Practical CRRT: Physician aspects

1
Practical CRRT Physician aspects

• R.T. Noel Gibney MB FRCP(C)
• Professor of Critical Care Medicine
• Faculty of Medicine and Dentistry
• University of Alberta
• Edmonton, AB

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Disclosure

• Research grant and speakers bureau
• Gambro

3
Outline

• Access
• Blood flow
• Filtration fraction
• Clots in de-aeration chamber
• Anticoagulation
• Discontinuation

4
Role of access catheter

• Flow K.radius4.1/length
• For best flows catheter should be non-kinkable.
• Need to access large central vein
• IJ-SVC 16 cm
• Fem-IVC 20 -24 cm
• If possible, avoid subclavian veins
• Consider flow interference by
• High abdominal pressures
• Low CVP
• Consider fibrin build up in poorly locked
  catheter

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Blood flow and hemofilter life
Baldwin I et al. Int Care Med 2004302074-2079
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Covidien Quinton Mahurkar
Soft tip
11 Fr Best for regular CRRT 13 Fr Best for
HVHF /IHD/SLED
Laser cut side holes -problem with rewiring!
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Bard Niagara Catheter
13.5 Fr 12.5-24 cm
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Gambro Prismaccess
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Catheter connections
Curved extension tubing
Straight extension tubing
Internal Jugular Vein
Subclavian Vein
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Citrate vs. Heparin for Catheter Locking

• Citrate is at least as effective as heparin in
  maintaining catheter patency
• Eliminates risk of HIT
• Eliminates risk of inadvertent heparin bolus.

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Citrate lock inhibits bacterial biofilm

• Citrate inhibits Staphylococcal biofilm formation
  on catheters.
• Citrate locking may decrease CRBSI
• 4 Trisodium citrate lock available as 10 ml
  syringes

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The circuit is clotting every 10-12 hours

• 48 year-old man receiving CRRT for AKI following
  aortic valve replacement.

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The circuit is clotting every 10-12 hours

• 48 year-old man (110 Kg) receiving CRRT for AKI
  following aortic valve replacement.

Filtration fraction QUf/Qb 4000/9000 44
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The circuit is clotting every 10-12 hours

• 48 year-old man (110 Kg) receiving CRRT for AKI
  following aortic valve replacement.

Filtration fraction QUf/Qb 4000/9000 44
Management options Increase blood pump speed
to at least 270 ml/min or Change mode to CVVHDF
2.0/2.0
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Filtration fraction (FF)

• The filtration fraction is the proportion of
  blood flow (QB) per min that is removed as plasma
  filtrate.
• FF QUF/QB  
• QUF the total Ultrafiltration rate
• QB blood flow rate
• FFgt25 Hemoconcentration ? clotting
• Where is the FF displayed on the Prismaflex
  numerically displayed on the set flow rate
  screen

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Filtration fraction
Hcrit 30
Hcrit 30
Blood flow 150 mls/hr
Blood flow 150 mls/hr
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Filtration fraction
Hcrit 30
Hcrit 60
Blood flow 100 mls/min
Blood flow 150 mls/min
Hemofiltration 50 mls/min

• Filtration fraction is the proportion of blood
  flow/min that is removed as plasma filtrate.
• Ideally keep lt25 and should not exceed 30

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Blood flow requirements for HVHF to maintain
filtration fraction at 25
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CVVH -predilution

• Fluid removal
• Solute clearance
• Convection
• Some of delivered replacement fluid lost by
  hemofiltration
• Lower anticoagulation requirements

Replacement fluid
Access
Return
UF
Flow
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CVVH -postdilution
Replacement fluid

• Replacement fluid delivered post-filter
• Higher delivered dose of hemofiltration

Access
Return
UF
Flow
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Clots in deaeration chamber

• Likely to occur in pre-filter replacement with
  heparin or no anticoagulation
• Blood/air interface in this chamber
• Resolution
• Post-filter replacement
• PrePost-filter replacement
• Citrate anticoagulant

air
blood
22
Clots in deaeration chamber

• Post dilution replacement prevents clot formation
  in the deaeration chamber
• Blood/fluid/air interface is created rather than
  an air/blood interface

air
fluid
blood
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Why anticoagulation during RRT?

• To preserve life of extracorporeal circuit
• To maximize RRT dose
• To minimize blood loss caused by clotting during
  RRT
• To reduce nursing workload and complexity of care

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Anticoagulation options

• No anticoagulation
• Unfractionated heparin
• LMW Heparin
• Citrate
• Prostaglandins - PGI2, PGE1
• Danaparoid
• r-Hirudin
• Argatroban

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No anticoagulation

• Shorter hemofilter life 6-18 hrs unless severe
  coagulopathy
• Significant system down-time in CRRT
• Lower CRRT dose
• Wasteful of nursing time
• Expensive at 190 per ST100 Prismaflex hemofilter
• However may be valuable if significant
  coagulopathy

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Heparin
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Heparin anticoagulation
Heparin
No reason to use mode other than CVVH with
heparin anticoagulation when using Prismaflex
Qb 150-300 mls/min
Dialysate effluent / Ultrafiltrate
Hemofilter
Replacement fluid Na 140, K 4,Cl 110.5, Mg
0.5,HCO3 32
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LMW Heparin

• Enoxaparin 8-30u/kg bolus
• Enoxaparin 5u/kg/hr infusion
• LMWH eliminated by kidneys
• Accumulates in renal failure
• No antagonist if bleeding occurs
• Bleeding rates similar to UF Heparin
• Monitoring
• Free factor Xa levels

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Complications of Heparin

• Bleeding
• Hemorrhage
• Heparin induced thrombocytopenia

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Trisodium citrate
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Citrate anticoagulation
Intrinsic pathway
XII
XIIa
Extrinsic pathway
XI
XIa
VII
IX
IXa
VIIa
Ca
VIII
Tissue factor
X
Xa
Coagulant active phospholipid (e.g. platelet
membrane)
Ca
V
Prothrombin
Thrombin
Fibrinogen
Fibrin
XIIIa
Cross linked fibrin
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Why regional citrate anticoagulation? Two
Randomized Controlled Trials

• Regional citrate anticoagulation
• No additional bleeding risk
• Longer hemofilter life

Monchi M et al. Intensive Care Med. 2004
30260-5
Kutsogiannis DJ et al. Kidney Int 2005672361-7
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UF Heparin vs. LMW Heparin vs. Citrate
Unfractionated Heparin
LMW Heparin
Citrate
Hoffbauer R et al. Kidney Int 1999561578-1583.
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Citrate anticoagulation
CitrateiCa
Calcium citrate
Biologically inactive measurable as total Ca

• No clotting if serum ionized Ca is lt 0.20
  mmol/l
• Minimal clotting if serum ionized Ca is lt 0.20
  mmol/l
• On return to patient blood has normal serum
  ionized calcium levels

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Citrate metabolism

• Citric acid has plasma half life of 5 mins
• Rapidly metabolized by liver, kidney and muscle
  cells

Na3Citrate 3H2CO3
Citric Acid 3NaHCO3
3H2CO3 H2O 3NaHCO3
4H2O 6CO2
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Commercial Citrate Solutions for CRRT
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Citrate anticoagulation CVVHDF
4 trisodium citrate
Ca gluconate infusion via separate central line
Qb150-170 mls/min
Dialysate effluent / Ultrafiltrate
Dialysate
Hemofilter
Na 110, K 4, Cl 110.5, Mg 0.5 Calcium 0
Replacement fluid Na 140, K 4,Cl 121, Mg 0.5,
HCO3 33.3 Calcium 0
Cai 0.25-0.35 mmol/l
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Metabolic consequences

• Citrate acts as a buffer
• 1 mmol citrate 3 mmol bicarbonate
• Metabolic alkalosis
• TSC contains substantial amt of Na
• Hypernatremia
• Calcium-citrate complex lost in UF
• Hypocalcemia
• Requires Ca replacement
• Citrate toxicity

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Calcium distribution in plasma
Complexed calcium (10)(salts, calcium
phosphate) 0.05 mmol/L
Protein-bound calcium (40) (albumin) 0.95
1.2 mmol/L
Total calcium 2.2 - 2.6 mmol/L 4.4-5.2
mEq/l 8.8-10.4 mg/dl
Ionized calcium (50) 1.1 1.3 mmol/L
40
Calcium
3
12
Complexed calcium
2
8
mmol/L
mg/dL
Protein bound calcium
Total calcium
1
4
Ionized calcium
41
Calcium gap
3
12
Complexed calcium
Calcium citrate
2
8
mmol/L
mg/dL
Protein bound calcium
Total calcium
1
4
Ionized calcium
42
Total to ionized calcium gap

• If high rate of citrate infusion or hepatic
  dysfunction
• Accumulation of calcium citrate (total)
• Progressive decrease in systemic ionized level
  indicative of citrate accumulation/toxicity

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Citrate accumulation/toxicity

• Progressive ionized hypocalcemia with increasing
  serum total calcium
• Cardiac arrhythmias-exceptionally rare with CRRT
• Avoid by
• Keeping patient Cai level gt 0.9 mmol/l
• Monitoring Cai/Total Ca ratio

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Monitoring

• Circuit serum ionized calcium q 6-8H
• keep 0.25-0.35 mmol/l
• Systemic serum ionized calcium q 6-8H
• keep 0.90-1.0 mmol/l
• Serum Total Ca, PO4 and Mg q 12 -24H

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Management of citrate accumulation

• Reduce blood flow rate if possible
• Reduce citrate infusion
• Increase diffusive clearance-increase dialysate
  flow
• Consider using no anticoagulation if marked
  coagulopathy
• Consider prostacycline if heparin undesirable

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Magnesium and Phosphate

• Hypophosphatemia and Hypophosphatemia occur in
  almost all patients on CRRT for 48 hours.
• Management
• Routinely supplement patients with IV MgSO4 and
  PO4 on regular basis
• Magnesium sulphate 2 gm IV q 8-12 H,
• Sodium phosphate 20 mmol in 250 mls IV fluid over
  3-4 hours q 8-12 hours

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Calcium replacement

• Progressive depletion of iCa with continuous
  citrate infusions
• Risk of hypocalcemia
• Calcium infusion - either CaCl2 or Ca gluconate
• Must be via CENTRAL LINE if CaCl2
• Risk of severe local tissue necrosis
• Preferably NOT via CRRT circuit
• Titrate to maintain systemic iCa 0.90-1.00 mmol/L

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Regional Citrate Anticoagulation for CRRT

• Advantages
• Anticoagulation restricted to extracorporeal
  circuit
• Decreased risk of bleeding
• Does not induce thrombocytopenia
• Longer hemofilter life
• Disadvantages
• Complex management of solutions
• Metabolic complications
• Requires close monitoring of calcium, pH,
  electrolytes and clotting times
• Citrate toxicity if citrate inadequately
  metabolized
• No citrate solution approved by Health Canada for
  intended use in CRRT

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Prostacycline PGI2

• Vasodilator
• Inhibits platelet function
• aggregation
• activation
• adhesion
• No effect on on intrinsic clotting system
• Short acting
• Main indication CRRT in hepatic failure
• 4ng/kg/min

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Prostacycline CVVHDF
PGI2 4ng/min
Replacement fluid Na 140, K 4,Cl 110.5, Mg
0.5,HCO3 32, Ca 1
Qb 180 mls/min
Effluent / Ultrafiltrate
Hemofilter
Dialysate Na 140, K 4,Cl 110.5, Mg 0.5,HCO3 32,
Ca 1
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Prostacycline issues

• Vasodilator
• Hypotension, especially if inadvertent bolus
  given
• Slight increased risk of cerebral edema
• Slight increased risk of variceal bleeding
• Slower gastric emptying

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Prostacycline challenges

• Not as effective as citrate or heparin
• Must be mixed in supplied diluent-high
  concentration.
• Must be infused via narrow non-compliant
  heparin tubing using syringe pump.
• Costly but no more so than citrate.

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When should we transition CRRT to IHD

• Little data
• Hemodynamically stable
• No vasopressor support
• Wish to mobilize patient
• Need CRRT machine for more unstable patient

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When should we stop CRRT?

• When urine output,
• Without diuretics, 450 mls/day
• With diuretics 2,400 mls/day

Uchino S et al Crit Care Med In Press
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Probability of successful CRRT discontinuation
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Probability of successful CRRT discontinuation
Diuretics (-)
436 ml
Diuretics ()
Sensitivity
2330 ml
1-specificity
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Summary

• Must have good dialysis access
• Keep Filtration Fraction 25
• Keep blood pump speed gt 150 mls/hr
• No anticoagulation is a viable option if severe
  coagulopathy
• Heparin if need for systemic anticoagulation
• Citrate is safe default if no need for systemic
  heparin
• Caution with citrate in liver disease
• Prostacycline if significant hepatic failure or
  citrate toxicity
• Remember to monitor and supplement Mg and PO4
• Transition to IHD when hemodynacilly stable
• Discontinue CRRT when adequate urine output

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Thank you for your attention!