brophy university of iowa citrate anticoagulation patrick brophy md, mhcds professor & director...

Brophy University of Iowa

Citrate Anticoagulation

Patrick Brophy MD, MHCDSProfessor & Director Pediatric

NephrologyUniversity of Iowa- Children’s Hospital

London 2015


Objectives

Review rationale for anticoagulation Options Available data


Relevance to CRRT

Functional circuit life is imperative to: Dose delivery Staff statisfaction Patient morbidity (changing lines) Cost of therapy—multi circuit use


Optimal Anticoagulation

Should be: Readily available Consistently delivered (protocols) Safe!!!! Easily monitored Commercially available Be associated with minimal side effects


Anticoagulants

Saline Flushes Heparin Peds Citrate regional

anticoagulation Peds Low molecular weight

heparin Prostacyclin Nafamostat mesilate Danaparoid* Hirudin/Lepirudin Argatroban (thrombin

inhibitor)*

* No antidote known


Sites of Thrombus Formation

Any blood surface interface Hemofilter Bubble trap Catheter (Especially Pediatrics)

Areas of turbulence resistance Luer lock connections / 3 way stopcocks


Citrate


How does citrate work

Clotting is a calcium dependent mechanism, removal of calcium from the blood will inhibit clotting

Adding citrate to blood will bind the free calcium (ionized) calcium in the blood thus inhibiting clotting

Common example of this is blood banked blood


CITRATE

CalciumDependentPathways


How is citrate used?

In most protocols citrate is infused post patient but prefilter often at the “arterial” access of the dual (or triple) lumen access that is used for hemofiltration (HF)

Calcium is returned to the patient independent of the dual lumen HF access or can be infused via the 3rd lumen of the triple lumen access


(Citrate = 1.5 x BFR150 mls/hr)

(Ca = 0.4 x citrate rate60 mls/hr) (8mg/ml)

Dialysate

Replacement Fluid

Calcium can be infused in 3rd lumen of triple lumen access if available.

(BFR = 100 mls/min)

Pediatr Neph 2002, 17:150-154


Citrate: Technical Considerations

Measure patient and system iCa in 2 hours then at 6 hr increments

Pre-filter infusion of Citrate Aim for system iCa of 0.3-0.4 mmol/l

Adjust for levels Systemic calcium infusion

Aim for patient iCa of 1.1-1.3 mmol/lAdjust for levels


Citrate: Advantages

No need for heparin Commercially available solutions exist (ACD-

citrate-Baxter) Less bleeding risk Simple to monitor

Many protocols exist


Advantages of Citrate

Has zero effect upon patient bleeding as opposed to heparin which effects system and patient bleeding

Easy to monitor with ionized calcium assay Activated Clotting Time (ACT) nor PTT needed Programs report less clotted circuits = less disposable cost

and less overtime nursing hours Bedside surveys demonstrate less work of machinery

allowing more attention to patient


Citrate: Problems

Metabolic alkalosis Metabolized in liver / other tissues May be associated with post CRRT raclcitrant hypercalcemia

Electrolyte disorders Hypernatremia Hypocalcemia Hypomagnesemia

Cardiac toxicity Neonatal hearts


Complications of Citrate:Metabolic alkalosis

Metabolic alkalosis due to citrate conversion to HCO3 Solutions with 35 meq/l

HCO3 NG losses TPN with acetate

component

Treatment Solutions with 35 meq/l

HCO3 Decrease bicarbonate

dialysis rate and replace at the same rate with NS (pH 5)

NG losses Replace with ½-2/3 NS

TPN with acetate component Use high Cl ratio


Complications of Citrate: “Citrate Lock”

Seen with rising total calcium with dropping/Stable patient ionized calcium Essentially delivery of citrate exceeds hepatic metabolism and

CRRT clearance Treatment of “citrate lock”

Decrease or stop citrate for 1 hr then restart at 70% of prior rate or Increase D or FRF rate to enhance clearance


Citrate or Heparin: literature


Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.

Citrate Unfractionated Heparin


Anticoagulation

In adults: Monchi M et al. Int Care Med 2004;30:260-65

Median filter life was 70 hr Citrate, 40 hr Heparin Fewer PRBC transfused in Citrate group (surrogate of

bleeding per study) 0.2 units/day of CVVH Citrate vs 1 units/day of CVVH Heparin


Heparin or Citrate?.

single center - 209 adults regional anticoagulation : trisodium citrate vs standard

heparin protocol ( customized calcium-free dialysate)

CitACG was the sole anticoagulant in 37 patients, 87 patients received low-dose heparin plus citrate, and 85 patients received only hepACG.

Both groups receiving citACG had prolonged filter life when compared to the hepACG group.

significant cost saving due to prolonged filter life when using citACG.

Morgera S, et.al. Nephron Clin Pract. 2004; 97(4):c131-6.


Seven ppCRRT centers 138 patients/442 circuits 3 centers: hepACG only 2 centers: citACG only 2 centers: switched from hepACG to citACG

HepACG = 230 circuits CitACG= 158 circuits NoACG = 54 circuits Circuit survival censored for

Scheduled change Unrelated patient issue Death/witdrawal of support Regain renal function/switch to intermittent HD


ppCRRT ACG Side Effects

Heparin 11 cases of systemic bleeding on heparin 5 cases no ACG used secondary to bleeding 1 case of HIT

Citrate 19 cases of metabolic alkalosis

1 change to heparin for hyperglycemia 1 change to heparin for alkalosis

3 cases of citrate lock


Anticoagulation and CRRT

Heparin and citrate anticoagulation most commonly used methods

Heparin: bleeding risk Citrate: alkalosis, citrate lock


Reference Tools

Adqi.net-web site for information on CRRT AKIN.org Crrtonline.com-web site for info on Dr Mehta’s meeting www.PCRRT.com Pediatric CRRT with links to other

meetings, protocols, industry PCRRT list serve (contact Tim Bunchman)

http://www.pcrrt.com/


Thanks

ppCRRT members Bedside ICU and Dialysis Nurses patients

brophy university of iowa citrate anticoagulation patrick brophy md, mhcds professor & director...

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