sepsis and the kidney.pdf - SASSiT

More documents

Recommendations

Info

218 klenzak & himmelfarb hemodialysis, there is a rebound effect on solutes that are intracellular or otherwise sequestered. The continuous aspect of CRRT allows for a more physiologic and consistent clearance, without rebound effects. Delivered dose of RRT may have an impact on survival. In a study of three dose levels, indicated by differing filtration rates, a survival benefit was demonstrated for patients receiving the most ultrafiltration by continuous venovenous hemofiltration (CVVH). This study compared prescribed doses of 20, 35, and 45 mL/h/kg. The survival rates were 41%, 57%, and 58%, respectively. In this study, patients with sepsis demonstrated more survival benefit than other critically ill patients with the increase in dialysis dose from 35 to 45 mL/h/kg [30]. This finding increased interest in using high-volume hemofiltration, or ultrafiltration beyond 3000 mL/h, in the treatment of sepsis-associated ARF. Animal models demonstrated survival and hemodynamic benefits for highvolume hemofiltration in endotoxemia. Furthermore, increases in ultrafiltration rate increase convective clearance, and increase clearance of middle molecules, which include most soluble mediators of sepsis. Controlled trials in patients have failed, however, to demonstrate a significant clearance of soluble cytokines in RRT. Specifically, a randomized controlled trial of patients with sepsis and preserved renal function allocated to either CVVH at 2 L/h or no hemofiltration demonstrated no difference in circulating cytokines or anaphylatoxins. CVVH in this setting did not improve clinical indicators, such as oxygenation, or the duration of pressor support [31]. Additionally, a study of patients with sepsisassociated ARF undergoing CVVH demonstrated no changes in circulating IL-6 or TNF levels. There was clearance of IL-6, demonstrated by its presence in the ultrafiltrate, but the plasma levels remained stable [32]. To pursue middle molecule clearance, high-permeability membranes were developed to provide better diffusive clearance for soluble mediators of inflammation through increased pore size. The inflammatory dysregulation in systemic inflammatory response syndrome is characterized by a decreased proliferative capacity and hyporesponsiveness of peripheral blood mononuclear cells. Studies of patients with sepsis-associated ARF have demonstrated an improvement in these circulating cells’ ability to respond ex vivo to stimuli after treatment with high-flux CRRT. Studies comparing high-flux with conventional CRRT have demonstrated restoration of the normal responsiveness to stimulation with anti- CD3 antibodies or endotoxin [33,34]. Morgera et al [33] additionally incubated peripheral blood mononuclear cells from healthy volunteers with the ultrafiltrate of septic patients and demonstrated the hyporesponsiveness characteristic of MOSF. There is likely a circulating suppressor of monocyte function. Plasmapheresis and adsorption Concurrent with interest in high-dose CRRT, it was postulated that normal inflammatory and anti-inflammatory balance could be restored with the use of other blood purification techniques, including plasmapheresis or plasma exchange, or adsorption techniques, in addition to RRT. A pilot study of adjunctive
treatment of 25 patients with plasma exchange in the setting of sepsis-associated MOSF, including renal failure, demonstrated a survival of 80%, higher than is expected [35]. Other studies have shown survival rates of 0% to 100%. A larger trial that included 106 patients randomized to receive plasma exchange or conventional treatment showed a mortality rate of 33.3% in the treated group versus 53.8% in the control group (P = .04). This study only included 19 patients who developed MOSF, however, 13 of whom were randomized to the control group [36]. Theoretically, not only the removal of the dysregulated cytokines and anaphylatoxins, including endotoxin, TNF, IL-6, IL-10, and PAI, but also the removal of cellular debris, lysosomal enzymes, proteases, activated complement, and coagulation components, could be beneficial. Additionally, in plasma exchange, the reconstitution with healthy plasma components may also help restore the normal balance between proinflammatory and anti-inflammatory cytokines. A more selective approach to the removal of harmful solutes in the plasma is the use of adsorbent technology. In this type of purification, the plasma is filtered through a column containing polymyxin B beads, which preferentially bind toxins and have been shown to decrease plasma levels of TNF. In a prospective pilot trial of 10 patients randomized to either 10 hours of plasma filtration adsorption with hemodialysis or continuous venovenous hemodiafiltration (CVVHDF), the investigators found that adsorption therapy increased monocyte responsiveness, as measured by LPS stimulation [37]. Bioartificial kidney sepsis and the kidney 219 A newer RRT being developed is the renal tubule-assist device. In animal models of septic shock, Fissell et al [38] demonstrated superior hemodynamics, cytokine profiles, and outcomes using the bioartificial kidney, which is hemofiltration in series with the renal tubule-assist device. The renal tubule-assist device is created by growing porcine renal tubular cells in confluent monolayers along the inner surface of the fibers in a standard hemofiltration cartridge. In theory, replacement of dialytic clearance with metabolically active tubular cells may provide a more physiologic metabolic milieu, possibly attenuating the course of MOSF. In an animal model of sepsis-associated ARF, which consisted of dogs with bilateral nephrectomies followed by intraperitoneal administration of Escherichia coli, the animals received either renal tubule-assist device therapy, or a sham renal tubule-assist device treatment (blood was hemofiltered, but without the tubular cell column). The renal tubule-assist device–treated dogs survived significantly longer and demonstrated improved hemodynamics. They had significantly higher TNF and IL-10 plasma levels, and better electrolyte homeostasis. The investigators also measured 1,25-(OH) 2 vitamin D 3 levels, and found that the sham renal tubule-assist device–treated dogs continued to show decline in plasma levels, whereas the renal tubule-assist device–treated group stabilized to pretreatment levels, demonstrating this metabolic activity in the renal tubule-assist device column [38]. In another experimental model, the dogs were nephrectomized, stabilized on CRRT with renal tubule-assist device or without
Page 1 and 2: Crit Care Clin 21 (2005) 211 - 222
Page 3 and 4: sepsis and the kidney 213 relied on
Page 5 and 6: sepsis and the kidney 215 NOS, by i
Page 7: inflammatory process by increasing
Page 11 and 12: sepsis and the kidney 221 [5] Mason

sepsis and the kidney.pdf - SASSiT

Create successful ePaper yourself

Delete template?

Save as template?