aquarius system · the crrt circuit is a key goal to effective patient management. as these...

Aquarius Systemwith Regional Citrate Anticoagulation

Pre-Reading

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2 Pre-Reading I Chapter 1

Notes

2

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 AquariusTM RCA ....................................................................................................................25

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

“The function of education is to teach one to think intensively and to think critically.”

Martin Luther King

3Pre-Reading I Chapter 1

Notes

3

The Clotting CascadeChapter 1


Notes

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

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

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

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 surgery9.


Notes

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

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-trose Solution A (ACD-A) is available as a preparation containing Sodium Citrate, Citric Acid, and Dextrose in water. ACD-A is routinely used for anticoagulation of extracorporeal circuits for apheresis and plasma exchange in the UK and for citrate anticoagulation in CRRT in Europe and the USA15, 16. In comparison 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.

Acid Citrate Dextrose Solution A (ACD-A)

Na 224 mmol/l

H 115 mmol/l

Citrate 113 mmol/l

Glucose 139 mmol/l


Notes

10


Notes

11

Advantages and Disadvantages of Citrate

Chapter 2


Notes

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

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

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.

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 work24 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.

ACCUSOL 35 ACCUSOL 35Potassium 2 mmol/l

ACCUSOL 35Potassium 4 mmol/l

COMPOSITION (mmol/l)*Ready to use solution

Sodium 140 140 140Potassium 0 2 4

Calcium 1.75 1.75 1.75Magnesium 0.5 0.5 0.5

Chloride 109.3 111.3 113.3Bicarbonate 35 35 35

Glucose 0 5.55 5.55Osmolarity (mOsm/l) 287 296 300

* Converted using formula mol=mass/Relative Atomic Mass

Solution for haemofiltration, haemodialysis and haemodiafiltration


Notes

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.

Citrate Dose

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.

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


Notes

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.

CITRATECITRATE

PUMP

ANTICOAGULANT PUMP

FILTRATION

FILTRATIONPUMP

CALCIUMPUMP

BLOODPUMP

PRE-DILUTION SUBSTITUTION PUMP

(NOT RUNNING)

ACCESS PRESSURE

PRE-FILTER PRESSURE

FILTRATION PRESSURE

RETURNPRESSURE

HEAT CONTROL

HEATER

SUBSTITUTIONSCALE

FILTRATIONSCALE

AIRBUBBLE

TRAP

AIRBUBBLE

DETECTOR

AUTOMATIC CLAMP

CALCIUMSCALE

BLOOD LEAKDETECTOR

CITRATESCALE

POST-DILUTION SUBSTITUTION PUMP

SUBSTITUTIONFLUID

CALCIUM

FILTER


Notes

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

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

The Puzzle of CitrateChapter 3


Notes

The Puzzle of Citrate

Created on TheTeachersCorner.net Crossword Maker

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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

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Notes

23

Practical Advice and Troubleshooting Guide

Chapter 4


Notes

24

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

25

Troubleshooting Guide AquariusTM RCA

Alarm Cause Resolution Action

High citrate flowBalancing exceeds

the setcitrate values

> 2.5 g

or

Low citrate flowBalancing deviates from the set citrate values by

- 2.5 g

- Citrate pump segment is loaded incorrectly into the citrate pump or not loaded at all

- Ensure the citrate pump segment is loaded correctly; ensure line is not “pinched” by the pump

Stop treatment and change lines if the alarm occurs repeatedly

Monitor patient for signs of citrate overload and control as per Unit protocol

- Citrate pump is running too fast

- Checked programmed value of the citrate pump

- Citrate bag is touching another bag or line set

- Ensure citrate bag is not touching other bags or the 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 on the citrate scale

- Hang a citrate solution bag on the citrate scale.

- It is not recommended to remove the bag while the treatment is running, stop the treatment first and then remove the bag

Press the blood pump key to resume the therapy

Citrate bag change - The citrate bag is empty

- Wait for blood pump to stop- Prepare for a bag change

(Ensure next bag is ready / prepared)

Press the blood pump key to resume the therapy

Citrate = BLACK pump and BLACK scale

Alarm Cause Resolution Action

High calcium flowBalancing exceeds

the setcalcium values

> than 2.5 g

or

Low Calcium flowBalancing deviates from the set Calcium values

by - 2.5 g

- Calcium pump is running too fast

- Check programmed value of the calcium pump

Stop treatment and change the line set if the alarm occurs repeatedly

Monitor and control patient’s systemic calcium levels

- Calcium bag is touching another bag or line set

- Ensure calcium bag is not moving / swinging

- Ensure calcium bag is not touching another bag or the line set

- Reduce the number of bags on the substitution and filtrate scales

- Calcium pump segment is loaded incorrectly into the calcium pump or not loaded at all

- Ensure calcium pump segment is loaded correctly; line is not “pinched” by the pump

- Calcium pump segment not correctly primed

- Ensure there are no clamps or kinks on the calcium line, including connection to the calcium bag

Calcium/Citrate scale overload

max. weight per scale = 2.2 kg

- Too much weight on the citrate and / or calcium scales

- Check that calcium / citrate bags are < 2.2 kg/bag

Restart the treatment

Calcium = SILVER pump and SILVER scale


Notes

26


Notes

27

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.

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

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