The document discusses key aspects of dialysis dose prescription, including: 1) Components of the dialysis prescription include dialyzer choice, time, blood and dialysate flow rates, ultrafiltration rate, dialysate composition, temperature, and anticoagulation. 2) Prescription goals are to restore the body's fluid and electrolyte balance and remove waste and excess water from patients with end-stage renal disease. 3) Important considerations for dialysis prescription include a patient's dry weight and risk of intradialytic hypotension.

1. Dialysis dose prescription
Presented by
Dr. Ujjawal

2. 1937:Nils Alwall used the
Alwall Kidney to perform
the first ever hemodialysis
treatment at the university
of Lund, Sweden

4. 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)

6. 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

10. Hemodialysis Circuit

11. 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 (HCO 3- & Ca++)
 Elimination of excess water volume from the patient via UF
 Prescription : individualized approach

12. 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

13.  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

14. 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

15.  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

16. Hollow fibre dialyzers
Hollow fibre dialyzer Parallel plate dialyzer
Large cylinders packed with hollow Multiple sheets of flat dialysis
fibres membrane stacked in a layered
configuration with separation of
blood & dialysate compartments
Blood compartment: more Non-compliant with fixed blood
compliant, varies more with volumes
transmembrane pressure
Lower blood volume compartment Require a larger blood vol
required (50-150 ml), hence more compartment, hence less
frequently used frequently used

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24.  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 Principles of measuring access
recirculation (AR)
measurement of disappearance
and lack of reappearance on
arterial side is used

25. 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

26. 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

27. 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

28. 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.

29.  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

30. 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

31. 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

32. 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

33. Chloride
 Chloride is the major anion in dialysate
 Dialysate chloride concentration  adjusted as to maintain
electrical neutrality in diaslate

34. Glucose
 Optimal dialysate glucose concentration for most pts :
100 to 200 mg/dL
 In diabetes, insulin doses may require adjustment during
dialysis : “glucose clamp”

35. 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)

36. 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

37.  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

38. 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 HD
TMP = desired weight loss/(UF coefficient × dialysis time)
 UF control system machines
 High performance
 Specially required when high flux dialyzers are used

39. 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

40. 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?

41. “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

42.  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.

43. 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)

44. 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

46. 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

47. The hemodialysis cycle and elements of kinetic modeling

48.  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.

49. 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.
Target spKt/V values should be about 15% higher than the minimum values shown.
a

50. 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 0.87 0.62
week
Five times per 0.64 0.46
week
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.

51. 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.