Evaluation of Hemodynamic Effects of Cascade Hemofiltration in Septic Shock
Evaluation of Hemodynamic Effects of Cascade Hemofiltration in Septic Shock
Septic shock is a major cause of mortality and morbidity in critically ill patients. Septic
 Shock is associated with an overwhelming, systemic overflow of pro inflammatory and
 anti-inflammatory mediators, which leads to generalized endothelial damage, multiple organ
 failure, and altered cellular immunological responsiveness. Although our understanding of the
 complex pathophysiological alterations that occur in septic shock has increased greatly as a
 result of recent clinical and preclinical studies, mortality associated with the disorder
 remains unacceptably high, ranging from 30% to 50%. To date, attempts to improve survival
 with innovative, predominantly anti-inflammatory therapeutic strategies have been
 disappointing. A standard hemofiltration rate of 35 ml/kg/hour has been successfully used to
 treat acute renal failure. However, this dose does not alter plasma levels of inflammatory
 mediators, suggesting that its ability to clear these mediators is suboptimal. Higher doses
 of hemofiltration (up to 120 ml/kg per hour) have been demonstrated to improve cardiac
 function and hemodynamics in several animal models of sepsis. High-volume hemofiltration
 (HVHF) was thus conceived and applied in patients with septic shock, showing an improvements
 in hemodynamics with decreased vasopressor requirements and improved survival in patients
 admitted after a cardiac arrest.

 The main benefit described with high volume hemofiltration is a hemodynamic improvement (e.g
 reduction in catecholamines' requirement). This improvement seems to be due to the removal of
 a badly defined network of middle molecular weight peptides. To remove efficiently these
 middle molecular peptides, a high filtration rate is needed. However, with high filtration
 rates, there is also a high clearance for smaller molecules, including antibiotics,
 electrolytes, vitamins, trace elements and amino acids.

 The cascade hemofiltration system has been designed for a more efficient removal of middle
 molecular weight peptides with a limited solute consumption.

 The goal of this study is the evaluation of the hemodynamic improvement using cascade
 hemofiltration in patients treated for septic shock.
Inclusion Criteria:

 -  Patient with a septic shock diagnosed by the medical staff team.

 -  Patient mechanically ventilated and treated by high doses of catecholamines after
 adequate fluid administration (≥ 1.0 mg/h of norepinephrine or epinephrine) for ≥ 120
 minutes and < 24h.

 Exclusion Criteria:

 -  Age (years) < 18 or > 85.

 -  Weight >120 kg

 -  Thrombocytopenia 50< G/l or Neutrophils <0.5 Giga/l

 -  Contra indication to heparin anticoagulation.

 -  Patient requiring catecholamines (epinephrine ≥ 1 mg/h or norepinephrine ≥ 1 mg/h) for
 >24h.

 -  Patient admitted to the ICU ≥ 7 days before the inclusion criteria.

 -  Comorbid conditions with an expected survival < 6 months

 -  Inclusion (<28 days) in another study interfering with the goals of the current
 investigation.

 -  Pregnancy

 -  Immune compromised patients (e.g. being treated for cancer, treated by
 immunosuppressors or steroids, AIDS).