Skip to main content
Top
Published in: Critical Care 1/2012

Open Access 01-02-2012 | Research

A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

Authors: Björn Meijers, Wim Laleman, Pieter Vermeersch, Frederik Nevens, Alexander Wilmer, Pieter Evenepoel

Published in: Critical Care | Issue 1/2012

Login to get access

Abstract

Introduction

The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens.

Methods

We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis.

Results

Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events.

Conclusions

Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure.
Appendix
Available only for authorised users
Literature
1.
go back to reference Laleman W, Verbeke L, Meersseman P, Wauters J, van Pelt J, Cassiman D, Wilmer A, Verslype C, Nevens F: Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Rev Gastroenterol Hepatol 2011, 5: 523-537. 10.1586/egh.11.47CrossRefPubMed Laleman W, Verbeke L, Meersseman P, Wauters J, van Pelt J, Cassiman D, Wilmer A, Verslype C, Nevens F: Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Rev Gastroenterol Hepatol 2011, 5: 523-537. 10.1586/egh.11.47CrossRefPubMed
2.
go back to reference Laleman W, Wilmer A, Evenepoel P, Verslype C, Fevery J, Nevens F: Review article: non-biological liver support in liver failure. Aliment Pharmacol Ther 2006, 23: 351-363. 10.1111/j.1365-2036.2006.02765.xCrossRefPubMed Laleman W, Wilmer A, Evenepoel P, Verslype C, Fevery J, Nevens F: Review article: non-biological liver support in liver failure. Aliment Pharmacol Ther 2006, 23: 351-363. 10.1111/j.1365-2036.2006.02765.xCrossRefPubMed
3.
go back to reference Tripodi A, Mannucci PM: The coagulopathy of chronic liver disease. N Engl J Med 2011, 365: 147-156. 10.1056/NEJMra1011170CrossRefPubMed Tripodi A, Mannucci PM: The coagulopathy of chronic liver disease. N Engl J Med 2011, 365: 147-156. 10.1056/NEJMra1011170CrossRefPubMed
4.
go back to reference Meijers BKI, Verhamme P, Nevens F, Hoylaerts MF, Bammens B, Wilmer A, Arnout J, Vanrenterghem Y, Evenepoel P: Major coagulation disturbances during fractionated plasma separation and adsorption. Am J Transplant 2007, 7: 2195-2199. 10.1111/j.1600-6143.2007.01909.xCrossRefPubMed Meijers BKI, Verhamme P, Nevens F, Hoylaerts MF, Bammens B, Wilmer A, Arnout J, Vanrenterghem Y, Evenepoel P: Major coagulation disturbances during fractionated plasma separation and adsorption. Am J Transplant 2007, 7: 2195-2199. 10.1111/j.1600-6143.2007.01909.xCrossRefPubMed
5.
go back to reference Faybik P, Bacher A, Kozek-Langenecker SA, Steltzer A, Krenn CG, Unger S, Hetz H: Molecular adsorbent recirculating system and hemostasis in patients at high risk of bleeding: an observational study. Crit Care 2006, 10: R24. 10.1186/cc3985PubMedCentralCrossRefPubMed Faybik P, Bacher A, Kozek-Langenecker SA, Steltzer A, Krenn CG, Unger S, Hetz H: Molecular adsorbent recirculating system and hemostasis in patients at high risk of bleeding: an observational study. Crit Care 2006, 10: R24. 10.1186/cc3985PubMedCentralCrossRefPubMed
6.
go back to reference Doria C, Mandala L, Smith JD, Caruana G, Scott VL, Gruttadauria S, Magnone M, Marino IR: Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system. Clin Transplant 2004, 18: 365-371. 10.1111/j.1399-0012.2004.00172.xCrossRefPubMed Doria C, Mandala L, Smith JD, Caruana G, Scott VL, Gruttadauria S, Magnone M, Marino IR: Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system. Clin Transplant 2004, 18: 365-371. 10.1111/j.1399-0012.2004.00172.xCrossRefPubMed
7.
go back to reference Bachli EB, Schuepbach RA, Maggiorini M, Stocker R, Mullhaupt B, Renner EL: Artificial liver support with the molecular adsorbent recirculating system: activation of coagulation and bleeding complications. Liver Int 2007, 27: 475-484. 10.1111/j.1478-3231.2006.01398.xCrossRefPubMed Bachli EB, Schuepbach RA, Maggiorini M, Stocker R, Mullhaupt B, Renner EL: Artificial liver support with the molecular adsorbent recirculating system: activation of coagulation and bleeding complications. Liver Int 2007, 27: 475-484. 10.1111/j.1478-3231.2006.01398.xCrossRefPubMed
8.
go back to reference Tan HK, Yang WS, Chow P, Lui HF, Choong HL, Wong KS: Anticoagulation minimization is safe and effective in albumin liver dialysis using the molecular adsorbent recirculating system. Artif Organs 2007, 31: 193-199. 10.1111/j.1525-1594.2007.00364.xCrossRefPubMed Tan HK, Yang WS, Chow P, Lui HF, Choong HL, Wong KS: Anticoagulation minimization is safe and effective in albumin liver dialysis using the molecular adsorbent recirculating system. Artif Organs 2007, 31: 193-199. 10.1111/j.1525-1594.2007.00364.xCrossRefPubMed
9.
go back to reference Yang WS, Tan HK, Lui HF, Chow PK, Choong HL, Wong KS: Albumin dialysis in critically ill patients: use versus omission of intradialytic heparin. Artif Organs 2008, 32: 411-416. 10.1111/j.1525-1594.2008.00560.xCrossRefPubMed Yang WS, Tan HK, Lui HF, Chow PK, Choong HL, Wong KS: Albumin dialysis in critically ill patients: use versus omission of intradialytic heparin. Artif Organs 2008, 32: 411-416. 10.1111/j.1525-1594.2008.00560.xCrossRefPubMed
10.
go back to reference Tan HK, Yang WS, Choong HL, Wong KS: Albumin Dialysis Without Anticoagulation in High-Risk Patients: An Observational Study. Artif Organs 2010. doi: 10.1111/j.1525-1594.2010.01065.x Tan HK, Yang WS, Choong HL, Wong KS: Albumin Dialysis Without Anticoagulation in High-Risk Patients: An Observational Study. Artif Organs 2010. doi: 10.1111/j.1525-1594.2010.01065.x
11.
go back to reference Evenepoel P, Maes B, Vanwalleghem J, Kuypers D, Messiaen T, Vanrenterghem Y: Regional citrate anticoagulation for hemodialysis using a conventional calcium-containing dialysate. Am J Kidney Dis 2002, 39: 315-323. 10.1053/ajkd.2002.30551CrossRefPubMed Evenepoel P, Maes B, Vanwalleghem J, Kuypers D, Messiaen T, Vanrenterghem Y: Regional citrate anticoagulation for hemodialysis using a conventional calcium-containing dialysate. Am J Kidney Dis 2002, 39: 315-323. 10.1053/ajkd.2002.30551CrossRefPubMed
12.
go back to reference Hofbauer R, Moser D, Frass M, Oberbauer R, Kaye AD, Wagner O, Kapiotis S, Druml W: Effect of anticoagulation on blood membrane interactions during hemodialysis. kidney int 1999, 56: 1578-1583. 10.1046/j.1523-1755.1999.00671.xCrossRefPubMed Hofbauer R, Moser D, Frass M, Oberbauer R, Kaye AD, Wagner O, Kapiotis S, Druml W: Effect of anticoagulation on blood membrane interactions during hemodialysis. kidney int 1999, 56: 1578-1583. 10.1046/j.1523-1755.1999.00671.xCrossRefPubMed
13.
go back to reference Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, Gangl A: Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med 2003, 31: 2450-2455. 10.1097/01.CCM.0000084871.76568.E6CrossRefPubMed Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, Gangl A: Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med 2003, 31: 2450-2455. 10.1097/01.CCM.0000084871.76568.E6CrossRefPubMed
14.
go back to reference Herget-Rosenthal S, Lison C, Treichel U, Saner S, Pietruck F, Broelsch C, Gerken G, Kribben A: Citrate anticoagulated modified fractionated plasma separation and adsoprtion: First clinical efficacy and safety data in liver failure. J Am Soc Nephrol 2003, 14: 729A. Herget-Rosenthal S, Lison C, Treichel U, Saner S, Pietruck F, Broelsch C, Gerken G, Kribben A: Citrate anticoagulated modified fractionated plasma separation and adsoprtion: First clinical efficacy and safety data in liver failure. J Am Soc Nephrol 2003, 14: 729A.
15.
go back to reference Faybik P, Hetz H, Mitterer G, Krenn CG, Schiefer J, Funk GC, Bacher A: Regional citrate anticoagulation in patients with liver failure supported by a molecular adsorbent recirculating system. Crit Care Med 2011, 39: 273-279. 10.1097/CCM.0b013e3181fee8a4CrossRefPubMed Faybik P, Hetz H, Mitterer G, Krenn CG, Schiefer J, Funk GC, Bacher A: Regional citrate anticoagulation in patients with liver failure supported by a molecular adsorbent recirculating system. Crit Care Med 2011, 39: 273-279. 10.1097/CCM.0b013e3181fee8a4CrossRefPubMed
16.
go back to reference Morgera S: Regional anticoagulation with citrate: expanding its indications. Crit Care Med 2011, 39: 399-400. 10.1097/CCM.0b013e318205c500CrossRefPubMed Morgera S: Regional anticoagulation with citrate: expanding its indications. Crit Care Med 2011, 39: 399-400. 10.1097/CCM.0b013e318205c500CrossRefPubMed
17.
go back to reference Gines P, Quintero E, Arroyo V, Teres J, Bruguera M, Rimola A, Caballería J, Rodés J, Rozman C: Compensated cirrhosis: natural history and prognostic factors. Hepatology 1987, 7: 122-128. 10.1002/hep.1840070124CrossRefPubMed Gines P, Quintero E, Arroyo V, Teres J, Bruguera M, Rimola A, Caballería J, Rodés J, Rozman C: Compensated cirrhosis: natural history and prognostic factors. Hepatology 1987, 7: 122-128. 10.1002/hep.1840070124CrossRefPubMed
18.
go back to reference Katoonizadeh A, Laleman W, Verslype C, Wilmer A, Maleux G, Roskams T, Nevens F: Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010, 59: 1561-1569. 10.1136/gut.2009.189639CrossRefPubMed Katoonizadeh A, Laleman W, Verslype C, Wilmer A, Maleux G, Roskams T, Nevens F: Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010, 59: 1561-1569. 10.1136/gut.2009.189639CrossRefPubMed
19.
go back to reference Mitzner SR, Stange J, Klammt S, Peszynski P, Schmidt R, Nöldge-Schomburg G: Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure. J Am Soc Nephrol 2001, 12: S75-S82.PubMed Mitzner SR, Stange J, Klammt S, Peszynski P, Schmidt R, Nöldge-Schomburg G: Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure. J Am Soc Nephrol 2001, 12: S75-S82.PubMed
20.
go back to reference Krisper P, Stauber RE: Technology insight: artificial extracorporeal liver support--how does Prometheus compare with MARS? Nat Clin Pract Nephrol 2007, 3: 267-276. 10.1038/ncpneph0466CrossRefPubMed Krisper P, Stauber RE: Technology insight: artificial extracorporeal liver support--how does Prometheus compare with MARS? Nat Clin Pract Nephrol 2007, 3: 267-276. 10.1038/ncpneph0466CrossRefPubMed
Metadata
Title
A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System
Authors
Björn Meijers
Wim Laleman
Pieter Vermeersch
Frederik Nevens
Alexander Wilmer
Pieter Evenepoel
Publication date
01-02-2012
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2012
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc11180

Other articles of this Issue 1/2012

Critical Care 1/2012 Go to the issue