Development and implementation of a streamlined
regional citrate anti-coagulation haemofiltration
protocol on the Aquarius CRRT platform Dr John R Prowle MD FFICM FRCP
Senior Clinical lecturer in Intensive Care Medicine, QMUL
Consultant in Renal and Intensive Care Medicine
The Royal London Hospital, Barts Health NHS Trust PM-0074-11/2015-1
Disclosure
The Royal London Hospital ACCU has received
institutional support for development of regional
citrate anticoagulation on the Aquarius Platform
at our site (training costs and subsidized
consumables)
Royal London Hospital
Major Trauma Centre
Major Renal and transplant
centre
44 bed Adult Critical Care Unit
>2000 ICU admissions a year
RRT in >200
CRRT Anticoagulation goals
Minimize circuit downtime due to early filter loss
Prevent blood loss from premature circuit loss
Maximize filter performance by avoiding
membrane fouling
Prevent use of consumables and nursing time
Avoid systemic complications of CRRT
anticoagulation
Clotting
Coagulation
Abnormal Surface
Stasis of Blood Flow
Clotting system
Maximizing circuit life
Achieve consistent blood flow
Optimal anti-
coagulation
Optimized extra-
corporeal circuit
Maximizing Circuit Lifespan
Coagulation System
Citrate Calcium Chelation
Ca2+
Citrate – Calcium chelation
CITRATE
[Ca2+]i → 0.3-0.5
CRRT Practice Guidelines
Crit Care Med 2015; 43:1622–1629
Crit Care Med 2015; 43:1622–1629
Crit Care Med 2015; 43:1622–1629
Citrate Evidence Summary
Longer filter survival
Bleeding
Citrate
Replacement
Fluid
Effluent
Cai 1.2 Cai 0.3
Simple Citrate
Some Ca Citrate loss
Lost Calcium
Replaced
Cai 1.2
Citrate
metabolized
to release
chelated Ca
Schematic representation of RCA for the different
continuous RRT modalities.
Santo Morabito et al. CJASN doi:10.2215/CJN.01280214
©2014 by American Society of Nephrology
Factors in the use of RCA
Metabolic acidosis
Hypocalcaemia
Citrate generates additional buffer
[C6H5O7]3- + 4.5(O2) → 3(CO2) + H2O + 3[HCO3]
-
Hypocalcaemia
Enhanced removal of chelated calcium in the haemofilter – Predictable
– Accommodated by Ca replacement
Accumulation of un-metabolized citrate in the blood – Unusual
– Fulminant liver failure
– Refractory shock with widespread mitochondrial dysfunction
– Rising need for Ca replacement
– Elevated Total: Ionised Ca ratio
– Indication to cease RCA
RCA
RCA is very promising
Could be challenging to give in a busy ICU
environment with bedside nurse delivered
CRRT
Need for machine microprocessor-controlled
citrate and calcium infusions
Complex algorithms introduce potential for
error
Anxiety regarding potential risks of citrate use
Relatively slow UK uptake of RCA therapies
RCA protocol for the Aquarius
Long history of use of Citrate CRRT with this device using bespoke circuits and separate pumps – Oudemans-van Straaten et al CCM 2009
Conversion of existing device to incorporate integrated citrate functionality
Post-dilution CVVHF mode chosen – Distinct from other integrated RCA
in the UK Market
Need for a dedicated protocol for
the new system
CVVH post-dilution with RCA
CVVH post-dilution with RCA
25
Copyright ©2015 NIKKISO Co., LTD. All rights reserved.
ACD-A mixed with blood
pre-filter Calcium Citrate is
removed in the filtrate.
Calcium infused post filter. Blood is returned to the
patient.
Constraints on our protocol Post-dilution CVVHF
– Simplicity
– Reliable dose
– Allows use of conventional replacement solution
– Only one solution needed
– Filtration fraction may be limiting
Citrate solution
– Anticoagulant Citrate Dextrose A
– Available off the shelf
– Established use in Apheresis in the UK
– CE marked as a medical device
Conventional Replacement Solution
– Accusol
– Calcium 1.75 mmol/L
– Bicarbonate 35 mmol/L
– Licensed
– Cost-effective
ACD-A
Na 224 mmol/L
H 115 mmol/L
Citrate 113 mmol/L
Glucose 139 mmol/L
Replacement solution Conventional replacement necessitates post
dilution
Conversely post-dilution enables use of conventional replacement solution
Issue is development of metabolic alkalosis
Use of ACD-A is less alkalinizing
Use of moderate dose Citrate only – Lower risk of hypocalcaemia and complications
– Lower sodium load
Modest dose of Citrate and Calcium containing replacement minimize need for addition CaCl infusion – Safer
– Cost-effective
Buffering of Sodium Citrate vs ACD-A
Tri-Sodium Citrate
3[Na]+ + [C6H5O7]3- + 4.5(O2) → 3(CO2) + H2O + 3[HCO3]
-
ACD-A (2:1 Sodium Citrate : Citric Acid)
2[Na]+ + [C6H6O7]2- + 4.5(O2) → 4(CO2) + 2(H2O) + 2[HCO3]
-
Easy to use bedside protocol Royal London Hospital Adult Critical Care Unit
CRRTRegionalCitrateAnticoagulationProtocol(RCA)
• Receivingsystemicanticoagulation
• LiverDiseasewithINR>2• Lactate>5mmol/L• Posthepaticresection
• Noradrenaline>0.5mcg/kg/min• IBW>90kg• Requiring>10u/hr insulininfusion• SerumSodium:<120or>160mmol/L
• pH>7.5orHCO3>40mmol/L
CurrentexclusionsfortheuseofRCA
• SetupanRCAequippedhaemofilterinCVVHmodeusinganRCAcircuitandHF12Filter
• Circuitshouldbeprimedwithheparin5000Uin1LofNaCl 0.9%unlessdiagnosedwithHITS
• Allnewpatientswillstartat35ml/kg/hr exchangerateonProtocol1below(unlessdirectedbyConsultant)
• Ifarterialionised Calcium(iCa)<1.0thensetupCalciumInfusion:
• UsingANTTadd10mlsofCalciumChloride(usingonespecific10mmolampouleforRCA)to990mlsNaCl
0.9%(thismakesCaCl solutionat10mmol/L)&mixwellandclearlylabeledwithdateandtime
• Ifarterialionised Calcium(iCa)≥1.0thenhang0.9%NaCl withoutCalcium
• NaCl bagMUSTBECLEARLYLABELLED‘NOCALCIUM’
• TheCaCl solutionor‘No-Calcium’bagMUSTbechangedevery24hours
• PatientcontinuingRCAtherapywithin24hoflastcircuitshouldstayonthepreviousProtocolandCalcium
Infusionrate,if>24hbreakthentreatasnewtherapy
Monitoring
BaselineABGfor iCa2+&HCO3-
Lab Bloodswithin12hforU&EMg2+TotalCa2+
ABGforiCa2+&HCO3- monitoring
OnehourafterstartingtherapyorifiCa<0.8SixhourlyifiCa 0.9-1.3ThreehourlyifiCa 0.8-0.89or>1.3
Aroundevery12hours:LabBloods:U&E;TotalCa2+;Mg2+ (AimMg>1mmol/L)
PostFilteriCa2+ (Takefromreturn-linesampleport)
SystemiciCa Initial rateofCaClsolution
<0.8DoNOTcommenceRCA
Medicalteam toreview&correctCalcium
0.8-0.89 75mL/h(0.75mmol/h)
0.9-1.0 50mL/h(0.5mmol/h)
>1.0 0mL/h(0mmol/h)
Use thistable only when firststartingRCA
Pleaseseesetupguide/RCASuper-usersformoreinformation.Seeoverleafforongoingcare
IBWkg
Post – dilutionmL/h
BloodPumpmL/min
ACD-A (Citrate)mL/h
<50 1400 120 180
50-59 1800 150 230
60-69 2100 180 270
70-79 2400 200 300
>80 2700 230 350
InitialCaCl rates&bloodmonitoring
PreparationandSetup
Version1114/10/15
[iCa] CaClinfusionadjustment(MAXIMUMRATE=175mL/hr): Recheck
<0.8
1. Doctortogive5ml,10%CaCl(3.4mmol)‘minijet’byslowIVbolusviaa
centrallineimmediately2. IfCaCl alreadyrunningthenincreaseinfusionby50ml/h3. Ifstarting CaCl setupCaCl infusion(overleaf).Startat100ml/h.
4. IfCaClinfusionalreadyat175ml/hceaseRCA &informICUConsultant
1h
0.8-0.89
1. IfCaCl alreadyrunningthenincreaseinfusionby25ml/h
2. Ifstarting CaCl setupCaCl infusion(overleaf).Startat75ml/h.3. IfCaCl infusionalreadyat175ml/hceaseRCA&informICUConsultant
3h
0.9-1.3 1. Nochange. 6h
>1.3
1. DecreaseCaClinfusionby25ml/h
2. IfCaClinfusionoffthenchecksystemic[iCa]in3hours3. InformDoctorif[iCa]risesto>1.5
3h
On-goingiCa2+MonitoringUsethisTablewhenFilterisRunning
On-goingpHandBicarbonate(HCO3-)monitoring
IBWkg
Post – dilutionmL/h
BloodPumpmL/min
ACD-A (Citrate)mL/h
<50 1100 100 150
50-59 1300 110 170
60-69 1500 130 200
70-79 1700 140 210
>80 1900 160 240
IBWkg
Post – dilutionmL/h
BloodPumpmL/min
ACD-A (Citrate)mL/h
<50 Reachedminimumbloodflowrate– DISCONTINUERCA
50-59 Reachedminimumbloodflowrate– DISCONTINUERCA
60-69 1500 100 150
70-79 1700 120 180
>80 1900 130 200
Step2: ifpH>7.5orHCO3- >40mmol/LonProtocol2 changesettingstoProtocol3(25ml/kg/hwith
increasedfiltrationratio)belowandmonitorevery6h
Step3:ifstillpH>7.5orHCO3- >40mmol/LDISCONTINUERCA
IfACIDOSISoccurs,considernewpathology&calldoctorforreview
Step1: ifpH>7.5orHCO3- >40mmol/LonProtocol1 ChangethesettingstoProtocol2(25ml/kg/h)
belowandcontinuetomonitorevery6h.(Protocol2mayalsobeselectedfordosereduction)
Exclusions
• Receiving systemic
anticoagulation
• Liver Disease with INR >2
• Lactate >5 mmol/L
• Post hepatic resection
• Noradrenaline > 0.5mcg/kg/min
• IBW> 90kg
• Requiring > 15u/hr insulin infusion
• Serum Sodium: <120 or >160 mmol/L
• pH> 7.5 or HCO3 >40mmol/L
Current exclusions for the use of RCA in our Pilot
Developing the protocol
Starting dose of 35ml/kg/h based on ideal body weight
– RLH local policy
Blood pump speed set to achieve Filtration Ratio of 20%
Aim Citrate concentration of 2.8mmol/L in filter (2.8/113 =
1/40)
– Aim for post filter Cai 0.3-0.5
60kg
– Exchange: 35 x 60 = 2100 ml/h
– Blood Flow: 2100 x 5 / 60 = 175 ml/min
– ACD-A: 175 / 40 = 4.4 ml/min = 260 ml/h
That’s it!
35 ml/kg/h
IBW
kg
Post – dilution
mL/h
Blood Pump
mL/min
ACD-A (Citrate)
mL/h
<50 1400 120 180
50-59 1800 150 230
60-69 2100 180 270
70-79 2400 200 300
>80 2700 230 350
Monitoring
Monitoring
Baseline ABG for iCa2+ & HCO3-
Lab Bloods within 12h for U&E Mg2+ Total Ca2+
ABG for iCa2+ & HCO3- monitoring
One hour after starting therapy or if iCa<0.8
Six hourly if iCa 0.9-1.3
Three hourly if iCa 0.8-0.89 or >1.3
Around every 12 hours:
Lab Bloods: U&E; Total Ca2+; Mg2+ (Aim Mg >1mmol/L)
Post Filter iCa2+ (Take from return-line sample port)
Initial Calcium Rate
Then check arterial Cai in 1h
Systemic
iCa
Initial rate of CaCl solution
<0.8
Do NOT commence RCA
Medical team to review & correct
Calcium
0.8-0.9 75 mL/h (0.75mmol/h)
0.9-1.0 50mL/h (0.5mmol/h)
>1.0 0mL/h (0mmol/h)
Use this table only when first starting RCA
Adjusting Calcium Infusion
[iCa] CaCl infusion adjustment (MAXIMUM RATE = 175mL/hr) Recheck
< 0.8
1. Doctor to give 5ml, 10% CaCl (3.4mmol) ‘minijet’ by slow IV
bolus via a central line immediately
2. If CaCl already running then increase infusion by 50ml/h
3. If starting CaCl then start at 100ml/h
4. If CaCl infusion already at 175ml/h cease RCA & inform ICU
Consultant
1h
0.8-0.89
1. If CaCl already running then increase infusion by 25ml/h
2. If starting CaCl then start at 75ml/h
3. If CaCl infusion already at 175ml/h cease RCA & inform ICU
Consultant
3h
0.9-1.3 1. No change 6h
>1.3
1. Decrease CaCl infusion by 25ml/h
2. If CaCl infusion off then check systemic [iCa] in 3 hours
3. Inform Doctor if [iCa] rises to >1.5
3h
Alkalosis
Start 35ml/kg/h
(Protocol 1)
•If pH >7.5 or HCO3
- >40
Reduce to 25ml/kg/h
(Protocol 2)
•If pH >7.5 or HCO3
- >40
Use 25ml/kg/h with 25% FR
(Protocol 3)
•If pH >7.5 or HCO3
- >40
Stop RCA
Adjustments for Alkalosis
IBW
kg
Post – dilution
mL/h
Blood Pump
mL/min
ACD-A (Citrate)
mL/h
<50 1100 100 150
50-59 1300 110 170
60-69 1500 130 200
70-79 1700 140 210
>80 1900 160 240
IBW
kg
Post – dilution
mL/h
Blood Pump
mL/min
ACD-A (Citrate)
mL/h
<50 Reached minimum blood flow rate – DISCONTINUE RCA
50-59 Reached minimum blood flow rate – DISCONTINUE RCA
60-69 1500 100 150
70-79 1700 120 180
>80 1900 130 200
Step 2: if pH>7.5 or HCO3- >40mmol/L on Protocol 2 change settings to Protocol 3 (25ml/kg/h with
increased filtration ratio) below and monitor every 6h
Step 1: if pH>7.5 or HCO3- >40mmol/L on Protocol 1 Change the settings to Protocol 2 (25ml/kg/h) below
and continue to monitor every 6h. (Protocol 2 may also be selected for dose reduction)
Step 3: if still pH>7.5 or HCO3- >40mmol/L DISCONTINUE RCA
Step 3: if still pH>7.5 or HCO3- >40mmol/L DISCONTINUE RCA
Step 3: if still pH>7.5 or HCO3- >40mmol/L DISCONTINUE RCA
Step 3: if still pH>7.5 or HCO3- >40mmol/L DISCONTINUE RCA
Step 3: if still pH>7.5 or HCO3- >40mmol/L DISCONTINUE RCA
Step 3: if still pH>7.5 or HCO3- >40mmol/L DISCONTINUE RCA
Energy – Nutritional considerations
Ideal BW (Kg) ACDA infusion rate KJ per 24h on therapy
<50 180 ml/h 2400
50-59 230 ml/h 3100
60-69 270 ml/h 3650
70-79 300 ml/h 4050
80-89 350 ml/h 4750
Protocol 1 (35ml/kg/h CVVH, FR 20%)
• We will give 180-350ml/hr of ACA-A of which >20% will be filtered-out
• Citrate is 2.48kJ/mmol
• Glucose 3.06 kJ/mmol
• Thus 1L ACD-A contains ~700kj energy of which 560kj would go to the
patient at a filtration ratio of 20%
Preliminary Results
We have treated only patients with contra-indication to heparin or those with unacceptable filter lifespan despite optimization of catheter position conventional anticoagulation and pre-dilution
Troubleshooting issues with low return pressure alarms
Our patients receive lots of interventions (Scans, Theatre, Plasma Exchange)
Data from 45 filters
Mean lifespan 22h
Supplemental Calcium given only on 8 occasions
No treatments stopped for alkalosis – Median highest pH during filter 7.45
– Median Lowest Cai 1.07
– Median Post-filter Cai 0.38
Conclusions
RCA can be provided on the Aquarius Platform safely and
effectively
The choice of post-dilution mode enables a streamlined
protocol which can be reliably implemented by bedside nurse
The post-dilution mode represents new option over existing
RCA products in the UK market improving consumer choice in
the market
Use of conventional replacement and ACD-A solution is cost-
effective and useful logistically
Using Accusol replacement additional calcium replacement is
rarely required
This protocol prioritizes consistency and ease of use over
“fine-tuning”
Integrated RCA on the Aquarius
Royal London Citrate CRRT Protocol
Royal London Hospital Pilot Regional Citrate
Anticoagulation Protocol for Aquarius CRRT
Platform
DOI: 10.13140/RG.2.1.2400.5600
