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MANAGEMENT OF CONTINUOUS HEMODIALYSIS APACVS CONFERENCE. July 12, 2013 Naveed Masani, MD General Principles I Solute removal may be accomplished via diffusion and/or convection Hemodialysis involves diffusive clearance only – two fluid compartments (patient’s blood and dialysate) separated by a semi-permeable membrane Passive diffusion between the two compartments of small molecules General Principles II Blood and dialysate do not come into contact with each other Dialysate and blood run countercurrent in order to maximize concentration gradients Excellent small molecule clearance with HD over a short period of time – i.e. potassium, creatinine, urea The rapid rate of solute removal may result in abrupt changes in osmolality resulting in fluid shifts and hypotension General Principles III Solute diffusion determined by concentration, time, molecular size, and permeability + surface area of dialyzer membrane Where small molecules in high concentrations require a short time, larger molecules in lower concentrations require much longer times for efficient removal General Principles IV Where dialysis involves diffusion, hemofiltration uses convective forces via solvent drag for molecular clearance Hemofiltration uses a hydrostatic pressure gradient to move plasma water across the membrane Hemofiltration is optimal when fluid removal is the primary goal, particularly in situations of hemodynamic flux Mechanisms I Mechanisms II Nomenclature SCUF - Slow Continuous UltraFiltration (slow fluid removal) – fluid removal only; minimal clearance CVVH – Continuous Veno-Venous Hemofiltration (convection) CVVHD – Continuous Veno-Venous HemoDialysis (diffusion) CVVHDF – Continuous Veno-Venous HemoDiaFiltration (convection + diffusion) Nomenclature II Technical Considerations Need for dual-lumen catheter access via femoral, IJ, or subclavian approach Requirement for separate Calcium/Magnesium replacement via central line Filter clotting frequency which often precludes true “continuous therapy” ICU care with one-to-one nursing Frequent monitoring of electrolytes and acidbase status Indications Hemodynamic instability Hypercatabolic state Nutritional demands ?Removal of Inflammatory Mediators in Sepsis High-volume, daily intravenous requirements, including pressors, anbx, blood products Indications II Anticoagulation I AC choice determined by patient needs, local expertise, and ease of monitoring Systemic Heparin Regional Heparin with protamine reversal LMWH Regional Citrate – frequent monitoring of ionized calcium, acid-base status Saline Flushes Prostacycline – platelet aggregation inhibition Anticoagulation II Outcomes I ARF occurs in 5% of hospitalized patients Increased incidence in ICU patients – up to 40% Mortality rate of 40% - 70% Short term survival improved with dialysis, though no change in overall mortality Mortality dependent on underlying disease Outcomes II Prospective study attempted to answer the question of HD vs. Continuous therapy 146 patients with ARF requiring dialysis randomized to intermittent vs. continuous Despite “randomization”, two groups differed significantly, with an increased severity of illness and more disease in continuous group Outcomes III PD vs CVVH studied in Vietnam – 70 patients with ARF and sepsis – clear mortality benefit for CRRT – 47% vs. 15% Criteria for use of CRRT are varied Use is increasing – Canadian study showed that CRRT was used for 26% of all treatments for ARF as opposed to 9% previously It is unclear if CRRT improves outcomes compared to intermittent therapy Principles of Drug Dosing Drug removal affected by size, concentration, distribution, and protein binding Only the free, unbound portion of any drug is available for removal Protein binding is influenced by pH, presence of uremic toxins, heparin, and concurrent medications which displace drugs from their binding sites Sieving Coefficient Represents the ability of any particular solute to cross a permeable membrane SC of 0 indicates no drug removal; SC of 1 indicates removal at a rate of blood concentration Increased rate of ultrafiltration leads to increased drug removal Drug removal also affected by charge and ability of membrane to bind the drug Continuous vs. Intermittent Less frequency of hypotension with continuous therapies Continuous therapies allow for excess fluid removal in hypotensive patients without an increase in pressor requirements Continuous solute clearance; no “saw-tooth” pattern seen with intermittent HD Per unit time, hemodialysis is more efficient at small solute removal Continuous vs. Intermittent Gentle fluid removal allows for “refill” time of peripheral edema (approx. 10 cc/min) Less complement activation with continuous therapy Less pulmonary leukostasis and capillary leak with continuous therapy CVVHDF road-map replacement fluid dialysate ~~~ ven <-- art --> effluent ultrafiltrate