MANAGEMENT OF MANAGEMENT OF CONTINUOUS CONTINUOUS

HEMODIALYSISHEMODIALYSISAPACVS CONFERENCE.APACVS CONFERENCE.

July 12, 2013July 12, 2013

Naveed Masani, MDNaveed Masani, MD

General Principles IGeneral Principles I

Solute removal may be accomplished Solute removal may be accomplished via diffusion and/or convectionvia diffusion and/or convection

Hemodialysis involves diffusive Hemodialysis involves diffusive clearance only – two fluid clearance only – two fluid compartments (patient’s blood and compartments (patient’s blood and dialysate) separated by a semi-dialysate) separated by a semi-permeable membrane permeable membrane

Passive diffusion between the two Passive diffusion between the two compartments of small moleculescompartments of small molecules

General Principles IIGeneral Principles II Blood and dialysate do not come into Blood and dialysate do not come into

contact with each othercontact with each other Dialysate and blood run countercurrent in Dialysate and blood run countercurrent in

order to maximize concentration order to maximize concentration gradientsgradients

Excellent small molecule clearance with Excellent small molecule clearance with HD over a short period of time – i.e. HD over a short period of time – i.e. potassium, creatinine, urea potassium, creatinine, urea

The rapid rate of solute removal may The rapid rate of solute removal may result in abrupt changes in osmolality result in abrupt changes in osmolality resulting in fluid shifts and hypotensionresulting in fluid shifts and hypotension

General Principles IIIGeneral Principles III

Solute diffusion determined by Solute diffusion determined by concentration, time, molecular size, concentration, time, molecular size, and permeability + surface area of and permeability + surface area of dialyzer membranedialyzer membrane

Where small molecules in high Where small molecules in high concentrations require a short time, concentrations require a short time, larger molecules in lower larger molecules in lower concentrations require much longer concentrations require much longer times for efficient removaltimes for efficient removal

General Principles IVGeneral Principles IV

Where dialysis involves diffusion, Where dialysis involves diffusion, hemofiltration uses convective forces via hemofiltration uses convective forces via solvent drag for molecular clearancesolvent drag for molecular clearance

Hemofiltration uses a hydrostatic Hemofiltration uses a hydrostatic pressure gradient to move plasma water pressure gradient to move plasma water across the membraneacross the membrane

Hemofiltration is optimal when fluid Hemofiltration is optimal when fluid removal is the primary goal, particularly removal is the primary goal, particularly in situations of hemodynamic fluxin situations of hemodynamic flux

Mechanisms IMechanisms I

Mechanisms IIMechanisms II

NomenclatureNomenclature

SCUF - Slow Continuous SCUF - Slow Continuous UltraFiltration (slow fluid removal) – UltraFiltration (slow fluid removal) – fluid removal only; minimal clearancefluid removal only; minimal clearance

CVVH – Continuous Veno-Venous CVVH – Continuous Veno-Venous Hemofiltration (convection)Hemofiltration (convection)

CVVHD – Continuous Veno-Venous CVVHD – Continuous Veno-Venous HemoDialysis (diffusion)HemoDialysis (diffusion)

CVVHDF – Continuous Veno-Venous CVVHDF – Continuous Veno-Venous HemoDiaFiltration (convection + HemoDiaFiltration (convection + diffusion)diffusion)

Nomenclature IINomenclature II

Technical ConsiderationsTechnical Considerations

Need for dual-lumen catheter access via Need for dual-lumen catheter access via femoral, IJ, or subclavian approachfemoral, IJ, or subclavian approach

Requirement for separate Requirement for separate Calcium/Magnesium replacement via Calcium/Magnesium replacement via central linecentral line

Filter clotting frequency which often Filter clotting frequency which often precludes true “continuous therapy”precludes true “continuous therapy”

ICU care with one-to-one nursingICU care with one-to-one nursing Frequent monitoring of electrolytes and Frequent monitoring of electrolytes and

acid-base statusacid-base status

IndicationsIndications

Hemodynamic instabilityHemodynamic instability Hypercatabolic stateHypercatabolic state Nutritional demandsNutritional demands ?Removal of Inflammatory Mediators ?Removal of Inflammatory Mediators

in Sepsisin Sepsis High-volume, daily intravenous High-volume, daily intravenous

requirements, including pressors, requirements, including pressors, anbx, blood productsanbx, blood products

Indications IIIndications II

Anticoagulation IAnticoagulation I

AC choice determined by patient needs, AC choice determined by patient needs, local expertise, and ease of monitoringlocal expertise, and ease of monitoring

Systemic Heparin Systemic Heparin Regional Heparin with protamine reversalRegional Heparin with protamine reversal LMWHLMWH Regional Citrate – frequent monitoring of Regional Citrate – frequent monitoring of

ionized calcium, acid-base statusionized calcium, acid-base status Saline Flushes Saline Flushes Prostacycline – platelet aggregation Prostacycline – platelet aggregation

inhibitioninhibition

Anticoagulation IIAnticoagulation II

Outcomes IOutcomes I

ARF occurs in 5% of hospitalized patientsARF occurs in 5% of hospitalized patients Increased incidence in ICU patients – up Increased incidence in ICU patients – up

to 40%to 40% Mortality rate of 40% - 70%Mortality rate of 40% - 70% Short term survival improved with Short term survival improved with

dialysis, though no change in overall dialysis, though no change in overall mortalitymortality

Mortality dependent on underlying Mortality dependent on underlying disease disease

Outcomes IIOutcomes II

Prospective study attempted to answer Prospective study attempted to answer the question of HD vs. Continuous the question of HD vs. Continuous therapytherapy

146 patients with ARF requiring dialysis 146 patients with ARF requiring dialysis randomized to intermittent vs. randomized to intermittent vs. continuouscontinuous

Despite “randomization”, two groups Despite “randomization”, two groups differed significantly, with an increased differed significantly, with an increased severity of illness and more disease in severity of illness and more disease in continuous groupcontinuous group

Outcomes IIIOutcomes III PD vs CVVH studied in Vietnam – 70 PD vs CVVH studied in Vietnam – 70

patients with ARF and sepsis – clear patients with ARF and sepsis – clear mortality benefit for CRRT – 47% vs. 15%mortality benefit for CRRT – 47% vs. 15%

Criteria for use of CRRT are variedCriteria for use of CRRT are varied Use is increasing – Canadian study Use is increasing – Canadian study

showed that CRRT was used for 26% of showed that CRRT was used for 26% of all treatments for ARF as opposed to 9% all treatments for ARF as opposed to 9% previouslypreviously

It is unclear if CRRT improves outcomes It is unclear if CRRT improves outcomes compared to intermittent therapycompared to intermittent therapy

Principles of Drug Principles of Drug DosingDosing

Drug removal affected by size, Drug removal affected by size, concentration, distribution, and concentration, distribution, and protein bindingprotein binding

Only the free, unbound portion of any Only the free, unbound portion of any drug is available for removaldrug is available for removal

Protein binding is influenced by pH, Protein binding is influenced by pH, presence of uremic toxins, heparin, presence of uremic toxins, heparin, and concurrent medications which and concurrent medications which displace drugs from their binding sitesdisplace drugs from their binding sites

Sieving CoefficientSieving Coefficient

Represents the ability of any particular Represents the ability of any particular solute to cross a permeable membranesolute to cross a permeable membrane

SC of 0 indicates no drug removal; SC SC of 0 indicates no drug removal; SC of 1 indicates removal at a rate of of 1 indicates removal at a rate of blood concentrationblood concentration

Increased rate of ultrafiltration leads Increased rate of ultrafiltration leads to increased drug removalto increased drug removal

Drug removal also affected by charge Drug removal also affected by charge and ability of membrane to bind the and ability of membrane to bind the drug drug

Continuous vs. Continuous vs. IntermittentIntermittent

Less frequency of hypotension with Less frequency of hypotension with continuous therapiescontinuous therapies

Continuous therapies allow for excess Continuous therapies allow for excess fluid removal in hypotensive patients fluid removal in hypotensive patients without an increase in pressor without an increase in pressor requirementsrequirements

Continuous solute clearance; no “saw-Continuous solute clearance; no “saw-tooth” pattern seen with intermittent HDtooth” pattern seen with intermittent HD

Per unit time, hemodialysis is more Per unit time, hemodialysis is more efficient at small solute removalefficient at small solute removal

Continuous vs. Continuous vs. IntermittentIntermittent

Gentle fluid removal allows for Gentle fluid removal allows for “refill” time of peripheral edema “refill” time of peripheral edema (approx. 10 cc/min)(approx. 10 cc/min)

Less complement activation with Less complement activation with continuous therapycontinuous therapy

Less pulmonary leukostasis and Less pulmonary leukostasis and capillary leak with continuous capillary leak with continuous therapytherapy

CVVHDF road-map CVVHDF road-map replacement fluid replacement fluid

dialysatedialysate

effluent ultrafiltrate

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