development and implementation of a streamlined regional ... · development and implementation of a...

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