Nebulized anticoagulants for acute lung injury - a systematic review of preclinical and clinical investigations

Critical Care

Volumn 16, Issue 2, 2012, Pages

  Tuinman, Pieter R ^a   Dixon, Barry ^b   Levi, Marcel ^a   Juffermans, Nicole P ^a   Schultz, Marcus J ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b ST VINCENT S HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICOAGULANT AGENT; ANTITHROMBIN; DANAPAROID; DROTRECOGIN; HEPARIN; LISOFYLLINE;

ACUTE LUNG INJURY; ANTICOAGULANT THERAPY; ARTICLE; ARTIFICIAL VENTILATION; BLEEDING; BLOOD CLOTTING DISORDER; DRUG DOSAGE FORM COMPARISON; DRUG EFFICACY; DRUG SAFETY; EMBASE; HUMAN; LUNG BURN; MEDLINE; NEBULIZATION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PNEUMONIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SINGLE DRUG DOSE; SURVIVAL; SYSTEMATIC REVIEW; ANIMAL; INHALATIONAL DRUG ADMINISTRATION; NEBULIZER;

ACUTE LUNG INJURY; ADMINISTRATION, INHALATION; ANIMALS; ANTICOAGULANTS; HUMANS; NEBULIZERS AND VAPORIZERS;

EID: 84861116554     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/cc11325     Document Type: Article

References (59)

1. Gunther A, Mosavi P, Heinemann S, Ruppert C, Muth H, Markart P, Grimminger F, Walmrath D, Temmesfeld-Wollbruck B, Seeger W. Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med 2000, 161:454-462.
2. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000, 342:1334-1349. 10.1056/NEJM200005043421806, 10793167.
3. Bastarache JA, Ware LB, Bernard GR. The role of the coagulation cascade in the continuum of sepsis and acute lung injury and acute respiratory distress syndrome. Semin Respir Crit Care Med 2006, 27:365-376. 10.1055/s-2006-948290, 16909370.
4. Schultz MJ, Haitsma JJ, Zhang H, Slutsky AS. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia - a review. Crit Care Med 2006, 34:871-877.
5. Levi M, Schultz MJ, Rijneveld AW, Van Der Poll T. Bronchoalveolar coagulation and fibrinolysis in endotoxemia and pneumonia. Crit Care Med 2003, 31:S238-S242. 10.1097/01.CCM.0000057849.53689.65, 12682446.
6. Afshari A, Wetterslev J, Brok J, Moller AM. Antithrombin III for critically ill patients. Cochrane Database Syst Rev 2008, CD005370.
7. Ware LB, Fang X, Matthay MA. Protein C and thrombomodulin in human acute lung injury. Am J Physiol Lung Cell Mol Physiol 2003, 285:L514-L521.
8. Ware LB, Matthay MA, Parsons PE, Thompson BT, Januzzi JL, Eisner MD. Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med 2007, 35:1821-1828. 10.1097/01.CCM.0000221922.08878.49, 2764536, 17667242.
9. Russell JA. Genetics of coagulation factors in acute lung injury. Crit Care Med 2003, 31:S243-S247. 10.1097/01.CCM.0000057870.61079.3E, 12682447.
10. Levi M, ten CH. Disseminated intravascular coagulation. N Engl J Med 1999, 341:586-592. 10.1056/NEJM199908193410807, 10451465.
11. 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. 10.1378/chest.101.3.816, 1531791.
12. Ware LB. Pathophysiology of acute lung injury and the acute respiratory distress syndrome. Semin Respir Crit Care Med 2006, 27:337-349. 10.1055/s-2006-948288, 16909368.
13. Laterre PF, Wittebole X, Dhainaut JF. Anticoagulant therapy in acute lung injury. Crit Care Med 2003, 31:S329-S336. 10.1097/01.CCM.0000057912.71499.A5, 12682461.
14. Gropper MA, Wiener-Kronish J. The epithelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care 2008, 14:11-15. 10.1097/MCC.0b013e3282f417a0, 18195620.
15. Dixon B, Schultz MJ, Smith R, Fink JB, Santamaria JD, Campbell DJ. Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial. Crit Care 2010, 14:R180. 10.1186/cc9286, 3219284, 20937093.
16. Scotton CJ, Krupiczojc MA, Konigshoff M, Mercer PF, Lee YC, Kaminski N, Morser J, Post JM, Maher TM, Nicholson AG, Moffat JD, Laurent GJ, Derian CK, Eickelberg O, Chambers RC. Increased local expression of coagulation factor × contributes to the fibrotic response in human and murine lung injury. J Clin Invest 2009, 119:2550-2563. 2735922, 19652365.
17. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001, 344:699-709. 10.1056/NEJM200103083441001, 11236773.
18. Dhainaut JF, Laterre PF, Janes JM, Bernard GR, Artigas A, Bakker J, Riess H, Basson BR, Charpentier J, Utterback BG, Vincent JL. Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial. Intensive Care Med 2003, 29:894-903.
19. Laterre PF, Garber G, Levy H, Wunderink R, Kinasewitz GT, Sollet JP, Maki DG, Bates B, Yan SC, Dhainaut JF. Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS study. Crit Care Med 2005, 33:952-961. 10.1097/01.CCM.0000162381.24074.D7, 15891319.
20. Liu KD, Levitt J, Zhuo H, Kallet RH, Brady S, Steingrub J, Tidswell M, Siegel MD, Soto G, Peterson MW, Chesnutt MS, Phillips C, Weinacker A, Thompson BT, Eisner MD, Matthay MA. Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am J Respir Crit Care Med 2008, 178:618-623. 10.1164/rccm.200803-419OC, 2542435, 18565951.
21. Angus DC. Drotrecogin alfa (activated) ... a sad final fizzle to a roller-coaster party. Crit Care 2012, 16:107. 10.1186/cc11152, 22309988.
22. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM. 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.286.15.1869, 11597289.
23. Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettila V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003, 290:238-247. 10.1001/jama.290.2.238, 12851279.
24. 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/s001340050642, 9722035.
25. Laterre PF, Opal SM, Abraham E, LaRosa SP, Creasey AA, Xie F, Poole L, Wunderink RG. A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (tifacogin) in patients with severe community-acquired pneumonia. Crit Care 2009, 13:R36. 10.1186/cc7747, 2689471, 19284881.
26. Wunderink RG, Laterre PF, Francois B, Perrotin D, Artigas A, Vidal LO, Lobo SM, San JJ, Hwang SC, Dugernier T, Larosa S, Wittebole X, Dhainaut JF, Doig C, Mendelson MH, Zwingelstein C, Su G, Opal S. Recombinant Tissue Factor Pathway Inhibitor in Severe Community-Acquired Pneumonia: A Randomized Trial. Am J Respir Crit Care Med 2011,
27. Cornet AD, Smit EG, Beishuizen A, Groeneveld AB. The role of heparin and allied compounds in the treatment of sepsis. Thromb Haemost 2007, 98:579-586.
28. Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, Munoz A. Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study). Crit Care Med 2009, 37:1185-1196. 10.1097/CCM.0b013e31819c06bc, 19242322.
29. Honeybourne D. Antibiotic penetration in the respiratory tract and implications for the selection of antimicrobial therapy. Curr Opin Pulm Med 1997, 3:170-174. 10.1097/00063198-199703000-00014, 9193864.
30. Vincent JL, Bernard GR, Beale R, Doig C, Putensen C, Dhainaut JF, Artigas A, Fumagalli R, Macias W, Wright T, Wong K, Sundin DP, Turlo MA, Janes J. Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med 2005, 33:2266-2277. 10.1097/01.CCM.0000181729.46010.83, 16215381.
31. Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, Francois B, Guy JS, Bruckmann M, Rea-Neto A, Rossaint R, Perrotin D, Sablotzki A, Arkins N, Utterback BG, Macias WL. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005, 353:1332-1341. 10.1056/NEJMoa050935, 16192478.
32. Maniatis NA, Letsiou E, Orfanos SE, Kardara M, Dimopoulou I, Nakos G, Lekka ME, Roussos C, Armaganidis A, Kotanidou A. Inhaled activated protein C protects mice from ventilator-induced lung injury. Crit Care 2010, 14:R70. 10.1186/cc8976, 2887192, 20403177.
33. Waerhaug K, Kuzkov VV, Kuklin VN, Mortensen R, Nordhus KC, Kirov MY, Bjertnaes LJ. Inhaled aerosolised recombinant human activated protein C ameliorates endotoxin-induced lung injury in anaesthetised sheep. Crit Care 2009, 13:R51. 10.1186/cc7777, 2689497, 19356243.
34. Slofstra SH, Groot AP, Maris NA, Reitsma PH, Cate HT, Spek CA. Inhalation of activated protein C inhibits endotoxin-induced pulmonary inflammation in mice independent of neutrophil recruitment. Br J Pharmacol 2006, 149:740-746. 10.1038/sj.bjp.0706915, 2014647, 17016502.
35. Kotanidou A, Loutrari H, Papadomichelakis E, Glynos C, Magkou C, Armaganidis A, Papapetropoulos A, Roussos C, Orfanos SE. Inhaled activated protein C attenuates lung injury induced by aerosolized endotoxin in mice. Vascul Pharmacol 2006, 45:134-140. 10.1016/j.vph.2006.06.016, 16959545.
36. Hofstra JJ, Cornet AD, de Rooy BF, Vlaar AP, Van Der Poll T, Levi M, Zaat SA, Schultz MJ. Nebulized antithrombin limits bacterial outgrowth and lung injury in Streptococcus pneumoniae pneumonia in rats. Crit Care 2009, 13:R145. 10.1186/cc8040, 2784363, 19740417.
37. Hofstra JJ, Vlaar AP, Cornet AD, Dixon B, Roelofs JJ, Choi G, Van Der Poll T, Levi M, Schultz MJ. Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury. J Aerosol Med Pulm Drug Deliv 2010, 23:105-111. 10.1089/jamp.2009.0779, 20073557.
38. Enkhbaatar P, Cox RA, Traber LD, Westphal M, Aimalohi E, Morita N, Prough DS, Herndon DN, Traber DL. Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation. Crit Care Med 2007, 35:2805-10. 10.1097/01.CCM.0000291647.18329.83, 18074480.
39. Enkhbaatar P, Esechie A, Wang J, Cox RA, Nakano Y, Hamahata A, Lange M, Traber LD, Prough DS, Herndon DN, Traber DL. Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation. Clin Sci (Lond) 2008, 114:321-329.
40. Ader F, Le BR, Fackeure R, Raze D, Menozzi FD, Viget N, Faure K, Kipnis E, Guery B, Jarraud S, Etienne J, Chidiac C. In vivo effect of adhesion inhibitor heparin on Legionella pneumophila pathogenesis in a murine pneumonia model. Intensive Care Med 2008, 34:1511-1519. 10.1007/s00134-008-1063-2, 18365173.
41. Murakami K, McGuire R, Cox RA, Jodoin JM, Bjertnaes LJ, Katahira J, Traber LD, Schmalstieg FC, Hawkins HK, Herndon DN, Traber DL. Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep. Shock 2002, 18:236-241. 10.1097/00024382-200209000-00006, 12353924.
42. Tasaki O, Mozingo DW, Dubick MA, Goodwin CW, Yantis LD, Pruitt BA. Effects of heparin and lisofylline on pulmonary function after smoke inhalation injury in an ovine model. Crit Care Med 2002, 30:637-643. 10.1097/00003246-200203000-00024, 11998809.
43. Dixon B, Santamaria JD, Campbell DJ. A phase 1 trial of nebulised heparin in acute lung injury. Crit Care 2008, 12:R64. 10.1186/cc6894, 2481447, 18460218.
44. Dixon B, Schultz MJ, Hofstra JJ, Campbell DJ, Santamaria JD. Nebulized heparin reduces levels of pulmonary coagulation activation in acute lung injury. Crit Care 2010, 14:445. 10.1186/cc9269, 3219269, 21067553.
45. Miller AC, Rivero A, Ziad S, Smith DJ, Elamin EM. Influence of nebulized unfractionated heparin and N-acetylcysteine in acute lung injury after smoke inhalation injury. J Burn Care Res 2009, 30:249-256. 10.1097/BCR.0b013e318198a268, 19165116.
46. Idell S. Anticoagulants for acute respiratory distress syndrome: can they work?. Am J Respir Crit Care Med 2001, 164:517-520.
47. Schultz MJ, Dixon B. A breathtaking and bloodcurdling story of coagulation and inflammation in acute lung injury. J Thromb Haemost 2009, 7:2050-2052. 10.1111/j.1538-7836.2009.03639.x, 19817992.
48. Shorr AF, Janes JM, Artigas A, Tenhunen J, Wyncoll DL, Mercier E, Francois B, Vincent JL, Vangerow B, Heiselman D, Leishman AG, Zhu YE, Reinhart K. Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated). Crit Care 2010, 14:R229. 10.1186/cc9382, 3219981, 21176144.
49. Abraham E, Reinhart K, Svoboda P, Seibert A, Olthoff D, Dal NA, Postier R, Hempelmann G, Butler T, Martin E, Zwingelstein C, Percell S, Shu V, Leighton A, Creasey AA. Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study. Crit Care Med 2001, 29:2081-2089. 10.1097/00003246-200111000-00007, 11700399.
50. Van Der Poll T, Levi M, Nick JA, Abraham E. Activated protein C inhibits local coagulation after intrapulmonary delivery of endotoxin in humans. Am J Respir Crit Care Med 2005, 171:1125-1128. 10.1164/rccm.200411-1483OC, 2718442, 15750041.
51. Yuda H, Adachi Y, Taguchi O, Gabazza EC, Hataji O, Fujimoto H, Tamaki S, Nishikubo K, Fukudome K, D'Alessandro-Gabazza CN, Maruyama J, Izumizaki M, Iwase M, Homma I, Inoue R, Kamada H, Hayashi T, Kasper M, Lambrecht BN, Barnes PJ, Suzuki K. Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice. Blood 2004, 103:2196-2204. 10.1182/blood-2003-06-1980, 14604971.
52. Dhand R. Aerosol delivery during mechanical ventilation: from basic techniques to new devices. J Aerosol Med Pulm Drug Deliv 2008, 21:45-60. 10.1089/jamp.2007.0663, 18518831.
53. McCullagh A, Rosenthal M, Wanner A, Hurtado A, Padley S, Bush A. The bronchial circulation - worth a closer look: a review of the relationship between the bronchial vasculature and airway inflammation. Pediatr Pulmonol 2010, 45:1-13.
54. Lahteenmaki K, Kuusela P, Korhonen TK. Bacterial plasminogen activators and receptors. FEMS Microbiol Rev 2001, 25:531-552.
55. Robriquet L, Collet F, Tournoys A, Prangere T, Neviere R, Fourrier F, Guery BP. Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response. Respir Res 2006, 7:41. 10.1186/1465-9921-7-41, 1435891, 16553944.
56. Kipnis E, Guery BP, Tournoys A, Leroy X, Robriquet L, Fialdes P, Neviere R, Fourrier F. Massive alveolar thrombin activation in Pseudomonas aeruginosa-induced acute lung injury. Shock 2004, 21:444-451. 10.1097/00024382-200405000-00008, 15087821.
57. Pruitt BA, Cioffi WG. Diagnosis and treatment of smoke inhalation. J Intensive Care Med 1995, 10:117-127.
58. Enkhbaatar P, Murakami K, Cox R, Westphal M, Morita N, Brantley K, Burke A, Hawkins H, Schmalstieg F, Traber L, Herndon D, Traber D. Aerosolized tissue plasminogen inhibitor improves pulmonary function in sheep with burn and smoke inhalation. Shock 2004, 22:70-75. 10.1097/01.shk.0000129201.38588.85, 15201705.
59. Tuinman PR, Schultz MJ, Juffermans NP. Coagulopathy as a therapeutic target for TRALI: rationale and possible sites of action. Curr Pharm Des 2012,