2. Continuous Renal Replacement Therapy
Also known as “slow Continuous Renal Replacement Therapy”.
“Any 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/day.”
R. Bellomo, C Ronco and R. Mehta,
Nomenclature for Continuous Renal
Replacement Therapies, AJKD, Vol 28,
November 1996
2
3. Why Choose CRRT?
CRRT closely mimics the native kidney.
• Slow, gentle and continuous reduce risk for hypotension
• Well tolerated by hemodynamically unstable patients
• Prevent further damage to kidney tissue
• Promote healing and renal recovery
• Regulates electrolytes, acid-base balance
• Removes large amounts of fluid and waste
products over time
3
4. CRRT is
Group of
words
• Continuous
• Renal
• Replacement
• Therapy
Groups of
Through group of
Mechanisms
• Ultrafiltration
• Diffusion
• Convection
• Adsorption
Describes group of
treatment modalities
• SCUF
• CVVHD
• CVVH
• CVVHDF
4
6. 6
Ultrafiltration
The movement of fluid through a semi-permeable
membrane driven by a pressure gradient.
The creation of a pressure gradient forces plasma water across the semi-
permeable membrane.
Effluent pump creates
negative pressure (pull)
Blood pump creates
positive pressure (push)
TMPTMP
Fluid volume
reduced
7. 7
Diffusion
Factors affecting diffusion :
Concentration gradient
Blood flow rate (QB)
Dialysis fluid flow rate (QD)
Molecular size
Filter characteristics
• Membrane type- thickness, surface area
Blood Pump
Movement of solutes from an area of higher to
lower solute concentration.
8. 8
Dialysate Flow and Diffusive Clearance
Counter current flow for effective diffusion
Assures efficient solute transport of
metabolic waste from blood to dialysate
Blood
Dialysate
Dialysate Flows counter current to blood flow.
9. 9
Convection
Effluent pump pulls
fluid and drags the
solutes from blood.
Fluid removed is
replaced into blood.
Solute drag depends on molecular weight and membrane characteristics
11. 11
Size of molecules cleared by CRRT
Molecular weights
Small Molecules
Diffusion is better than
convection
Middle Molecules
Convection better than
diffusion
Nothing above 50.000 is cleared
Mode of removal
Large Molecules
Convection or adsorbtion
14. Continuous VV Hemofiltration
Mechanism : Convection,
ultrafiltration
Goals: Safe fluid removal,
removal of small -middle
molecules
Solution: Replacement
AccessAccess
ReturnReturn
EffluentEffluent
ReplacementReplacement
pre or post filterpre or post filter
PRISMA
M100
Blood Pump
Effluent
Pump
Replacement
Pump
14
15. 15
Pre vs Post Filter Dilution
Pre - dilution
Dilutes blood before filter
(Hct )
Reduces filter clotting
Prolonged filter life
Reduces effective
clearance (appr. 15%)
More replacement solution
required
Increase QB to overcome
reduction in clearance
Post - dilution
No reduction of clearance
due to dilution of blood
Less replacement solution
required
Increased need of
anticoagulant
Limits on UF rates due to
hemoconcentration of
blood
18. 18
TMP Trans Membrane Pressure
Software calculated
A safety parameter, measuring function of filter
Maximum TMP ~ + 450 mmHg
Increased TMP protein coating or clotting of fibers
TMP = - Effluent P
Filter P + Return P
-------------------------
2
Pos Neg
Or
Pos
Pressure difference between blood & fluid compartment
19. 20
Replacement Solution
Fluid infused into the blood compartment pre or post filter
Contains electrolytes at physiological levels
Replaces the amount of fluid removed by the effluent or U.F pump
• does not affect the patient’s fluid status
Drives convective transport
Facilitates the removal of both small and middle size solutes
20. PBP Solution
Fluid infused into the blood compartment at the Access
PBP pump can be used for
• Anticoagulation (citrate)
• Pre-dilution replacement
• Other solution
Total U.F = PBP + Replacement + pt. fluid removal rates
PBP linked to blood pump
Pre Blood Pump (PBP): Max 8L/hr
21
22. 23
Clinical Indications for CRRT
Renal IndicationsRenal Indications
• ARF with oliguria or anuria
• Azotemia (a medical condition characterized
by abnormal levels of urea, creatinine,
various body waste compounds, and other
nitrogen-rich compounds in the blood as a
result of insufficient filtering of the blood by
the kidneys)
• Fluid overload
• Tumor lysis syndrome
• Sepsis
• Cerebral edema
Non-renal IndicationsNon-renal Indications
• Drug overdose
• Metabolic disorders
• Crush injuries
• Sepsis
• ARDS
• Fluid overload
Bellomo, Ronco. Continous hemofiltration in the intensive care unit. Crit Care, 2000; 4(6)
23. 24
Role of CRRT in ARF
•Removal of toxins (urea, creatinine)
•Regulate electrolyte and water balance
•Regulate acid-base balance
•Prevent further damage to the kidney tissues
•Promote healing and renal recovery
24. Role of CRRT in CHF
Maintain 24/7 fluid balance (All CRRT therapies)
• Reduce ascites and peripheral edema
• Relieve Pulmonary edema
Normalize cardiac filling pressures
Maintain 24/7 Electrolyte and acid/base balance (CVVHD,
CVVHDF)
• - Dialytic control of electrolytes
• - Delivery of bicarbonate or lactate buffer
Possibly prevent further renal damage or prolong renal
Insufficiency
Possibly reduce length of stay
Refractory Congestive Heart Failure: Overview and Application of Extracorporeal
Ultrafiltration, Paul Blake and Emil P. Paganini, Advances in RRT, Vol 3, No2 (April), 1996:
pp 166-173
25
25. 26
Role of CRRT in ARDS
•Maintain acid base balance
•Fluid control
•Regulate electrolyte balance
•Removal of toxins
26. 27
Role of CRRT in Sepsis
•Removal of middle to large molecule septic mediators by
convection and adsorption including TNF-α, IL-1, IL-6 and IL-8
through:
•Removal of excess fluid and waste products
•Maintenance of acid-base balance
•Improve cardiovascular hemodynamic → removal of
cardiodepressants (caused by inflammatory mediators)
•Thermoregulation
Bruce A. Molitoris. Critical Care Nephrology 2005. 28-34
27. 28
Role of CRRT for
Rhabdomyolysis
•Maintain fluid, electrolyte, acid/base balance.
•Prevent further damage to kidney tissue
•Removal of small to middle protein molecules - 17,000 Dalton
through convection
• May cause nuisance BLD alarms
28. Characteristics
Ascites
Coagulopathy
Elevated bilirubin
Hypomagnesemia
MOF
Inc. ICP/Cerebral edema
Role of CRRT
Regulate and maintain fluid,
electrolyte and acid-base
balance *
• Dec. ICP*
• All CRRT
Remove toxins
• excess bilirubin*
• Inflammatory mediator
*A new direction for dialysis. Sonia M. Astle, RN, MS, CCRN. RN Magazine, July 2001, pgs. 56-60
Hepatic FailureHepatic Failure
29
30. 31
Role of CRRT in Intoxications
Removal of small molecules by Dialysis
• Dialysate up to 4l/h
• Optional replacement up to 500ml/h
Duration: depends on clearance of toxic medication
32. 33
Initiation of CRRT
When do you start CRRT?When do you start CRRT?
There is no clear consensus on when to start treatment.
However, there are a few studies that favor earlier start to
improve survival of patients.
“Earlier initiation of CRRT, based on pre-CRRT
BUN, may improve the rate of survival of trauma
patients who develop ARF.”
Dr. L.G. Gettings, Baltimore USA, 1989 to 1997
33. 34
RIFLE Criteria
Established in 2002 ADQI conference, Vicenza, Italy
Presented in San Diego CRRT Conference in 2003
Purpose: To categorize patients based on renal function
Classification
• Risk
• Injury
• Failure
Outcome:
• Loss
• End-stage renal disease
Bell, et. al., Optimal follow-up after CRRT in ARF patients stratified with RIFLE criteria.
Nephrol Dialysis and Transplantation, 2005
34. 35
RIFLE Criteria
Risk
Injury
Failure
Loss
GFR Criteria Urine Output Criteria
Increased creatinine x 1.5
or GFR decrease >25% UO < 0.5ml/kg/hr x 66 hours
Increased creatinine x 2
or GFR decrease >50%
UO <0.5 ml/kg/hr x 1212 hours
Increased creatinine x 3 or
GFR decrease >75% or
Serum Creatinine > 4mg/dl
in setting of acute rise of >
0.5 mg/dl
UO <0.3 ml/kg/hr x 24 hours
or anuria x 12 hours
Persistent ARF = complete loss of
renal function >4 weeks
End-stage renal disease (>3
months)ESRD
EarlyEarly
InitiationInitiation
35. 36
1) Solute clearance – urea, creatinine
• Kt/V = K (dialyzer clearance) * t (treatment time)/ V (patient’s volume)
• PRU (% reduction in urea)
• In IHD, calculated as PRU = Pre – post/ pre
• In CRRT, PRU = Access - return (urea/creatinine)
• In CRRT, PRU= Effluent value in CVVHD, or post CVVH/DF
2) Effluent flow rate rather than solute clearance
• Based on survival study by Ronco, Bellomo
CRRT Dose
Clearance (K) - volume of blood completely cleared
of a substance/unit of time (ml/min).
36. 37
CRRT Dose
“What is an adequate dose for ARF?”
Ronco, Bellomo, et. al.. Effects of different doses in CVVH on outcome of ARF. Lancet, 2000
37. 38
CVVH Dose - Outcome
Group Dose
(ml/kg/hr)
Survival
1 20 41%
2 35 57%
3 45 58%
Ronco, Bellomo, et. al.. Effects of different doses in CVVH on outcome of ARF. Lancet, 2000
38. 39
CVVH Dose - Outcome
Treatment dose has an impact on mortality/ morbidity of ARF
patients
• Start CVVH at 35 ml/h/kg (eg. 70 kg patient = 2450 ml/h)
Continuous is more efficient and clinically tolerated than
intermittent approaches
Early start has positive impact on outcome
Ronco, Bellomo, et. al.. Effects of different doses in CVVH on outcome of ARF. Lancet, 2000
39. 40
Therapy Table (Example)
Acute Renal Failure Sepsis Rhabdomyolyse
Dose (ml/kg/BW/hr) 35 50 35
Blood flow (ml/min) 150-350 250-450 > 150
Patient 60 kg
Dialysate
Replacement Post
Replacement Pre = PBP
60 x 35 = 2100 ml
900 ml
400 ml
800 ml
60 x 50 = 3000 ml
1200 ml
600 ml
1200 ml
60 x 35 = 2100 ml
500 ml
550 ml
1050 ml
Patient 70 kg
Dialysate
Replacement Post
Replacement Pre = PBP
70 x 35 = 2450 ml
1000 ml
450 ml
1000 ml
70 x 50 = 3500 ml
1300 ml
700 ml
1400 ml
70 x 35 = 2450 ml
500 ml
650 ml
1300 ml
Patient 80 kg
Dialysate
Replacement Post
Replacement Pre = PBP
80 x 35 = 2800 ml
1000 ml
600 ml
1200 ml
80 x 50 = 4000 ml
1400 ml
900 ml
1800 ml
80 x 35 = 2800
500 ml
750 ml
1550 ml
Patient 90 kg
Dialysate
Replacement Post
Replacement Pre = PBP
90 x 35 = 3150 ml
1050 ml
700 ml
1400 ml
90 x 50 = 4500 ml
1500 ml
1000 ml
2000 ml
90 x 35 = 3150
500 ml
900 ml
1750 ml
40. 41
Calculation: 60kg x 35 ml/kg/h = 2100 ml/h
Flow rates
900 ml Dialysate
1200 ml Replacement
2100 ml Total
400 ml Post-Replacement
800 ml Pre-Dilution (PBP)
Exercise on Dosing
Mr. Smith, 60 kg, ARF
Required dose: 35ml/kg BW/hr
Mode: CVVHDF
• Pre: 66%
• Post:33%
• Dialysate: 900ml/hr
41. 42
Calculation: 100kg x 35 ml/kg/h = 3500 ml/h
Flow rates:
3500 ml Total Replacement 1500 ml Post-Replacement
1500 ml Pre-Replacemnt
500ml PBP
Exercise on Dosing
Mrs. Jones, 100 kg, Polytrauma with Rhabdomyolysis
Required dose: 35ml/kg BW/hr
Mode: CVVH
• Pre-Replacement : 50%
• Post-Replacement :50%
• PBP: 500ml/hr
42. 43
Calculation: 120 kg x 45 ml/kg/h = 5400 ml/h
Flowrates:
1200 ml Dialysatee
4200 ml Replacement
5400 ml Total
1400 ml Post-Dilution (Replacement)
2800 ml Pre-Dilution (PBP)
Exercise on Dosing
Mr.Tan, 120 kg, ARF, pulmonary edema, and sepsis
Required dose: 45 ml/kg BW/hr
Mode: CVVHDF
• Pre- Replacement: 66%
• Post- Replacement:33%
• Dialysate: 1200ml
46. 47
The Basic Hemofilter
Hollow Fiber
membranePotting
Blood In
Effluent Out
Dialysate In
Blood Out
Outside
(Dialysate)
Inside
(blood)
Cross Section
47. 48
Solutions in CRRT
Composition approximate to normal plasma water
All CRRT techniques (except SCUF)
require the use of sterile Dialysate
and/or Replacement solution.
Goal: Correct electrolyte imbalance
and achieve specific metabolic levels.
Commercially available or prepared
by Hospital Pharmacy
48. 49
Solution Buffers
Lactate
Stable
Less costly
Requires metabolic activity to
convert to bicarbonate
Bicarbonate
More costly
Less stable
More physiological and better
tolerated
Improved control and correction of
acidosis
Gambro Bicarbonate Solutions
• two-compartment bag
•Fast, safe, and easy easy mixture
of bicarbonate
•Prescription flexibility
49. 50
Warmers
Substantial heat loss in CRRT due to large fluid volume exchange
Warmers prevents heat loss, maintain energy balance, and improve
patient comfort
Prismatherm II
Blood warmer only
Editor's Notes
Why choose CRRT as oppose to the intermittent form of renal replacement therapies?
CRRT provides a slow, gentle treatment for ARF and fluid overload very much like the native kidney. The control of azotemia, acid-base balance and fluid volume can be easily achieved and continuously maintained therefore, generally well tolerated by critically ill, hemodynamically unstable patients.
This slow and gentle nature prevent the peaks and troughs of intermittent treatment therefore preventing further damage to diseased kidney tissues and promotes healing and renal recovery.
CRRT like IHD regulates fluid, electrolyte, acid/base balance but maintains the levels more consistently than IHD.
It is possible to remove large volume of fluid and waste products over time allowing other supportive measures , like nutritional support, without the risk of fluid overload.
The principles involved in the movement of solutes and solvents in different body compartments were discussed in Section 2, Basic Physiology. How do these principles apply in the removal of excess fluid and uremic solutes in CRRT? We will now discuss the following principles involved in this process.
Ultrafiltration is defined as the movement of fluid through a semi-permeable membrane driven by a pressure gradient, the difference between the positive and negative pressures in the circuit. Also known as transmembrane pressure or TMP. The main goal of ultrafiltration is fluid removal. In CRRT, the effluent pump creates the negative pressure pulling the plasma water across the semi-permeable membrane in the filter.
The blood pump exerts a positive pressure on the membrane as it pushes the blood into the hollow fibers of the hemofilter. It is the combination of the positive and negative pressure that make up the transmembrane pressure (TMP will be discussed later). This forces the water to leave the blood, penetrate the membrane and enter the effluent bag (or waste bag).
The rate of patient fluid removal, or ultrafiltration rate, is managed by the operator by setting the parameter accordingly on the CRRT system.
The driving force for the diffusion of small solutes across a semi-permeable membrane in the filter is the difference in concentration between blood and dialysis fluid. Solutes always move from an area of higher concentration to an area of lower concentration. By regulating the composition of the dialysis fluid we can determine the direction of the diffusive transport, i.e. whether to remove or to add a certain solute to the blood.
Dialysate is free from uremic solutes found in the blood of a patient with ARF therefore these unwanted solutes will move across the semi-permeable membrane into the dialysate compartment of the filter.
Diffusion will occur until solute equilibrium is achieved.
Other factors affecting the rate of the diffusive transport include: blood and dialysate flow rate, size of the molecule and characteristics of the filter.
Blood and dialysate flows in a counter current direction through the filter. In this way the blood always meets a dialysate with lower concentration of solutes than in the blood. This maintains the concentration gradient – required for diffusive transport – throughout the whole filter.
The removal of metabolic waste solutes from the blood is achieved since the dialysate does not contain any such solutes (e.g. dialysate does not contain urea or creatinine). To maintain normal serum electrolyte levels however, dialysate fluid must contain sodium, chloride and magnesium levels that are equal to serum concentrations (removal of these electrolytes should only occur if the blood level exceeds normal serum concentrations).
The patients electrolyte levels must be monitored closely during CRRT and the level in the dialysate adjusted to maintain normal serum concentrations.
Convection is the movement of solutes with fluid, often referred to as “solute drag”. The more fluid volume or the faster the flow, the more solutes are dragged. Plasma water and certain solutes (depending on molecular weight and filter pore size) are forced across the semi-permeable membrane in the filter by movement of large amount of fluid. Convection is the main transport mechanism for middle and large molecules.
In CRRT, the fluid removed by ultrafiltration is replaced simultaneously by the replacement pump. The replacement solution is infused into the blood either before or after the hemofilter.
Adsorption is defined as the molecular adherence to the surface or interior of a semi-permeable membrane. With the type of synthetic membrane that are used in hemofilters, some larger molecules which some are believed to be involved in unwanted inflammatory reactions adhere to the membrane surface [beta 2-microglobulin (MW 11.8 kD), TNF (MW 52 kD)]. Removal or clearance of these inflammatory mediators is achieved through adsorption.
Compared with the transport mechanisms discussed in previous slides adsorption has a lesser affect, but but is still seen in all types of CRRT where hemofilters are used mainly in AN69.
To understand solute removal in CRRT the concept of different molecular size has to be understood.
For removal of small solutes from blood, e.g. urea and creatinine, diffusion is by far the most efficient transport principle. With increasing size, however, molecules move more slowly and the diffusive transport is therefore reduced. For solutes with a molecular weight of several thousand, convective transport is more important than diffusion.
CRRT describes a group of therapies namely:
SCUF - Slow Continuous Ultrafiltration
CVVH - Continuous Veno-Venous Hemofiltration
CVVHD - Continuous Veno-Venous Hemodialysis
CVVHDF - Continuous Veno-Venous Hemodiafiltration
The choice of therapy mode will depend on the specific goal/s for the treatment.
Here is the schematic for SCUF. Notice the blood pump, effluent pump and the PBP are accessible.
This schematic represents a CVVH circuit. It is similar to SCUF with the addition of a replacement pump for infusion of replacement fluid, either before or after the filter. The amount of fluid in the effluent bag is equal to the fluid removed from the patient plus the equal volume of replacement fluid infused.
Principles used in this therapy are ultrafiltration for fluid removal (using the effluent pump) and convection for removal of small, middle and large molecules.
The primary indications for CVVH are uremia, severe acid-base and / or electrolyte imbalance, with or without fluid overload.
Systemic Inflammatory Response Syndrome (SIRS), rhabdomyolysis, etc. .
Remember, the target therapy “dose” for CVVH as suggested by Ronco’s studies is 35 ml/kg/hr. Therefore, if your patient weighs 70 kg, your replacement flow rate and patient fluid removal rate combined should be 2,450 ml/hr.
*To provide adequate solute removal, ultrafiltration rates of 35 /ml / kg / h has been suggested in the Ronco study.
Replacement fluids can be infused either pre (before) or post (after) the filter.
Pre-dilution dilutes the blood in the filter, reducing clotting. This method of re-infusion is believed to enhance filter life and may be considered in patients with frequent clotting of the filter, it might also diminish the need for anticoagulation for some patients. At present however, pre-dilution should be not be considered as an alternative, but rather as an adjunct to anticoagulation.
Pre-dilution also appears to enhance the achievable ultrafiltration rate (may be especially important in high volume CVVH). However, for the same ultrafiltration rate, pre-dilution results in a reduction in small molecule clearance because of dilution of solutes at blood entry into the filter. At conventional flow rates (of 2 L/h or less), pre-dilution results in a nearly 15% decrease in urea clearance. Therefore additional ultrafiltration volume and replacement fluid are required to achieve similar clearances as in post-dilution. The higher ultrafiltration flow rates will also result result in enhanced convective transport of larger molecules.
Pre-dilution may also be be considered in combination with post-dilution, when extracorporeal clearance is limited by the achievable blood flow. (when filtration fraction is too high by using mainly post-dilution)
Post-dilution concentrates the blood in the filter, enhancing clearance since the concentration gradient between blood and fluid is greater. Some physicians prefer post-filter administration of replacement fluid since any blood samples drawn post-filter have not been diluted by replacement fluid, and these laboratory values can be used to gauge the efficiency of the filter. The resulting hemoconcentration may increase filter clotting and therefore anticoagulation requirements.
This schematic depicts a CVVHD circuit. It is similar to SCUF with the addition of a dialysate pump to infuse dialysate into the fluid side of the filter. The blood and dialysate do not mix. They are always separated by the semipermeable membrane.
In CVVHD the effluent bag contains not only fluid removed from the patient but also the spent dialysate solution. No replacement fluid is used.
The dialysate on the fluid side of the filter provides solute exchange by diffusion. Dialysate is typically infused counter current to the blood flow at a rate of 1 - 3 L / h. or 15-45 ml/min to achieve adequate solute clearance. The faster the flow rate, the greater the clearance. Fluid removal occurs with the effluent pump through ultrafiltration.
You can now see in the schematic that both replacement fluids (pre or post filter) and dialysate solutions are infused. Dialysate functions to remove small molecular weight substances, and replacement fluid allows additional convective clearance of middle and large molecules. Therefore this therapy is indicated most especially for disease conditions requiring both small, middle and large molecular clearance such as in ARF, SIRS, multi-organ failure (MOF), sepsis, rhabdomyolysis, etc.
In CVVHDF, the effluent bag contains fluid removed from the patient, spent dialysate and replacement solutions.
It can be performed with or without net fluid removal from the patient.
With CVVHDF the optimum overall solute clearance can be achieved by maximizing both replacement and dialysate solution flow rates.
TMP or Trans Membrane Pressure is the pressure exerted on the filter membrane, it reflects the pressure difference between the fluid and blood compartment of the filter. This pressure is automatically calculated by the CRRT system according to this formula. The TMP is a safety parameter that indicates the function of the filter. The maximum allowable TMP is around 450mmHg. An increased TMP during a patient treatment signifies decreased permeability of the membrane possibly due to protein coating on the blood side of the membrane. Clotting of the fibers is another factor that will lead to increase in TMP.
CRRT is usually indicated for symptoms associated with renal failure like fluid overload and azotemia.
In some cases, CRRT has been used for non-renal indications such as drug overdose, metabolic disorders, crush injuries, sepsis, and acute respiratory disease syndrome. (Bellomo, Ronco. Continous hemofiltration in the intensive care unit. Crit Care, 2000; 4(6)
CRRT has also been used in conjunction with other mechanical device like cardio-pulmonary bypass (CPB), intra-aortic balloon pump (IABP), and extracorporeal mechanical oxygenator (ECMO).
Azotemia is a medical condition characterized by abnormal levels of urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood as a result of insufficient filtering of the blood by the kidneys.
Uremia can be used as a synonym, or can be used to indicate severe azotemia, in which symptoms are produced.
Azotemia can be classified according to its cause. In prerenal azotemia the blood supply to the kidneys is inadequate. In postrenal azotemia the urinary outflow tract is obstructed. Other forms of azotemia are caused by diseases of the kidneys themselves.
Other causes of azotemia include congestive heart failure, shock, severe burns, prolonged vomiting or diarrhea, some antiviral medications, or trauma to the kidney(s).
CRRT may be applied to CHF patients for fluid, electrolyte, and acid/base balance around the clock. A study performed by Drs. Blake and Paganini in 1996 showed that patients with class II to VI CHF with urine output less than 1000 ml/day were successfully treated by ultrafiltration (SCUF). It relieved pulmonary edema, reduced ascites and peripheral edema, normalized filling pressures, and advanced the response to diuretic therapy. Early results showed that “ongoing therapy may be associated with decreased hospital readmissions, or, at the very least, shorten ICU length of stay”.
The ADQI group suggests initiating CRRT before renal complications begin. A lot of CHF patients are in some form of Renal Insufficiency after awhile, which will eventually lead to End Stage Renal Disease if CHF is unsuccessfully treated. Wouldn’t it be nice to put off ESRD a little longer and improve the patient’s current quality of life?
Patients with acute respiratory distress syndrome (ARDS) are usually treated in the intensive or critical care unit of a hospital. The main concern in treating ARDS is getting enough oxygen into the blood until the lungs heal enough to work on their own again.
If the patient becomes tired from breathing so hard, it may become necessary to connect the patient to a breathing machine (ventilator). This can be done by placing a tube through the mouth or nose into the windpipe (trachea) in a procedure called endotracheal intubation (or just intubation) and connecting the tube to the ventilator. Sometimes the connecting tube is inserted through a surgical opening in the neck (this procedure is called a tracheotomy). The breathing machine can be set to help or completely control breathing. It will deliver the minimum amount of air every minute. If the extra oxygen and help with breathing are not enough, the breathing machine can be set to Positive End Expiratory Pressure (PEEP) to maintain the surface for gas exchange.
PEEP keeps some air in the lungs at the end of each breath. It helps keep the air sacs open instead of collapsing. The setting on the breathing machine can be adjusted to fit the needs of the patient. Other settings on the breathing machine control the number of breaths per minute (rate control) and the amount of air the ventilator uses to inflate the lungs in each breath (tidal volume).
Many different kinds of medicines are used to treat ARDS patients. Some kinds of medicines often used include:
Antibiotics to fight infection
Pain relievers
Drugs to relieve anxiety and keep the patient calm and from &quot;fighting&quot; the breathing machine
Drugs to raise blood pressure or stimulate the heart
Muscle relaxers to prevent movement and reduce the body&apos;s demand for oxygen
With breathing tubes in place, ARDS patients cannot eat or drink as usual. They must be fed through a feeding tube placed through the nose and into the stomach. If this does not work, feeding is done through a vein. Sometimes a special bed or mattress, such as an airbed, is used to help prevent complications such as pneumonia or bedsores. If complications occur, the patient may require treatment for them.
Better understanding of the role of cytokines in sepsis and septic schock has led to the theory that removing them by hemofiltration may improve outcomes. Many studies have evaluated the effect of hemofiltration on cytokine levels and have shown that cytokines, including TNF-α, IL-1, IL-6 and IL-8 appear in the ultrafiltrate. While a few studies have shown a reduction in the amount of cytokines in the plasma with hemofiltration, the preponderance of studies have shown no reduction in plasma cytokine levels. The high production rate and rapid endogenous clearance of many cytokines mean that the amount being removed by hemofiltration is too minor to change circulating levels. It also appears that a large percentage of the clearance of cytokines occurs as a result of adsorption to the dialysis membrane, which soon becomes saturated, limiting further clearance.
Read slide..
BLD alarms because of the colour (orange-red caused by the myoglobin) of the effluent: BLD Normalisation
Hepatic failure is is accompanied by cytokines and inflammatory mediators. It is characterized by ascites (accumulation of fluid in the peritoneal cavity), coagulopathy, elevated bilirubin, and hypomagnesemia, leading to multiorgan failure. Increased intracranial pressure leads to cerebral edema in cases of fulminant liver failure, which is one cause of death in liver patients.
CRRT provides a means to reduce fluid overload, and maintain fluid balance, remove toxins such as excess bilirubin and inflammatory mediators.
As illustrated in an abstract by Astle in, 2001, CRRT was able to stabilize the patient and provided a bridge to transplantation for a patient with Fulminant liver failure who progressed to ARF.
Methanol is intoxicating but not directly poisonous. It is toxic by its breakdown (toxication) by the enzyme alcohol dehydrogenase in the liver by forming formic acid and formaldehyde which cause blindness by destruction of the optic nerve. [3] Methanol ingestion can also be fatal due to its CNS depressant properties in the same manner as ethanol poisoning. It enters the body by ingestion, inhalation, or absorption through the skin.
Lithium metal is used primarily in heat-transfer applications, batteries (mainly cell phone and camera batteries), household appliances such as toasters and microwaves, and in high performance alloys such as those used for aircraft construction. Lithium compounds are used pharmacologically as a class of mood stabilizing drugs, a neurological effect of the lithium ion Li+.
The active principle in these salts is the lithium ion Li+, which interacts with the normal function of sodium ions to produce numerous changes in the neurotransmitter activity of the brain. Therapeutically useful amounts of lithium are only slightly lower than toxic amounts, so the blood levels of lithium must be carefully monitored during treatment.
Valproat Natrium: Anti epilepticum
Phenobarbital is the most widely used anticonvulsant worldwide and the oldest still in use. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the benzodiazepines for these indications
The World Health Organization recommends its use as first-line for partial and generalized tonic–clonic seizures (Insult) in developing countries.
Phenobarbital causes a &quot;depression&quot; of the body&apos;s systems, mainly the central and peripheral nervous systems; thus, the main characteristic of phenobarbital overdose is a &quot;slowing&quot; of bodily functions, including decreased consciousness (even coma), bradycardia, bradypnea, hypothermia, and hypotension (in massive overdoses). Overdose may also lead to pulmonary edema and acute renal failure as a result of shock.
Metformin is the most popular anti-diabetic drug in the United States and one of the most prescribed drugs overall, with nearly 30 million prescriptions filled in 2005
The main use for metformin is in the treatment of diabetes mellitus type 2, especially when this accompanies obesity and insulin resistance.
The most serious side effect of metformin is lactic acidosis; this complication is rare if the contra-indications are followed, as it seems limited to those with impaired liver or kidney function.
Phenformin, another biguanide, was withdrawn because of an increased risk of lactic acidosis (up to 60 cases per million patient-years). However, metformin is safer and the risk of developing lactic acidosis is not changed by the medication, so long as it is not prescribed to the known high-risk groups.[15]
Two questions have been identified as determinants of outcome for patients on CRRT, when to start and how much therapy is enough?
Several studies have been carried out from the early stages of conception of the therapy to suggest that improving outcome depends on how early treatment is initiated. Examples of these studies that explored timing of therapy are: Paganini Study and the Gettings Study.
The next question in relation to this would be how early is early? Some new guidelines have been established to answer this question, one of the latest would be through the RIFLE criteria to help clinicians classify patients and select patients for the therapy.
Therapy dose is another point of controversy in the medical community. The Ronco, Bellomo study suggests a selected effluent dose that increases survival. Let’s look at these points in detail.
When do you start CRRT? There is no clear consensus on when to start treatment. However, there are a few studies that favor earlier start to improve survival of patients. One of the earlier studies is by Dr. Gettings, done in 1989 to 1997, in which 100 adult trauma patients with ARF were enrolled. The result was that patients who started CRRT with BUN &lt; 60 mg / dl had 39% survival compared to patients who started with BUN &gt; 60 mg / dl had 20 % survival
(Normal BUN (Blood Urea Nitrogen) is 7 - 18 mg / dl)
The mortality rate for intensive care patient with ARF continues to rise from 43% to as high as 88%. It is believed this is linked to the inability of the medical community to agree upon a definition of ARF and no classification system to assist with treating ARF.
In May of 2002 the Acute Dialysis Quality Initiative (ADQI) met in Vicenza, Italy and established the RIFLE criteria to categorize patients based on their renal function. This criteria was preented a year after at the CRRT conference in San Diego. The patient is then classified into one of three severity categories based on renal fucntion: 1. Risk 2. Injury and 3. Failure with two outcome categories, Loss and End-stage renal disease.
The RIFLE criteria classifies patients according to their renal function based on decrease in GFR, serum creatinine from patient’s baseline, as shown on the left side of this table, and urine output as shown on the right side of the table. For example, a patient with a creatinine that has increased by 1.5 or a decrease in GFR of &gt;25% from baseline, or UO of &lt;0.5ml/kg/hr for 6 hours is placed in the Risk category. Whereas, a patient with a decrease in GFR of &gt;75% and a UO of &lt;0.5ml/kg/hr for 12hrs is placed in the Failure category. It is suggested that se creatinine alone is not enough parameter to use to classify the patient but rather the combination of GFR reduction and total urine output. (It might be helpful to know that a minimum of 30ml/hr is required to excrete toxic wastes.)
A patient who is on chronic renal failure and develops ARF is categorized according to the acute rise of se creatinine which could still be misleading. This is why the study done by Bell, et al, placed these patients in either Loss or ESRD even though these are the outcome levels rather than the classification.
Dosing for CRRT had been typically adapted to the measurement of clearance used in intermittent hemodialysis. As we learned in the basic level, clearance is the volume of blood completely cleared of a substance in a given time. In IHD, urea or creatinine are the substances used for measurement because these are easy to measure. Several methods are used for this purpose:
Kt/V is calculated from the dialyzer urea clearance, the treatment t stands for treatment time, and patient’s volume.
Example:
K = Dialyzer urea clearance- 300ml/min; T = Treatment time- 3 hours or 180 mins; V = patient’s volume in Liters- 70kg X .60 = 42 Liters
(K)t/V = 300ml (180mins) = 54,000ml or 54 liters / 42 liters = 1.2 ( meets DOQI guidelines)
Over time the limitation of this calculation is realized and several adjustments have been made to make this unit of measurement more reliable. In some cases, clinicians have used the plain PRU (percent reduction in urea) as a simple means of quantifying clearance. PRU is measured from urea value before and after treatment. In CRRT this measurement is adapted using the urea value taken from the access and the return sample ports. In CVVH or in post-dilution CVVHDF, where the effluent is not diluted by the solution infused into the blood compartment, this value may be taken from the effluent sample. In some units, this value provides a means to assess the efficiency of the filter. (A significant reduction in the value means it is time to change the filter.)
Not until July 2000, Bellomo and Ronco revealed a study investigating the effect of effluent dose on the survival of patients in CRRT.
Ronco and Bellomo’s study attempted to answer the question, “what is an adequate dose for ARF patients?” using total effluent rate in relation to patient body size (ie, mL/kg/hr). Consequently the effect of the effluent dose on patient outcome was also explored.
This table describes the methodology for the study. Out of 492 patients considered, 425 patient were randomized and assigned one of the three dosage groups: 20ml/kg/hr, 35ml/kg/hr, and 45ml/kg/hr. The study was conducted using only convection therapy. All replacement solution was delivered post-filter, and UFR was used to measure dosing. This is based on the concept that solute movement across the membrane is proportional to UFR.
The result of the study demonstrated that survival was significantly higher for patients receiving more ultrafiltration dose and that 35ml/kg. BW/hr is the most efficient way of doing this.
In conclusion, the results of the study suggested the following:
Treatment dose has an impact on the mortality/morbity of ARF patients
Start CVVH at 35 ml/h/kg (eg. 70 kg patient = 2450 ml/h)
Continuous treatment is more efficient solute removal, maintaining solute equilibrium, and is clinically tolerated by ICU patients than intermittent approaches.
Early start has positive impact on outcome.
This is becoming widely accepted as the gold standard for dosing in CRRT and the basis of further clinical studies about dosing and survival.
The following components are required in order to perform CRRT.
Continuous renal replacement therapy requires the use of a vascular access such as a special double-lumen catheter placed in a large central vein like the jugular, subclavian, or femoral vein. The success of the treatment depends highly on the proper placement and size of the catheter, and proper assessment of patency of the catheter before the treatment.
Usually, the patient’s blood is pulled by the blood pump from the access limb (red) of the catheter and returned to the return limb (blue) of the catheter. It maybe necessary to reverse the connection in case of resistance from the access limb of the catheter (but this is not recommended; this will reduce the clearance via recirculation).
The blood in the EC circuit comes in contact with foreign materials which favors initiation of the clotting cascade. Therefore, the use of some form of anticoagulant is usually required to maintain the patency of the circuit. This poses a challenge as acutely ill patients usually have bleeding tendencies and use of anticoagulants may aggravate patient conditions. The usual type of anticoagulants used are heparin and citrate. Anticoagulation in CRRT will be discussed extensively in Section 9 of this Learning Module.
All hemo-filters share some basic features. There are four external ports, two for the entry and exit of blood and two for the entry and exit of dialysis fluid. Blood and dialysis fluid run in different channels separated by a membrane. The geometry of these flow paths are designed so that both blood and dialysis fluid are in contact with the largest possible membrane surface area.
During the treatment blood and dialysis fluid flow in opposite directions, in a so called counter-current flow. The internal volume – especially of the blood compartment – must be small since the volume of blood outside the body should be minimized. The blood volume needed to fill up the blood compartment is called the priming volume. The membrane in the filter is in the form of a bundle of thousands of fine capillaries. The blood runs through the these fine capillaries, which are surrounded by dialysis fluid. The fibers has a stiff wall, i.e. their inner volume is fixed and independent of pressure. The fiber bundle is fixed and anchored at both ends to the housing, separating the blood from the dialysis fluid. For this purpose a glue or potting material is used, usually polyurethane (PUR).
All CRRT techniques (except SCUF) require the use of sterile solution for Dialysate (for CVVHD and CVVHDF) and/or Replacement (for CVVH and CVVHDF). The goal of the solutions is to correct electrolyte imbalance and achieve specific metabolic levels.
The ideal CRRT solution must have composition that are physiologic or similar to normal plasma water.
Although many hospitals prefer to use their own admixtures, commercially available solutions are most frequently used. The replacement solution usually has the same electrolyte additives as the dialysate. The solutions are sterile, and commercially prepared solutions are available in 1 to 5-liter bags. Addition of electrolytes to both commercially prepared and hospital-prepared solutions may be done through the medication injection port on the bags.
The acids formed in the body during metabolism are taken care of by various buffering systems, among which bicarbonate (HCO3) is the most important. Since patients with ARF generally has low serum bicarbonate levels and are suffering from metabolic acidosis, some source of buffer is added to the dialysate. The aim is not only achieve normal acid base balance but also to prevent additional loss of serum bicarbonate through the diffusive process.
The usual buffers used for CRRT solutions are lactate and bicarbonate. Lactate is quickly converted to bicarbonate in the liver. The capacity to convert lactate to bicarbonate may however be limited in a critically ill patient, especially with multi organ and liver failure. Lactate based preparations have a long stability, making them less expensive to prepare.
Bicarbonate, on the other hand, is generally better tolerated. It does not require metabolic activity and is available for immediate use of the body. Because bicarbonate is only stable for a short period in solution, it can only be added to the rest of the components of the solutions just prior to use.
The Gambro offers bicarbonate solution in a two compartment-bag, which assures stability of the solution, fast, safe, and easy mixture of bicarbonate to the rest of the components of the solutions.
Substantial heat can be lost from the extracorporeal CRRT circuit, leading to clinically significant hypothermia. Warmers maybe used to prevent heat loss, maintain energy balance, and comfort for patients on CRRT. The two warmers available with Gambro are the Prismaflo and Prismatherm 2.
The Prismaflo is an accessory for the Prisma System. The Prismaflo can warm either blood or dialysate. It uses a thermal sleeve that fits over blood or fluid lines, eliminating the need for extension lines.This system is limited in its ability to warm blood or solutions at high volumes.
The Prismatherm II Blood Warmer is another device which maybe used for either the Prisma or the Prismaflex. It is a more efficient system especially with the use of higher fluid volume. The Prismatherm is installed and stored on the back of the Prisma System. It requires the use of a A disposable extension line that is easily connected to the hemofilter set. .
