brophy university of iowa pediatric crrt anticoagulation patrick brophy md director pediatric...

Brophy University of Iowa

Pediatric CRRT Anticoagulation

Patrick Brophy MDDirector Pediatric NephrologyUniversity of Iowa- Children’s HospitalPCRRT Orlando June 2008


Objectives

Review rationale for anticoagulation Options Heparin/citrate 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


Heparin


Heparin UnFrac

LowMW Hep


LMWH: Theoretic advantages

Reduced risk of bleeding Less risk of HIT


LMWH

No difference in risk of bleeding

No quick antidote Increased cost No difference in filter life


Heparin Protocols Heparin infusion prior to filter with post

filter ACT measurement and heparin adjustment based upon parameters

Bolus with 10-20 units/kg Infuse heparin at 10-20 units/kg/hr Adjust post filter ACT 180-200 secs Interval of checking is local standard and

varies from 1-4 hr increments


Heparin Protocols Benefit and Risks

BenefitsBenefits Heparin infusion

prior to filter with post filter ACT measurement

Bolus with 10-20 units/kg Infuse at 10-20 units/kg/hr

Adjust post filter ACT 180-200 secs

RisksRisks Patient Bleeding Unable to inhibit

clot bound thrombin

Ongoing thrombin generation

Activates - damages platelets /thrombocytopenia


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/l Adjust 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.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)


Thanks

ppCRRT members Bedside ICU and Dialysis Nurses Mary Lee Neuberger/Rhonda Cass patients

brophy university of iowa pediatric crrt anticoagulation patrick brophy md director pediatric...

Documents

protocols citrate

triple lumen access

lumen of triple lumen

infused post patient

patient ica

clottingadding citrate

free calcium ionized

removal of calcium