Coupled plasmafiltration-adsorption (CPFA) in septic shock with normal renal function

Multi-organ dysfunction syndrome (MODS) is the most frequent cause of death in patients admitted to intensive care units. Severe sepsis and septic shock are the primary causes of MODS and develop as a result of the host response to infection and to bacterial wall components, such as the lipid-A containing lipopolysaccharide (LPS). The host response involves both the cellular and humoral arms of the immune system and the generation of pro- and anti-inflammatory molecules. The anti-inflammatory response may lead to a state of 'immunoparalysis'. Continuous renal replacement therapies (CRRT) remove several soluble pro- and anti-inflammatory mediators simultaneously, albeit at low rates. However, large pore membranes, such as those used for plasmafiltration, may enhance cytokine removal and clearance. We recently observed that the use of coupled plasma filtration adsorption (CPFA) improved survival in a rabbit model of septic shock [1]. The outcome was not correlated with single cytokines or mediators (such as TNFa, platelet-activating factor or endotoxin), but rather with a global sepsis severity score. The results of this study suggested that a non-selective removal of various septic mediators was beneficial. A pilot, prospective, cross-over study tested the hypothesis that CPFA combined with hemodialysis might exert similar beneficial effects on hemodynamics and leukocyte responsiveness in humans with established septic shock and that it might prove superior to continuous veno-venous hemodiafiltration (CVVHDF) alone [2].

Objective

To assess the effect of continuous plasmafiltration adsorbtion (CPFA) on biochemical markers of inflammation, cytokines, organ dysfunction, haemodynamic and 28-day mortality in human sepsis.

Design

Prospective.

Setting

Intensive care unit.

Patients

Five patients (3 males and 2 female; mean age 52 ± 19.9 years) with clinical evidence of infection and septic shock were enrolled. Three patients had normal renal function.

Interventions

All patients received protocol-driven supportive intensive care, and those randomized to CPFA received intermittent plasma treatment (10 hours a day) for 10 days using a two-step, modular system made of plasma separation and adsorption on a hydrophobic resin, with final reinfusion of the plasmafiltrate into the patient's line before the hemofilter.

Measurements and main results

Illness severity and risk of death were calculated with the Acute Physiology and Chronic Health Evaluation II (adults) scales. Plasma samples were assayed for acutephase proteins (C-reactive protein and cytokines [interleukin-6, interleukin 10]). The Apache II score before treatments was 26 ± 5.6, after 14 ± 3.5. Statistically significant improvements were recorded about the differences pre/post treatments concerning Mean Arterial Pressure 78 ± 14.9 vs 86 ± 18.3 mmHg (P < 0.0001), Cardiac Index 3.88 ± 1.03 vs 3.24 ± 0.86 l/m²/min (P < 0.001), Systemic Vascular Resistances 1423 ± 552 vs 1862 ± 657 dyne × s/cm⁵(P < 0.001), PaO₂/FiO₂ ratio 199 ± 70 vs 244 ± 81 (P < 0.001). Laboratory data showed a sharp decline of C-reactive protein along the treatment time from 29.7 ± 11.4 to 6.9 ± 4.8 (-77%); data concerning IL-6, IL-10 showed a reduction to 2.8%, 36.6% in respect of starting values. All patients but one were discharged alive from ICU after 36.8 ± 14.1 days (range 18-57).

Conclusions

CPFA caused a significant attenuation of the acute-phase response in sepsis. The procedure induced a sort of immunomodulation process, and showed a reduction of both pro-inflammatory and anti-inflammatory immunoactive mediators. Our data suggest that this procedure might be beneficial in septic shock patients despite the absence of acute renal failure.