Dialysis dose prescription

Presented byDr. Ujjawal

1937:Nils Alwall used the

Alwall Kidney to perform

the first ever hemodialysis

treatment at the university

of Lund, Sweden

Basics of dialysis

Mechanisms of solute transport through membrane pores

Difffusion & ultrafiltration (convection)Diffusion The movement of solutes due to

random molecular motion Larger the mol. wt. of a solute,slower

will be its rate of transport across a semipermeable memb.

The processes of diffusion (top) and ultrafiltration (bottom)

Ultrafiltration Water driven by either a hydrostatic or an osmotic force is

pushed through the membrane (convective transport) Purpose: removing water accumulated either by

ingestion of fluid metabolism of food during the interdialytic period

Pts with acute fluid overload need more rapid fluid removal Hence, the clinical need for UF ranges from 0.5-1.5 L/hr During HD, UF and diffusive clearance are typically

performed simultaneously

Hemodialysis Circuit

The Dialysis Prescription

The goal of HD in ESRD – to restore the body's intracellular and extracellular fluid environment as healthy individuals

HD as renal replacement therapy – accomplished by Solute removal from the blood into the dialysate (potassium, urea,

and phosphorous)

Addition of solute from the dialysate into the blood (HCO3- & Ca++)

Elimination of excess water volume from the patient via UF

Prescription : individualized approach

Components of the Dialysis Prescription Dialyzer (membrane, configuration, surface area) Time Blood flow rate Dialysate flow rate Ultrafiltration rate Dialysate composition Dialysate temperature Anticoagulation Intradialytic medications Dialysis frequency

The device containing the semipermeable membrane is the hemodialyzer

Blood and dialysate are circulated on opposite sides of a semipermeable membrane

Benefits Passage of solutes elevated in CKD Restricting the transfer blood proteins & cellular element

Removal of water Mainly by hydrostatic pressure gradient Augmented by increasing the osmolality of the dialysate fluid

Dialyzer Choice Three most critical determinants

Capacity for solute clearance Capacity for UF or fluid removal Nature of dialyzer membrane & interactions with components of

the blood and their potential clinical sequelae (referred to as biocompatibility)

Solutes >300 Da – relatively lower diffusive clearance values as compared to smaller solutes (like urea & potassium)

Clearance of larger solutes depends on convection

The ideal HD membrane High clearance of LMW & middle-mol-wt. uremic toxins Negligible loss of vital solutes Adequate UF to maximize efficiency & reduce adverse

metabolic effects due to HD Additional characteristics of ideal dialyzer

low blood volume compartment beneficial biocompatibility effects high reliability low cost

Urea – most often used in evaluating dialyzer solute clearance characteristics

Capacity for fluid removal by a dialyzer – described by its UF coefficient

Hollow fibre dialyzers

Hollow fibre dialyzer Parallel plate dialyzer

Large cylinders packed with hollow fibres

Multiple sheets of flat dialysis membrane stacked in a layered configuration with separation of blood & dialysate compartments

Blood compartment: more compliant, varies more with transmembrane pressure

Non-compliant with fixed blood volumes

Lower blood volume compartment required (50-150 ml), hence more frequently used

Require a larger blood vol compartment, hence less frequently used

Anticoagulation for Hemodialysis

Thrombin deposition due to activation of clotting cascade in dialyzer hollow fibers results in dialyzer dysfunction

Determinants of Dialyzer thrombogenicity Dialysis membrane composition Surface charge Surface area, and configuration UF rate prescribed (owing to hemoconcentration) Length, diameter Composition of blood lines Patient factors – Inherited coagulopathies, neoplasia, malnutrition,

hemoglobin concentration, and presence or absence of CHF

Heparin

Most widely used anticoagulant Easy to administer, low cost & relatively short t½ Administered as single bolus or incrementally For patients at high risk of bleeding, occasionally

administered as regional anticoagulation In routine HD anticoagulation is not measured ACT – Activated clotting time :

whole blood mixed with an activator of extrinsic clotting cascade time necessary for blood to first congeal measured

Fractional heparinization For less intensive anticoagulation Candidates: higher risk of bleeding complications

Regional heparinization Prevents extracorporeal thrombogenesis Minimal systemic anticoagulation Systemic administration of 500-750 U/hr into arterial line Parallel administration of protamine into the venous line Now rarely used due to technical constraints For high bleeding risk pts, dialysis without anticoagulation

Guidelines for anticoagulation for patients at high risk from hemorrhage

Dialysis without heparinization or regional anticoagulantion Patients at significant risk for bleeding Within 7 days after a major operative procedure Within 14 days after intracranial surgery Within 72 hours after a biopsy of a visceral organ Patients with pericarditis

Fractional heparinization Patients who are more than 7 days past a major surgery 72 hours past a biopsy / minor surgical procedures

Blood and Dialysate Flow Definition of solute clearance: volumetric removal of the

solute from the patient

Prescriptions of the blood flow & dialysate flow rates Critical elements which can be altered to modify solute clearance

Blood flow rate to be kept as 50 100 desired level (generally 350 for acute dialysis;for chronic-500)

Acute dialysis: usual solution flow rate is 500 mL/min

Recirculation When “dialyzed” blood re-enters the dialytic circuit with

backflow from the venous to arterial side Problem: ed efficiency of solute clearance Causes

Venous outflow restriction Impaired arterial flow when dialysis needles are placed in close approximation within the

dialysis access

Recirculation measurement

approaches “systemic blood” sample drawn

blood from a vein in the

contralateral arm – Inaccurate and

tends to overestimate recirculation

More accurate method: indicator

(saline) is infused, and

measurement of disappearance

and lack of reappearance on

arterial side is used

Principles of measuring access recirculation (AR)

Dialysis Time Sole variable to augment solute clearance in 1 HD session Efficiency of solute removal declines gradually –

“diminishing returns”

Longer duration of the dialysis procedure Allows lower UF rate/hr for a targeted UF goal Fewer intradialytic symptoms – hypotension & cramping Long HD t/t with slow UF rates: excellent long-term survival Initial t/t – when predialysis BUN high

dialysis session length blood flow rate

Dialysis composition

HD: countercurrent flow is utilized Goal : to maintain conc. gradient as

a driving force for solute transport

Selection of dialysis solute conc is a critical component of the dialysis procedure Goal – achieve body fluid and

electrolyte homeostasis

Sodium(Na+) Major determinant of tonicity of extracellular fluids Readily crosses dialysis membranes : plays a crucial role in

determining CV stability during HD To dialysis disequilibrium & intradialytic hypotension :

prescription of high-sodium dialysate But in dialysate Na+ concentration results in

Polydipsia interdialytic wt gain & interdialytic hypertension hence offsets beneficial effects of intradialytic hemodynamic

stability

Potassium (K+)

Only 1% to 2% is present in extracellular space

In ESRD -accumulates: life-threatening conc. can result

Removal of excess K+: achieved by use of a dialysate K+ conc. lower than plasma conc.

During HD, ~70% of the removed K+ derived from intracellular compartment

Rate of K+ removal during dialysis is largely a function of the predialysis K+ conc.

Generally, a dialysate K+ conc of 1 to 3 mEq/L is used

If predialysis serum potassium level is <4.0 mmol/L, the dialysis solution K+ level should be ≥ 4.0 mM

In predialysis plasma K+ level >5.5 mmol/L Dialysis solution K+ level of 2.0 in stable patients

But dialysis solution K+ conc. should be raised to 2.5 or 3.0 in: Patients at risk for arrhythmia

Those receiving digitalis

Calcium

Now a days standard dialysate Ca++ conc of 2.5-3.0 mEq/L is employed to prevent interdialytic hypercalcemia Cause

use of calcium-containing salts and phosphorous binders

aggressive use of vit D analogs

Magnesium(Mg2+)

S. Mg2+ conc.-poor determinant of total body Mg2+ stores(as k+)

Only approximately 1% of total body Mg2+ content is present in the extracellular fluid

Only 60% of extracellular Mg2+ is free & diffusible

Mg2+ flux during HD is difficult to predict

The ideal S. Mg2+ conc in ESRD & appropriate dialysate Mg2+ conc. are unresolved

Most centers use a dialysate Mg2+ conc of 1 mEq/L

Buffers Hydrogen ions produced in body rapidly buffered by plasma

buffers (HCO3- & others)

HD : cannot remove large quantities of free hydrogen ion Goal of HD – Correction of uremic metabolic acidosis Correction of acidosis in HD

dialysate of higher conc. of alkaline equivalents than blood promotes flux of base from the dialysate into the blood

Acetate buffer a/w adverse metabolic and hemodynamic effects hence replaced by bicarbonate(HCO3-)

Dialysate HCO3- conc. of 30 to 35 mEq/L are now commonly used

Chloride

Chloride is the major anion in dialysate

Dialysate chloride concentration adjusted as to maintain electrical neutrality in diaslate

Glucose

Optimal dialysate glucose concentration for most pts :100 to 200 mg/dL

In diabetes, insulin doses may require adjustment during dialysis : “glucose clamp”

Composition of a standard hemodialysis solution

Component Concentration (mM)

Sodium 135-145

Potassium 0-4

Calcium

1.25-1.75mM

(2.5-3.5 mEq/L)

Magnesium

0.25-0.375

(0.5-0.75 mEq/L)

Chloride 98-124

Acetate or citratea 2-4

Bicarbonate 30-40

Glucose 0-11

PCO2 40-110 (mm Hg)

pH 7.1-7.3 (units)

Dialysate Temperature Maintained between 36.5°C and 38°C Low temp. of 35° to be used in hypotension prone pts Dialysate temp.: important determinant of intradialytic BP UF-induced volume contraction during HD

peripheral vasoconstriction, limits peripheral heat loss & raises

core body temp

reflex dilatation of peripheral blood vessels

reduces peripheral vascular resistance

intradialytic fall in blood pressure

Benefits of lowering dialysate solution temperature

hemodynamic stability in hypotension-prone dialysis patients

Increase cardiac contractility

Improve oxygenation

Increase venous tone

Reduce complement activation during dialysis

Temp. monitors failure severe hemolysis reported

Ultrafiltration Rate

Factors determining net pressure across dialyser membrane osmotic pressure oncotic pressure across the membrane hydraulic pressure – highest hence only one taken into account

(arithmetic mean of the inlet and outlet pressures)

TMP : effective pressure to achieve required fluid loss in HDTMP = desired weight loss/(UF coefficient × dialysis time)

UF control system machines High performance Specially required when high flux dialyzers are used

Prescription of UF rate in HD: patient factors

Dry weight Rate of vascular refilling Monitoring of blood volume changes Hydration status during HD

Dry weight – defined as the lowest weight a patient can tolerate without the development of signs or symptoms of intravascular hypovolemia

Acute vs Chronic Hemodialysis Prescription

Initial t/t – when predialysis BUN is high dialysis session length blood flow rate

A urea reduction ratio of <40% should be targeted. Blood flow rate of 250 mL/min for adults along with 2-hr t/t

time If large amount of fluid (e.g., 4.0 L) to be removed

dialysis solution flow can initially be shut off isolated ultrafiltration can be performed for 1-2 hours, removing 2-

3 kg of fluid Only after that dialysis should be performed. Why?

“Disequilibrium syndrome” Appearance of obtundation, or even seizures and coma, during

or after dialysis Cause

when the predialysis BUN is high excessively high blood flow rates in acute setting excessively rapid removal of blood solutes

After the initial dialysis session patient can be re-evaluated should generally be dialyzed again the following day

Length of 2nd HD can be to 3 hrs, provided predialysis BUN <100 mg/dL

Subsequent dialysis sessions can be as long as needed Length of single dialysis treatment not ≥ 6 hrs unless the

purpose of dialysis is t/t of drug overdose

Patients with ARF – mortality in 6 wk regimen vs alternate day schedule

Alternate day schedule : t/t length be set at 4-6 hrs, to deliver a single-pool Kt/V of at least 1.2-1.3, as recommended for chronic therapy

For first couple of HD sessions: best avoiding high-efficiency dialyzers

For acute dialysis,usual sol. flow rate is 500 mL/min.

Ultrafiltration Orders

Removal of fluid not >2-3 L over single HD session Exceptions – pedal edema, pulm congestion, anasarca

Fluid removal requirement = zero in pts with little / no jugular venous distention

Patients in pulmonary edema may need removal upto 4 L during the initial session.

Blood flow rate shd be initially kept as 50 100 desired level

(generally 350 for acute dialysis; for chronic-500)

Hemodialysis Adequacy

The Ideal Marker of Dialysis Adequacy Retained in renal failure Eliminated by dialysis Proven dose-related toxicity Generation and elimination representative of other toxins Easily measured

The National Cooperative Dialysis Study

Developed by Gotch and Sargent, changes in serum urea concentrations are measured over time, so that “average” concentration of urea for the treatment session can be expressed: TACurea (timed average urea concentration)

From the intradialytic curve, the index related to the elements of the dialysis treatment and the size of the patient or Kt/V can be calculated and from the interdialytic curve urea generation can be determined

The hemodialysis cycle and elements of kinetic modeling

Std-Kt/V is a frequency-independent measure of dialysis dose. It is a weekly expression (normalized to V) of an equivalent urea clearance, which in turn defined as the urea generation rate divided by the mean peak predialysis serum urea nitrogen (SUN) level.

It can be seen that, when three times per week dialysis sessions are given, each lasting about 3.5 hours and delivering an single-pool (sp) Kt/V of 1.2, the resulting std-Kt/V will be 2.0.

Table 9-1. Minimuma spKt/V values for various frequency schedules of dialysis (achieving an estimated standard Kt/V = 2.0)

Scheduleb Kr <2 mL per min per 1.73 m2 Kr >2 mL per min per 1.73 m2

Two times per week Not recommended 2.0

Three times per week 1.2 0.9

Four times per week 0.8 0.6

Assumes session lengths of 3.5-4 hours.

aTarget spKt/V values should be about 15% higher than the minimum values shown.

Minimum spKt/V values for various frequency schedules of dialysis (achieving an estimated standard Kt/V = 2.0 for an average-size patient)

Schedule Kr <2 mL/min/1.73 m2 Kr >2 mL/min/1.73 m2

Four times per week

0.87 0.62

Five times per week

0.64 0.46

Six times per week 0.51 0.37

Adapted from the National Kidney Foundation's (NKF) Kidney Disease Outcome Quality Initiative (KDOQI) 2006 adequacy guidelines, CPR #4. Based on a 120 minute treatment time.

Typical SDHD and NHD prescriptions

  SDHD NHD

Frequency (sessions per week) 6-7 5-7

Duration (hours) 1.5-3.0 6-10

Dialyzer (high flux preferred) Any Any (smaller)

QB (mL per minute) 400-500 200-300

QD (mL per minute) 500-800 100-300

Access Any Any

Remote monitoring None Optional

Dialyzer reuse Optional Optional

SDHD, short daily hemodialysis; NHD, nocturnal hemodialysis.