Coupled Plasma Filtration Adsorption in Experimental Peritonitis-Induced Septic Shock

Abstract

The 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. In 16 anesthetized, mechanically ventilated, and instrumented pigs, the hyperdynamic septic shock secondary to peritonitis was induced by intraperitoneally inoculating feces and maintained for 22 h with fluid resuscitation and norepinephrine infusion as needed to maintain MAP above 65 mmHg. After 12 h of peritonitis, animals were randomized to receive either supportive treatment (control, n = 8) or CPFA treatment (CPFA, n = 8). Systemic, hepatosplanchnic, and renal hemodynamics; oxygen exchange; energy metabolism (lactate/pyruvate and ketone body ratios); ileal mucosal and renal cortex microcirculation; systemic inflammation (TNF-alpha, IL-6); nitrosative/oxidative stress (thiobarbituric acid reactive species, nitrates + nitrites); and endothelial/coagulation dysfunction (asymmetric dimethylarginine, von Willebrand factor, thrombin-antithrombin complexes, platelet count) were assessed before and 12, 18, and 22 h of peritonitis. Coupled plasma filtration adsorption neither delayed 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 and even aggravated sepsis-induced disturbances in coagulation and oxidative/nitrosative stress. In this porcine model of septic shock, the early treatment with CPFA was not capable of reversing the 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.

Effects of the Volume of Processed Plasma on the Outcome, Arterial Pressure and Blood Procalcitonin Levels in Patients with Severe Sepsis and Septic Shock Treated with Coupled Plasma Filtration and Adsorption

“…Some experimental and clinical studies have been addressed to evaluate the efficacy of CPFA: in rabbits given i.v. endotoxin, the CPFA was associated with a better survival compared with the control group that underwent a sham CPFA [20]; conversely, in a surgical model of septic shock caused by a fecal peritonitis, Sykora et al [21] failed to demonstrate any beneficial effect of CPFA which was initiated 12 h after the onset of hypotension; furthermore, these investigators attributed also the worsening of some coagulation abnormalities and of the oxidative stress to the technique itself; however, this study clearly does not reflect the clinical practice as the procedure was initiated several hours following the occurrence of shock, and the infectious focus was not surgically drained. In a randomized crossover study, a group of septic shock patients needing vasopressors were treated alternatively with CPFA or continuous venovenous hemodiafiltration: only the former treatment was associated with a decrease in the administration of norepinephrine used as a surrogate of hemodynamic improvement [22].…”

Effects of Coupled Plasma Filtration Adsorption on Septic Patients with Multiple Organ Dysfunction Syndrome

“…The nonselective removal of inflammatory mediators is achieved by hydrophobic styrene resin, which has high affinity and capacity for many cytokines and mediators. 13 Therefore, we performed a study to test the hypothesis that CPFA may be superior to remove these inflammatory mediators and the clinical responses of the septic patients with multiple organ dysfunction syndrome (MODS).…”

Advances in Hemodialysis Techniques

“…Finally, adsorption techniques have been used successfully, in conjunction with plasma filtration and hemofiltration, in clearing efficiently pro-inflammatory mediators in experimental animals [108] and in humans with acute kidney injury and sepsis [109]. This is known as "coupled plasma filtration adsorption" (CPFA) technique, where the treatment consists of the separation of plasma from the whole blood, using a plasma filter with high cutoff membrane of 800,000 Dalton, coupled with adsorption of the inflammatory mediators and cytokines from plasma, using a cartridge contains hydrophobic resins, followed by hemofiltration using a hemofilter.…”