Immunomodulatory Effect of Continuous Venovenous Hemofiltration during Sepsis: Preliminary Data

Abstract

Introduction. Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many pro- and anti-inflammatory mediators, such as interleukin-6 (IL-6), play a strategic role in septic syndrome. Continuous renal replacement therapy (CRRT) removes in a nonselective way pro- and anti-inflammatory mediators. Objective. To investigate the effects of continuous venovenous hemofiltration (CVVH) as an immunomodulatory treatment of sepsis in a prospective clinical study. Methods. High flux hemofiltration (Qf = 60 ml/Kg/hr) was performed for 72 hr in thirteen critically ill patients suffering from severe sepsis or septic shock with acute renal failure (ARF). IL-6 gene expression was measured by real-time PCR analysis on RNA extracted from peripheral blood mononuclear cell before beginning of treatment (T0) and after 12, 24, 48, and 72 hours (T1–4). Results. Real-time PCR analysis demonstrated in twelve patients IL-6 mRNA reduction after 12 hours of treatment and a progressive increase after 24, 48, and 72 hours. Conclusions. We suggest that an immunomodulatory effect might exist during CVVH performed in critically ill patients with severe sepsis and septic shock. Our data show that the transcriptional activity of IL-6 increases during CVVH.

Effects of High Volume Haemodiafiltration on Inflammatory Response Profile and Microcirculation in Patients with Septic Shock

“…While treatment of infection with antibiotics is well established [ 3 ], control of systemic inflammation is equally important but difficult to achieve due to the extremely complicated nature of the reaction and numerous mediators involved. Haemofiltration has been suggested as beneficial in restoring immunohomeostasis [ 4 , 5 ]. Since the study of Ronco et al [ 6 ], demonstrating better intensive care patient survival with increased ultrafiltration rates of renal replacement therapy (RRT), high filtration volumes have been used in septic patients with the aim of controlling systemic inflammation and improving patient outcomes.…”

Cytokine Clearances in Critically Ill Patients on Continuous Renal Replacement Therapy

“…This study size is a limitation, as our trial was not adequately powered to detect differences between the 2 modalities in terms of cytokine clearance differences. However, it should be noted that similar studies done in the past that did note differences between the 2 modalities recruited similar numbers of patients [12,14,29]. Our sample size does not permit us to detect differences in a variety of outcomes including mortality and renal recovery.…”

“…Servillo et al [29] investigated the impact of high-flux CVVH on IL-6 gene expression in patients with AKI and septic shock. In this single group prospective observational study of 13 patients, 12 patients had a reduction in IL-6 mRNA after the first 12 h of CVVH with a subsequent increase after 24, 48, and 72 h. This study did not have a comparison group and as such it is difficult to determine if these changes in mRNA expression were due to CVVH or to the patients underlying sepsis [29]. In our study, while we did not measure mRNA expression, IL-6 levels consistently decreased over the first 48 h, regardless of the CRRT modality.…”

“…Our study is also limited by the number of cytokines that were examined; we cannot exclude the possibility that other molecules not included in this analysis could not be filtered differently by CRRT modalities and contribute to differential patient outcomes. However, the cytokines that were chosen for this analysis were a combination of those with previously published data, validated commercial assays, with known clinical relevance and a mix of pro-and anti-inflammatory actions [2,6,28,29].…”

The effect of continuous blood purification on P38MAPK signaling pathway in patients with multiple organ dysfunction syndrome

“…Under the stressful state, such as severe trauma, shock, burn, or ICU, intestinal mucosa is in danger of aseptic injury, which increases the membrane permeability of the intestinal mucosa, leading to the dysfunction of the intestinal mucosa. The change of the membrane permeability is also the trigger causing distal organ injury . It was demonstrated that when the intestinal mucosa was impaired, the pro‐inflammatory cytokines from intestinal would flow into intestinal lymphatic system, rendering the systemic inflammatory response, and exacerbating further injury of tissues and organs, which was closely associated with MODS.…”