Bleeding and coagulopathy are complications of cardiac surgery, particularly in procedures involving prolonged CPB. This study assessed the ability of ROTEM data to predict which patients are at high risk of bleeding after cardiac surgery with CPB. Our results suggest that ROTEM data do not substantially improve prediction of chest tube drainage, beyond frequently used clinical and laboratory parameters. Although several ROTEM parameters were individually associated with CTO, they did not significantly improve predictive accuracy when added to statistical models comprising clinical and routine laboratory parameters.
Several methods of comparing clinical and laboratory predictors of CTO (model 1) to model 2, which additionally included ROTEM data, yielded equivocal results as to ROTEM's predictive efficacy. Using CTO as a continuous outcome, inclusion of ROTEM data significantly improved prediction of CTO. When CTO was dichotomized at the 75th and 90th percentiles, Nagelkerke R2 and F tests also indicated that inclusion of ROTEM data led to significant improvement in prediction of CTO. However, AUC and net reclassification improvement measures of significance indicated that inclusion of ROTEM data did not significantly improve prediction over clinical and laboratory data alone.
Despite the inconsistency of the results, the AUC and NRI are thought to be more accurate measures of predictive model performance.24 With their incorporation of sensitivity, specificity, and reclassification tables, they tend to be more conservative and clinically applicable than other statistical tests of significance. A criticism of the AUC is that large independent associations between a new model covariate and the outcome are required to lead to significant changes in the AUC. Nevertheless, the concurrent insignificance of our NRI results strengthens our conclusion that ROTEM data do not significantly improve the model's ability to predict bleeding.
A strength of this study is that the ROTEM results were not provided to clinicians caring for the patients. This allowed robust interpretation of the value of ROTEM in predicting CTO, without therapies being based on the ROTEM values that might have affected CTO. This strength is also a limitation, because it precluded assessment of the value of ROTEM in determining transfusion outcomes. Other limitations of this study include the relatively low amount of bleeding (median = 390 mL, interquartile range = 260–600 mL) and few patients with severe blood loss, even after selecting patients at high risk of bleeding during the second part of the study. AUC, NRI, sensitivity, and PPV estimates will have been affected by the low CTO. Another important limitation of this study is that it is a single-center study. Clinical and transfusion practices particular to this institution likely affected CTO and ROTEM values obtained in this study. It is possible that institutions with higher average CTO or transfusion rates may see larger effect sizes of ROTEM variables with a CTO outcome.
Despite these limitations, our results are consistent with previous studies assessing the ability of ROTEM to predict bleeding after cardiac surgery. One study of 58 patients undergoing a coronary artery bypass graft procedure found that ROTEM parameters had high NPV and specificity, but low PPV and sensitivity. The investigators concluded that postoperative ROTEM data poorly predicted massive postoperative bleeding.25 The authors of another study of 150 patients with cardiac surgery involving CPB, which found that ROTEM had PPVs ranging from 63% to 73% and sensitivities ranging from 86% to 95%, concluded that ROTEM was not sufficiently sensitive and specific to use in screening for patients at high risk of bleeding.26 These findings are not surprising given the numerous factors that can contribute to massive blood loss in the setting of cardiac surgery, such as surgical bleeding, hypothermia, and acidosis, which ROTEM parameters would not assess.
Common measures of coagulopathy, such as platelet count, fibrinogen, INR, and PTT, have also been shown to be poor predictors of bleeding, but are often used in the management of bleeding.26,27 Despite its poor prediction of CTO, ROTEM may have value in reducing transfusion by more accurately determining coagulation status than common measures of coagulation.14,19 Several studies found that providing ROTEM values to clinicians reduced transfusion of coagulation products.28,29 A meta-analysis of 9 randomized controlled trials of 776 patients found that use of ROTEM was significantly associated with decreased bleeding and decreased platelet and plasma transfusions, but postoperative mortality remained the same.30,31 Although some institutions report incorporating ROTEM parameters into their transfusion algorithms,32,33 future studies are needed to determine the efficacy of adding ROTEM data to these guidelines.34
Although ROTEM parameters may not improve clinicians' ability to predict bleeding after cardiac surgery, ROTEM results seem to be equally or more strongly associated with bleeding than current clinical and laboratory data, as indicated by our data and prior studies.19,25,26,30 ROTEM technology has advantages over current laboratory tests and thromboelastrography, because of its ease of use and more rapid provision of results than conventional laboratory tests such as fibrinogen, INR, and PTT. Additionally, because of its variety of tests, ROTEM can suggest a cause for the patient's coagulopathy, such as rebound heparinization, hyperfibrinolysis, functional thrombocytopenia, or factor deficiency.17,20,35–39 These diagnoses are rarely obtainable with conventional laboratory tests.
In this study, we evaluated the extent to which adding ROTEM to traditional bleeding risk factors improves classification of risk of bleeding after cardiac surgery using AUC and NRI measures. Although some ROTEM parameters were independently associated with CTO, including them in models of bleeding did not significantly improve the models' predictivity. Nevertheless, ROTEM technology quickly provides a global assessment of coagulopathy that may be effective in the management of bleeding after cardiac surgery involving CPB.
1. Paparella D, Brister SJ, Buchanan MR. Coagulation disorders of cardiopulmonary bypass: a review. Intensive Care Med 2004;30:1873–81
2. Karkouti K, McCluskey SA, Syed S, Pazaratz C, Poonawala H, Crowther MA. The influence of perioperative coagulation status on postoperative blood loss in complex cardiac surgery. Anesth Analg 2010;110:1533–40
3. Besser MW, Klein AA. The coagulopathy of cardiopulmonary bypass. Crit Rev Clin Lab Sci 2010;47:197–212
4. Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg 2009;108:759–69
5. Goodnough LT. Risks of blood transfusion. Anesthesiol Clin North Am 2005;23:241–52
6. Koch CG, Li L, Duncan AI, Mihaljevic T, Loop FD, Starr NJ, Blackstone EH. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Ann Thorac Surg 2006;81:1650–7
7. Bennett-Guerrero E, Zhao Y, O'Brien SM, Ferguson TB Jr, Peterson ED, Gammie JS, Song HK. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA 2010;304:1568–75
8. Goodnough LT, Johnston MFM, Toy PTCY; Transfusion Medicine Academic Award Group. The variability of transfusion practice in coronary artery bypass surgery. JAMA 1991;265: 86–90
9. Hessel EA, Levy JH. Guidelines for perioperative blood transfusion and conservation in cardiac surgery. Anesth Analg 2010;111:1555–9
10. Likosky DS, FitzGerald DC, Groom RC, Jones DK, Baker RA, Shann KG, Mazer CD, Spiess BD, Body SC. Effect of the Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery Clinical Practice Guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists upon clinical practices. Anesth Analg 2010;111: 316–23
11. Hardy JF, de Moerloose P, Samama M. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anaesth 2004;51:293–310
12. Ferraris VA, Ferraris SP, Saha SP, Hessel EA, Haan CK, Royston BD, Bridges CR, Higgins RSD, Despotis G, Brown JR, Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Clinical Practice Guideline. Ann Thorac Surg 2007;83:S27–S86
13. Murphy MF, Stanworth SJ, Yazer M. Transfusion practice and safety: current status and possibilities for improvement. Vox Sang 2011;100:46–59
14. Sniecinski RM, Levy JH. Bleeding and management of coagulopathy. J Thorac Cardiovasc Surg 2011;142:662–7
15. Ebinger T, Ruland A, Lakner M, Schwaiger M. Validity, regulatory registration and approval of ROTEM thromboelastometry. Blood Coagul Fibrinolysis 2010;21:106–7
16. Flisberg P, Rundgren M, Engström M. The effects of platelet transfusions evaluated using rotational thromboelastometry. Anesth Analg 2009;108:1430–2
17. Straub A, Schiebold D, Wendel HP, Hamilton C, Wagner T, Schmid E, Dietz K, Ziemer G. Using reagent-supported thromboelastometry (ROTEM) to monitor haemostatic changes in congenital heart surgery employing deep hypothermic circulatory arrest. Eur J Cardiothorac Surg 2008;34:641–7
18. Leemann H, Lustenberger T, Talving P, Kobayashi L, Bukur M, Brenni M, Brüesch M, Spahn DR, Keel MJB. The role of rotation thromboelastometry in early prediction of massive transfusion. J Trauma 2010;69:1403–9
19. Roullet S, Pillot J, Freyburger G, Biais M, Quinart A, Rault A, Revel P, Sztark F. Rotation thromboelastometry detects thrombocytopenia and hypofibrinogenaemia during orthotopic liver transplantation. Br J Anaesth 2010;104:422–8
20. Luddington RJ. Thromboelastography/thromboelastometry. Clin Lab Haematol 2005;27:81–90
21. Franz RC. ROTEM analysis: a significant advance in the field of rotational thromboelastography. S Afr J Surg 2009;47:2–6
22. Lang T, Bauters A, Braun SL, Potzsch B, von Pape KW, Kolde HJ, Lakner M. Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis 2005;16:301–10
23. Nagelkerke NJD. A note on a general definition of the coefficient of determination. Biometrika 1991;78:691–2
24. Pencina MJ, D'Agostino RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008;27:157–72
25. Davidson SJ, McGrowder D, Roughton M, Kelleher AA. Can ROTEM thromboelastometry predict postoperative bleeding after cardiac surgery? J Cardiothorac Vasc Anesth 2008;22: 655–61
26. Reinhofer M, Brauer M, Franke U, Barz D, Marx G, Losche W. The value of rotation thromboelastometry to monitor disturbed perioperative haemostasis and bleeding risk in patients with cardiopulmonary bypass. Blood Coagul Fibrinolysis 2008;19:212–9
27. Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005;45:1413–25
28. Spalding G, Hartrumpf M, Sierig T, Oesberg N, Kirschke C, Albes J. Cost reduction of perioperative coagulation management in cardiac surgery: value of ‘bedside' thrombelastography (ROTEM). Eur J Cardiothorac Surg 2007;31:1052–7
29. Anderson L, Quasim I, Soutar R, Steven M, Macfie A, Korte W. An audit of red cell and blood product use after the institution of thromboelastometry in a cardiac intensive care unit. Transfus Med 2006;16:31–9
30. Afshari A, Wikkelso A, Brok J, Moller AM, Wetterslev J. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion. Cochrane Database Syst Rev 2011;3:CD007871
31. Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999;88:312–9
32. Levi M, Fries D, Gombotz H, van der Linden P, Nascimento B, Callum JL, Bélisle S, Rizoli S, Hardy JF, Johansson PI, Samama CM, Grottke O, Rossaint R, Henny CP, Goslings JC, Theusinger OM, Spahn DR, Ganter MT, Hess JR, Dutton RP, Scalea TM, Levy JH, Spinella PC, Panzer S, Reesink HW. Prevention and treatment of coagulopathy in patients receiving massive transfusions. Vox Sang 2011;101:154–74
33. Theusinger OM, Spahn DR, Ganter MT. Transfusion in trauma: why and how should we change our current practice? Curr Opin Anaesthesiol 2009;22:305–12
34. Wikkelsoe AJ, Afshari A, Wetterslev J, Brok J, Moeller AM. Monitoring patients at risk of massive transfusion with thrombelastography or thromboelastometry: a systematic review. Acta Anaesthesiol Scand 2011;55:1174–89
35. Theusinger OM, Wanner GA, Emmert MY, Billeter A, Eismon J, Seifert B, Simmen HP, Spahn DR, Baulig W. Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM®
) is associated with higher mortality in patients with severe trauma. Anesth Analg 2011;113:1003–12
36. Schöchl H, Frietsch T, Pavelka M, Jámbor C. Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J Trauma 2009;67:125–31
37. Ganter MT, Hofer CK. Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg 2008;106:1366–75
38. Chen A, Teruya J. Global hemostasis testing thromboelastography: old technology, new applications. Clin Lab Med 2009;29:391–407
39. Johansson PI, Ostrowski SR, Secher NH. Management of major blood loss: an update. Acta Anaesthesiol Scand 2010;54: 1039–49