Ultrafiltration during cardiopulmonary_bypass

Ultrafiltration during
cardiopulmonary
bypass
Dr Amarja
www.cardiacanaesthesia.in | DrAmarja

Introduction
During CPB patients often develop –
 Fluid overload
 Hemodilution
 Electrolyte imbalance
 Increased capillary permeability
 Shifting of fluid to extravascular spaces

Introduction (contd)
Ultrafiltration is used to manage
 Blood volume
 Hemoglobin
 Proteins
 Certain electrolytes
 SIRS

What is Ultrafiltration ?
 UF is the movement of water across a
membrane as a result of hydrostatic pressure
gradient or transmembrane pressure (TMP)
 No dialysate is required on the opposite side of
the membrane
 As the water diffuses it creates a solute
concentration gradient across the membrane ,
also termed as ‘convection’.
 The fluid removed is ‘ultrafiltrate’ or ‘plasma
water’. www.cardiacanaesthesia.in | DrAmarja

 It is an effective means of blood conservation
 It increases the volume of RBCs , platelets and
coagulation factors.

What is dialysis ?
 Dialysis is a process in which blood is separated
from a crystalloid solution or dialysate by a
semipermeable membrane
 A solute concentration gradient exist between
blood and dialysate causing the solute transfer
by diffusion from higher to lower concentration

History
 In 1854,Thomas Graham, a Scottish chemist,
presented a paper entitled “Osmotic Force,”
which described the process of separating
substances using a semipermeable membrane
 Willem Kolff built an artificial kidney
employing the regenerated cellulose membrane,
cellophane termed as Kolff-Brigham kidney
 Leonard Skeggs & Jack Leonards developed flat
or parallel plate dialyzer in 1947

Mechanism of UF
 During UF , blood passes through a bundle of
hollow fibres made of microporous membrane.
The hollow fibres are of 180-200 µm in diameter
and pores of 5-10 nm.
 The bundle of this hollow fibres is encased in a
polycarbonate shell
 As blood passes this hollow fibres of
ultrafiltrator ( also called as hemoconcentrator ),
a positive pressure is created. This pressure
difference between the blood side and thewww.cardiacanaesthesia.in | DrAmarja

Mechanism ( contd )
atmosphere on the ultrafiltrate side drives water
across the membrane.
By convection, solutes smaller than pore size
move with the water to equalize the solute
concentration gradient.
The pressure gradient between the blood and the
ultrafiltrate is called the transmembrane pressure
( TMP ) . This is expressed as the formula –

Mechanism ( contd )
TMP = ( P in + P out ) / 2 + V
 TMP = transmembrane gradient
 P in = blood inlet pressure
 P out = blood outlet pressure
 V = negative pressure applied on the
effluent side of the hemoconcentrator

Mechanism (contd )
 TMP should not exceed 500 -600 mmHg to
avoid rupture of membrane.
Rate of UF depends on –
 Membrane permeability
 Blood flow
 TMP
 Hematocrit

Membrane permeability is related to –
 Pore size
 Membrane material
 Membrane thickness
 And is described by ultrafiltration coefficient:
Kuf

Ultrafiltration coefficient
 Kuf is the rate of water removal to the TMP for
a particular device at a constant blood flow.
 Typical rates are 2-50 mL/hr/mmHg
 Increase in TMP increase the rate of UF
 Kuf also depends on blood flow so higher the
blood flow results in higher Kuf.

 As the UF removes the plasma water and
diffusible solutes in equal concentrations, the
overall concentration of diffusible solutes is not
affected
 Depending on the membrane material and the
pore size , solutes > 65000 d are not removed
 Celullar elements, plasma proteins & protein
bound solutes are not removed therefore get
concentrated.

Sieving Coefficient
 The ability of the solute to filter depends on
molecular weight of the solute compared with
the pore size , proportion of the solute that is
membrane bound and the surface charge of the
solute.
 The ‘sieving coefficient’ is the ratio of
ultrafiltrate solute concentration to plasma
solute concentration.
 It ranges from 0 – 1 . When it is 1 it indicates
that the ultrafiltrate solute concentration andwww.cardiacanaesthesia.in | DrAmarja

the plasma solute concentration are equal and that
the solute passes freely across the membrane.
 And the value of 0 indicates that none of the
solute passes through the membrane.
 All small MW solutes that are not protein bound
are easily removed by UF and have a seiving
coefficient of 1.
 Generally,solutes >50,000 daltons do not pass
through the membrane pores. ( Albumin has a
molecular mass of 65,000 daltons ).www.cardiacanaesthesia.in | DrAmarja

Indications
Pts undergoing CPB have significant hemodilution
due to :-
 Circuit prime
 Through cardioplegia line
 Surgical irrigation from cardiotomy suction
 Patients may have CCF / renal failure
UF removes this excess fluid however, the
amount of fluid removed is limited by the
minimal level in the venous reservoir.

 Also, the SIRS increases the capillary
permeability, causing a dilutional decline in
hemoglobin and serum protein concentrations
 The capillary leak causes fluid shifts to the
interstitial spaces causing tissue edema and
decreased end organ function.
 UF can concentrate blood without removal of
plasma proteins, thus causing
hemoconcentration, reduction in tissue edema &
removal of inflammatory mediators.www.cardiacanaesthesia.in | DrAmarja

UF helps by ……
 Decreasing the TBW ( total body water )
 Decreased postop blood loss
 Decreased usage of blood products
 Improves LV systolic function
 Improves A-a O2 gradient
 Increase pulmonary compliance
 Decrease duration of postop ventilation
 Decreased incidence of pleural effusion after
superior cavopulmonary connections/ Fontan .www.cardiacanaesthesia.in | DrAmarja

Advantages of UF
 Hemoconcentration without removal of protein
segment of blood, thus maintaining albumin &
clotting factors.
 The concentration of albumin increases the
colloid oncotic pressure and reduces edema by
drawing blood out of extravascular space.
 In pts with renal impairment, its concomitant
use with dialysis can optimize electrolytes and
blood urea nitrogen.

Advantages of UF (contd)
 The pulmonary compliance is increased & there
occurs faster recovery of pulmonary function is
mainly because of leukocyte stability and
decreased degranulation of polymorphonuclear
neutrophils in the pulmonary capillaries.

Studies….
 Ann Thorac Surg. 1997 Aug;64(2):521-5.
 Modified ultrafiltration after
cardiopulmonary bypass in pediatric cardiac
surgery.
 Draaisma AM, concluded that Modified
ultrafiltration decreases blood transfusion
requirements and chest drain loss after pediatric
cardiac surgical procedures.

Factors that influence UF…..
 Type of UF
 Type of MUF- arteriovenous/ venovenous
 Duration of UF
 Volume of ultrafiltrate obtained
 End-point chosen for termination of MUF
 Type of filter
 Use of PUF
 Concomitant anti-inflammatory therapies like
steroids www.cardiacanaesthesia.in | DrAmarja

 Patient characteristics ( young age, presence of
PAH )
 CPB variables like prime volume , type of prime
 Complexity of surgery – use of DHCA

Risks with UF
 Plasma levels of heparin may increase. The
heterogeneous molecular size of heparin varies
the amount of heparin retained in the
hemoconcentrated blood.
 Aortic cannula may entrain air
 Hemodynamic instability
 High flow rates through ultrafilter decrease the
CBF velocities & cerebral mixed venous O2
saturation
 MUF increases the CPB time.www.cardiacanaesthesia.in | DrAmarja

Contraindications for UF
 Biocompatibility
 Leukopenia
 Complement activation
 RBC trauma & release of plasma free Hg
 Retention of heparin in hemoconcentrated
blood
 Cost analysis

Technical Applications
 The ultrafiltrator is set in parallel to the extracorporeal circuit as
a passive shunt from a point of higher pressure to lower
pressure. The inflow to the ultrafiltrator originates from a
connection off the high-pressure arterial line and the outflow
returns to a lower pressure connection located on the venous
line or the venous reservoir.
 Without the pump, the flow through the ultrafiltrator is
dependent on the pressure differential between the inflow and
outflow of the ultrafiltrator. During CPB, the perfusionist
monitors line pressure distal to the arterial pump, which ranges
between 150 mm Hg and 250 mm Hg, and is dependent on
blood flow rate and resistance. The resistance to flow is
determined by arterial cannula, size, design, and placement, as
well as the patient's arterial blood pressure.www.cardiacanaesthesia.in | DrAmarja

Technical Applications (contd)
 Tubing from the effluent side of the ultrafiltrator is
attached to a collection canister and, given that
ultrafiltrators used for CPB have relatively high
ultrafiltration rates (also termed high flux), sufficient
rates of fluid removal are achieved by establishing a
hydrostatic pressure gradient by altering the height
between the ultrafiltrator and the canister.
 The hydrostatic gradient can vary between 60 - 90
mmHg resulting in an effective hydrostatic pressure of
approximately 45 - 65 mm Hg. The TMP may be
augmented by applying a vacuum source to the effluent
side of the ultrafiltrator.www.cardiacanaesthesia.in | DrAmarja

Technical Applications (contd)
 The process of ultrafiltration may potentially
lead to hypovolemia, with increased osmolarity
in the intravascular volume causing interstitial
fluid to slowly shift into the vascular space.
 A patient supported on CPB can tolerate a
higher rate of ultrafiltration without becoming
hemodynamically unstable because the cardiac
output is controlled by the bypass pump and
does not depend on the intravascular volume.

Types of UF
 Conventional UF
 Modified UF
 Dilutional UF
 Zero – balanced UF
 Prime UF

Prime UF
 Priming of the ECC with non-hemic solutions
results in hemodilution that ranges from 33% to
200% of the pt’s volume
 After cardiac surgery the extravascular fluid load
may increse greater than 1/3rd of the adult pt’s
prebypass volume
 In paediatric perfusion the volume of
hemodilution may far exceed the preoperative
blood volume.

Prime UF
 Banked PRBCs are used to perform PUF
 It lowers the plasma concentrations of
bradykinin & HMW kininogen
 Less tissue edema
 Improved cardiorespiratory status
 Reduced duration of mechanical ventilation &
ICU stay.

MUF
 In 1991, Naik, Knight and Elliot et al described
a procedure, following termination of CPB, the
residual contents of the ECC were ultrafiltrated
and tranfused back while the pts were still
cannulated.
 This was then called modified ultrafiltration
 In MUF, nearly all the contents of the circuit are
concentrated and transfused back decreasing the
risk of hypervolumia while the circuit remains
primed with the crystalloid solution.www.cardiacanaesthesia.in | DrAmarja

MUF circuit
 Arterial line….arterial filter…..roller pump…..
…..cardioplegia device BCD .......ultrafilter……
…….venous line
MUF circulation – from patient to patient
MUF is continued until the hematocrit value is
40% or no blood remains in the bypass circuit.

MUF (contd)
 At the termination of CPB, MUF requires a separate
roller pump to transfer blood from the patient through
the arterial line to an ultrafiltrator and back into the
patient through the venous line. As the patient's blood
volume is concentrated, the arterial pump is used to
transfuse blood from the circuit.
 Once the venous reservoir is emptied, crystalloid
solution is added to the reservoir. While the circuit
blood continues to be transfused to the patient, it is
displaced by the crystalloid solution until all the residual
blood is transfused to the patient and the circuit is left
primed with crystalloid.www.cardiacanaesthesia.in | DrAmarja

MUF (contd)
 Pumping the blood from the patient using the
cardioplegia pump, which is already connected
to the arterial side of the extracorporeal circuit.
The cardioplegia system works well because it
contains a heat exchanger to avoid cooling the
patient, pressure monitoring, a bubble trap, and
a cardioplegia infusion line that is easily attached
to the venous line.

MUF (contd)
 Some have also advocated venous to venous
MUF. in which blood is withdrawn from the
right atrium and returned to the right atrium. No
direct comparisons of the effectiveness of
arteriovenous MUF and venovenous MUF have
been performed.

Risk in doing MUF
 Because the blood is being aspirated from the arterial cannula
with the use of a pump, there is a risk of air being entrained from
the arterial cannulation purse strings. Once MUF is initiated, the
arterial cannula must be checked for air, particularly if the blood
flow through the arterial cannula changes from retrograde to
antegrade flow. This would occur if CPB has to be reinstituted
or if the infusion rate of the circuit blood exceeds the flow rate
of the MUF pump. The pressure in the circuit must be
monitored to avoid any negative pressure occurring in the circuit,
which would draw air across the pores of a microporous
membrane oxygenator. Negative pressure would result if the
arterial line were to be kinked or clamped.

Risk in doing MUF
 To increase the efficiency of MUF, high blood flows
have been used to pull blood from the arterial line. This
raises concerns regarding the increased aortic diastolic
runoff and the potential for intracranial steal.
 Rodriguez et al. studied the effect of MUF blood flow
rates on cerebral blood velocities and cerebral mixed
venous oxygen saturations during various MUF blood
flows in a group of pediatric patients. They found that
MUF blood-flow rates resulted in a decrease in cerebral
blood-flow velocities and cerebral mixed venous
oxygen saturations.

Paediatric Patients
 MUF seems to be most effective in paediatric
patients, probably due to the large prime volume
relative to the patient's blood volume and use of
deep hypothermia in paediatric cardiac surgery.

Advantages with MUF
The results associated with MUF are very encouraging –
 Reduction in post-op morbidity
 Reduced blood loss and blood usage
 Reduced inflammatory mediators
 Improvement in myocardial function & in cerebral
oxygenation
 During MUF, there is increase in MAP related to
changes in SVR associated with increased blood
viscosity & via removal of vasoactive substances.

MUF and HEART
 MUF was more effective in preventing
accumulation of TBW and myocardial edema.
 It also resulted in a significant improvement in
left ventricular contractility, assessed by the
preload recruitable stroke work index.
 The effect of MUF on LV systolic function
using load-independent measures of myocardial
performance, changes in left ventricular systolic
function were shown to correlate positively with
the degree of hemoconcentration.www.cardiacanaesthesia.in | DrAmarja

MUF over CUF
 The concentration of inflammatory mediators in
the filtrate does not differ between CUF and
MUF. However, because the volume of filtrate
removed is significantly greater with MUF,
removal of mediators is correspondingly more.
 Thus, whether the mechanism is reduction in
TBW or removal of inflammatory mediators,
MUF is more effective then CUF because a
greater volume of filtrate can be removed.

MUF (contd)
Disavantage of MUF -
 Patient remains cannulated for more 10-20 min
 Protamine administration has to be withheld.
Criteria chosen for termination of MUF -
 MUF can be continued until the circuit
contents were completely salvaged , use a time-
based criterion , use a hematocrit end point or a
filtrate-volume end point.

Studies……
 Effects of CPB and Use of Modified Ultrafiltration by
Ross M (Ann Thorac Surg 1998;65:S35–9)
Modified ultrafiltration in pediatric CPB reduces total
body water and serum levels of inflammatory
mediators. It results in an elevated hematocrit without
the need for transfusion, improved pulmonary
compliance in the immediate postbypass period, and
probably improved cerebral metabolic recovery after
DHCA.
 Conclusions. MUF can be performed safely in neonatal
patients after CPB and offers advantages in comparison
with CUF.

Studies…..
 J Thorac Cardiovasc Surg 2001;122:209-211
© 2001 The American Association for Thoracic
Surgery
Editorials
Use of ultrafiltration during and after
cardiopulmonary bypass in children
J. William Gaynor, MD

Studies…..
 Thompson and colleagues report results of a study
comparing outcomes after CUF and MUF whena
standardized volume of fluid is removed. The stated
goal of the study was to determine whether "MUF has
any intrinsic benefitover CUF aside from the
potentially greater volume of fluidremoved. . . ." The
volume of filtrate removed was arbitrarily set at 50% to
60% of the "effective fluid balance," definedas the
priming volume plus volume added during CPB, less
the urine output.

 Despite the standardization of CPB, CUF patients received a
significantly larger priming volume and a largervolume was
added during CPB. The reasons for the increased priming
volume are unclear; however, it is likely that more volume was
added during CPB to maintain the reservoir level during CUF.
Because of this additional volume, a significantly greater volume
of filtrate was removed during CUF than during MUF.
 There was no difference in outcome between the 2 groups.The
study design suggests a misunderstanding of the rationalefor
MUF. MUF was introduced to allow safe removal of a
greater volume of fluid than possible during CUF and thus more
effectively prevent accumulation of TBW, not because any
special efficacy of ultrafiltration performed after separation from
CPB. www.cardiacanaesthesia.in | DrAmarja

 The composition of the filtrate remains the same
whether ultrafiltration is performed during rewarming
or a few minutes later after separation from CPB.
 Indeed, one of the authors of this study stated ina
recent editorial that "modified ultrafiltration filters
the CPB perfusate in exactly the same way as
conventional ultrafiltration, except the filtration process
is performed after separationfrom cardiopulmonary
bypass.
 The beneficial effects of MUF compared with CUF are
dependent on more aggressive fluid removal.

ZERO-BALANCED UF
 Because most cytokine and complement levels reach their peak
during rewarming, continuous UF during this period would
further attenuate the inflammatory response.
 To allow continuous UF during the rewarming phase, replace
the ultrafiltrate with a balanced electrolyte solution.
 The ultrafiltration rate is matched with the infusion rate by
loading the ultrafiltration effluent line and the electrolyte
solution infusion tubing into a single roller pump. The effluent
and infusion tubing are loaded in opposite directions so that the
ultrafiltration rate was equal to the infusion rate and the patient
remained isovolemic.www.cardiacanaesthesia.in | DrAmarja

Z-BUF (contd)
 Z-BUF has also been used to correct hyperkalemia.
Potassium loads originate from hyperkalemic
cardioplegia and homologous red blood cells and may
exceed the patient's ability to clear excess potassium
through normal glomerular filtration.
 As the patient's blood volume is reduced by
ultrafiltration, the potassium level is not affected
because the ultrafiltrate potassium levels will always be
in equal concentration to the plasma.

Z-BUF (contd)
 When the purpose of Z-BUF is to remove
inflammatory mediators, the replacement fluid
such as Hartman's solution, lactated Ringers can
be used.
 When using Z-BUF to reduce potassium levels,
the previously mentioned replacement solutions
do not efficiently dilute potassium levels hence
0.9% sodium chloride is often used.

Studies….
 J Thorac Cardiovasc Surg 2006;132:1291-1298
 Modified and conventional ultrafiltration
during pediatric cardiac surgery: Clinical
outcomes compared
This prospective, randomized study of 60
infants found no difference in clinical outcome
between patients who received DCUF only,
patients who received MUF only, and patients
who received both DCUF and MUF.www.cardiacanaesthesia.in | DrAmarja

UF & Hemodialysis in ECMO
 Critically ill patients undergoing long-term
ECMO often present with fluid overload due to
renal insufficiency or failure.
 Because the circuit is closed in ECMO and the
patient is only on partial bypass, they are still
dependent on their native cardiac output. If too
much fluid is removed from the vascular space
the patient may become hypovolemic, causing
the ECMO flow as well as the patient's native
cardiac output to decrease.www.cardiacanaesthesia.in | DrAmarja

SIRS with the Use of a
Semipermeable Membrane
 SIRS is triggered owing to contact with the
artificial surfaces of the CPB circuit, ischemia-
reperfusion injury, and operative trauma.
 The older cellulose and modified cellulose
hemodialysis and ultrafiltration membrane
materials have been shown to increase
inflammatory mediators and initiate complement
activation. The newer synthetic membrane
materials such as polysulphone invoke minimal
complement activation.www.cardiacanaesthesia.in | DrAmarja

Thank you

Ultrafiltration during cardiopulmonary_bypass

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