DIALYSIS

FACULTY OF MEDICINEISLAMIC UNIVERSITY OF MALANG

Dialysis is the process of removing waste products and excess fluids from the body

Definitions

Dialysis is on of the primary modalities for pts with RF

Dialysis can do two of the principal functions of the kidney; 1. removal of endogenous waste products 2. maintenance of water balance

Dialysis is the process of separating elements in a solution by diffusion across a semipermeable membrane (diffusive solute transport) down a concentration gradient

This is the principal process for removing the end-products of nitrogen metabolism (urea, creatinine, uric acid), and for repletion of the bicarbonate deficit of the metabolic acidosis associated with renal failure in humans

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Advanced renal failure with:

1. Hyperkalemia

2. Fluid overload

3. Severe metabolic acidosis (PH<2)

4. Pericarditis

5. Encephalopathy

6. Pulmonary oedema

7. Peripheral neuropathy

8. Uraemic symptoms

Indication for dialysis;

Normal renal function:

1. Poisoning

2. Nephrotic syndrome with oedema

3. Hypercalcemia

A. Acute dialysis

B. Acute dialysis

1. ESRD with or without complications

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Signs of adequate dialysis;1. Well looking

2. Eats normal

3. Normal BP

4. No oedema

5. Normal heart size

6. HB >=10

7. Albumin >35

Hemodialysis

• Blood is removed from the body and pumped by a machine outside the body into a dialyzer (artificial kidney)

• The dialyzer filters metabolic waste products from the blood and then returns the purified blood to the person

• The total amount of fluid returned can be adjusted• A person typically undergoes hemodialysis at a

dialysis center• Dialysate is the solution used by the dialyzer

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• HD consists of perfusion of heparinized blood and physiologic salt solution on opposite sides of a semipermeable membrane

• Waste products (urea, creatinine,…ets) move from blood into the dialysate by passive diffusion along concentration gradient

• Diffusion rate depends on;1. The difference between solute concentrations in the

blood and dialysate

2. Solute characteristics

3. Dialysis filter composition

4. Blood and dialysate flow rate

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Blood from the patient is circulated through a synthetic extracorporeal membrane and returned to the patient. The opposite side of that membrane is washed with an electrolyte solution (dialysate) contain- the normal constituents of plasma water

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Dialysate;1. Water

2. Glucose

3. Acetate

4. Bicarbonate

5. Calcium

6. Sodium

7. Potassium

Used 3 times a week

Duration; 4 hrs

Complicated, need to be done in a center

Heparin required

Temporary arteriovenous access

Permanent arteriovenous access

Access

The access is where the needles are placed to remove blood from the body and return it to the body after it is filtered by the dialysis machine

Three types of accesses exist: natural fistula, artificial grafts, and jugular vein catheters

A vein and an artery are joined. Within 6 to 8 weeks, the vein becomes much bigger and is strong enough to be used as an access for dialysis

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How a fistula access works 1. During dialysis, two needles are placed into the fistula. One needle will remove the blood so it can be cleaned. The other needle will return filtered blood to the body

2. The needles are attached by plastic tubing to a special filter called a dialyzer (or artificial kidney)

3. A pump pushes the blood through the dialyzer. Blood passes on one side of the filter, and solution made by the machine passes on the other side. The blood does not mix with the solution. Instead, the solution pulls extra fluid and waste out of the blood by a process called dialysis

4. The "clean" blood returns through the plastic tube. It passes back into the patient's body through the second needle

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A graft is another type of access, which is used if a person's own veins are too small or weak to create a fistula. Usually, a graft is a soft, synthetic tube that connects to an artery at one end and a vein at the other. It is placed under the skin of the arm or thigh, like a natural vein. The patient's blood flows through it, like it flows through natural veins

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Sometimes hemodialysis is needed right away, and there is no time to create a fistula or graft. If this happens, a tube called a catheter may be inserted into a large vein in the neck (jugular vein), behind the collarbone (subclavian vein) or in the groin (femoral vein). The patient's blood can flow through this tube

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Complications;1. Vascular access

a. Thrombosis

b. infection

2. Procedure relateda. Decrease BP

b. Headache

c. Cramps

d. Fever

3. Long terma. Cardiovascular diseases

b. Renal bone diseases

c. Aluminum disease

d. Social problems

4. Chronic uraemiaa. Anaemia

b. Infection

c. Gonadal dysfunction

d. Increase BP

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Standard HDCharacteristics:1. Low permeability (low flux)

2. Membranes are made of natural products (cellulose)

3. Each session takes 4-5 hrs

Rapid high efficiency HD (RHED)Characteristics:1. Increase clearance of low molecular weight

solutes (urea)

2. Shorter procedure time

3. Increase blood and dialysate flow rates

4. Clearance of middle and high MW solutes including drugs is not increased

High flux dialysis (HFD)Characteristics:1. Shares the advantages of RHED

2. Membrane pores are more open

3. Higher clearance rate for middle molecules

4. More expensive

5. Needs experts to avoid large rapid fluid shift

Peritoneal Dialysis

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The dialysis membrane is the person's own peritoneum

The dialysis fluid provides the 'container' in which waste products and excess water can be removed from the body

Dialysis membrane acts as a filter

It keeps the dialysis fluid and the blood separate from each other, but it allows certain substances and water to pass through it

During dialysis, waste toxins and excess water pass from the blood into the dialysis fluid, and this is drained out of the body after a few hours

A new bag of dialysis fluid is drained in, and the process is repeated

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PD needs to be done every day

PD involves draining dialysis fluid out of, and into the body (known as an exchange), and leaving dialysis fluid in the body while dialysis takes place

Draining fluid out usually takes around 20 minutes and draining fluid in takes around 5-10 minutes

The 'used' dialysis fluid, containing the water and waste (toxins) that the kidneys would normally have passed into the urine, is drained out of the body

The person then needs to drain between 1.5 and 3 litres of 'new' dialysis fluid into their abdomen

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The dialysis fluid is then left inside the peritoneum to allow dialysis to take place. The length of time it is left there varies (between 1 and 8 hours), depending on individual requirements and the type of PD

There are no 'set' times to carry out the exchanges

It is easy for people to adapt the timing of exchanges to their own needs. For example, if a person wants to go out for the day, they could

delay the mid-day exchange, and do two 'quick bags' (say, 3 hours apart) after they come home

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A four-bag regime 'fits' into a typical dayFor example, • The first bag might be exchanged before breakfast• The second before lunch• The third before the evening meal• The fourth before going to bed (leaving the fluid

for the last exchange in through the night)

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A plastic tube is permanently inserted into the abdomen

This tube is called a PD catheter

It is about 30 cm (12 in) long and as wide as a pencil

The PD catheter is placed through the lower abdominal wall, into the peritoneal cavity

Half of the catheter lies inside the abdomen, and half lies outside the body

It comes out to one side of the navel (belly button)

The PD catheter acts as a permanent pathway into the peritoneal cavity from outside the body

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The catheter is usually 'left alone' for 5 days or more after the operation before it is used for dialysis

This allows it to 'settle in' and gives the abdominal wound time to heal

PD could be done at home

Much less efficient than HD, this is why it is used more frequent

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Dialysate;1. Water

2. Glucose

3. Dextrose; 1.5-4.25%

4. Acetate

5. Bicarbonate

6. Calcium; 3.5 or 2.5 mEq/l

7. Chloride; 102mEq/l

8. Lactate; 35mEq/l

9. Magnesium; 1.5mEq/l

10. Sodium; 132mEq/l to reduce the movement of sodium from the blood by gradient method

11. No potassium in PD

12. High osmolarity; 350-480mOsm/L (serum=280mOsm/l) to provide a drawing force from the blood into the peritonium

PET; peritoneal equilibrium test• Is a diagnostic test that determines the peritoneal

membrane clearance and ultrafiltration characteristics, and quantitates the ability to transfer solutes and water across the membrane

• PET results determine which type of PD is appropriate for each individual

Indications;1. DM

2. No vascular access

3. CVS unstable

4. Children

5. Old adults

6. Pts unwilling to accept blood transfusion

7. Severe anaemia

8. Severe HD related symptoms e.g disequilibrium

Contraindications;1. Peritonea adhesion

2. Severe lung disease

3. Abdominal sepsis

4. Massive polycystics

Complications;a. Malnutrition

b. Peritonitis:

c. 70% Gm positive cocci

d. IP antibiotic is preferred

e. vancomicin or aminoglycosides. First dose in the first 2L exchange, scond dose at day 7

f. Gentamicin 1.5 mg/kg IP in the first 2L exchange followed by 4-8 mg/L IP in each exchange for 10 days

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Pharmacokinetics of dialysis

Factors affecting drug dialysability;1. Drug characteristicsA. MW; drugs with MW >500 are not dialyzable in

the conventional HD. E.g vancomicin, digoxin

Using high flux HD; the above mentioned drugs are dialyzable

B. Water solubility; solutes which are insoluble in water will not easily move into aqueous dialysate, e.g glutethimide

D. Volume of distribution; drugs with large VD are not appreciably removed by HD, e.g digoxin, aminoglycosides

E. Protein binding; only unbound drugs can pass through the dialyser membrane, e.g phenytoin, propranolol, oxacillin

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2. Dialysis conditionsA. Counter-current vs concurrent flow

B. Blood flow rate

C. Dialysate flow rate

3. Membrane characteristicsA. Thickness

B. Material type / pore size

C. Surface area

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Clearance of large MW drugs depends on pore size, surface area and flow rate

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Therapeutic considerations1. Supplementary dose should be administered post

dialysis. If the drug is administered at the beginning of HD, the fraction would be removed, since it is not yet distributed in the body

2. Drugs with NTW, plasma level should be monitored to verify the predicted estimation

3. Drugs with wide therapeutic window, decision based on pt’s clinical status

4. Blood sample should be drawn at least 1 hr post dialysis to allow redistribution from the tissue, other references recommend 6-12 hrs post dialysis

5. Drugs which plasma concentration can be measured but some times no published data on the pharmacokinetic of certain drugs. if the pharmacokinetics are known then replacement dose could be calculated

6. Drugs with wide therapeutic range and serum concentration cannot be measured; single daily dose can be administered after dialysis

Categories of drug dialyzability;

1. Dialyzable; 50% - 100% removed

2. Moderately dialyzable; 20% - 50% removed

3. Slightly dialyzable; 5% - 20% removed

4. Not dialyzable; <5% removed

Estimating the supplementary dose in dialysis pt

1. The supplementary doses can be calculated from the pharmacokinetic data reported in the literature

2. The equations and pharmacokinetic utilized are based only on linear first order kinetics and one compartment model

3. More complex kinetics seem to be unnecessary for general dosage recommendations for repeatedly administered drugs

4. For pts on dialysis; the total clearance of the drog from the plasma (ClT) can be defined as the sum of the pt’s residential endogenous clearance and the dialysis clearance (ClD)

i.e ClT = Cl + ClD

If ClD >>>Cl then the drug will be eliminated much more rapidly during dialysis

t1/2 0.693 X VDClT

=

Clearance can be related to half life by the following equation

t1/2 0.693 X VDCl + ClD

=

VD is the volume of distribution of the drug

The actual amount of drug removed by HD is the product of the concentration of the drug in the recovered dialysate and the dialysate volume

XAmount in dialysate

drug conc. in dialysate

volume of the dialysate=

It is not clinically feasible or analytically practical to measure dialysate drug concentration

This value divided by total body stores of drug prior to dialysis yield the actual fraction of drug removed by dialysis (FD)

FD = amount of dialysate drug / TBs

TBS = drug conc. X VD

The following equation may be used to determine the fraction of the total amount of drug in the body removed during dialysis

FD = 1 - e -(Cl+ClD)(t/VD)

t is the duration of dialysis

To use this equation, the values of Cl, ClD must be obtained from the literature

Unfortunately, clearance dtat are not always available

Half life is more available, so we use another equation

FD = 1 - e -(0.693/t1/2 OD) X (t)

t1/2 OD is the half life during dialysis

t is the duration of dialysis

This method can be used to calculate the fractional drug removed but it is inaccurate

But it is useful in the clinical setting when clearance data is not available

Example:

NN on amikacin, Wt 70 kg

Estimated amikacin Cl 5ml/min (endogenous clearance)

Under go 4 hr HD (t OD = 4hrs)

Calculate the replacement dose for NN??

Assuming VD= 0.2 L/Kg

ClD = 35 ml/min

Answer:

ClT = Cl + ClD

= 5 + 35 = 40 ml/min = 2.4 L/hr

t1/2 0.693 X VDCl + ClD

=

Then

= 0.693 X 0.2L/Kg X 70 Kg2.4 L/hr

= 4 hrs

FD = 1 - e -(Cl+ClD)(t/VD)

Or

FD = 1 - e -(0.693/t1/2 OD) X (t)

After we get the answer. It will be replaced after dialysis