosal and renal cortex microcirculation, systemic inflammation (TNF-α, IL-6), nitrosative/oxidative stress (thiobarbituric acid reactive species, nitrates+nitrites), endothelial/coagulation dysfunction (asymmetric dimethylarginine, von Willebrand factor, thrombin-antithrombin complexes, platelet count) were assessed before and at 12, 18, and 22 hours of peritonitis. CPFA did not delay the development of hypotension nor reduced the dose of norepinephrine. The treatment failed to attenuate sepsis-induced alterations in microcirculation, surrogate markers of cellular energetics, endothelial injury and systemic inflammation. Similarly, CPFA did not protect from lung and liver dysfunction or aggravated sepsis-induced disturbances in coagulation and oxidative/nitrosative stress.

Conclusions:
In this porcine model of septic shock, early treatment with CPFA was incapable of reversing sepsis-induced disturbances in various biological pathways and organ systems. Both the efficacy and safety of this method require further rigorous experimental validation in clinically relevant models.

Keywords:
sepsis – septic shock – experimental model – coupled plasma filtration adsorption – microcirculation – energy metabolism – oxidative stress – nitrosative stress – coagulation – endothelial dysfunction


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Labels
Anaesthesiology, Resuscitation and Inten Intensive Care Medicine
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