Removal of inflammatory cytokines and endotoxin by veno-venous continuous renal replacement therapy for burned patients with sepsis
Introduction
Infection is a major complication following severe burns. As an initial factor, sepsis and multiple organ dysfunction syndrome (MODS) caused by sepsis are a principal cause of death in burned patients. Despite the impressive advance in our understanding of the basic mechanisms of sepsis, mortality rates in burned patients associated with sepsis remains high.
Sepsis due to bacterial infection or systemic inflammatory response syndrome (SIRS) due to non-infectious causes, such as trauma burns develop in part from the release of many biologically active inflammatory mediators. In recent years, several new therapies were developed, focusing on blocking the production of a particular component of the SIRS cascade or neutralizing these with antibodies [1]. These include anti-tumor necrosis factor α (TNFα) monoclonal antibodies, interleukin-1 (IL-1) receptor antagonists and platelet activating factor (PAF) antagonists. Although preliminary studies were encouraging, large multi-centre trials failed to show clear benefits [2]. In fact, higher doses of some of these antibodies increased mortality. The failure of these mediator-directed therapies aimed at blocking a single factor would be insufficient to effect the complex inflammatory network. Recently, a new approach based on the extracorporeal removal of the mediators or endotoxin by continuous renal replacement therapy (CRRT) has renewed interest in mediator-directed therapy of sepsis aiming to reduce the mortality rates and improve the clinical outcomes [3], [4].
Indications for CRRT are divided into renal and non-renal. At our institution, CRRT is indicated for eliminating sepsis mediators that damage other organs in septic patients without renal failure. Some studies concerning the usefulness of continuous renal replacement therapy for burned patients with acute renal failure have also been reported [5], [6]. However, the utility of CRRT to remove systematic inflammatory mediators is yet to be confirmed. In the present study, we measured the levels of inflammatory cytokines and endotoxin in severe burned patients associated with sepsis after the initiation of CRRT to evaluate the clinical usefulness of CRRT on the removal of key mediators.
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Patients
The study included 20 adult patients who were septic after burn admitted to the institute of burn research of our hospital between June 2001 and October 2001. Total body surface area (TBSA) of burns in these patients was at least 50%. Patients with severe associated trauma and pre-existing diseases were excluded. The criteria for diagnosing sepsis were based on the clinical and laboratory findings when at least two or more of the following criteria were fulfilled: (1) body temperature, >38 or
Changes of plasma endotoxin after CRRT initiation
Plasma endotoxin levels were no different between groups (0.694 ± 0.315 EU/ml for Control) (0.770 ± 0.397 EU/ml for CRRT) before CRRT initiation. Results in Fig. 1 show that the plasma endotoxin levels quickly decreased 1 h after the start of CRRT (0.238 ± 0.104 EU/ml) and remained so until 60 h after the start of CRRT (0.014 ± 0.003 EU/ml). The decreased range with CRRT reached 70% at 1 h and 98% at 60 h after the start of CRRT. Plasma endotoxin levels showed significantly elevated levels at 12, 36 and 60 h
Discussion
The technique of CRRT has found increasing applicability in the treatment of patients with renal failure combined with cardiovascular instability, severe fluid overload, cerebral edema or hypercatabolism and high fluid requirements [8], [9]. CRRTs commonly use three mechanisms: diffusion, convection and adsorption by the filtering membrane. In addition to removing excess fluid and sodium in burned patients, the possibility that CRRT may remove bacterial LPS and other mediators introduced the
Acknowledgements
We are grateful to Dr. Yuesheng Huang, Xusheng Liu and Qizhi Luo for their assistance in the clinical investigation.
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