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2 fundamental processes underlie continuous renal replacement
therapy – diffusion and convection
Diffusion / dialysis–
movement of solutes from compartment in which they are in high
concentration to 1 in which they are in lower concentration – along an
electrolyte solution runs countercurrent to blood flowing on other side
of semipermeable (small pore) filter.
Small molecules such as urea move along concentration gradient into
Larger molecules are poorly removed by this process.
Solute removal is directly proportional to the dialysate flow rate.
Convection / ultrafiltration –
solute is carried (in solution) fluid across a semipermeable membrane
in response to a transmembrane pressure gradient (known as solvent
This mimics what actually happens in normal human kidney.
rate of ultrafiltration depends upon porosity of membrane &
hydrostatic pressure of blood, which depends upon blood flow.
very effective in removal of fluid, middle-sized molecules, thought to
cause uremia. Moreover, most of the cytokines involved in sepsis are
Conventional hemodialysis blood flow 350-
450 ml/min, dialysate flow 500-800 ml/min. In
continuous hemodialysis (CVVHD) blood flow
is usually set at 100-200 ml/min, dialysate
flows at 1000-2000 ml/hr.
Internal Jugular Vein
Primary site of choice due to lower associated risk of complication and
simplicity of catheter insertion.
Patient immobilized, the femoral vein is optimal and constitutes the
easiest site for insertion.
The least preferred site given its higher risk of pneumo/hemothorax and
its association with central venous stenosis.
The length of the catheter chosen will depend upon the site used
Size of the catheter is important in the pediatric population.
The following are suggested guidelines for the different sites:
RIJ= 15 cm French
LIJ= 20 cm French
Femoral= 25 cm French
most efficient & large amounts of fluid can be removed,
electrolyte abnormalities can be rapidly corrected.
However, not suitable in unstable patients: 20-30% of patients
with ARF who are being hemodialysed become hypotensive, with
huge associated osmotic shifts – disequilibrium syndrome.
Many ICU patients are intolerant of such shifts.
Moreover it appears that the hemodynamic changes that occur
during hemodialysis (hypotension) may worsen the pre-existing
renal injury by increasing the ischemic insult.
rapid shifts in plasma volume and solute composition,
necessity for anticoagulation and dialysis membrane
set up is double lumen catheter, pump which forces blood into
filter (semi permeable membrane), dialysate (usually deionized
water) which flows in and out, return line to patient.
blood flow rate 200-400ml/minute, dialysate flow approx
500ml/minute, filtration rate btwn 300 & 2000ml/hour, urea
clearance of 150-250 ml/min.
With this high flow & clearance rate pts, depending on extent of
catabolism, only require 3-4 hrs of dialysis, 2-3 times/wk.
There are huge swings in fluid between intravascular &
extravascular compartments, causing transient hypotension &
Vascular access for short-term hemodialysis or hemofiltration is
usually achieved using double-lumen catheter inserted into IJV.
Anticoagulation with heparin is std method for preventing
thrombosis of extracorporeal circuit during acute intermittent
Dialysis Disequilibrium Syndrome
self-limited condition characterized by nausea, vomiting,
headache, altered consciousness, and rarely seizures or coma.
It typically occurs after first dialysis in very uremic patients.
triggered by rapid movement of water into brain cells following
development of transient plasma hypo-osmolality as solutes
rapidly cleared from bloodstream during dialysis.
incidence has fallen in recent yrs with more gradual institution of
dialysis, precise prescription of dialysis to include such variables
as membrane size, blood flow rate, and sodium profile.
simple, cost effective.
major disadvantages of PD are –
poor solute clearance,
poor uremic control,
risk of peritoneal infection
mechanical obstruction of pulmonary & cardiovascular
How PD Works
In PD, catheter used to fill abdomen with dialysis solution.
peritoneum allows waste products & extra fluid to pass from
blood into dialysis solution.
usually contains dextrose that will pull wastes & extra fluid into
used solution, containing wastes and extra fluid thrown away.
process of draining and filling is called an exchange, takes about
30- 40 minutes.
period the dialysis solution is in abdomen - dwell time.
typical schedule calls for 4 exchanges/day, each with dwell time
of 4- 6 hrs.
Different types of PD have different schedules of daily exchanges.
peritoneal dialysis (CAPD),
doesn’t require machine.
can walk around with dialysis
solution in abdomen.
Another form of PD,
peritoneal dialysis (CCPD),
requires machine called a cycler
to fill & drain your abdomen,
usually while you sleep. Also
called automated peritoneal
standard catheter for PD
made of soft tubing for
It has cuffs made of Dacron
that merges with scar tissue
to keep it in place.
end of tubing that is inside
abdomen has many holes to
allow free flow of solution.
tubing that connects bag of dialysis solution to catheter.
When catheter is first placed, exposed end of tube will be securely
capped to prevent infection.
Under the cap is a universal connector.
requires sterile technique.
Pt & nurse wear surgical masks. nurse soaks transfer set & end of
catheter in antiseptic solution for 5 minutes before making connection,
wearing rubber gloves.
tubing that connects to transfer set includes piece that can be clamped
at end of an exchange.
Dialysis solution comes in 1.5-, 2-, 2.5-, or 3-liter bags.
dialysis dose can be increased by using a larger bag, but within limit of
amount abdomen can hold.
Solution storage. At beginning of session, pt connect bags of dialysis
solution to tubing that feeds cycler.
Pump. sends solution from storage bags to heater bag before it enters
body, then to disposal container/drain line after use.
Heater bag. measured dose is warmed to body temperature. Once
solution is right temperature & previous exchange has been drained,
clamp is released to allow warmed solution to flow into abdomen.
Fluid meter. cycler’s timer releases clamp to let the used dialysis
solution drain from abdomen into disposal container/drain line.
Disposal container or drain line.
Alarms. Sensors will trigger an alarm and shut off the machine if
there’s a problem with inflow or outflow.
Continuous hemodiafiltration techniques
developed to overcome deficiencies of IHD.
In critical illness phenomenon of capillary leak increases
interstitial volume and makes patients edematous.
This makes the clearance of solute difficult to calculate and
indeed to carry out.
Continuous techniques lead to more effective urea clearance,
controlled fluid removal.
Is an extracorporeal blood purification therapy intended to
substitute for impaired renal function over an extended period of
time and applied for or aimed at being applied for 24 hours a
ICU pts particularly suited to these techniques as they are, bed
bound, intolerant of fluid swings associated with IHD.
Mimic the functions and physiology of the native
Qualitative and quantitative blood purification
Restore and maintain of homeostasis
Avoid complications and good clinical tolerance
Provide conditions favoring recovery of renal
set up as follows:
A double lumen catheter.
A line leading to the filter where blood flow is
controlled by a series of roller pumps: blood flow
is usually set at 120ml/min.
Anticoagulant – to prevent blood clotting on the
Dialysis fluid, which runs in countercurrent to
the blood, the standard rate is 1litre per hour.
This can be increased to improve clearance.
A bag to collect the ultrafiltrate.
Replacement fluid, to replace the excess
ultrafiltrate over and above the required fluid
surface through which dialysis or ultrafiltration occurs: core
component of hemofilter.
Different membranes used in RRT: may be cellulose
cellulose membranes are "low-flux" - very thin, low permeability
co-efficient, strongly hydrophilic: known to activate
inflammatory cascades, particularly complement, thus unsuitable
(bioincompatible) in critical illness.
Synthetic membranes should be used in this setting for both
intermittent & continuous hemodialysis.
These membranes tend to be slightly thicker than cellulose, have
very high sieving coefficients at wide range of molecular wts:
effective at convective clearance.
Thus regardless of the technique involved, RRT with synthetic
filters will always include significant ultrafiltration.
Principles of CRRT clearance
CRRT clearance of solute is dependent on the following:
The molecule size of the solute
The pore size of the semi-permeable membrane
higher the ultrafiltration rate (UFR), greater solute clearance.
Small molecules pass through membrane driven by diffusion & convection.
Middle & large size molecules are cleared primarily by convection.
Semi-permeable membrane remove solutes with mol wt of upto 50 KDaltons.
Plasma proteins or substances highly protein—bound will not be cleared.
Sieving Coefficient - ability of substance to pass through membrane from
blood compartment of the hemofilter to the fluid compartment.
sieving coefficient of 1 will allow free passage of a substance; but at a coefficient
of 0, the substance is unable to pass.
0 albumin will not pass
continuous venovenous hemofiltration - form of convective dialysis.
ultrafiltration rate is high, replacement electrolyte solution required to
maintain haemodynamic stability.
effective for clearing mid sized molecules, eg. inflammatory cytokines.
hypothesized that removal of such mediators play role in improving
outcome in sepsis. simple version of this is SCUF - slow continuous
ultrafiltration, used for volume control in overloaded patients.
SCUF does not require replacement fluid,
fluid removal is 300ml to 500ml per hour.
continuous venous venous hemodialysis– continuous diffusive dialysis
dialysate driven in direction countercurrent to blood.
provides reasonably effective solute clearance, although mostly small
molecules are removed.
continuous venous venous hemodiafiltration
most popular method of dialysis in ICU, combines convective and
Both small and middle molecules are cleared
dialysate & replacement fluids are required.
CVVHDF similar to IHD in slow motion:
blood flow 100 – 200ml/min
dialysate flow 1000ml/hour
filtration rate 10-20ml/hour (very efficient)
urea clearance is 10-20ml/hour.
continuous hemofiltration is as efficient as IHD at fluid removal
by ultrafiltration, but not as efficient at dialysis (diffusion), due
to slow fluid flows.
to increase urea/creatinine clearance - should increase dialysate
flow /blood flow/ both.
Most of these modes can remove up to 1 l/hr of fluid.
rare that this volume of fluid removal is required in ICU
(critically ill patients rarely tolerate any significant fluid
HD clears fluid out of intravascular space at rapid rate, usually
faster than it can be replaced from extravascular space.
In healthy pts this often causes hypotension.
In ICU pts, who often have intravascular hypovolemia (decreased
oncotic pressure due to capillary leak), this hypotension may be
may precipitate ischemic injury to various organs, particularly
recovering kidneys, which have temporarily lost pressure-flow
autoregulation (new ischemic injuries have been demonstrated
after HD sessions).
many pts, particularly those with head injuries, cannot tolerate
osmotic changes associated with HD.
Pts who are otherwise healthy (except for CRF) have tremendous
venous capacitance, & can tolerate fluid accumulation between
Critically ill patients with leaky capillaries may develop
significant PE btwn sessions - daily IHD is often required.
Feeding & nutrient delivery significant problem in critical illness.
pts are severely catabolic; more metabolic byproducts to be
To prevent further loss of protein, feeding is essential, fluid
restriction is not an option.
If IHD strategy is used, in early critical illness, daily therapy is
Clinical Conditions to Consider
ARF and need for fluid management related to:
Unstable on IHD
CHF /volume overload
Post CV surgery
Post trauma patients
Advantages of CRRT
Suitable for use in hemodynamically unstable patients.
Precise volume control, immediately adaptable to
Very effective control of uremia, hypophosphatemia and
Rapid control of metabolic acidosis
Improved nutritional support (full protein diet).
Available 24 hours a day with minimal training.
Safer for patients with brain injuries and cardiovascular
disorders (particularly diuretic resistant CCF).
May have an effect as an adjuvant therapy in sepsis.
Probable advantage in terms of renal recovery.
Disadvantages of CRRT
Blood loss - Hemorrhage due to
therapy - Clotting of hemofilter
Severe depletion of electrolytes –
particularly K+ and PO4, where
care is not taken.
Acid/base imbalance - Renal
Vascular access - Vascular spasm,
Movement of catheter against
vessel wall, Improper length of
hemodialysis catheter inserted,
Hypotension - Intravascular
volume depletion, Underlying
High ultrafiltration rates (high
Inadvertent disconnection in the
Blood filter leaks
Hypothermia in CRRT
Patient’s blood in extracorporeal circuit at room temperature
Administration of large volumes of room temperature fluids
(replacement and dialysate)
Signs and Symptoms
Skin pallor, coolness and cyanosis
Anticoagulation & its problems
necessary to prevent clotting
may be a problem in pts who
at risk for bleeding/had recent
surgery. Classically heparin
has been used.
1. risk of bleeding due to
2. Heparin requires presence
of antithrombin III, often
deficient in ICU population.
3. may cause
Agents used instead of heparin
1. PGE1 and PGI2, which have
anti platelet effects.
2. Citrate, which binds calcium
and inhibits the coagulation
cascade – and is metabolized
to bicarbonate in the liver.
3. Low molecular weight
dialysate & replacement solutions should mirror what one wishes
blood chemistry to be – closest solution is RL (Hartmann’s
reason for this - as time passes, blood & dialysate levels of
electrolytes will equilibrate, whereas in IHD, one rigorously
cleans blood & ECF for few hrs & awaits reaccumulation.
In CRRT any depletion of electrolytes during process will
continue until dialysate prescription is changed.
potassium and phosphate loss: standard dialysate solutions
contain neither – levels can drop very low.
KPO4 supplementation often necessary.
Note also that there is no NaHCO3 in dialysate, leading to loss of
bicarbonate: compensated for by passage of lactate (anionic, a
base) into bloodstream.
Calcium may also be required, although Ca & HCO3 cannot be
given together, because they precipitate.
This is usually metabolized into bicarbonate in the liver.
In liver failure, wiser to use a lactate free dialysate – such as
normal saline, adding bicarbonate
Therapeutic Plasma Exchange
process to remove plasma while replacing it with another
blood will be drawn directly from blood vessel in arm/through a
small tube (catheter) placed in a vein.
blood will be separated into plasma & blood cells (RBCs WBCs &
platelets) by centrifuge.
plasma will be removed while blood cells & plasma
replacement returned to in opposite arm or catheter
During the procedure, an anticoagulant solution is slowly added
blood to prevent unwanted clotting
plasma replacement – albumin/FFP.
High volume haemofiltration
High-volume haemofiltration (HVHF) is an extra-corporeal
blood purification therapy aiming at non-selectively reducing
circulating levels & activity of both pro- & anti-inflammatory
Haemofiltration membranes exhibit some adsorption properties
allowing capturing of HMW molecules in membrane itself.
Therefore, during septic shock, more the adsorption properties,
the more cytokines & inflammatory mediators removed from
Thus, associating convection with adsorption for blood
HVHF - extracorporeal blood purification therapy aimed at non-
selectively reducing circulating levels & activity of pro-& anti-
inflammatory mediators in sepsis & MODS.
Numerous in vitro studies shown that HF capable of removing nearly
every known substance involved in sepsis to a certain degree.
Recent human studies demonstrated that HVHF improves
haemodyamics with decreased vasopressor requirements & improved
survival of septic patients.
technical requirements of HVHF – i.e. high blood flows, tight
ultrafiltration control & large amounts of costly sterile fluids – are
therefore ‘pulse HVHF’ technique developed - applied for short periods
of upto 6-8 hrs/day, providing intense plasma water exchange.
Biological and Clinical Rationale for HVHF
clinical picture of sepsis - overwhelming, systemic overflow of
pro- and antiinflammatory mediators, leading to generalised
endothelial damage, multiple organ failure and altered cellular
includes mediators with autocrine & paracrine actions, cellular &
TNF-α, IL-1, IL-6, platelet activating factor (PAF) & NO - role in
pro- & anti-inflammatory factors become upregulated - interact
with each other, leading to various rises in mediator levels that
change over time.
Continuous renal replacement therapies (CRRTs) allow
extracorporeal treatment in critically ill patients with
hypercatabolism & fluid overload.
3 types of depurative mechanisms: convection, diffusion &
adsorption by filtering membrane.
In addition to removing excess fluid & waste products in septic
patients, convective modalities have advantage of removing
HMW substances, including many inflammatory mediators.
Adsorption to filter membrane is saturable process with
timeframe of few hrs.
augmented by increasing membrane surface area & ultrafiltration
‘Pulse HVHF’ – A New Approach
Ultrafiltration rates >50–60ml/kg/h (60 l/day including net
ultrafiltration) in continuous HF mode considered high &
defined as HVHF.
To reach UF rates 85ml/kg/hr, vascular access that can ahieve
constant flow of atleast 300ml/min required (e.g. 14F catheters).
Filtration fraction of 25% can be set.
If catheter/cannulated vessel too small, resistance of arterial
lumen of catheter creates -ve pressure before pump which may
reach as high as -300mmHg, resulting –ve impact on dialyzer
Return/venous pressure may be greater because of
haemoconcentration that accompanies high rates of ‘netUF’. (net
UF -volume of fluid removed from pt less volume of substitution
despite high exchange volume during ‘pulse therapy’, net UF
maintained as low as possible, or even at zero balance.
with high filtration fraction of pulse HVHF, increased blood
viscosity & hct within filter mandates adequate anticoagulation
to avoid clot formation &filter clotting.
PHVHF requires large haemofilter with surface area of 1.8–2m2
(in 70kg pt) to achieve such a high UF rate.
biocompatible, synthetic membrane with permeability coefficient
ranging 30–40ml/h/mmHg recommended, with sieving
coefficients close to 1 for wide spectrum of molecular weights.
Bicarbonate buffered HF fluid (35mmol/L) should be
administered both pre-dilution (33–50%) & postdilution (50–
66%); temperature of replacement fluid set around 38.5–39.5°C.
Other important aspects of general patient care - temperature
monitoring, antibiotic dose adjustments & nutritional
adjustments (derived from amino acid, phosphate, vitamin
haemodynamic &oxygenation improvements reasonable
objectives for adjuvant therapy of hypotensive septic/MODS pt
resistant to volume resuscitation &pressors.
CRRT ensures adequate creatinine clearance in hemodynamically stable
environment. CRRT superior to IHD for volume control.
Hemodynamic stability added advantage of preventing secondary ischemic
injury to kidneys due to hypotensive episodes during hemodialysis.
biggest single problem with continuous hemodiafiltration - anticoagulation in
pts who are, invariably, coagulopathic or bleeding.
Care must be taken to ensure electrolyte balance, ideally dialysate should
mirror that of ideal blood electrolyte composition.
Due to tendency for bicarbonate to caused precipitation, usually replaced by
lactate in dialysis solutions.
If pt in liver failure, lactate not metabolized – cause academia.
Hemofiltration - role in management of septic patients, as a plasma cytokine
filter, modulating the inflammatory response, but there is no evidence that this
alters outcomes in humans.