Molecular Absorbents Recirculating System MARS Albumin Dialysis

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Molecular Absorbents Recirculating System
(MARS)Albumin Dialysis

• Marco Maggiorini
• Intensive Care Unit
• Department of Internal Medicine
• University Hospital Zurich

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Liver failure - endogenous intoxication
Ongoing Imbalance of
water-soluble and non-soluble
substances
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Transport of protein bound substances
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Accumulation of non-water-soluble substances
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Accumulation of non water-soluble substances
Albumin binding capacity in liver failure
Klammt et al., 3rd ISAD 2001
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Toxin removal
MARS Therapy
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Main indication groupsInternational MARS
Registry
13 Liver failure post LTx
5 LF post liver surgery
5 Others
51 Decompensated chronic liver disease
26 Acute liver failure / dysfunction
n287, 51 centers
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Liver Failure
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MARS therapy - currently investigated in

• Decompensated chronic liver disease
• Acute-on-Chronic Liver Failure
• Decompensated end-stage cirrhosis
• Acute liver failure / liver dysfunction
• Acute liver failure
• Acute drug induced cholestasis
• Hypoxic liver failure
• Liver failure / dysfunction post liver
  transplantation
• Primary graft dysfunction
• Primary graft non function
• Liver failure / dysfunction post liver surgery
• Intractable pruritus in chronic cholestatic
  syndromes
• Multi organ failure

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The MARS and PRISMA
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The MARS principle
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The MARS membrane
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The MARS membrane


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The MARS membrane
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The DiaFLUX filter
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MARS Absorber cartridges

• Activated charcoal column (diaMARS AC250)
• Anion-exchanger resin column (diaMARS IE 250)

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Intermittent MARS treatment strategy

• Albumin circuit
• 600 ml 20 human albumin
• Flow 150-250 ml/min ( 20 less then blood flow)
• Patient circuit
• Blood flow 150-250 ml/min
• Dialysate flow intermittent strategy 300-500
  ml/min
• Dialysate flow CRRT strategy 2l/h
• Duration of treatment
• Liver dysfunction 6-8h MARS
• Liver and renal dysfunction 6-8h MARS 16-18h
  CRRT

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MARS circuit anticoagulation

• Unfractioned heparin
• Wash MARS circuit with 10000 IU heparin
• 200-800 IU heparin infusion before MARS filter
• ACT optimal range 150-180 s

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MARS associated alteration of coagulation
factors

• Retrospective analysis of coagulopathy/ bleeding
  complications observed during 83 consecutive MARS
  sessions in 21 patients (11 men)
• INR 1.7 ? 1.8 (n81, plt0.0001)
• fibrin D-dimers 1.54 ? 2.46 mg/l (n61,
  plt0.0001)
• platelet counts 68 ? 50 x 109/l (n82,
  plt0.0001)
• Fibrinogen 1.9 ? 1.6 g/l (n80, plt0.0001)

Schüppbach et al (sumbitted)
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MARS associated alteration of coagulation
factors

• Retrospective analysis of coagulopathy/ bleeding
  complications observed during 83 consecutive MARS
  sessions in 21 patients (11 men)
• - median age 46 y.
• median 3 sessions/pat.
• median duration/session 8 hours.

Schüppbach et al (sumbitted)
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MARS associated alteration of coagulation
factors
Schüppbach et al (sumbitted)
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MARS associated alteration of coagulation
factors

• pre-treatment values of bleeding vs. non-bleeding
  sessions
• bleeding non-bleeding
• median INR 2.1 vs. 1.6 (p0.001)
• platelet count (x109/l) 40 vs. 68 (p0.042)
• plasma fibrinogen (g/l) 0.8 vs. 2.0 (p0.008)
• fibrin D-dimer (mg/l) 5.75 vs. 1.38 (p0.044)

Schüppbach et al (sumbitted)
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Univariate/Multivariate analysis of factors
associated with bleeding
Independent predictors in multivariate analysis
Schüppbach et al (sumbitted)
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MARS associated alteration of coagulation
factors
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MARS circuit anticoagulation

• Prostacyclin I2 (Epoprostenol)
• Rational Reversible inhibition of platelet
  activation by decreasing the expression of
  platelet fibrinogen receptor and P-selectin, and
  reduction of the heterotypic platelet-leukocyte
  aggregation.
• Prior to treatment up-titration (1ng/kg/min) to
  reach 5 ng/kg/min within 30 min.
• Treatment start 3-5ng/kg/min before MARS filter
• Ev. add heparin to reach an ACT between 120-150 s

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Thromboelastography (TEG)
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Thromboelastography (TEG)
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Thromboelastography (TEG)
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Modified thromboelastography (TEG)
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Thromboelastography (TEG)
Before
30 min.
Within 1h of end
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Thromboelastography (TEG)
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MARS associated alteration of coagulation
factors

• Safety considerations
• Anticoagulation regimen
• Prostaglandin I2 is preferred (transitory
  platelets inhibition)
• Add heparin if necessary (ACT 120-150 s)
• Monitoring
• TEG preferred to standard coagulation parameters
• Substitution with FFP in high risk patients
• Contraindication
• Overt DIC
• Fibrinogen lt 1.0 g/l
• Platelet lt 30000 /µl

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MARS associated alteration of coagulation
factors

• TEG in Patients at high risk of bleeding

Doria et al. Clin Transp 2004, 18365
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MARS associated alteration of coagulation
factors

• Safety considerations
• Patients at high risk of bleeding
• Platelets lt 50000 /µl
• TEG reaction time gt 800 s
• TEG constant time gt 1500 s
• TEG ? angle lt 30 degree
• TEG maximal amplitude lt 45 mm

Doria et al. Clin Transp 2004, 18365