1. Including: Anticoagulation Prescribing Protocol
Concepts of Continuous Renal Replacement Therapy in Adult critical care at LTHT
Including:
Anticoagulation
Prescribing
Protocol

2. Introduction
The machine used at Leeds Teaching Hospitals to deliver Continuous Renal Replacement Therapy (CRRT) is the Fresenius MultiFiltrate machine
The mode of treatment we use is continuous veno-venous haemodialysis (CVVHD)
The first line anticoagulation is Regional Citrate Anticoagulation (RCA)

3. Indications for CRRT High serum potassium Acidosis Pulmonary Oedema
WHEN TO USE
High serum potassium
Acidosis
Pulmonary Oedema
Control of uremic symptoms
Hyperpyrexia
Filter metabolites/Septic mediators
Drug poison removal
Hyperkalaemia k⁺ >6.5mmol/L
Metabolic Acidosis Ph <7.1
Pulmonary Oedema (not responsive to diuretics)
Uremic Encephalopathy/Neuropathy
Non emergency initiation
Fluid management
Solute control
Pre-existing ESRF
Lactate is not removed by dialysis

4. CVVHD
During CVVHD diffusion of molecules takes place between blood in one fluid compartment of the dialyser and dialysis fluid in the other fluid compartment
Haemodialysis utilizes counter current flow where the dialysate is flowing in the opposite direction to blood flow in the extracorporeal circuit
Counter-current flow maintains the concentration gradient across the membrane at a maximum and increases the efficiency of the dialysis

5. Anticoagulation
Anticoagulation of blood is required to avoid clotting in the filter circuit
The default choice of anticoagulation at Leeds is Regional Citrate Anticoagulation (RCA)
This reflects a change from historic practice where heparin was used
RCA offers longer filter life and may reduce complications, it also avoids systemic anticoagulation

6. Alternative anticoagulation options
Unfractionated heparin
None if INR >2.5 and platelets <80
Prostacycline used rarely

7. Regional Citrate Anticoagulation
Negatively charged ion
Binds with ionised calcium
Forms a single negatively charged chelate complex
Concentration of free ionised calcium in blood is reduced in the circuit
Ionised calcium is essential to the coagulation cascade – reducing it reduces clotting
Some of the citrate-calcium complex is removed by the filter and rest passes into patient where it is metabolised by the liver

8. Regional Citrate Anticoagulation
Clotting cascade cannot function if ionised calcium in bloods falls <0.5 mml/L
<0.3 mmol/L clotting abolished
Target calcium concentration in the circuit for optimal function is

9. Fresenius Multifiltrate
This is the machine used in Leeds
It can be used with RCA or heparin
Ci-Ca is the system for RCA
Multibic with heparin (separate protocol)

10. Fresenius Ci-Ca system4 3 5 2 1

11. Fresenius Ci-Ca System
4+2 pump-system
Citrate infusion is coupled to the blood flow
Citrate and calcium infusion is automatically taken into account for fluid balancing
Dedicated Zero-Ca, Low- Bicarb dialysate and Ci-Ca cassette with pre-connected citrate and calcium lines

12. Fresenius Ci-Ca System

13. Dialysate Fluid
Sodium and Bicarbonate reduced in order to compensate for the systemic infusion of Sodium Citrate
Calcium free to avoid unnecessary increase of citrate requirements.
It is a double chamber bag
Fluid is stable for 24 hours once mixed
At Leeds we only use K⁺ 4 mmol/L bags if patient has hyperkalaemia use 35mL/Kg/Hr dialysis dose
Fluid Constitution
Na⁺
133 mmol/L K⁺
4 mmol/L
Mg⁺⁺
0.75 mmol/L
Ca⁺⁺
0 mmol/L
HCO3⁺
20 mmol/L
Cl⁻
116.5 mmol/L
Glucose
1 g/L

14. Core safety concepts Protocol must be followed
Prescription must be written before patient connected to system and then daily
RCA interferes with normal calcium homeostasis - maintain a safe serum ionised calcium level

15. Core safety concepts
Safety check via T:I ratio – this is the total:ionised calcium ratio and is a marker of citrate accumulation
RCA interferes with acid-base balance - be aware that the blood flow and dialysate flow need to be balanced (1:20 ratio) to prevent iatrogenic acidosis or alkalosis
Liver patients may not tolerate RCA – separate guidance

16. Limits Maximum treatment duration is 120 hours per filter
Washback, recirculation and disconnection - circuit can be reconnected up to four hours
Recirculation with blood – circuit can be reconnected up to 30 mins

17. Dose choice
Dialysis dose can be chosen as 25 ml/kg/hr or 35 ml/kg/hr – weight based guidance charts in protocol
25 is the default choice
35 should be chosen in patients with:
Severe hyperkalaemia (>7mmol/l)
Severe acidosis (pH <7.0)
Ethylene glycol poisoning
Inadequate treatment on 25 ml/kg/hr

18. Calcium Management
Refer to the protocol for guidance in calcium management
Around 60% of patients in critical care need to be pre-treated with calcium
Be mindful that in all patients the systemic ionised calcium will drop in the first hours, this is not a citrate accumulation unless the T:I ratio is > 2.5
Calcium management is the single most important factor of citrate anticoagulation

19. Fluid management CRRT is a powerful tool for correcting fluid balance
Prescription should state a range of removal rates and a target fluid balance
Start the removal rate based upon current input and target balance and adjust in response to changes over the course of the day

20. Fluid management example
Hourly input total 50ml (propofol/alfentanil/feed)
50x24=1200
Anuric, no drains/loose stools etc
Target balance –ve 1000ml/24 hours
Set initial removal at 100ml/hr (approximated)
=2200
2200/24=92
After 12 hours patient given 500ml blood
Balance, before blood, at 12 hours is -600ml [(50x12)-(100x12)]
After blood is -100ml with 12 hours left, input still 50ml/hr
Aim remains -1000ml
Set removal at 125ml/hr
(50x12) = +500
=1500; 1500/12=125

21. Acid-Base Management Citrate is metabolised in the liver
The by-product of citrate metabolism is bicarbonate
One molecule of citrate produces 3 molecules of bicarbonate
You require a prescription at a 20:1 (dialysate flow:blood flow) ratio to maintain homeostasis
Any derangement in acid-base must be assessed to ascertain if it is a due to patient pathology or due to the RCA itself

22. Metabolic acidosis potential causes
Is it the patients underlying condition?
Has therapy been running long enough?
Inadequate dialysis dose? May need to increase dialysis to 35mL/kg/hr
Dialysate flow rate too high in relation to blood flow rate, i.e. not 20:1 (was the prescription previously written for metabolic alkalosis?)
Citrate accumulation due to impaired metabolism. T:I ratio will be >2.5

23. Prescribing for Metabolic Acidosis
Either:
Decrease dialysate flow
Less removal of citrate by filter therefore effectively increased bicarbonate delivered to patient
Increase blood flow (increases citrate flow)
More citrate delivered to system without increased removal by filter, therefore also effectively increasing bicarbonate delivery
Could consider increasing dialysis to 35mL/kg/hr
Increased dose of dialysis will aid clearance of pathological acidosis
This should be done if there is no other reason for the patient to be acidotic.

24. Metabolic alkalosis potential causes
Check patients underlying condition
Dialysate flow rate too low in relation to blood flow rate (<20:1)
Check for medications that may cause alkalosis
Filter age
As treatment continues the filter slowly blocks resulting in reduced clearance and a greater proportion of citrate reaching patient
This increased delivery of citrate is converted to bicarbonate

25. Prescribing for Metabolic Alkalosis
Decrease blood flow (this should be the first action)
Decreased citrate into the system so effectively less bicarbonate delivered to patient
Increase dialysate flow
Increased clearance of citrate by filter so effectively less bicarbonate delivered to patient
Consider changing the filter set if >72 hours old
This should be done if there is no other reason for the patient to have an alkalosis

26. Citrate Accumulation
Problems may occur if the patient is unable to adequately metabolise citrate in the presence of acute severe liver failure and/or severe lactic acidosis
Signs include
T:I ratio >2.5
Marked drop in systemic Ca2+
Elevated total calcium (>3)
Anion gap acidosis
Protocol dictates management if suspected

28. Liver Patients
Altered protocol if lactate >8 and total to ionised (TI) calcium ratio >2
Always pretreat with calcium
Increased initial calcium flow rates
At increased risk of citrate accumulation. Vigilance required

29. Summary
Main indications for CRRT are hyperkalaemia, acidosis or fluid overload
Anticoagulation is usually with citrate which works by binding to ionised calcium which prevents activation of the clotting cascade
You must monitor and control patients and filters Ca2+ levels
Fluid balance targets must be adhered to
Be aware that the system can both cause and correct an acid-base imbalance
T:I ratio is an essential safety check – risk of citrate accumulation

30. Points of contact Charlotte Trumper – Clinical Nurse Specialist
James Beck – ICM Consultant
Andy Lewington – Renal Consultant