sepsis and the kidney.pdf - SASSiT
sepsis and the kidney.pdf - SASSiT
sepsis and the kidney.pdf - SASSiT
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218<br />
klenzak & himmelfarb<br />
hemodialysis, <strong>the</strong>re is a rebound effect on solutes that are intracellular or o<strong>the</strong>rwise<br />
sequestered. The continuous aspect of CRRT allows for a more physiologic<br />
<strong>and</strong> consistent clearance, without rebound effects. Delivered dose of RRT may<br />
have an impact on survival. In a study of three dose levels, indicated by differing<br />
filtration rates, a survival benefit was demonstrated for patients receiving<br />
<strong>the</strong> most ultrafiltration by continuous venovenous hemofiltration (CVVH).<br />
This study compared prescribed doses of 20, 35, <strong>and</strong> 45 mL/h/kg. The survival<br />
rates were 41%, 57%, <strong>and</strong> 58%, respectively. In this study, patients with <strong>sepsis</strong><br />
demonstrated more survival benefit than o<strong>the</strong>r critically ill patients with <strong>the</strong><br />
increase in dialysis dose from 35 to 45 mL/h/kg [30].<br />
This finding increased interest in using high-volume hemofiltration, or<br />
ultrafiltration beyond 3000 mL/h, in <strong>the</strong> treatment of <strong>sepsis</strong>-associated ARF.<br />
Animal models demonstrated survival <strong>and</strong> hemodynamic benefits for highvolume<br />
hemofiltration in endotoxemia. Fur<strong>the</strong>rmore, increases in ultrafiltration<br />
rate increase convective clearance, <strong>and</strong> increase clearance of middle molecules,<br />
which include most soluble mediators of <strong>sepsis</strong>. Controlled trials in patients have<br />
failed, however, to demonstrate a significant clearance of soluble cytokines in<br />
RRT. Specifically, a r<strong>and</strong>omized controlled trial of patients with <strong>sepsis</strong> <strong>and</strong><br />
preserved renal function allocated to ei<strong>the</strong>r CVVH at 2 L/h or no hemofiltration<br />
demonstrated no difference in circulating cytokines or anaphylatoxins. CVVH<br />
in this setting did not improve clinical indicators, such as oxygenation, or <strong>the</strong><br />
duration of pressor support [31]. Additionally, a study of patients with <strong>sepsis</strong>associated<br />
ARF undergoing CVVH demonstrated no changes in circulating IL-6<br />
or TNF levels. There was clearance of IL-6, demonstrated by its presence in <strong>the</strong><br />
ultrafiltrate, but <strong>the</strong> plasma levels remained stable [32].<br />
To pursue middle molecule clearance, high-permeability membranes were developed<br />
to provide better diffusive clearance for soluble mediators of inflammation<br />
through increased pore size. The inflammatory dysregulation in systemic<br />
inflammatory response syndrome is characterized by a decreased proliferative<br />
capacity <strong>and</strong> hyporesponsiveness of peripheral blood mononuclear cells. Studies<br />
of patients with <strong>sepsis</strong>-associated ARF have demonstrated an improvement in<br />
<strong>the</strong>se circulating cells’ ability to respond ex vivo to stimuli after treatment with<br />
high-flux CRRT. Studies comparing high-flux with conventional CRRT have<br />
demonstrated restoration of <strong>the</strong> normal responsiveness to stimulation with anti-<br />
CD3 antibodies or endotoxin [33,34]. Morgera et al [33] additionally incubated<br />
peripheral blood mononuclear cells from healthy volunteers with <strong>the</strong> ultrafiltrate<br />
of septic patients <strong>and</strong> demonstrated <strong>the</strong> hyporesponsiveness characteristic of<br />
MOSF. There is likely a circulating suppressor of monocyte function.<br />
Plasmapheresis <strong>and</strong> adsorption<br />
Concurrent with interest in high-dose CRRT, it was postulated that normal<br />
inflammatory <strong>and</strong> anti-inflammatory balance could be restored with <strong>the</strong> use of<br />
o<strong>the</strong>r blood purification techniques, including plasmapheresis or plasma exchange,<br />
or adsorption techniques, in addition to RRT. A pilot study of adjunctive