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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