Regional Citrate Anticoagulation

Valentine Lobo,

Dept Of Nephrology,

King Edward Memorial Hospital, Pune

Prerequisites for regional Citrate

Anticoagulation

• Dialysate : HCO3- based without Ca

• Monitoring of Ionic calcium levels .

• External Pump to deliver Calcium.

• Central venous access other than dialysis access.

pCRRT Protocol • Place a 3 way stop cock to both the “arterial” and venous ports of the dialysis

access.

• Attach the Citrate ACD(A) Solution 1000cc to a regular IV pump and then attach it to the “arterial” stop cock.

• Start the citrate rate in ccs/hr at 1.5 x the blood flow rate of the PRISMA machine at ccs/min.

• Set up the Ca++ infusion (ie. 8gms Calcium Chloride in 1L NS or 23.5 gms of Calcium Gluconate in 1L of NS) as ordered via central line other than the dialysis access.

• This will run at 40% of the citrate flow rate.

• Net Ultrafiltration rate + Citrate rate + Calcium infusion rate = Pt. Fluid Removal Rate.

• Connect the Hemofiltration machine circuit to the dialysis catheter as per procedure and press start.

• 2 hour after initiation of therapy and every 6 hours thereafter, check

Post-filter ionized Ca++ (drawn from the return line, blue sample port)

Systemic ionized Ca++ (drawn from patient (true) arterial line )

• Chemistries (eg Lytes, BUN, Cr, Ca, Phos, Albumen)

pCRRT Protocol • Metabolic alkalosis occurs due to citrate metabolism to

bicarbonate and due to bicarbonate in the Dialysate.

• Call Pediatric Nephrologist if the Serum Bicarb is >35 meq/l

• Add in NS as a replacement soln @ 200-400 cc/hr and decrease the dialysate rate by the same amount.

• Systemic Ionized Ca++ < 0.75 mmol/L. (Stop citrate for 1 hours and resume at 30% of the citrate flow rate and increase Ca infusion by 10%)

• Na+ > 150 mmol/L. Consider changing replacement solution to 0.45% NaCl.

• In children <10 kg on blood transfusion when going on, avoid the use of citrate for the first 15 minutes for it may exacerbate the Bradykinin release syndrome seen in some children. (Only with M-100)

Titrating Regional Citrate Anticoagulation

Prisma ionized Ca++ (mmol/L) Citrate Infusion Adjustment

> 20 kg

< 20 kg

< 0.35

Decrease rate by 10

ml/hr

Decrease rate by 5 ml/hr

0.35 – 0.5 (Optimum Range) No adjustment

0.5 – 0.6

Increase rate by 10 ml/hr

Increase rate by 5 ml/hr

> 0.6

Increase rate by 20 ml/hr

Increase rate by 10

ml/hr

Patient ionized Ca++ (mmol/L) Calcium Infusion Adjustment

> 1.3

Decrease rate by 10

ml/hr

Decrease rate by 5 ml/hr

1.1-1.3 (Optimum Range) No adjustment

0.9-1.1

Increase rate by

10ml/hr

Increase rate by 5 ml/hr

< 0.9

Increase rate by

20ml/hr

Increase rate by 10 ml/hr

Fluids for regional Citrate Anticoagulation

Composition

mmol/L

Prismasol

(Gambro)

Regiocit

(Baxter)

Biphozyl

(Baxter)

Prisma0Cal

(Baxter)

Acid Citrate

Dextrose

Sodium 140 140 140 140 224

Potassium 0 0 4 0 0

Calcium 1.75 0 0 0 0

Magnesium 1 0 0.75 0.5 0

Chloride 110 86 122 106 0

Bicarbonate 32 0 22 32 0

Phosphate - -- 1 - 2 0 0

Glucose 0 0 0 0 136

Citrate - 18 - 0 113

Osmolality

(mOs/L)

287 244 290 280 488

ISN HD guidelines for RCA • We recommend that regional citrate anticoagulation be used for patients

undergoing CRRT in whom systemic anticoagulation is contraindicated

• We recommend monitoring the blood and circuit levels levels of ionic calcium 2 hourly and adjusting infusion rates . We suggest not using the option “Citrate anticoagulation with External Pump” in children or if used decreasing the blood flow to 2 to 2.5 ml/kg/hour.

• We suggest that regional anticoagulation with Regiocit and Biphozyl may be performed as follows:

• Set desired blood flow rate.

• Start Regiocit (ml/hour) on the PBP line at 6 to 7.5 times the blood flow rate (ml/min).

• Prepare Calcium gluconate solution of 250 ml of 10% calcium gluconate with 750 ml 0.9% N.Saline.

• Start Ca gluconate infusion (ml/hour) through a separate central line and infusion pump at 0.5 times the blood flow (ml/min)

• Adjust the rate of dialysate and replacement fluid with Biphozyl, desired ultrafiltration and Calcium gluconate infusion to obtain a total effluent volume of 2L/hour/1.73m2 or 30 ml/kg/hour.

• Monitor ionic calcium, potassium and pH from the blood and ionic calcium from the circuit blue sampling port every 2 to 4 hours and adjust infusion rates.

ISN HD guidelines for RCA monitoring

Circuit ionic calcium Citrate dose adjustment

Patient weight >20 kg < 20 kg

< 0.35 Decrease by 40 to 50 ml/hr Decrease by 20 ml/hr

0.35 to 0.5 No change No change

0.5 – 0.6 Increase by 40 to 50 ml/hr Increase by 20 ml/hr

>0.6 Increase by 80 to 100 ml/hr Increase by 40 ml/hr

Patient ionic calcium Calcium dose adjustment

>1.2 Decrease by 10 ml/hr Decrease by 5 ml/hr

1.0 – 1.2 No change No change

0.9 – 1.0 Increase by 10 ml/hr Increase by 5 ml/hr

<0.9 Increase by 20 ml/hr Increase by 10 ml/hr

Case 1 • A 5 year old boy received an orthotopic liver allograft from his mother on 10th December 2014.

• Native Disease – Budd Chiari Syndrome.

• Uneventful course for 3 years. Pre morbid weight = 21 kg.

• Admitted in July 2017 with fever and left pleural effusion

• Paracentesis done- 5000 cells mainly lymphocytes with atypical nuclei and altered nucleo-

cytoplasmic ratio.

• PET Scan – Multiple FDG avid nodes in mediastinum abdomen and left axilla. Spleen and sternum

and ribs also show increased activity.

• LN biopsy confirmed PTLD.

• Patient received R-CHOP 1 cycle with withdrawl of tacrolimus.

• Developed high grade fever , shock and anuria.

• Needed mechanical ventilation

• Rt femoral arterial line inserted BP – 68/40, started on Noradrenaline, vasopressin added.

• BP was 92/60 (50th centile ) on 0.5 mcg/kg/min noradrenaline and 0.04 U/min of vasopressin

• BUL = 102mg%, Creat = 3.4 mg% Serum electrolytes 160/4.7/102.

• Hb = 4.5, TLC = 1200/mm3, platelets = 23000/mm3, INR = 2.7, aPTT = 53/32

• CXR:- Bilateral inhomogeneous opacities.

• Obligatory fluid intake = 700 ml for antibiotics, blood products, vasopressors and nutrition.

• Taken for CRRT with 8F rt femoral vein cannulation and regional citrate anticoagulation.

Calcium Infusion

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactate

7.161 46.9 91.4 16.1 160 4.7 114 1.03 5.6

Initial Settings 25/8/2017 - 2 pm

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactat

e

Artery 7.121 42.3 93.8 13.2 145 4.6 117 0.88 5.9

Circuit 7.091 45.6 44.8 12.2 126 4.5 109 0.25 5.5

Calcium Infusion

25/8/2017 – 4 pm

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactate

Artery 7.13 46 84 15.3 144 4.8 112 1.10 10.2

Circuit 7.108 45.6 44.8 13.8 142 4.5 109 0.44 11

25/8/2017 – 10 pm

Calcium Infusion

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactate

Artery 7.215 41.8 70.5 16.3 136 4.2 109 1.02 4.8

Circuit 7.183 40.4 36.8 14.6 0.35 134 3.9 0.35 4.5

26/8/2017 – 5 am

Calcium Infusion

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactate

Artery 7.31 36.8 104 18.4 134 4.7 107 1.25 4

Circuit 7.255 40.3 40.8 17.3 129 3.7 99 0.34 3.4

26/8/2017 – 12 pm

Calcium Infusion

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactate

Artery 7.31 34.3 89.9 17.4 130 4.4 114 1.17 3.5

Circuit 7.26 41.9 41.4 18.6 133 4.0 122 0.40 2.0

Calcium Infusion

26/8/2017 -6 pm

Case 2 • An 18 year old boy, P-U valves in childhood, developed CKD -5D in 2011, and

started on HD through Rt IJV -2LC.

• AVF not possible, switched to CAPD after 3 months, apparently uneventful course.

• Had 1 episode of Peritonitis in November 2018, temporary HD and restarted on PD. Weight around 39 – 40 kg.

• Admitted in February 2019 with high grade fever, rigors and altered sensorium.

• Intubated and ventilated in EMD, had unrecordable BP, started on Noradrenaline.

• 2000 ml fluid bolus given and Vasopressin added.

• PD fluid cell count = 11800 cells, 90% PMNs, 10% lymphocytes.

• Received intraperitoneal Vancomycin and IV Meropenem.

• BUL = 132, Creat = 8.5mg%, Ser Na+ = 132, K+ = 4.5,

• Taken for emergency removal of CAPD catheter and peritoneal lavage

• Needed intra operative Adrenaline infusion.

• Hb= 8.8, TLC = 44500/mm3, platelets = 89000/mm3, INR = 2.5, aPTT = 45/28,

• S. Bil = 2.1, SGPT = 980, SGOT = 776, PCT = 65.

• 24 hour fluid intake = 3800 ml

• Needed RRT for severe metabolic acidosis, anuria and pulmonary edema.

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactate AG

7.137 34.5 73.8 11.2 134 3.5 104 1.04 11.8 20

CRRT Initial Settings 22/2/2019 – 10 pm

Calcium Infusion

pH pCO2 pO2 HCO3- Na+ K+ Cl- iCa2+ Lactate

Artery 6.996 31.4 80.5 6.9 133 3.9 100 0.92 11.7

Circuit 6.891 46 35.8 8.1 134 3.3 98 0.27 10.4

CRRT Settings 23/2/2019 – 1 am

Calcium Infusion

pH pCO2 pO2 HCO3

-

Na+ K+ Cl- iCa2+ Lactate

Artery 7.016 28.3 83.1 6.9 132 4.4 108 1.23 11.3

Circuit 6.960 43.2 38.2 9.2 130 3.7 101 0.32 8.2

CRRT Settings 23/2/2019 – 6 am

Calcium Infusion

pH pCO2 pO2 HCO3

-

Na+ K+ Cl- iCa2+ Lactate

Artery 7.006 30.6 72.9 7.3 132 4.9 108 1.24 10.4

Circuit 6.956 43.8 32.1 9.3 131 3.8 101 0.31 7.5

CRRT Settings 23/2/2019 – 12 MD

Calcium Infusion

pH pCO2 pO2 HCO3

-

Na+ K+ Cl- iCa2+ Lactate

Artery 6.978 30.9 72 6.9 135 4.0 98 0.61 8.7

Circuit 6.947 41 33.4 8.5 127 4.4 99 0.40 8.8

CRRT Settings 23/2/2019 – 6 pm

Calcium Infusion

pH pCO2 pO2 HCO3

-

Na+ K+ Cl- iCa2+ Lactate

Artery 6.933 30.3 101 6.1 135 4.3 99 0.53 10.1

Circuit 6.856 43.6 38.5 7.3 128 4.0 99 0.31 8.5

CRRT Settings 23/2/2019 – 10 pm

Calcium Infusion

• What do you think happened and why?

• How will you confirm the diagnosis?

• How should this patient be managed?

Citrate Toxicity

22/2 @

10 pm

23/2 @

1 am

23/2 @

6 am

23/2 @

12 MD

23/2 @

6 pm

23/2 @

10 pm

23/2 @

12MN

pH 7.137 6.966 7.016 7.006 6.978 6.933 7.074

pCO2 34.5 31.4 28.3 20.6 30.8 30.3 29.9

HCO3- 11.2 6.9 6.9 7.3 6.9 6.1 9.6

AG 20 26 17 17 30 30 19.4

Lactate 11.8 11.7 11.3 10.4 8.7 10.1 8.7

iCa2+ 1.04 0.92 1.23 1.24 0.61 0.53 1.10

Serum total Calcium = 10.38 mg% ( 2.59 mmol/L)

Total/ionic Ca ratio = 4.9, s/o “citrate lock”, secondary to inadequate clearance

All fluids changed to Prismasol.

Patient ID-NAT – Hepatitis C positive