Aquarius System

with Regional Citrate Anticoagulation

Pre-Reading

Access your CRRT & Aquarius

education platform
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Resources & Education
 Table of contents
Chapter 1 The Clotting Cascade 3
The Clotting Cascade revisited.................................................................................................................................... 4

The Intrinsic Clotting Pathway ..................................................................................................................................... 5

The need for Anticoagulant.......................................................................................................................................... 6

What type of Anticoagulant?........................................................................................................................................ 6

How does Heparin work?............................................................................................................................................. 7

What is Citrate?............................................................................................................................................................ 8

How Citrate works....................................................................................................................................................... 9

Process of Citrate Metabolism..................................................................................................................................... 9

Acid Citrate Dextrose Solution A (ACD-A)................................................................................................................... 9

Chapter 2 Advantages and Disadvantages of Citrate 11

Advantages and Disadvantages of Citrate................................................................................................................. 12

AquariusTM System with Regional Citrate Anticoagulation (RCA).............................................................................. 13

RCA Therapy with AquariusTM System....................................................................................................................... 15

Convection................................................................................................................................................................. 16

100 % Convection: Post-dilution CVVH..................................................................................................................... 16

Renal Dose................................................................................................................................................................. 17

Fluid Balance.............................................................................................................................................................. 17

Monitoring.................................................................................................................................................................. 18

Chapter 3 The Puzzle of Citrate 19

The Puzzle of Citrate.................................................................................................................................................. 20

Crossword Clues........................................................................................................................................................ 21

Chapter 4 Practical Advice and Troubleshooting Guide 23

Practical Advice with AquariusTM RCA....................................................................................................................... 24

Troubleshooting Guide Aquarius TM RCA..................................................................................................................... 25

References................................................................................................................................................................. 27

Notes
“The function of education is to teach one to think intensively and to think critically.”
Martin Luther King

2 Pre-Reading I Chapter 1
The Clotting Cascade
Chapter 1

Notes

Pre-Reading I Chapter 1 3
 The Clotting Cascade revisited
Anticoagulant strategies during Continuous Renal Replacement Therapy (CRRT) concentrate on slowing
the natural activation process of clotting that occurs as the patient’s blood comes into contact with the
extracorporeal tubing. The adjustment of systemic anticoagulants, addition of pre-dilution, careful use of
lower filtration fraction or ratio are typical ICU team tactics included in everyday practice. To understand
the clinical innovations within a different method; Regional Citrate Anticoagulation, it may first be helpful to
revisit the normal process of clotting.

Circulation is maintained by blood flowing through intact vessels that are lined by endothelial cells. Injury to
a vessel wall exposes collagen fibres and with this and the tissue injury, a series of reactions occur in order
to form a clot. The process of clot formation is a series of chemical reactions that leads to the formation of
fibrin threads which corrects the trauma and leads to the return to haemostasis1, 2.

The process of clotting is a complex cascade of enzyme reactions in which each clotting factor activates
many molecules of the next stage in a fixed sequence2. As a result a large quantity of the end result (in-
soluble fibrin) is formed2. There are two arms of the clotting cascade; the extrinsic and intrinsic pathways.
The extrinsic pathway concerns tissue trauma and the intrinsic pathway concerns blood trauma. We will
now concentrate on the intrinsic pathway as this is the pathway most involved in anticoagulation and CRRT.

Notes

4 Pre-Reading I Chapter 1
The Intrinsic Clotting Pathway2
• The intrinsic pathway is named as the activa-
tors of the pathway are in direct contact with
blood or contained within (intrinsic to) blood.
• If endothelial cells become roughened or dam-
aged, blood can come into contact with colla-
gen fibres in the connective tissue around the
blood vessel.
• This trauma to the endothelial cells causes dam-
age to platelets which results in the release of
phospholipids by the platelets (see diagram 1).
• Contact with collagen fibres activates clotting
factor XII which begins the sequence of reac-
tions that will lead to the activation of factor X.
• Platelet, phospholipids and Ca2+ also participate
in the activation of factor X. When factor X is
activated, it will combine with factor V to form
the active enzyme prothrombinase which com-
pletes the intrinsic pathway.
• The intrinsic pathway can be considered as
stage 1. Now that this is completed, the com-
mon pathway follows on as stage 2.
• This process involves prothrombinase and cal-
cium converting prothrombin (a plasma protein
found in the liver) into the enzyme thrombin
which completes stage 2.
• The third and final stage of the coagulation
cascade uses thrombin and calcium to convert
fibrinogen, a soluble plasma protein, into insolu-
ble strands of fibrin which will form the threads
of the clot.
• Thrombin also activates factor XIII (also known
as thrombin stabilising factor) which will streng-
then and stabilise the fibrin strands into a
sturdy clot.

Notes

Pre-Reading I Chapter 1 5
 The need for Anticoagulant
In CRRT as the blood moves through the extracorporeal circuit and makes contact with the filter fibres both
the extrinsic and intrinsic clotting pathways are activated. To prevent the activation of the clotting cascade
during CRRT the patient often needs to be continuously anticoagulated3.

What type of Anticoagulant?

Historically, unfractionated heparin has been globally used as the preferred choice of anticoagulant for
CRRT 4. Unfractionated heparin has been used due to its wide availability, short half-life, ability to be moni-
tored, low cost and ease of reversal. The use of unfractionated heparin however, comes with the disadvan-
tage of having to systemically anticoagulate the patient to achieve the desired result within the filter fibres.
It also has a very narrow therapeutic range and often unpredictable kinetics due to the fact that it works
on multiple parts of the clotting cascade. Patients may also develop heparin resistance or Heparin Induced
Thrombocytopenia (HITs) in prolonged use4.

In 2012 the Kidney Disease Improving Global Outcomes (KDIGO) produced new guidelines which state
“for anticoagulation in CRRT, we suggest using regional citrate anticoagulation rather than heparin in
patients who do not have contraindications for citrate”5. The primary reason that the use of citrate is now
the preferred choice of anticoagulant is that it leads to a regional anticoagulation, virtually restricted to
extracorporeal circuit. Therefore, citrate anticoagulation does not increase patient risk of bleeding, i. e.
citrate is specifically indicated in patients with a high risk of bleeding6.

Notes

6 Pre-Reading I Chapter 1
How does Heparin work?
Unfractionated heparin works by enhancing the
action of antithrombin III which then inhibits the action
of factors IIa and Xa. Because this type of heparin is
unfractionated, it is made up of molecules which are
of different molecular sizes. The larger molecules tend
to promote anti-IIa activity and are absorbed much
more easily, whereas the smaller molecules tend to
have more of an anti-Xa activity and are not so readily
absorbed. This highlights that unfractionated heparin
works on multiple sites of the clotting cascade which can sometimes make its anticoagulant effect unpre-
dictable7.

A large proportion of unfractionated heparin anticoagulation properties depend on its ability to increase
the effect of antithrombin. In acutely unwell patients with sepsis or systemic inflammation the amount
of antithrombin available is often significantly less as a result of consumption through activation of
coagulation. This lack of antithrombin to potentiate drastically reduces the anticoagulant effects of
unfractionated heparin and can lead to heparin resistance in the acutely unwell patient requiring
CRRT8.

The most significant disadvantage of using unfractionated heparin to anticoagulate the CRRT
system is that it requires systemic anticoagulation of the patient. Not only does this increase
the bleeding risk in the critically unwell patient but it also requires reversal if the patient
needs a procedure that carries a bleeding risk, such as line insertion or removal or surgery 9.

Notes

Pre-Reading I Chapter 1 7
 What is Citrate?
CRRT has become established as the treatment of choice for supporting critically ill patients with acute
kidney injury. Typically, these patients have activation of the coagulation cascades, peripheral mononuclear
cells and platelets, but also a reduction in natural anticoagulants, and are therefore prothrombotic. For
continuous modes of renal replacement therapy to be effective, in terms of both effective solute clearance
and also fluid removal, the extracorporeal circuits must operate continuously. Thus, preventing clotting in
the CRRT circuit is a key goal to effective patient management. As these patients may also be at increased
risk of bleeding, regional anticoagulation with Citrate is increasing in popularity, particularly following the
introduction of commercially available CRRT systems specifically designed for citrate anticoagulation10.

By summarising the history of Citrate we can understand recent advances in its adaptability for CRRT.

The main problem that stood in the way of the devel-

opment of the first blood transfusions was the ten-
dency for the blood to clot and to block the tubes or
apparatus connected to the recipient. Throughout the
20th century, milestones in the advancement of blood
transfusion are synchronised with the onset of military
conflict around the world. The practice of blood trans-
fusion advanced with the outbreak of the First World
War, mainly due to the new knowledge of matching
different blood groups and the use of an anticoagu-
lant that facilitated indirect transfusion. In 1914, the
Belgian Adolph Hustin discovered that sodium citrate
in tolerable quantities could anticoagulate blood for
transfusion. Further work by Luis Agote in Argentina
and Richard Lewisohn in the USA in 1915 showed that
sodium citrate would effectively anticoagulate blood
at a concentration that could be transfused without
harming the recipient11.

Citrate is a small negatively charged molecule with a Molecular Weight of 192 Daltons. Citrate has a short
systemic half-life , approximately 8 min, and is metabolized predominantly by mitochondria in the liver,
skeletal muscle and the kidney. Citrate is infused into the blood at the start of the extracorporeal circuit
and provides anticoagulation by chelating (binding to) ionized calcium10. Calcium is present in blood in two
forms; as Ca2+ that is bound to protein and Ionized Calcium (iCa2+)12.

Notes

8 Pre-Reading I Chapter 1
How Citrate works
For optimal anticoagulation, the Citrate infusion is adjusted in proportion to the blood flow. The target ex-
tracorporeal blood Citrate concentration to inhibit coagulation is a range from 2–6 mmol/l, corresponding to
a post-filter iCa2+ concentration of < 0.5 mmol/l. Some ICU teams are known to choose below 0.25 mmol/l
or 0.33 mmol/l, where a near total inhibition of coagulation is noted13, 14. As Citrate is a small molecule, a
significant proportion of the Calcium–Citrate complex is freely filtered during hemofiltration and is lost in
the ultrafiltrate10.

Process of Citrate Metabolism

The remaining Calcium-Citrate complexes enter
the patient via the return line where coagulation is
restored. This is due to the diluted blood being re-
turned into the patient’s circulation. Citrate is also
rapidly metabolised in the mitochondrial citric acid
cycle in liver, kidney and muscle, releasing the
bound calcium14. During this metabolism, for every
Citrate molecule broken down, 3 bicarbonate ions
are produced. As a result, Citrate has anticoagulant
properties only within the circuit and not in the pa-
tient14. Ca2+ levels would eventually become lower
due to the calcium lost in the ultrafiltrate, supple-
mentary Calcium is required. This can be provided
by the replacement fluid or as an infusion if addition-
al replacement is required.

Acid Citrate Dextrose Solution A (ACD-A)

Acid Citrate Dextrose Solution or Acid Citrate Dex-
Acid Citrate Dextrose Solution A (ACD-A)
trose Solution A (ACD-A) is available as a preparation
containing Sodium Citrate, Citric Acid, and Dextrose Na 224 mmol/l
in water. ACD-A is routinely used for anticoagulation H 115 mmol/l
of extracorporeal circuits for apheresis and plasma
Citrate 113 mmol/l
exchange in the UK and for citrate anticoagulation
in CRRT in Europe and the USA15, 16. In comparison Glucose 139 mmol/l
to other Citrate solutions such as Tri-Sodium Citrate
solution, ACD-A has the advantage of lower Sodium
load and a lesser tendency for the patient to develop
a metabolic alkalosis17.
It is considered the most appropriate solution for
use in combination with conventional bicarbonate
buffered replacement solution17 such as Accusol 35.

Notes

Pre-Reading I Chapter 1 9
 Notes

10 Pre-Reading I Chapter 2
Advantages and Disadvantages of Citrate
Chapter 2

Notes

Pre-Reading I Chapter 2 11
 Advantages and Disadvantages of Citrate

Advantages8, 18
• Reduced incidence of bleeding with no need for systemic anti-
coagulation.
• Can be used in patient with heparin induced thrombocytopenia
(HIT).
• Has been shown to prolong CRRT filter life.
• Proven to be a safe and effective form of anticoagulant in CRRT.
• Has the potential of providing a reduction in inflammatory mediator
release compared to heparin which has a pro-inflammatory response.

Disadvantages10, 19, 20
• Has been shown to have a higher incidence of hypocalcaemia than heparin.
• Has been shown to have an increased risk of metabolic alkalosis.
• Lower clearance rate of citrate in liver failure patients limits its use in this subgroup.
• Magnesium also binds to citrate which may result in systemic hypomagnesemia.

The benefits of using Citrate as an anticoagulant for CRRT is continuing to be researched but it is becoming
more common as the first choice of anticoagulant. The potential metabolic complications that are seen
to be a disadvantage “depend on the type of fluids used and are largely prevented by the use of a strict
protocol, training and integrated Citrate software14”.

Notes

12 Pre-Reading I Chapter 2
AquariusTM System with Regional
Citrate Anticoagulation (RCA)
To perform the most effective convective therapy,
the AquariusTM System with RCA uses the modality
of 100 % post-dilution CVVH with regional citrate
anticoagulation.

100 % of replacement fluid will be returned to the

patient through post-dilution.

Pre-dilution has been used in regular therapy to

prevent clotting of the extracorporeal circuit and to
extend filter life21. The ratio that is widely accept-
ed in regular CVVH is to commence therapy with
a pre- and post-dilution ratio of 1/3 pre-dilution and
2/3 post-dilution22.

The use of pre-dilution leaves the therapy less ef-

ficient because it reduces the effects of haemoconcentration; diluting the blood while simultaneously
reducing the efficiency of treatment21. Prior to the introduction of citrate to CRRT, these disadvantages of
pre-dilution were the necessary trade made to obtain acceptable clearances, while preventing clotting
of the extracorporeal circuit and extending circuit life.

Citrate acts an as enabler: it binds to ionised Calcium, allowing full anticoagulation and access to
the benefits of increased clearances by using more aggressive treatments than were previously
possible with Heparin, whilst simultaneously offering up to 80 h filter lifespan. The dose of citrate
administered is prescribed with aim of reducing the ionised calcium level in the extracorporeal
circuit to <0.3 mmol/l effectively preventing clots forming within the circuit without having an
impact on systemic patient coagulation.

Notes

Pre-Reading I Chapter 2 13
 The use of 100 % convection and post-dilution replacement fluid via the AquariusTM System with RCA
greatly reduces the potential for fluid errors: one replacement solution can be stocked for both regular and
RCA therapies, Accusol 35.
A tabular overview of the properties of Accusol 35 is shown below, with its appropriate Calcium concen-
tration.

Solution for haemofiltration, haemodialysis and haemodiafiltration

ACCUSOL 35 ACCUSOL 35 ACCUSOL 35

Potassium 2 mmol/l Potassium 4 mmol/l

COMPOSITION (mmol/l)*
Ready to use solution
Sodium 140 140 140
Potassium 0 2 4
Calcium 1.75 1.75 1.75
Magnesium 0.5 0.5 0.5
Chloride 109.3 111.3 113.3
Bicarbonate 35 35 35
Glucose 0 5.55 5.55
Osmolarity (mOsm/l) 287 296 300
* Converted using formula mol=mass/Relative Atomic Mass

Citrate is a small molecule (Molecular Weight of 192 Daltons10), Calcium-Citrate complexes are partially
removed by convection23, Calcium supplementation is required. Citrate binds to Calcium, which lowers the
serum concentration of Calcium inside the hemofilter.

Accusol 35 contains 1.75 mmol/l of Calcium, reducing the requirement for systemic Calcium replace-
ment. Recent work 24 where a calcium containing replacement fluid was used, suggested an appropriate
calcium replacement content to be around 1.75 mmol/l. Using a replacement solution with this calcium
content would indicate that most patients are unlikely to need additional calcium infusions.

This method has the added advantage of being cost-effective with no requirement for additional / premium
replacement fluids, little or no additional Calcium supplementation other than that already contained in
Accusol 35 being required for most RCA treatments.

Notes

14 Pre-Reading I Chapter 2
RCA Therapy with AquariusTM System
Citrate anticoagulation for the AquariusTM System applies to the CVVH Post-Dilution therapy. An additional
black pump on the AquariusTM System infuses citrate solution directly into the access part of the tubing
system. The flow rate of the black pump, seen below, is normally calculated from the concentration of the
citrate solution and targeted to the intended citrate dose, usually expressed in mmol per litre (mmol / l) of
blood according to a clinical protocol.

To calculate the flow rates, ICU teams take into

consideration separate aspects of the therapy. An
Ideal Body Weight example of 70 kg patient weight
is used:

Treatment Dose
70 kg patient, treated at 35  ml/kg/h. Multiplying
the two: patient weight by dose gives an indi-
vidualised prescription for our patient of around
2400 ml/h, typically this is used as a value for
Aquarius CVVH post-dilution programming.
70 kg x 35 ml/kg/h ≈ 2400 ml/h

Blood Flow
2400 ml/h CVVH post-dilution prescription, with a
blood flow of 200 ml/min, gives an acceptable filtra-
tion fraction of approximately 20 %. The blood flow
per hour is 12 litres.

The black pump delivers citrate and the silver pump delivers
Citrate Dose additional calcium replacement if required.

The measurement of Citrate levels inside the extracorporeal circuit is not routinely practiced in ICU. Most
Arterial Blood Gas (ABG) analyzers do have the ability to measure Ionised Calcium (iCa2+), it has become
the most common biochemical value used to adjust treatment, as the clotting cascade becomes inactive
when the iCa2+ within the blood is less than 0.33 mmol/l 1.

ICU teams typically calculate a Citrate dose by considering blood flow and Citrate flow linked by a ratio,
with current clinician choices of Citrate dose ranging between 2.0-4.0 mmol/l of blood having popularity.
Giving more Citrate than is needed means a greater amount of Calcium requirement, and a greater Citrate
metabolism demand. The alternative, giving just enough Citrate to have an anticoagulant effect requires
significanlty less Calcium, is cheaper, advantageous to ICU teams with greater Calcium concentrations in
their substitution fluid, and allows the treatment of patients whose bicarbonate metabolism prevents a
higher Citrate dose. Experienced ICU teams typically keep the measured values within their chosen refer-
ence range by maintaining a consistent flow of Citrate solution and 3-6 hourly ABG monitoring of patient
iCa2+ during treatment.

Notes

Pre-Reading I Chapter 2 15
 Convection
Convection can be defined as; ‘the movement of
fluid across a semi-permeable membrane creating
a solute drag’. Pressure difference between the
blood and ultrafiltrate causes plasma water to be
filtered across. This causes solvent drag for small
and large molecules across the membrane leading
to their removal from the blood. The ultrafiltrate
containing the solute should be replaced by substi-
tution solutions. Convection is an active transport
mechanism, its solute clearance being predictable
for a given amount of therapy11.

100 % Convection: Post-dilution CVVH

• As blood leaves the patient, citrate is infused via the black pump on the AquariusTM System into the
acess blood flow.
• As blood passes through the Aquamax filter, with a membrane pore size of 55,000 Daltons, the filtrate
is removed undiluted.
• By using the active transport mechanism of convection small, middle and large molecules including
some septic mediators, and some anticoagulation compounds, will cross into the ultrafiltrate.
• As the blood leaves the Aquamax, it is then mixed with the replacement substitution solution, warmed
by the integrated heater, via the post-dilution pump. Accusol 35 contains most or all of the Calcium
required as a supplement for RCA.
• Some patients may require additional replacement calcium. If this is the case, the calcium replace-
ment solution will be infused from the silver calcium replacement pump into the circuit directly above
the air detector to ensure patient safety.

CITRATE
SCALE ANTICOAGULANT PRE-DILUTION
PUMP SUBSTITUTION PUMP POST-DILUTION
(NOT RUNNING) SUBSTITUTION PUMP

CITRATE BLOOD
CITRATE PUMP PUMP

HEAT
CONTROL
FILTER

PRE-FILTER RETURN
PRESSURE PRESSURE HEATER

FILTRATION CALCIUM AIR

PUMP PUMP BUBBLE
ACCESS TRAP
PRESSURE
FILTRATION CALCIUM SUBSTITUTION
SCALE SCALE SCALE

AIR
BUBBLE
DETECTOR
FILTRATION
PRESSURE AUTOMATIC
CLAMP
FILTRATION BLOOD LEAK CALCIUM SUBSTITUTION
DETECTOR FLUID

Notes

16 Pre-Reading I Chapter 2
Renal Dose
The research currently underpinning prescribing practice in relation to delivered dose draws its conclusions
from a large, multi-centre observational study. These conclusions are simple; it is not the prescription dose,
but the delivered dose to that patient that is key to understanding the therapy effect. A significant differ-
ence between the prescribed dose and the delivered dose has been clearly identified. Typically, therapy
dose would be prescribed at 35 ml/kg/h, in practice the delivered therapy dose was on average 8 ml/kg/h
less25.

The accuracy of the prescription should be assessed by the quality of the delivered renal dose. Prescribed
dose of therapy should be assessed daily to account for any measured shortfalls in delivered dose25. Ideally,
the dose prescribed would always be an informed clinician choice, based on individual patient presentation,
and specific to the target of treatment.

The AquariusTM System displays on the main screen the actual delivered dose in ml/kg/h. This allows the
clinician to review and adjust the programmed dose to easily achieve the desired treatment dose. This
useful tool calculates, rather than estimates the delivered dose, therefore ensuring ideal delivered dose
and effective patient treatment. The user is fully aware of the dose of treatment given to the patient. This
allows effective delivered therapy easily.

Fluid Balance
A key aspect of CRRT prescription is fluid balance. It has been identified since the beginning of CRRT that
there is the possibility to make fluid balance errors26. The automated Total Fluid Loss Management (TFL)
feature on the AquariusTM System provides total control over fluid balance and automatically corrects fluid
balance variance back to zero, so that fluid discrepancies are eliminated. This feature helps to reduce risks
to the patient by avoiding fluid imbalance accumulation over time due to multiple balance alarms. During
RCA therapy, all volume distributed by either or both the citrate pump and calcium pump are automatically
removed by the filtration pump as part of the AquariusTM System fluid balance.

Notes

Pre-Reading I Chapter 2 17
 Monitoring
In the largest randomized controlled trial to date,
metabolic control with citrate was better than
with heparin14.
Metabolic complications of citrate are deemed
to be a potential disadvantage of this type of
anticoagulation according to Oudemans-van
Straaten et al. “the frequency of these depends
on the type of fluids used and are largely prevent-
ed by the use of a strict protocol, comprehensive
training and integrated citrate software15”.

Citrate protocols are adjusted during treatment as the patient’s presentation changes. There are two com-
mon choices made by clinical teams monitoring ionised calcium (iCa2+), either to adjust treatment by taking
a blood sample from the circuit after the filter (post-filter iCa2+), on the basis that this controls and monitors
the anticoagulation within the filter. The alternative choice measures an arterial blood sample iCa2+, taken
from the patient, on the basis that this sample has the advantage of also observing the metabolic process
secondary to the anticoagulant.

Both choices use arterial blood gas analyzers that are typically located in the clinical environment. The
results guide any adjustments required to citrate dose, blood pump speed and calcium replacement rate
by following a set protocol. A current practice debate exists: analyzers calibrated for physiological levels
of iCa2+ levels may not have equal accuracy at the lower concentrations found in the post-filter sampling
choice 27. A single patient ABG sample taken at 6 hourly intervals is a popular clinician choice of monitor-
ing that streamlines the nursing intervention requirements for RCA and permits the observation of CRRT
parameters at the same time as, for example; ventilatory and metabolic monitoring from the same blood
gas sample.

Notes

18 Pre-Reading I Chapter 2
The Puzzle of Citrate
Chapter 3

Notes

Pre-Reading I Chapter 3 19
 The Puzzle of Citrate
1

3 4

5 6
1 7

10 11

12 13

14

15

16

17

18

Created on TheTeachersCorner.net Crossword Maker

Notes

20 Pre-Reading I Chapter 3
Crossword Clues

Down
1. A complex sugar, found mainly in the liver, a
common anticoagulant, typically used to treat
thrombosis (7)
2. Carbonic and Hydrochloric …...., with a pH of
less than 7.35, are found in parts of the human
body (4)
3. A solute transport mechanism associated with
haemofiltration and solute drag
4. Replacement fluid or Plasma is infused by the
upper green pump after the filter, or …….. (4,8)
7. An element: Kalium, Atomic Number 19, associ-
ated with heart rhythm stability (9)
8. Atoms or radicals which are a group of atoms,
that have gained electrons (5)
9. An element which is bound to Citrate and typi-
cally replaced just after the drip chamber during
RCA (7)
10. A soluble base compound closely monitored
during RCA, also found in antacids and baking
powder (11)
13. Bicarbonate based substitution fluid with two
safety seals which confirm mixing and flow (7)
16. With a pH < 7.35, it’s not alkalosis, it’s _____ (8)

Across
5. Heparin is typically used for Systemic anticoagulation, Citrate for ________ anticoagulation (8)
6. Global organization developing and implementing evidence based clinical practice guidelines in kidney
disease (5)
11. Chemical element with the symbol Na (6)
12. With a pH > 7.45, it’s not Acidosis, it’s ________ (9)
14. A routine type of Calcium measurement used to adjust supplementation (7,7)
15. A simple sugar, part of the anticoagulant solution, monitored closely during therapy (7)
17. The scientific term which describes the binding of Citrate to Calcium (9)
18. Preferred anticoagulant for CRRT therapy because of its safety and effectiveness (7)

The citrate crossword answers can be found on page 27.

Notes

Pre-Reading I Chapter 3 21
 Notes

22 Pre-Reading I Chapter 4
 Practical Advice and Troubleshooting Guide
Chapter 4

Notes

Pre-Reading I Chapter 4 23
 Practical Advice with AquariusTM RCA
• Citrate = BLACK pump and BLACK scale – keep
all parts of the CITRASET RCA with a black line
to the left side of the scale handle.

• Calcium = SILVER pump and SILVER scale –

keep all tubing lines of the CITRASET RCA with
a white line to the right side of the scale handle.

• When only using citrate anticoagulation, please

ensure you replace the white cap on the heparin
line with an occlusive cap to prevent air enter-
ing the circuit.

• Select and confirm bag weight of 100 g - 150 g

for 500 - 1000 ml Citrate and Calcium solution
bags.

• If using 1 x 10 ml ampule of Calcium Chloride

(10 mmol) in 990 ml Sodium Chloride 0.9 % for
Calcium replacement, remember to withdraw
10 ml of Sodium Chloride 0.9 %solution from
the 1000 ml bag first.

• Patient Weight should be entered before

commencing therapy to activate the prescribed
and delivered Renal Dose display throughout
the therapy.

• Do not let the Citrate and Calcium bags swing during treatment; this may be a spurious cause for
Citrate or Calcium flow alarms.

• The blood pump will slow down and come to a complete STOP when changing any substitution or
filtrate bag.

• Please STOP the Blood Pump before changing the Citrate or Calcium solution bags. Wait for the Blood
Pump to come to a complete STOP before changing the appropriate bag. Restart the Blood Pump
once you have changed the bag.

• When changing a Citrate or Calcium bag, avoid turning the bags upside down.

• At each anticoagulant bag change, please re-check that each drip chamber on the Citrate and Calcium
lines is AT LEAST 2/3 full to prevent air entering the circuit.

• All volumes distributed by both or either Citrate pump and Calcium pump are removed by the filtration
pump. Anticoagulant volumes are automatically included in the AquariusTM System fluid balance.

Notes

24 Pre-Reading I Chapter 4
Troubleshooting Guide AquariusTM RCA
Citrate = BLACK pump and BLACK scale

Alarm Cause Resolution Action

High citrate flow - Citrate pump - Ensure the citrate pump segment is Stop treatment
Balancing exceeds segment is loaded loaded correctly; ensure line is not and change lines
the set incorrectly into “pinched” by the pump if the alarm occurs
citrate values the citrate pump repeatedly
> 2.5 g or not loaded at all
Monitor patient
or - Citrate pump is - Checked programmed value for signs of citrate
running too fast of the citrate pump overload and
Low citrate flow control as per Unit
Balancing deviates from protocol
the set citrate values by - Citrate bag is - Ensure citrate bag is not touching other
- 2.5 g touching another bags or the line set
bag or line set - Reduce the number of substitution and
filtrate bags per scale
- Ensure there are no kinks or clamps on
the citrate line, including connection to
the citrate bag
Citrate bag missing - No bag is hanging - Hang a citrate solution bag on the Press the blood
on the citrate scale citrate scale. pump key to
- It is not recommended to remove the bag resume the
while the treatment is running, stop the therapy
treatment first and then remove the bag

Citrate bag change - The citrate bag - Wait for blood pump to stop Press the blood
is empty - Prepare for a bag change pump key to
(Ensure next bag is ready / prepared) resume the
therapy

Calcium = SILVER pump and SILVER scale

Alarm Cause Resolution Action

High calcium flow - Calcium pump is - Check programmed value of the Stop treatment and
Balancing exceeds running too fast calcium pump change the line set
the set if the alarm occurs
calcium values - Calcium bag is - Ensure calcium bag is not repeatedly
> than 2.5 g touching another moving / swinging
bag or line set Monitor and
or - Ensure calcium bag is not touching control patient’s
another bag or the line set systemic calcium
Low Calcium flow - Reduce the number of bags on the levels
Balancing deviates from substitution and filtrate scales
the set Calcium values - Calcium pump - Ensure calcium pump segment is loaded
by - 2.5 g segment is loaded correctly; line is not “pinched”
incorrectly into the by the pump
calcium pump or not
loaded at all
- Calcium pump - Ensure there are no clamps or kinks on
segment not the calcium line, including connection to
correctly primed the calcium bag

Calcium/Citrate - Too much weight - Check that calcium / citrate bags are Restart the
scale overload on the citrate < 2.2 kg/bag treatment
Notes
max. weight per scale = and / or calcium
2.2 kg scales

Pre-Reading I Chapter 4 25
 Notes

26 Pre-Reading I Chapter 4
References
  1 Murphy, M.F. Wainscoat, J. Colvin, B.T. Chapter 8 – Haematological disease in Kumar, P. Clark, M. Clinical Medicine 6th Edition 2005;
Elsevier Saunders: Edinburgh; pg 467.
 2 Tortora, G.J Grabowski, S.R. Principles of Anatomy and Physiology 10th Edition 2003; John Wiley & Sons, Inc.; pg 648-649.
  3 Fischer, K.G. Essentials of anticoagulation in hemodialysis; Hemodialysis International 2007; 11: 178–189.
  4 Davenport, A. Review article: Low-molecular-weight heparin as an alternative anticoagulant to unfractionated heparin for routine
outpatient haemodialysis treatments; Nephrology 2009; 14:455–461.
  5 Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute
Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138
  6 Mariano,F. et al. Citrate Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients: Success and Limits
International Journal of Nephrology, Vol. 2011.
  7 Tolwani, T.J. Wille, K.M. Anticoagulation for Continuous Renal Replacement Therapy. Seminars in Dialysis 2009;
Vol 22, No 2 (March–April); pg 141-145.
  8 Oudemans-van Straaten, H.M. et al. Clinical review: anticoagulation for continuous renal replacement therapy-heparin or citrate?
Critical Care 2011; 15:202.
  9 Morabito, S. et al. Continuous renal replacement therapies, anticoagulation in the critically ill at high risk of bleeding;
J Nephrol 2003; 16:566–571.
10 Davenport, A. Tolwani A. Citrate anticoagulation for continuous renal replacement therapy (CRRT) in patients with acute kidney
injury admitted to the intensive care unit Clinical Kidney Journal 2009; 2(6) 439-447.
11 Institute of Biomedical Science: A brief history of blood transfusion Biomedical Scientist November 2005 Accessed;
February 19th 2016 https://www.ibms.org/go/nm:history-blood-transfusion .
12 Jones T Crash Course: Renal and Urinary Systems, 4th Edition 2015; Mosby Elsevier: London; pg 33
13 Mariano,F. et al. Citrate Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients:
Success and Limits International Journal of Nephrology, Vol. 2011.
14 Oudemans-Van Straaten HM, Bosman RJ, Koopmans M, van der Voort PH, Wester JP, van der Spoel JI Dijksman LM,
Zandstra DF: Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med 2009, 37:545-552.
15 Oudemans-van Straaten H.M. Ostermann, M. Bench-to-bedside review: Citrate for continuous renal
replacement therapy, from science to practice. Critical Care 2012; 16(6):249.
16 Tobe, S.W. et al. A novel regional citrate anticoagulation protocol for CRRT using only commercially
available solutions; Journal of critical care 2003; 18:12.
17 Prowle J. et al. Royal London Hospital Pilot Regional Citrate Anticoagulation Protocol for Aquarius CRRT Platform,
Digital Object Identifier (DOI): 10.13140/RG.2.1.2400.5600 .
18 Betjes, M.G. et al. Regional citrate versus heparin anticoagulation during venovenous hemofiltration in patients at
low risk for bleeding; similar hemofilter survival but significantly less bleeding; J Nephrol. 2007; 16:602–608.
19 Egi, M. et al. The acid-base effect of changing citrate solution for regional anticoagulation
during continuous venovenous hemofiltration; Int J Artif Organs. 2008; 16: 228–236.
20 Aman, J. et al. Metabolic effects of citrate- vs bicarbonate-based substitution fluid in continuous
venovenous hemofiltration; a prospective sequential cohort study. J Crit Care. 2010; 16:120–127.
21 Kellum J. et al. Continuous Renal Replacement Therapy 2010; Oxford: New York; pg. 86-87.
22 Ronco, C. et al. Effects of different doses in continuous veno-venous haemofiltration on
outcomes of acute renal failure: a prospective randomised trial. Lancet 2000; 356 (9223):26-30.
23 Morabito, S. et al. Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous
veno-venous hemofiltration protocol with a low concentration citrate solution; Critical Care 2012; 16(3).
24 Tolwani A.J et al. A continuous veno-venous hemofiltration protocol with anticoagulant citrate dextrose formula
A and a calcium-containing replacement fluid; International Journal of Artificial Organs 2014; 37 (6) 499-502.
25 Vesconi, S. et al. Delivered dose of renal replacement therapy and mortality in
critically ill patients with acute kidney injury; Critical Care 2009;13(2).
26 Ronco C. et al. Management of fluid balance in CRRT: a technical approach. International Journal
of Artificial Organs 2005; 28 (8) 765-776.
27 Schwarzer, P. et al. Discrepant post filter ionized calcium concentrations by common blood
gas analyzers in CRRT using regional citrate anticoagulation Critical Care 2015; 19:321.

Notes
Down: 1 Heparin, 2 Acid, 3 Convection, 4 Post Dilution, 7 Potassium, 8 Anion, 9 Calcium, 10 Bicarbonate, 13 Accusol, 16 Acidosis
Across: 5 Regional, 6 KDIGO, 11 Sodium, 12 Alkalosis, 14 Ionized Calcium, 15 Glucose, 17 Chelation, 18 Citrate
Citrate Crossword Answers:

Pre-Reading I Chapter 4 27
 Continuous ABP
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