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Published in: Critical Care 2/2006

Open Access 01-04-2006 | Research

Antithrombin supplementation for anticoagulation during continuous hemofiltration in critically ill patients with septic shock: a case-control study

Authors: Damien du Cheyron, Bruno Bouchet, Cédric Bruel, Cédric Daubin, Michel Ramakers, Pierre Charbonneau

Published in: Critical Care | Issue 2/2006

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Abstract

Introduction

Acquired antithrombin III (AT) deficiency may induce heparin resistance and premature membrane clotting during continuous renal replacement therapy (CRRT). The purpose of this study was to evaluate the effect of AT supplementation on filter lifespan in critically ill patients with septic shock requiring CRRT.

Methods

We conducted a retrospective case-control analysis based on a 4-year observational study with prospectively collected data in two medical intensive care units in a university hospital. In all, 106 patients with septic shock underwent CRRT during the study period (55 during 2001 to 2002 and 51 during 2003 to 2004). Of these, 78 had acquired AT deficiency (plasma level below 70%) at onset of renal supportive therapy, 40 in the first 2-year period and 38 in the last 2-year period. In the latter intervention period, patients received AT supplementation (50 IU/kg) during CRRT each time that plasma AT activity, measured once daily, fell below 70%.

Results

In a case-control analysis of the 78 patients with acquired AT deficiency, groups were similar for baseline characteristics, except in severity of illness as assessed by a higher Simplified Acute Physiology Score (SAPS) II after 2002. In comparison with controls, cases had a significantly greater AT level after AT supplementation, but not at baseline, and a smaller number of episodes of clots, without excess bleeding risk. The median hemofilter survival time was longer in the AT group than in the heparin group (44.5 versus 33.4 hours; p = 0.0045). The hemofiltration dose, assessed by the ratio of delivered to prescribed ultrafiltration, increased during intervention. AT supplementation was independently associated with a decrease in clotting rate, whereas femoral angioaccess and higher SAPS II were independent predictors of filter failure. However, mortality did not differ between periods, in the control period the observed mortality was significantly higher than predicted by the SAPS II score, unlike in the treatment period.

Conclusion

In sepsis patients requiring CRRT and with acquired AT deficiency, anticoagulation with unfractionated heparin plus AT supplementation prevent premature filter clotting and may contribute to improving outcome, but the cost-effectiveness of AT remains to be determined.
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Literature
1.
go back to reference Annane D, Aegerter P, Jars-Guincestre MC, Guidet B: Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 2003, 168: 165-172. 10.1164/rccm.2201087CrossRefPubMed Annane D, Aegerter P, Jars-Guincestre MC, Guidet B: Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 2003, 168: 165-172. 10.1164/rccm.2201087CrossRefPubMed
2.
3.
go back to reference Seitz R, Wolf M, Egbring R, Havemann K: The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution. Eur J Haematol 1989, 43: 22-28.CrossRefPubMed Seitz R, Wolf M, Egbring R, Havemann K: The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution. Eur J Haematol 1989, 43: 22-28.CrossRefPubMed
4.
go back to reference Wilson RF, Mammen EF, Robson MC, Heggers JP, Soullier G, DePoli PA: Antithrombin, prekallikrein, and fibronectin levels in surgical patients. Arch Surg 1986, 121: 635-640.CrossRefPubMed Wilson RF, Mammen EF, Robson MC, Heggers JP, Soullier G, DePoli PA: Antithrombin, prekallikrein, and fibronectin levels in surgical patients. Arch Surg 1986, 121: 635-640.CrossRefPubMed
5.
go back to reference Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P: Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest 1992, 101: 816-823.CrossRefPubMed Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P: Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest 1992, 101: 816-823.CrossRefPubMed
6.
go back to reference Lorente JA, Garcia-Frade LJ, Landin L, de Pablo R, Torrado C, Renes E, Garcia-Avello A: Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 1993, 103: 1536-1542.CrossRefPubMed Lorente JA, Garcia-Frade LJ, Landin L, de Pablo R, Torrado C, Renes E, Garcia-Avello A: Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 1993, 103: 1536-1542.CrossRefPubMed
7.
go back to reference Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF: Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Crit Care 2004, 8: R82-R90. 10.1186/cc2459PubMedCentralCrossRefPubMed Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF: Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Crit Care 2004, 8: R82-R90. 10.1186/cc2459PubMedCentralCrossRefPubMed
8.
go back to reference Salmon J, Cardigan R, Mackie I, Cohen SL, Machin S, Singer M: Continuous venovenous haemofiltration using polyacrylonitrile filters does not activate contact system and intrinsic coagulation pathways. Intensive Care Med 1997, 23: 38-43. 10.1007/s001340050288CrossRefPubMed Salmon J, Cardigan R, Mackie I, Cohen SL, Machin S, Singer M: Continuous venovenous haemofiltration using polyacrylonitrile filters does not activate contact system and intrinsic coagulation pathways. Intensive Care Med 1997, 23: 38-43. 10.1007/s001340050288CrossRefPubMed
9.
go back to reference Singer M, McNally T, Screaton G, Mackie I, Machin S, Cohen SL: Heparin clearance during continuous veno-venous haemofiltration. Intensive Care Med 1994, 20: 212-215. 10.1007/BF01704703CrossRefPubMed Singer M, McNally T, Screaton G, Mackie I, Machin S, Cohen SL: Heparin clearance during continuous veno-venous haemofiltration. Intensive Care Med 1994, 20: 212-215. 10.1007/BF01704703CrossRefPubMed
10.
go back to reference Williams MR, D'Ambra AB, Beck JR, Spanier TB, Morales DL, Helman DN, Oz MC: A randomized trial of antithrombin concentrate for treatment of heparin resistance. Ann Thorac Surg 2000, 70: 873-877. 10.1016/S0003-4975(00)01550-2CrossRefPubMed Williams MR, D'Ambra AB, Beck JR, Spanier TB, Morales DL, Helman DN, Oz MC: A randomized trial of antithrombin concentrate for treatment of heparin resistance. Ann Thorac Surg 2000, 70: 873-877. 10.1016/S0003-4975(00)01550-2CrossRefPubMed
11.
go back to reference Anonymous: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20: 864-874.CrossRef Anonymous: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20: 864-874.CrossRef
12.
go back to reference Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M: Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001, 86: 1327-1330.PubMed Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M: Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001, 86: 1327-1330.PubMed
13.
go back to reference Le Gall JR, Lemeshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 270: 2957-2963. 10.1001/jama.270.24.2957CrossRefPubMed Le Gall JR, Lemeshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 270: 2957-2963. 10.1001/jama.270.24.2957CrossRefPubMed
14.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-710.CrossRefPubMed Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-710.CrossRefPubMed
15.
go back to reference Ilias W, List W, Decruyenaere J, Lignian H, Knaub S, Schindel F, Keinecke HO, Heinrichs H, Thijs LG: Antithrombin III in patients with severe sepsis: a pharmacokinetic study. Intensive Care Med 2000, 26: 704-715. 10.1007/s001340051236CrossRefPubMed Ilias W, List W, Decruyenaere J, Lignian H, Knaub S, Schindel F, Keinecke HO, Heinrichs H, Thijs LG: Antithrombin III in patients with severe sepsis: a pharmacokinetic study. Intensive Care Med 2000, 26: 704-715. 10.1007/s001340051236CrossRefPubMed
16.
go back to reference Kellum JA, Mehta RL, Angus DC, Palevsky P, Ronco C: The first international consensus conference on continuous renal replacement therapy. Kidney Int 2002, 62: 1855-1863. 10.1046/j.1523-1755.2002.00613.xCrossRefPubMed Kellum JA, Mehta RL, Angus DC, Palevsky P, Ronco C: The first international consensus conference on continuous renal replacement therapy. Kidney Int 2002, 62: 1855-1863. 10.1046/j.1523-1755.2002.00613.xCrossRefPubMed
17.
go back to reference Kozek-Langenecker SA, Kettner SC, Oismueller C, Gonano C, Speiser W, Zimpfer M: Anticoagulation with prostaglandin E1 and unfractionated heparin during continuous venovenous hemofiltration. Crit Care Med 1998, 26: 1208-1212. 10.1097/00003246-199807000-00021CrossRefPubMed Kozek-Langenecker SA, Kettner SC, Oismueller C, Gonano C, Speiser W, Zimpfer M: Anticoagulation with prostaglandin E1 and unfractionated heparin during continuous venovenous hemofiltration. Crit Care Med 1998, 26: 1208-1212. 10.1097/00003246-199807000-00021CrossRefPubMed
18.
go back to reference Shulman RI, Singer M, Rock J: Continuous renal replacement therapy. Keeping the circuit open: lessons from the lab. Blood Purif 2002, 20: 275-281. 10.1159/000047020CrossRefPubMed Shulman RI, Singer M, Rock J: Continuous renal replacement therapy. Keeping the circuit open: lessons from the lab. Blood Purif 2002, 20: 275-281. 10.1159/000047020CrossRefPubMed
19.
go back to reference Zimmerman JL: Use of blood products in sepsis: an evidence-based review. Crit Care Med 2004, 32: S542-S547. 10.1097/01.CCM.0000145906.63859.1ACrossRefPubMed Zimmerman JL: Use of blood products in sepsis: an evidence-based review. Crit Care Med 2004, 32: S542-S547. 10.1097/01.CCM.0000145906.63859.1ACrossRefPubMed
20.
go back to reference Kutsogiannis DJ, Gibney RT, Stollery D, Gao J: Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 2005, 67: 2361-2367. 10.1111/j.1523-1755.2005.00342.xCrossRefPubMed Kutsogiannis DJ, Gibney RT, Stollery D, Gao J: Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 2005, 67: 2361-2367. 10.1111/j.1523-1755.2005.00342.xCrossRefPubMed
21.
go back to reference Bastien O, French P, Paulus S, Filley S, Berruyer M, Dechavanne M, Estanove S: Antithrombin III deficiency during continuous venovenous hemodialysis. Contrib Nephrol 1995, 116: 154-158.CrossRefPubMed Bastien O, French P, Paulus S, Filley S, Berruyer M, Dechavanne M, Estanove S: Antithrombin III deficiency during continuous venovenous hemodialysis. Contrib Nephrol 1995, 116: 154-158.CrossRefPubMed
22.
go back to reference Fourrier F, Jourdain M, Tournoys A: Clinical trial results with antithrombin III in sepsis. Crit Care Med 2000, 28: S38-S43. 10.1097/00003246-200009001-00009CrossRefPubMed Fourrier F, Jourdain M, Tournoys A: Clinical trial results with antithrombin III in sepsis. Crit Care Med 2000, 28: S38-S43. 10.1097/00003246-200009001-00009CrossRefPubMed
23.
go back to reference Eisele B, Lamy M, Thijs LG, Keinecke HO, Schuster HP, Matthias FR, Fourrier F, Heinrichs H, Delvos U: Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 1998, 24: 663-672. 10.1007/s001340050642CrossRefPubMed Eisele B, Lamy M, Thijs LG, Keinecke HO, Schuster HP, Matthias FR, Fourrier F, Heinrichs H, Delvos U: Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 1998, 24: 663-672. 10.1007/s001340050642CrossRefPubMed
24.
go back to reference Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, et al.: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. Jama 2001, 286: 1869-1878. 10.1001/jama.286.15.1869CrossRefPubMed Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, et al.: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. Jama 2001, 286: 1869-1878. 10.1001/jama.286.15.1869CrossRefPubMed
25.
go back to reference Levy JH, Despotis GJ, Szlam F, Olson P, Meeker D, Weisinger A: Recombinant human transgenic antithrombin in cardiac surgery: a dose-finding study. Anesthesiology 2002, 96: 1095-1102. 10.1097/00000542-200205000-00011CrossRefPubMed Levy JH, Despotis GJ, Szlam F, Olson P, Meeker D, Weisinger A: Recombinant human transgenic antithrombin in cardiac surgery: a dose-finding study. Anesthesiology 2002, 96: 1095-1102. 10.1097/00000542-200205000-00011CrossRefPubMed
26.
go back to reference Lemmer JH Jr, Despotis GJ: Antithrombin III concentrate to treat heparin resistance in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 2002, 123: 213-217. 10.1067/mtc.2002.119060CrossRefPubMed Lemmer JH Jr, Despotis GJ: Antithrombin III concentrate to treat heparin resistance in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 2002, 123: 213-217. 10.1067/mtc.2002.119060CrossRefPubMed
27.
go back to reference Avidan MS, Levy JH, Scholz J, Delphin E, Rosseel PM, Howie MB, Gratz I, Bush CR, Skubas N, Aldea GS, et al.: A phase III, double-blind, placebo-controlled, multicenter study on the efficacy of recombinant human antithrombin in heparin-resistant patients scheduled to undergo cardiac surgery necessitating cardiopulmonary bypass. Anesthesiology 2005, 102: 276-284. 10.1097/00000542-200502000-00007CrossRefPubMed Avidan MS, Levy JH, Scholz J, Delphin E, Rosseel PM, Howie MB, Gratz I, Bush CR, Skubas N, Aldea GS, et al.: A phase III, double-blind, placebo-controlled, multicenter study on the efficacy of recombinant human antithrombin in heparin-resistant patients scheduled to undergo cardiac surgery necessitating cardiopulmonary bypass. Anesthesiology 2005, 102: 276-284. 10.1097/00000542-200502000-00007CrossRefPubMed
28.
go back to reference Lima EQ, Dirce MT, Castro I, Yu L: Mortality risk factors and validation of severity scoring systems in critically ill patients with acute renal failure. Ren Fail 2005, 27: 547-556. 10.1080/08860220500198771CrossRefPubMed Lima EQ, Dirce MT, Castro I, Yu L: Mortality risk factors and validation of severity scoring systems in critically ill patients with acute renal failure. Ren Fail 2005, 27: 547-556. 10.1080/08860220500198771CrossRefPubMed
29.
go back to reference Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G: Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000, 356: 26-30. 10.1016/S0140-6736(00)02430-2CrossRefPubMed Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G: Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000, 356: 26-30. 10.1016/S0140-6736(00)02430-2CrossRefPubMed
Metadata
Title
Antithrombin supplementation for anticoagulation during continuous hemofiltration in critically ill patients with septic shock: a case-control study
Authors
Damien du Cheyron
Bruno Bouchet
Cédric Bruel
Cédric Daubin
Michel Ramakers
Pierre Charbonneau
Publication date
01-04-2006
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2006
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc4853

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